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Dissertations / Theses on the topic 'Marfaing'

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Published: 4 June 2021
Last updated: 9 February 2022

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1

Rosset, Culleron Sophie. "André Marfaing : les toiles entre 1952 et 1970." Paris 1, 1999. http://www.theses.fr/1999PA010548.

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André Marfaing, originaire de Toulouse, né en 1925, s'installe à Paris en 1949 avec la ferme décision de se consacrer à la peinture. De formation autodidacte, ce jeune artiste, poussé par un profond désir d'échapper au dictat culturel prôné par le milieu artistique toulousain, affiche très tôt une volonté d'indépendance à l'égard de tout enseignement artistique. Sans vouloir réfuter les apports des formes d'art du passé, il estime néanmoins devoir s'en écarter afin d'exprimer le monde qui est en lui. En 1952, sa peinture devient non-figurative et ses toiles, bien qu'encore imprégnées de préoccupations esthétiques de certains de ses illustres ainés, se caractérisent par une palette sombre, sourde et déjà radicale et arbitraire. Marfaing franchit très vite le pas de l'abstraction et la couleur noire s'impose alors comme couleur de prédilection. Préférant travailler les valeurs aux dépens de la couleur, il invente un langage dans lequel noirs, blancs et gris se côtoient, s'épousent ou se heurtent dans un dialogue toujours renouvelé. De leur rencontre nait ce qui apparait le propos fondamental de sa recherche picturale : la traduction de la lumière. D'abord chargées de matière, parfois proches de l'illisibilité, ses toiles deviennent ensuite chaotiques, exprimant le lyrisme d'un geste libéré mais la lucidité du peintre, épris d'ordre et de rigueur et soucieux de garder le contrôle de sa toile, l'engage à épurer toujours son propos. A l'économie de la palette s'ajoute donc une économie de moyens. La matière s'amenuise, se fait lisse ; les contrastes s'accentuent et le nombre de formes se réduit. Travaillant chaque toile avec une même obstination, Marfaing poursuit avec fidélité son entreprise. Dès lors, l'ascétisme de la palette, l'évolution et l'intégrité de sa démarche projette sa peinture au rang d'une peinture jugée difficile d'accès voire austère. Elle engage le spectateur à s'interroger à la fois sur le but recherche et les moyens mis en œuvre pour l'atteindre
Andre Marfaing, born in Toulouse in 1925, settles in paris in 1949 with the firm decision de dedicate himself to painting. Self-taught, this young artist guided by a deep desire to flee the toulousian artistic context, displays very early a will of independence towards all artistic teaching. Without wanting to refute the contributions of the forms of past art, he considers nevertheless to get aside in order to express the world within him. In 1952, his art becomes non-representational and his paintings, though imbued of aesthetic researches of some of his illustrious elders, characterized by a dark palette, muted and already radical and arbitrary. Marfaing passes over quickly the step of abstract art and black appears as a predilection colour. Preferring to work the values at the expense of colours, he invents a language where black, white and grey encounter, join or collide in an always-renewed dialogue. From their encounter arises the fundamental intention of his pictorial research: the translation of light. First weighted with matter, sometimes closed to illegibility, his paintings become then chaotic, expressing the lyrism with a liberated gesture. But the consciousness of the painter, smitten with order and harshness and concerned to keep control of his painting, engages him to always simplify his intention. To the limited palette adds thrift of means. The matter becomes lighter; the contrasts are accentuated and the number of forms is reduced. Working each painting with a same obstinacy, Marfaing pursues faithfully his venture. From that time, the asceticism of his palette, the evolution and integrity of his creative steps casts his painting to the rank judged by some as difficult to reach or even perhaps austere. His painting involves the spectator to wonder on the objective in demand and on the way to reach it
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2

Duval, Catherine. "La maladie de marfan." Clermont-Ferrand 1, 1993. http://www.theses.fr/1993CLF1M009.

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3

Tamarat, Sylvie. "Le syndrome de Marfan néo-natal : à propos d'une observation familiale." Bordeaux 2, 1992. http://www.theses.fr/1992BOR2M081.

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4

Collod, Gwenaëlle. "Hétérogénéité du syndrome de Marfan." Paris 5, 1996. http://www.theses.fr/1996PA05CD01.

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Le syndrome de Marfan (MFS) est une maladie autosomique dominante du tissu conjonctif, caractérisée par des anomalies touchant essentiellement trois systèmes : squelettique, oculaire et cardio-vasculaire. Jusqu'à ce jour, seules des mutations dans le gène de la fibrilline (FBN1), localisé sur le chromosome 15 ,et, composant majeur du réseau microfibrillaire, étaient reconnues comme responsables de ce syndrome. Nous avons étudié une famille de plus de 200 individus présentant une forme incomplète du syndrome de Marfan puisqu'aucune anomalie du système oculaire n'a été observée. L'implication de la fibrilline dans l'apparition de la maladie a été exclue par des études de liaison démontrant l'existence d'un deuxième locus (MFS2) et donc d'une hétérogénéité génétique dans ce syndrome. Des études de liaison, réalisées à l'aide de marqueurs microsatellites anonymes régulièrement répartis sur l'ensemble du génome, nous ont permis de localiser le gène MFS2 sur le bras court du chromosome 3. Deux recombinaisons critiques placent actuellement le gène MFS2 dans un intervalle de moins de 6cM entre les marqueurs D3S1293 et D3S1567, localisés en 3p24. 2-p25. Dans cette région du bras court du chromosome 3, a été localisé le gène codant pour la fibuline de type 2 (FBLN2). Cette protéine de la matrice extra-cellulaire récemment identifiée représentait un excellent candidat tant sur le plan positionnel que sur le plan fonctionnel. Pour évaluer l'identité possible entre MFS2 et FBLN2, nous avons combiné 3 approches : protéique, moléculaire et génétique. L'analyse protéique n'a révélé aucune anomalie et l'analyse moléculaire a permis d'identifier 2 marqueurs polymorphes. Par approche gène candidat, trois recombinants ont été identifiés démontrant ainsi que FBLN2 n'était pas le gène MFS2. D'autre part, bien que l'hétérogénéité génétique du syndrome ait été confirmée par la découverte d'une seconde famille Finlandaise, recombinant avec les marqueurs du gène FBN1, aucune évaluation de l'étendue de cette hétérogénéité n'a encore été réalisée. Pour évaluer la contribution des mutations du locus MFS2 au syndrome de Marfan, nous avons établi une étude collaborative internationale. Son objectif est de réunir un nombre suffisamment important de familles pour évaluer le pourcentage de familles liées soit au locus FBN1 soit au locus MFS2. Les résultats de l'analyse correspondant à l'étude de 11 premières familles évaluent le nombre a de familles liées à FBN1 à 65%, le nombre ß de familles liées au locus MFS2 à 20%, et le nombre ? de familles qui ne sont liées ni à FBN1 et ni au locus MFS2 à 15%. Enfin, les travaux de recherche de ces dernières années ont montré que des anomalies moléculaires dans le gène codant pour la fibrilline localisé en 15q15-q21 (gène FBN1) sont associées tant aux formes classiques, variantes et néonatales du syndrome de Marfan qu'à un ensemble de pathologies ne représentant qu'une partie seulement des symptômes du MFS. Bien que de nombreuses mutations aient déjà été identifiées, il n'a pas encore été possible d'établir des corrélations génotype/phénotype. Dans le cadre d'une collaboration internationale dont l'objectif est la caractérisation d'un très grand nombre de défauts moléculaires de ce gène, nous avons entrepris une recherche de mutations chez une quarantaine de cas index présentant soit une forme classique, soit une forme incomplète de MFS. L'analyse des 5 premiers exons a permis de mettre en évidence des profils anormaux pour trois individus. Afin d'analyser l'ensemble des altérations délétères identifiées, nous avons constitué une base de données Marfan (regroupement de toutes les mutations publiées ainsi que du phénotype clinique associé à la mutation) et élaboré un programme informatique afin d'établir des corrélations génotype/phénotype.
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5

Burnitz, Kristopher K. "Phenotypic variation in the expression of Marfan syndrome and the relationship to age." Virtual Press, 2008. http://liblink.bsu.edu/uhtbin/catkey/1390651.

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This research has provided an analysis of how the issue of age is related to the expression of specific symptoms characteristic of the genetic disorder known as Marfan syndrome. Marfan syndrome occurs when the body cannot produce, or produces too little fibrillin-1, a component of the connective tissues. The body systems affected by Marfan syndrome include the skeletal, cardiovascular, ocular, and pulmonary systems. Evidence drawn from medical case studies showed that while not statistically significant, illustrated that symptom expression increases with age, especially during the period of adolescence. The evidence also suggested that the type of physician involved in a diagnosis may affect the information provided in case studies.
Department of Anthropology
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6

Hutchinson, Sarah. "Molecular analysis of the Marfan syndrome." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343402.

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7

Lipscomb, Karen Jane. "A clinical study of Marfan syndrome." Thesis, St George's, University of London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343719.

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8

Wendt, Kristin [Verfasser], and Irmtrud [Akademischer Betreuer] Jonas. "Vergleichende Palatummessungen von Marfan- und gesunden Neutralbisspatienten." Freiburg : Universität, 2011. http://d-nb.info/1123462836/34.

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9

Machado, Lucia Valeria da Silva Teixeira. "Análise de ligação na síndrome de Marfan." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-30042010-084608/.

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A síndrome de Marfan (MFS) é uma doença autossômica dominante do tecido conjuntivo que afeta o coração, vasos sanguíneos, pulmões, olhos, ossos e os ligamentos. Mutações no gene codificante da fibrilina 1 (FBN1) causam a síndrome de Marfan e doenças relacionadas do tecido conjuntivo. Fibrilina 1 é o componente principal das microfibrilas de 10-12nm encontradas na matriz extracelular (ECM). A ECM tem um papel estrutural na organização específica do tecido e participa na regulação de várias citocinas e fatores de crescimento. Uma quantidade crescente de evidências demonstra um relacionamento entre fibrilina 1 e o receptor do fator de transformação do crescimento (TGF-). A Homologia entre fibrilina 1 e TGF- latente (LTGF) permite que os microfibrilas sirvam de reservatório para esta citocina. Recentemente foram descritos nos pacientes com MFS, mutações nos genes receptores I e II do TGF- (TGFBRI/II). O objetivo deste estudo foi analisar a heterogeneidade genética da síndrome de Marfan. Nós realizamos análises de ligação para 6 marcadores dos gene FBN1 e TGFBRII em 34 famílias e sequenciamos o TGFBRI e TGFBRII. A análise de ligação dos haplótipos em relação aos marcadores do gene FBN1 indicou co-segregação em 70,58%, exclusão em 17,64% e homozigozidade em 11,76%; em relação aos marcadores do gene TGFBRII indicou co-segregação em uma família. Conseguimos demonstrar a heterogeneidade de lócus e a utilidade do teste diagnóstico na assistência das famílias pré-sintomáticas com manifestações atípicas ou ambíguas da MFS.
Marfan syndrome is an autosomal dominant disorder of connective tissue that can affect the heart, blood vessels, lungs, eyes, bones, and ligaments. Mutations in the gene encoding fibrillin 1 (FBN1) cause Marfan syndrome (MFS), and related connective tissue disorders. Fibrillin-1 is the main component of the 10-12 nm microfibrils found in the extracellular matrix (ECM). ECM displays a structural role in the tissue-specific organization and takes part in the regulation of various cytokines and growth factors. A growing body of evidence supports a narrow relationship between fibrillin 1 and TGF-beta. Homology between fibrillin 1 and latent TGF-beta (LTGF) allows microfibrils to be a reservoir for this cytokine. Recently, mutations in the gene for transforming growth factor-beta (TGF-) receptor type I and II (TGFBRI/II) have been described in patients with MFS. The aim of this study was to analyze the genetic heterogeneity of Marfan syndrome. We have performed linkage analysis for 6 FBN1 and TGFBRII gene markers in 34 families and sequenced both TGFBRI and TGFBRII. The haplotype linkage analysis concerning the FBN1 gene markers indicated co-segregation at 70.58%, exclusion at 17.64% and homozygosity at 11.76%; in relation to the TGFBRII gene markers, it indicated co-segregation in one family. We were able to demonstrate the heterogeneity of locus and the utility of the diagnostic test in the assistance of the daily pre-symptomatic families with atypical or ambiguous manifestations of MFS.
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10

Yuan, Xuemei. "NMR studies of a TB module from human fibrillin-1." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298231.

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11

Suk, Ji Young. "Molecular consequences of protein misfolding mutations in FBN1." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270282.

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12

McGettrick, Aileen Jane. "Molecular consequences of mutations in FBNI." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249501.

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13

Mátyás, Gábor. "Molecular basis of Marfan syndrome and related disorders /." Schwerzenbach, 2007. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000253402.

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14

Boileau, Catherine, and J. P. GELOSO. "Syndrome de marfan et hypercholesterolemie : modeles d'heterogeneite genetique." Paris 7, 1993. http://www.theses.fr/1993PA077318.

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Le syndrome de marfan (sm) et l'hypercholesterolemie familiale (hf) correspondent a deux groupes de pathologies a transmission autosomique dominante pour lesquelles une heterogeneite genetique a longtemps ete soupconnee. Pour identifier les facteurs genetiques associes a ces maladies, nous avons utilise une approche combinant des methodes genetiques et moleculaires, appliquees tant a des analyses de familles que de populations. Par l'approche gene candidat utilisee dans l'etude d'une grande famille presentant une forme variante du sm, nous avons montre que, a la difference des formes classiques, la maladie n'etait pas liee au gene de la fibrilline (fib15). Ce resultat a conduit a la definition d'une nouvelle entite clinique et moleculaire. Apres l'exclusion de genes codant pour d'autres constituants de la matrice extracellulaire, nous avons entrepris une carte d'exclusion genomique qui a deja permis d'eliminer plus de 65% du genome. Dans le cas de l'hf, nous avons identifie 7 nouvelles mutations du gene du recepteur ldl (ldlr) demontrant ainsi une importante heterogeneite allelique. Nous avons aussi retrouve la mutation 3500 du gene de l'apo b (apob) chez un sujet. Cette mutation etait associee a un haplotype identique a celui rapporte chez d'autres proposants, confirmant la nature unique et europeenne de cette mutation. Par ailleurs, la liaison aux genes ldlr et apob a pu etre exclue dans une fraction importante de familles de hf, demontrant ainsi l'implication d'au moins un troisieme facteur genetique a effet dominant. Enfin, nous n'avons pas observe de desequilibre de liaison entre l'hypercholesterolemie et les marqueurs des genes apoa1-c3-a4. L'ensemble de ces resultats va maintenant etre suivie de l'identification des nouveaux facteurs genetiques impliques dans le sm et l'hf permettant ainsi de tendre vers des tests de diagnostic specifiques
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15

Fotopoulos, Pauline. "Developing a Caenorhabditis elegans Model for Marfan Syndrome." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/631.

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Marfan Syndrome (MFS) is one of the most common monogenic diseases and affects approximately 1 in 5,000 individuals worldwide. The syndrome is characterized by elongated extremities, tall stature, slender frame, and cardiac, and vision abnormalities due to severe connective tissue defects. It is caused by mutations in the fbn1 gene, which encodes an extracellular matrix glycoprotein, and is required for proper cardiac and skeletal development and for sequestration of TGFβ (transforming growth factor beta) and BMP (bone morphogenetic protein) within the extracellular matrix (ECM). The primary objective of this study was to establish a C.elegans MFS model and use this model to determine which genes interact with a C.elegans fbn1 homolog, MUA-3 and ascertain the role of metabolic rate in the development of MFS pathology. We isolated a temperature sensitive mutant of mua-3, a fbn1 homolog. We found that at the fourth larval molt, when animals shed the exoskeleton and rebuild a new one, the mutants die due to extensive mechanical stress in connective tissue shown as fragmented internal structures. Using this mutant, an unbiased forward genetic screen to isolate the genetic interactors of the fibrillin gene homolog, was completed. A collagen gene, that has been implicated to genetically interact with a bone morphogenetic protein (BMP), was isolated. This suggests that mua-3(uy19) may interact with genes involved in TGFβ regulation during the L4 molt and that fibrillin-1, TGF-β, and metalloproteases may act in-concert to modulate TGFβ availability and connective tissue integrity in C. elegans. In addition, we found that two independent mutations of mua-3 show temperature-sensitive phenotypes. Based on this result, we propose that increase of temperature aggravates the phenotype potentially due to increased metabolism. This hypothesis, if correct, will suggest a potential connection between metabolic rate and severity of MFS pathology.
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16

Cardy, Caroline Maria. "The structure and function of calcium binding epidermal growth factor-like domains in human fibrillin-1." Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360210.

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17

Laudahn, Björn. "Das Marfan-Syndrom die indirekte Genotypdiagnostik als diagnostisches Verfahren." Saarbrücken VDM Verlag Dr. Müller, 2002. http://d-nb.info/989207129/04.

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18

Oliveira, Sobrinho Ruy Pires de. "Padrão de perfil metacarpofalangeano no diagnostico da sindrome de Marfan e outros quadros marfanoides." [s.n.], 1995. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316675.

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Orientador: Denise Yvonne Janovitz Norato
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-07-20T14:33:00Z (GMT). No. of bitstreams: 1 OliveiraSobrinho_RuyPiresde_M.pdf: 5997909 bytes, checksum: cd9e24de89364498d6e521b57dcf6bab (MD5) Previous issue date: 1995
Mestrado
Genetica
Mestre em Ciências Biológicas
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19

DANDOY, JEAN-PHILIPPE. "La maladie de marfan : a propos d'un cas revele par une complication arterielle peripherique primitive isolee." Lille 2, 1991. http://www.theses.fr/1991LIL2M103.

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20

Lima, Bruno Lazzari de. "Caracterização da variabilidade fenotípica em um modelo animal para Síndrome de Marfan." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/41/41131/tde-26082011-111713/.

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A Síndrome de Marfan (SMF) é uma doença de tecido conjuntivo, com caráter autossômico dominante, que acomete cerca de 1 em 5.000 indivíduos. As principais manifestações clínicas incluem aneurismas e rompimento da aorta, crescimento excessivo dos ossos, escoliose e deformidades torácicas. Mutações no gene FBN1, que codifica a proteína de matriz extracelular fibrilina-1, foram relacionadas à doença, fazendo com que essa fosse classificada no grupo das fibrilinopatias. Mais de 500 mutações já foram identificadas e, com exceção de um pequeno grupo de mutações recorrentes, as mutações são únicas, sendo encontradas em famílias isoladas. A doença caracteriza-se pela grande variabilidade tanto intra quanto interfamilial, não sendo possível fazer uma correlação precisa entre genótipo e fenótipo. Este trabalho visa discutir os mecanismos responsáveis pela variabilidade clínica inter e intra familiar da SMF através da caracterização qualitativa e quantitativa da variabilidade fenotípica observada no modelo murino para SMF MGΔloxPneo . Neste sentido, caracterizamos o modelo mgΔloxPneo em duas linhagens de camundongos diferentes, C57BL/6 e 129/Sv. Os animais mutantes de ambas as linhagens apresentaram deficiência na deposição de microfibrilas, cifose de coluna, enfisema pulmonar e degeneração da parede aórtica. Contudo, a idade de início dos sinais fenotípicos mostrou-se mais tardia em animais da linhagem C57BL/6 em comparação com os animais 129/Sv, indicando a presença de genes modificadores entre as duas linhagens. Além disso, caracterizamos uma grande variabilidade fenotípica entre os animais 129/Sv mutantes, o que é sugestivo do envolvimento de fatores epigenéticos na gravidade da doença. Finalmente, demonstramos uma forte correlação negativa entre os níveis globais de transcrição do gene Fbn1 e a gravidade do fenótipo. Esses resultados corroboram a hipótese de que o nível de expressão da proteína normal está relacionado com a gravidade do quadro clínico da SMF em humanos. Com base nisso, o trabalho também visa o estudo de novas estratégias terapêuticas para a SMF nesse mesmo modelo.
The Marfan syndrome (MFS) is an autosomal dominant disease of connective tissue, which affects 1 in 5,000 individuals. The main clinical manifestations include aneurysms and aortic disruption, excessive growth of bones, scoliosis and thoracic deformities. Mutations in the FBN1 gene, which encodes the fibrillin-1 protein, were genetically linked to the MFS, classifying this disease in the fibrilinopathies group. Over 500 mutations have been identified and, except for a small group of recurrent mutations, the mutations are unique, being found in unrelated families. The disease is characterized by a wide clinical variability both within and between families, and it is not possible to make a precise genotypephenotype correlation. This work concerns the analysis of the mechanisms associated with the clinical variability present within and between MFS families, by qualitative and quantitative characterization of the phenotypic variability observed in the mgΔloxPneo model for MFS. We characterize the model mgΔloxPneo, in two different mouse strains, the C57BL/6 and the 129/Sv strain. Mutant animals from both strains present defective microfibrillar deposition, emphysema, deterioration of aortic wall and kyphosis. However, the onset of a clinical phenotypes is earlier in the 129/Sv than in C57BL/6 background, indicating the existence of genetic modifiers of MFS between these two mouse strains. In addition, we characterized a wide clinical variability within the 129/Sv heterozygotes, suggesting involvement of epigenetic factors in disease severity. Finally, we show a strong negative correlation between overall levels of Fbn1 expression and the severity of the phenotypes. These results corroborated with studies, using animal models, as well with MFS patients, where the levels of normal fibrillin-1 seem to have the potential to modulate the clinical severity of the disease. In addition, the study also aims to evaluate new treatment possibilities for MFS in this same model.
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21

Fernandes, Gustavo Ribeiro. "Variabilidade fenotípica de um modelo murino para a Síndrome de Marfan - Triagem de genes modificadores do fenótipo." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/41/41131/tde-07062013-105020/.

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A Síndrome de Marfan (SMF) (OMIM# 154700) é a mais comum das doenças genéticas do tecido conjuntivo Herdada de forma autossômica dominante, ela apresenta incidência de 1 em cada 5.000 indivíduos. Apesar de apresentar grande variabilidade clínica inter e intrafamiliar, o fenótipo da SMF possui penetrância completa, e suas manifestações clínicas afetam primariamente os sistemas esquelético, ocular e cardiovascular. Afim de estudar os mecanismos patogênicos da SMF foi desenvolvido um modelo murino, mgΔneoLoxP, que reproduz as manifestações ósseas, cardiovasculares e pulmonares da síndrome. O modelo foi estabelecido nas linhagens isogênicas 129/Sv e C57BL/6, que apresentam diferenças tanto quanto a idade de acometimento quanto a gravidade das alterações, é possível que as diferenças alélicas existentes entre essas linhagens alterem a manifestação fenotípica, ou seja, que existam genes modificadores para a SMF. Assim, objetivo deste projeto é utilizar este modelo experimental para identificar genes modificadores do fenótipo da SMF e tentar entender melhor a arquitetura genética da síndrome. Ao todo foram gerados 82 animais 129xB6 F2 heterozigotos para o alelo mgΔneoLoxP, a analise de ligação utilizando microssatélites e SNPs nos animais com fenótipos mais extremos mostraram ligação sugestiva do fenótipo ósseo com as regiões compreendidas entre as posições 56 cM e 68 cM do cromossomo 3; e 2 cM e 20 cM do cromossomo X; ligação significativa entre as posições 41cM e 49 cM do cromossomo 6; além de mostrar ligação sugestiva do fenótipo cardiovascular do 66 cM ao 70 cM do cromossomo 4; e do 44 cM ao 52 cM do cromossomo 13. Além da variabilidade entre linhagens, os animais 129 apresentam uma grande variabilidade fenotípica interna, o que por se tratar de animais isogênicos causada por fatores aleatórios ou devido a modificações epigenéticas que alterem o nível de expressão de alguns genes e assim o fenótipo. A comparação entre animais 129 leves e graves levou a identificação de 25 genes diferencialmente expressos dos quais 11 apresentavam funções relevantes para a SMF, entretanto foram aferidos os níveis de expressão de 2 destes que não validaram os resultados obtidos devido a uma grande variação observada entre os animais de todos as classes fenotípicas. Também foram identificadas 46 vias que se apresentavam mais frequentes nos conjuntos de genes obtidos entre as duas classes fenotípica de animais heterozigotos contra os animais selvagens. Tanto as vias, quanto os genes identificados através de ligação quanto diferença de expressão mostram uma convergência para as funções dos genes de interesse, sendo que entre eles existem genes já associados com a SMF, controle de ativação de TGF-B e da biogênese das microfibras da matriz extracelular, quanto genes que ainda não foram associados mas são possíveis modificadores do fenótipo, tais como genes envolvidos nos processos de enovelamento e degradação protéico e nos processos de endocitose e exocitose de vesículas, que podem alterar a quantidade de fibrilina-1 truncada disponível e assim o fenótipo
The Marfan syndrome (MFS) (OMIM # 154700) is the most common genetic disorder of the connective tissue and is inherited in a autosomal dominant fashion, it has an incidence of 1 in 5,000 individuals. Despite a great clinical variability being one of the \"trademarks\" of the syndrome, the phenotype of the MFS has complete penetrance and its clinical manifestations primarily affect the skeletal, ocular and cardiovascular systems. In order to study the pathogenic mechanisms of MFS was developed a mouse model, named mgΔneoLoxP, which reproduces the skeletal, cardiovascular and pulmonary manifestations of the syndrome. The model was established in inbred mouse strains 129/Sv and C57BL / 6, which phenotypes differ as to age of onset and severity of manifestation. It is possible that allelic differences between these inbred strains alter the phenotyic manifestation of disease, leading to the conclusion that may exist modifier genes involved in the for MFS. This study inteds to use this experimental model to identify phenotype modifier genes of MFS so a better understand the genetic architecture of the syndrome. Altogether, 82 129xB6 F2 heterozygous animals were generated so that a linkage analysis using microsatellite and SNP could be conducted. The linkage analysis using a selective genotyping procedure showed a suggestive linkage of the skeletal phenotype with regions included between positions 56 cM and 68 cM on chromosome 3, and 2 cM and 20 cM on chromosome X; and a significant linkage between positions 41cM and 49 cM on chromosome 6; also showing suggestive linkage of the cardiovascular phenotype from 66 cM to 70 cM on chromosome 4, and 44 cM to 52 cM on chromosome 13. Besides the variability between strains, 129 animals have a wide inner strain phenotypic variability, which in the case of isogenic animals should be caused by random factors or due to epigenetic modifications that may alter the expression level some genes and thus the phenotype. The comparison between animals of the 129 strain with mild and severe alterations led to the identification of 25 differentially expressed genes of which 11 showed relevant functions to the MFS, however it was only possible to measure the expression levels of two genes using real-time PCR, although those did not validate the results obtained from the expression microarray due to a large expression variation in all phenotypic classes. It was also identified 46 pathways that were more frequent in the gene lists obtained from the comparison between the two phenotypic classes of heterozygous animals against 129 wildtype animals. There is a similarity in the function of genes or pathways of interest found in pathways analysis and genes identified, either by differential expression or linkage analisys, and among them there genes already associated with the MFS, such as in the control activity of TGF-B and biogenesis of microfibers in the extracellular matrix, as also genes that were not associated with MFS but are possible phenotype modifier genes, such as genes involved in protein folding and degradation processes and of endocytosis and exocytosis processes of vesicle, which can change the amount of truncated fibrillin-1 available and thus the phenotype
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22

Goergen, Barbara [Verfasser]. "Ophthalmologische Befunde beim Marfan-Syndrom : eine retrospektive Studie / Barbara Goergen." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2017. http://d-nb.info/1133492428/34.

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23

Allman, Amy Jane. "Effects of UV radiation on Marfan syndrome cells in culture." Virtual Press, 1993. http://liblink.bsu.edu/uhtbin/catkey/879841.

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Ultraviolet radiation causes an alteration in DNA by modifying neighboring thymine bases resulting in the formation of a dimer. These dimers block the processes of transcription and translation and ultimately no protein is synthesized and the cell dies. However, DNA repair mechanisms correct this damage by excising the dimer from the DNA strand and inserting replacement bases which are joined to the original strand by DNA ligase. This allows transcription to resume and ultimately protein synthesis to take place.This research focused on determining the DNA damage and subsequent repair levels in a connective tissue disorder, namely Marfan syndrome. This information is important in understanding the clinical expression and management of life threatening conditions in Marfan syndrome individuals.Preliminary results indicate that at 20-25J/m2 UV dose (254nm) Marfan syndrome skin cells show a mean reduced survival value of 12% compared to normal human skin cells. Gel electrophoresis indicates a reduced DNA repair level 24h post UV irradiation for Marfan syndrome skin cells compared to normal human skin cells. These results suggest Marfan syndrome skin cells have reduced survival and DNA repair levels compared to normal human skin cells.
Department of Biology
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24

Gahagnon, Solène. "Etude in vivo du comportement mécanique du derme par une méthode élastographique haute résolution : applications à l'exploration d'anomalies du tissu élastique (syndrome de Marfan)." Thesis, Tours, 2009. http://www.theses.fr/2009TOUR3116/document.

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25

Nollen, Gijsbert Jakob. "Anatomical and functional evaluation of the cardiovascular system in Marfan syndrome." Amsterdam : Amsterdam : [s.n.] ; Universiteit van Amsterdam [Host], 2004. http://dare.uva.nl/document/71999.

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26

Dubosc, de Pesquidoux Olivier. "La maladie de Marfan : mise au point d'un diagnostic biologique par immunomarquage de la fibrilline." Université Claude Bernard - Lyon I, 1994. http://www.theses.fr/1994LYO1M098.

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27

Braga, Guilherme Gambogi 1985. "Avaliação da elastogênese em cultura de células obtidas de camungongos deficientes em Fibrilina-1 : estudo do efeito do Losatan." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314063.

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Orientador: Claudio Chrysostomo Werneck
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Fibrilina-1 é um importante componente da rede de microfibrilas da matriz extracelular. As microfibrilas estão presentes nas fibras elásticas que são responsáveis pela elasticidade e resistência de tecidos dos pulmões, pele e grandes vasos. Mutações no gene da Fibrilina-1 estão associadas com a síndrome de Marfan. Pacientes com esta síndrome apresentam muitas manifestações clínicas nos pulmões, sistema cardiovascular e olhos. Modelos de síndrome de Marfan tem sido criados no sentido de obter informações sobre o desenvolvimento desta doença. Estudos recentes em modelos de camundongos tem sugerido a importância da atividade exacerbada do TGF ? promovendo a quase totalidade das alterações fenotípicas encontradas nestes camundongos, o que pode ser revertido pelo tratamento com o Losartan. O principal objetivo deste projeto foi avaliar a formação de fibras elásticas em cultura de células obtidas de animais deficientes em fibrilina-1, bem como o possível efeito do tratamento destas células com losartan. Os fibroblastos derivados de animais deficientes em fibrilina- 1 foram estudados usando imunofluorescência, western blotting, microscopia eletrônica de varredura e transmissão e real-time PCR. Assim, a deficiência em fibrilina-1 ocasionou uma redução conjunta da deposição de fibrilina-2, MAGP-1 e tropoelastina na matriz extracelular em cultura de fibroblastos de derme. Foi possível verificar aumento no níveis de expressão das metaloproteinases MMP-2 e MMP-9. O tratamento dos fibroblastos derivados de animais deficientes em fibrilina-1 com o fármaco losartan levou a recuperação parcial da deposição das proteínas Fibrilina-2, MAGP-1 e tropoelastina na matriz extracelular de cultura in vitro. Porém, o tratamento dos fibroblastos derivados de animais deficientes em fibrilina-1 com fármaco Captopril e os peptídeos de Angiotensina I e II não influenciaram na deposição das mesmas na matriz extracelular de cultura in vitro
Abstract: Fibrillin-1 is an important microfibril network component. Microfibrils are present in elastic fiber responsible for resilience and elastic properties from structures like lungs, skin and large vessels. Mutations in Fibrillin-1 gene are associated with Marfan's Syndrome. Marfan's Syndrome patients shown many different clinical manifestations in lungs, cardiovascular system and eyes tissues. Marfan's models have been created to get better insights about this disease development. Recent studies from mice models have suggested an important role to unbalanced TGF ? activity promoting almost whole alterations found in those mice which might be rescued by losartan treatment. Our main goal were evaluate elastic fiber formation in cell culture obtained from fibrillin-1 defficient mice as well as losartan's treatment effect on those cells. The fibroblasts derived from deficient animals in fibrillin-1 were studied using immunofluorescence, western blotting, scanning electron microscopy and transmission and real-time PCR. Thus, the deficiency in fibrillin-1 led to a joint reduction of the deposition of fibrillin-2, MAGP-1 and tropoelastin in the extracellular matrix in culture of fibroblasts in the dermis. It was possible to observe an increase in levels of expression of metalloproteinases MMP-2 and MMP-9 were found. The treatment of the fibroblasts derived from deficient animals in fibrillin-1 with the drug losartan has led to the partial recovery of the deposition of protein fibrillin-2, MAGP-1 and tropoelastin in the extracellular matrix of culture in vitro. However, the treatment of fibroblasts derived from deficient animals in fibrillin-1 with drug Captopril and the peptides of Angiotensin I and II not influenced in the deposition of the same in the extracellular matrix of culture in vitro
Mestrado
Bioquimica
Mestre em Biologia Funcional e Molecular
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28

Pereira, Catherine Natália 1987. "Avaliação da função da fibrilina-1 na trombogênese arterial : análise proteômica." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314060.

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Orientador: Claudio Chrysostomo Werneck
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Fibrilina-1 (FBN-1) é um importante componente da rede de microfibrilas da matriz extracelular (MEC). As microfibrilas estão presentes nas fibras elásticas que são responsáveis pela resiliência de tecidos como pulmões, pele e grandes vasos. Mutações no gene da fibrilina-1 estão associadas à Síndrome de Marfan, doença autossômica dominante, caracterizada por uma desordem do tecido conjuntivo. Pacientes com esta Síndrome apresentam anomalias no sistema esquelético e trato cardiovascular. Dados da literatura relacionam a menor quantidade de FBN-1 na MEC com a atividade exacerbada do TGF-? promovendo a quase totalidade das alterações fenotípicas encontradas. Estudos preliminares em nosso laboratório com camundongos que possuem menor quantidade de FBN-1 de um camundongo normal tem demonstrado que necessitam do dobro do tempo para a formação de trombo em um modelo de trombose arterial. As plaquetas tem fundamental importância neste processo, quando são ativadas secretam várias moléculas que determinam a formação dos trombos. Realizamos um estudo comparativo do proteoma de plaquetas e da artéria aorta de camundongos selvagens e deficientes em FBN-1, através da técnica de eletroforese bidimensional (2DE) juntamente com a espectrometria de massas a fim de encontrar diferenças no perfil proteico que justificassem tais sintomas. Diversas proteínas plaquetárias foram encontradas apenas no grupo controle, como endoplasmina, fator de von Willebrand, calpaína, dentre outras; assim como a proteína vinculina foi encontrada apenas no grupo deficiente em FBN-1. Todas as proteínas encontradas podem ser de grande interesse para o esclarecimento a respeito do maior tempo de formação de trombo e os sintomas relacionados à Síndrome de Marfan
Abstract: Fibrillin-1 (FBN-1) is an important microfibril network component of extracellular matrix (ECM). Microfibrils are present in elastic fibers responsible for tissues resiliency, such as lungs, skin and great vessels. Mutations in fibrillin-1 gene are associated with Marfan Syndrome, a dominant autosomal disease characterized by connective tissue disorder. Patients with this syndrome show abnormalities in skeletal system and cardiovascular tract, aorta dilatation and aneurysms. Literature data relate less FBN-1 in the ECM with TGF-? heightened activity, promoting almost all the phenotypic alterations. Preliminary studies in our laboratory demonstrated that mice containing half amount of FBN-1 presented prolonged thrombosis time when compared to wild-type mice submitted to an arterial thrombosis model. Platelets are important in this process, when activated they release several molecules and factors which determine thrombi formation. We conducted a comparative proteome study of platelet and aorta from wild-type against FBN-1 deficient mice by two-dimensional electrophoresis (2DE) coupled with mass spectrometry in order to find some differences in protein profile that could justify such symptoms. Several platelet proteins were found only into control group, as endoplasmin, von Willebrand factor, calpain; as well as vinculin was found only in the FBN-1 deficient group. All proteins found may have great interest for understanding the prolonged thrombus formation time, and symptoms related to Marfan Syndrome
Mestrado
Bioquimica
Mestra em Biologia Funcional e Molecular
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29

Kawahara, Elisa Ito. "Caracterização do fenótipo ósseo do modelo mgΔloxPneo da síndrome de Marfan e análise dos mecanismos de patogênese." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/41/41131/tde-21032017-152240/.

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A Síndrome de Marfan (SMF) é uma doença de caráter autossômico dominante que acomete o tecido conjuntivo. As principais manifestações clínicas afetam o sistema cardiovascular, ótico e ósseo. A SMF é causada por mutações no gene FBN1, que codifica a proteína extracelular fibrilina-1, componente principal das microfibrilas, que formam as fibras elásticas. Estudos mostraram que mutações no gene da fibrilina-1 levam a um aumento indiscriminado do TGF-Β ativo na matriz, que resulta nos principais fenótipos da doença. O Sistema Renina Angiotensina (RAS) tem como produto principal a Angiotensina II (Ang-II), envolvida na regulação da massa óssea e da atividade do TGF-Β. Estratégias terapêuticas para a SMF utilizando fármacos que agem no RAS têm sido alvos de estudos em modelos animais. Em camundongos, Ramipril, inibidor da ACE (Angiotensin-converting enzyme inhibitor, ACEi), aumenta a transcrição do gene Fbn1 em 35% e melhora a cifose, característica do fenótipo ósseo no modelo animal mgΔloxPneo. O mecanismo de ação do Ramipril no sistema ósseo ainda não está totalmente elucidado, sendo que pode agir por diminuição na produção de Ang-II e consequente diminuição nos níveis de TGF-Β, ou pela inibição de degradação da bradicinina (BK) pela Ang-II. A bradicinina ativa diretamente seu receptor B2R, que induz ações fisiológicas opostas às da Ang-II. O objetivo deste trabalho foi avaliar e compreender os mecanismos gerais da patogênese óssea do modelo murino mgΔloxPneo para a SMF. Para tanto, foi analisado o fenótipo ósseo dos animais mgΔloxPneo e selvagens controle e tratados com Ramipril. Foi verificado que, além da cifose, os animais mutantes apresentaram pior estrutura óssea. O tratamento melhorou a cifose, porém não alterou a qualidade óssea dos animais mutantes. Portanto, o efeito benéfico do Ramipril na cifose dos animais mgΔloxPneo não se deve a uma melhora da estrutura óssea, e pode estar relacionado à integridade do ligamento que sustenta a coluna vertebral. Com o intuito de testar a hipótese de que a sinalização pelo receptor B2R da BK possa estar envolvida no desenvolvimento do fenótipo ósseo dos animais mgΔloxPneo, foram gerados animais mgΔloxPneo e knockout para o receptor B2R. Os resultados mostram que o receptor B2R não interfere no desenvolvimento da cifose, sendo apenas o genótipo para Fbn1 o fator determinante para a manifestação desse fenótipo. Foi realizada a análise de RNA-seq para verificar genes e vias diferencialmente expressas que possam explicar o mecanismo de desenvolvimento do fenótipo ósseo dos animais mgΔloxPneo. Foram encontradas vias como da adesão focal, interação receptor-meio extracelular (MEC), junção ocludente, reparação por excisão de nucleotídeo e de reparação missmatch, que podem explicar alterações no metabolismo de células ósseas. Além disso, foram encontradas diferenças de expressão de genes relacionados ao metabolismo muscular esquelético, o que está de acordo com a hipótese de regulação parácrina entre o tecido muscular e ósseo, levando a uma pior estrutura óssea
Marfan syndrome (MFS) is an autosomal dominant disease that affects the connective tissue. The main clinical manifestations affect the cardiovascular, optical and bone systems. MFS is caused by mutations in the FBN1 gene, that encodes the extracellular protein fibrillin-1, a major component of microfibrils, which form elastic fibers. Studies have shown that mutations in the fibrillin-1 gene lead to an indiscriminate increase in active TGF-Β in the matrix, which results in the major phenotypes of the disease. The Renin Angiotensin System (RAS) has as its main product Angiotensin II (Ang-II), involved in bone mass regulation and TGF-Β activity. Therapeutic strategies using drugs targeting the RAS have been studied in animal models. Ramipril, an ACE inhibitor (Angiotensin-converting enzyme inhibitor, ACEi), increase Fbn1 gene expression in 35% and improve kyphosis index in the mgΔloxPneo mouse model for SMF. Its mechanism of action in bone tissue is not completely elucidated, and it may act by decreasing Ang-II production and consequent reduction in TGF-Β levels, or by inhibiting degradation of bradykinin (BK) by Ang II. BK directly activates its B2R receptor, which induces opposite physiological actions to Ang-II. This study aims to evaluate and understand the general mechanisms of bone pathogenesis in the mgΔloxPneo mouse model. We analyzed the bone phenotype of mgΔloxPneo and wildtype animals treated, or not, with Ramipril by measuring the kyphosis index (KI), micro computed tomography (μCT) and Real-time PCR (RT-PCR). We found that mutant animals showed a greater degree of kyphosis and an altered bone structure. Ramipril improved kyphosis but did not alter bone quality of mutant animals, while in wild type animals Ramipril decreased bone structure without altering KI. Therefore, the beneficial effect of Ramipril on mgΔloxPneo animals\' kyphosis is not due to an improvement in bone structure. In order to test the hypothesis where signaling through BK B2R receptor may be involved in the development of bone phenotype of mgΔloxPneo animals, a mouse model with the mgΔloxPneo mutation and knockout for B2R receptor was generated. The analysis of these animals show that the B2R receptor does not interfere with the development of kyphosis, with Fbn1 genotype as sole determinant for this phenotype manifestation. RNA-seq analysis was performed to verify differential expression of genes and altered cellular pathways, which could reveal mechanisms of bone phenotype development in mgΔloxPneo animals. Altered pathways found included focal adhesion, receptor- extracellular matrix (ECM) interaction, tight junction, nucleotide excision repair and missmatch repair, which may explain changes in bone cells metabolism. In addition, there were differences in gene expression related to skeletal muscle metabolism, which is in agreement with the paracrine regulation of bone and muscle tissue, leading to worst bone structure
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30

Herzer, Lena Mareike [Verfasser], and Raoul [Akademischer Betreuer] Arnold. "Beurteilung der aortalen Hämodynamik bei Marfan Syndrom mittels 4D-Fluss MRT." Freiburg : Universität, 2012. http://d-nb.info/1123469997/34.

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31

Siegert, Anna-Maria Elisa. "Membrane Trafficking of TGF-β and Transcriptome Analysis in Marfan Syndrome." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/461936.

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Marfan Syndrome (MFS) is a rare, autosomal dominant disorder of the connective tissue that affects between 1.5 and 17.2 in 100.000 live births. MFS is caused by mutations in the extracellular matrix (ECM) glycoprotein Fibrillin-1 (FBN1). FBN1 is the main constituent of microfibrils, which, together with elastin, form the elastic fibres of the connective tissue throughout the body. MFS is multisystemic in its nature and can affect various organ systems in a variety of combinations and with consequences ranging from mild to severe. Approximately 3000 FBN1 mutations have been annotated to date and different mutation types have been attempted to be correlated with the organ system involved as well as the severity of disease outcome. Due to the large heterogeneity, mutations have been clustered into dominant negative and haploinsufficient phenotype based on the protein outcome. Yet, roughly a third of mutations cannot be assigned to either group and is therefore excluded from studies, which, to this date, show modest correlation. The most severe clinical outcome of MFS is the formation of ascending aortic aneurysms. These originate in the tunica media which consists of vascular smooth muscle cells (VSMC) and elastic fibres. FBN1 is crucial for the structural ECM integrity but has also been shown to be important in the regulation of Transforming Growth Factor-β (TGF-β). TGF-β is a ubiquitous cytokine whose release from the ECM is controlled by FBN1 binding. In MFS, the fragmentation of elastic fibres due to FBN1 mutation leads to increased release of TGF-β into the extracellular environment and increased TGF-β signalling. TGF-β endocytosis takes place through early endosomes and caveolin-1-positive vesicles. Endocytosis through early endosomes is associated with signal transduction and SARA-dependent recruitment of SMAD2 to the receptor complex as well as SMAD nuclear translocation which elicits changes in approximately 500 target genes. Increased TGF-β signalling induces the deposition of ECM proteins and is associated with fibrosis. CAV-1-dependent endocytosis on the other hand leads to inhibitory SMAD7 binding and signal abrogation. We assessed whether alterations in the compartmentalization of TGF-β contribute to increased TGF-β signalling in MFS. Furthermore, we examined transcriptomic alterations in MFS patients with ascending aortic aneurysms. We found increased membrane enrichment and TGF-β receptor interaction of SARA and SMAD2 as well as higher colocalization of SARA with the early endosome marker EEA1 in MFS VSMC. Using fluorescent TGF-β we found that internalized TGF-β showed equal colocalization with EEA1 and CAV-1 in VSMC from Marfan patients and controls. However, colocalization of TGF-β at SARA-positive early endosomes was increased in MFS, indicating increased signalling through the early endosomal pathway in MFS. In addition, RAB5 has been described to control SARA enrichment at early endosomes. We showed increased RAB5 enrichment at cell membranes as well as gene expression in MFS, indicating that the increased signalling at early endosomes might be controlled by RAB5. Furthermore, the CAV-1- and early endosome-associated pathways have been shown to partially merge to form double-positive vesicles associated with signal abrogation. We found decreased colocalization of TGF-β with EEA1/CAV-1 double positive structures, indicating decreased TGF-β signal abrogation through this pathway in MFS. We furthermore performed sequencing of VSMC derived mRNA from MFS and controls. We identified a FBN1 3´UTR mutation with a clear gene ontological profile of transient endoplasmic reticulum (ER) stress, potentially due to the loss of a micro RNA (miRNA) binding site. In clinical settings, non-coding regions are usually omitted, yet ER stress induced by mutations in these regions has been linked to other connective tissue and cardiovascular diseases. We suggest that the inclusion of non-coding regions could improve the low genotype-phenotype correlation and the prediction of disease severity.
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32

Halliday, Dorothy Jean. "Molecular analysis of FBN1 mutations in Marfan syndrome and related disorders." Thesis, University of London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272202.

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33

Austin, Elise Garza. "Marfan syndrome : current practices in evaluation and use of genetic testing /." Oklahoma City : [s.n.], 2009.

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34

Pitcher, Alex. "Cardiovascular manifestations of Marfan syndrome : insights from advanced cardiovascular magnetic resonance." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:e47f70d4-a777-4c1d-8bb4-3758231ef38a.

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Marfan syndrome (MFS) is the commonest inherited disorder of connective tissue and is associated with a high risk of potentially life-threatening complications, including aortic aneurysm, dissection and rupture, and, perhaps, ventricular disease. This work describes the prospective application of advanced cardiovascular magnetic resonance techniques to the aorta and heart of consecutive, unselected subjects with MFS, and to appropriately matched control populations. Comprehensive 3D visualisation of blood flow in the entire thoracic aorta of subjects with MFS was achieved using a time-resolved phase-contrast magnetic resonance technique with 3-directional velocity encoding (4D flow), demonstrating a high prevalence of major flow disturbance (87 ± 12%), compared to controls (28 ±18%), localising to those regions of the aorta known to be most prone to aortic dissection (sinuses of Valsalva and proximal descending aorta). Wall shear stress, recently identified as a potentially important determinant of aneurysm progression and rupture, was interrogated in these datasets at the sinuses of Valsalva (SOV), ascending aorta (AA), arch, and proximal (PDA) and distal descending aorta (DDA), using the 4D flow datasets, and was shown to be significantly reduced at each location (SOV -15%; AA -12%; Arch -17%; PDA -18%; and DDA -14%, p<0.05 for each), in subjects with MFS compared to healthy subjects. 4D flow datasets were used to generate relative pressure maps in healthy subjects and in subjects with several aortic diseases. A novel method for the separate evaluation of the components of relative pressure was applied, revealing marked differences in the relative contribution of the components of pressure (unsteady > convective >> viscous), and characteristic differences between subjects in overall relative pressure, and its components. Left ventricular volumes and function were evaluated in subjects with MFS, and did not differ significantly from healthy subjects in the absence of significant valvular regurgitation and / or shunt. Left ventricular end-diastolic volume varied markedly with degree of regurgitation (r=0.75, p=0.0001). The mechanistic implications of these findings, and the potential role of these techniques in the evaluation of cardiovascular disease, are discussed.
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Cipriano, Graziella França Bernardelli [UNIFESP]. "Avaliação espirométrica e cardiovascular em pacientes portadores da síndrome de Marfan." Universidade Federal de São Paulo (UNIFESP), 2010. http://repositorio.unifesp.br/handle/11600/9119.

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Introdução: A Síndrome de Marfan (SM) é uma doença autossômica dominante do tecido conjuntivo (TC) que envolve diversos sistemas tais como, sistema músculo-esquelético, ocular, cardiovascular, pulmonar, tegumentar e neurológico. Estas mutações que causam a SM podem produzir modificações no TC, que causa alteração nas propriedades viscoelásticas do sistema cardiovascular, elasticidade da pele, matriz para calcificação óssea e parênquima pulmonar. Objetivos: Avaliar a função pulmonar (FP) de pacientes com a SM, relacionar com os aspectos da avaliação clínica, especialmente as possíveis alterações de caixa torácica (ACT) e identificar as manifestações do sistema cardiovascular durante o exame espirométrico (EE). Métodos: De uma amostra inicial de 75 sujeitos, foram avaliados 46 pacientes com SM, sendo 29 do sexo feminino, idade média 20±8 anos, submetidos à avaliação clínica, antropométrica, ecocardiográfica, radiográfica e função pulmonar; 51 sujeitos (33 com SM) foram monitorizados pelo eletrocardiograma (ECG) durante o teste de FP. Estes indivíduos foram pareados e comparados a um grupo controle compostos por indivíduos saudáveis. Resultados: A capacidade vital forçada (CVF) e volume expiratório forçado no primeiro segundo (VEF1) dos pacientes com SM foram significativamente menores quando comparado com o GC (p=0.012 e 0.0006) e quando comparado com o previsto (p=0.04 e 0.003). Nos subgrupos baseados nas ACT observamos diferenças entre pacientes com SM com duas ACT combinadas (pectus + escoliose) quando comparados com o GC (p=0.012 e 0.002) e nos pacientes sem ACT (p=0.05 e 0.06). Alguns aspectos da avaliação clínica (relação envergadura/altura e relação da cirtometria axilar/xifóide), comportamento cardiovascular (Índice de massa do ventrículo esquerdo-IMVE, g/m2 e diâmetro da Aorta – Ao, mm) e FP (VEF1/CVF,%) apresentaram correlação moderada. Não foi observada diferença na análise de arritmia durante o esforço para o EE. Conclusões: A FP encontrou-se reduzida nos pacientes com SM e a presença de deformidades da caixa torácica parece contribuir com esta redução. Alguns aspectos clínicos, cardiovasculares e FP estão associados na SM. Apesar das alterações aparentes na estrutura do sistema cardiovascular desta população jovem, o esforço durante a avaliação da função pulmonar parece ser seguro em relação às alterações no ECG.
Background: Marfan syndrome (MS) is a dominant autosomal connective tissue disease that impacts multiple systems, such as the musculoskeletal, ocular, cardiovascular, pulmonary, tegumentary and neurological. This mutation may produces impairment in the connective tissue which causes modifications in the vascular viscoelastic properties, tegumentary elasticity, bone calcification matrix and pulmonary parenchyma. Purpose: To evaluate pulmonary function test (PFT) in patients with MS and relate it to clinical evaluation aspects, especially possible thoracic cage abnormalities (TCA), and the occurrence of cardiac arrhythmias during the spirometric exam (SE). Method: From a sample of 75 subjects, we evaluate 46 MS patients, 29 female and aged 20±0,51 years, who was underwent clinical, anthropometric, echocardiographic, radiographic and PF evaluation; 51 subjects (33 with MS) had their electrocardiography information evaluated during PFT. These individuals were matched and compared to a healthy control group (CG). Results: Forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) in the patients with MS were significantly lower in comparison to the CG (p=0.012 and p=0.0006) and predicted values (p=0.04 and p=0.003). Subgroup analysis based on TCA revealed differences between patients with MS with two combined abnormalities (pectus + scoliosis) in comparison to both the CG (p=0.012 and p=0.002) and patients without abnormalities (p=0.05 and p=0.006). Some aspects from clinical evaluation (Arm span to height ratio,m and axillary to xiphoid perimetry ratio,cm), cardiovascular behavior (Left ventricular mass Index-LVMI, g/m2 and Aortic Diameter- Ao,mm) and PF (FEV1/FVC%) has demonstrated a moderate correlation. There were no differences regarding the occurrence of arrhythmia during exertion on the SE. Conclusion: PF is reduced in patients with MS, and deformities in the thoracic cage appear to contribute to this reduction. Some aspects clinical, cardiovascular and PF are associated in MS. Despite the apparent structural alterations in the cardiovascular system in this young population, exertion during the spirometric exam appears to be safe in relation to electrocardiography modifications.
TEDE
BV UNIFESP: Teses e dissertações
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36

Ades, Lesley Carole. "The Marfan syndrome and related phenotypes : delineation of various phenotypes and analysis of the fibrillin gene (FBN1) for putative mutations /." Title page, abstract and contents only, 1995. http://web4.library.adelaide.edu.au/theses/09MD/09mda232.pdf.

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KERAUDREN, DOMINIQUE. "Syndrome cca (congenital contractural arachnodactyly) : formes avec manifestations cardiaques : a propos d'une observation." Aix-Marseille 2, 1988. http://www.theses.fr/1988AIX20060.

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38

Yang, Huei-Hsin Clarice. "Oxidative stress compromises vasomotor function of the thoracic aorta in Marfan Syndrome." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/15003.

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Introduction: Marfan syndrome is an autosomal dominant connective tissue disorder that causes life-threatening cardiovascular complications such as thoracic aortic dilatation and aneurysm. We have demonstrated that Marfan syndrome compromises contractile function of the aorta and impairs nitric oxide-mediated relaxation. We hypothesize that oxidative stress impairs contractility and endothelium-dependent relaxation in the thoracic aorta of Marfan mice. Methods: Adrenergic contractions and cholinergic relaxations of thoracic aorta from mice heterozygous for FBN1 allele (Fbn1C¹⁰³⁹G/+ , n=40; age=3,6,9 months), a well-defined model of Marfan syndrome, were compared with those from control littermates (n=40). Results: At 3 and 6 months, oxidative stress, as indicated by the plasma 8-isoprostane level, was 50% greater in the Marfan group than in the control. In 9 months old Marfan mice, the depressed phenylephrine-induced contraction was normalized by the preincubation of superoxide dismutase (SOD) which increased the maximal contractile response (Emax) and pEC₅₀ for phenylephrine-stimulated contraction by 91% and 2.75-fold. The compromised endothelial function was also restored by SOD which increased the sensitivity to acetylcholine by 10.7 and 12.3-fold at 3 and 6 months, respectively. Such improvement was absent in the controls. In 9 months old Marfan mice, the phenylephrine-contraction was potentiated 141% by 1400W, an inducible nitric oxide synthase (iNOS) inhibitor. The pEC₅₀ was normalized by 1400W and allopurinol, an inhibitor of xanthine oxidase. In the same group, both Emax and pEC₅₀ of acetyicholine was normalized by apocynin, an inhibitor of NAD(P)H oxidase. Protein expression of SOD was decreased at 3 and 9 months in the Marfan group, whereas expression of xanthine oxidase, iNOS, gp9lphox, p47phox and p67phox, the subunits of NAD(P)H oxidase, was all increased. Conclusions: The compromised vasomotor function in Marfan thoracic aorta could be associated with oxidative stress resulting from decreased expression of SOD and increased expression of iNOS, xanthine oxidase, and NAD(P)H oxidase.
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39

Robinson, Peter [Verfasser]. "Molekulare und klinische Untersuchungen beim Marfan-Syndrom und verwandten Erkrankungen / Peter Robinson." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2010. http://d-nb.info/1024105156/34.

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40

Hewett, Duncan Robert. "The genetics of the Marfan syndrome and the characterisation of causal mutations." Thesis, University of Oxford, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359444.

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41

Williams, Andrew. "The diagnosis and treatment of myocardial and arterial dysfunction in Marfan Syndrome." Thesis, Cardiff University, 2011. http://orca.cf.ac.uk/38024/.

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Marfan Syndrome is a genetic, cardiovascular disease caused by a defect in the fibrillin 1 gene on chromosome 15. This defect causes abnormal deposition of elastin throughout the body. Elastin is found in many organs including the aorta. Marfan Syndrome is diagnosed by the Ghent criteria. The mean age at death is 44 years for men and 47 years for women, and about 70% die from acute cardiovascular complications, mainly aortic dissection. The assessment and treatment of the aortic complications of Marfan Syndrome has not changed for many years. Serial echocardiography is performed to measure the aortic root diameter. If thought to be increasing in size, beta blockers are prescribed to delay aortic dilatation and surgery, and to prevent aortic dissection or rupture despite the paucity of good research data. I have investigated three novel diagnostic tools: Tissue Doppler Imaging, Applanation Tonometry and Wave Intensity Analysis which have potential advantages in the assessment of the left ventricle and aorta and their interaction in Marfan Syndrome. I also investigated three drugs a beta blocker, an angiotensin converting enzyme inhibitor and a calcium channel blocker to look at their impact on some of the parameters measured by these three novel tools in a double-blinded, randomised cross-over trial. I conclude that these three novel tools would be useful adjuncts in monitoring Marfan Syndrome and their response to treatment. I also found that beta blockers may still have a role to play in delaying and preventing aortic complications when given together with an angiotensin converting enzyme inhibitor, calcium channel blocker or angiotensin receptor blocker. There are, however, other issues that need addressing to improve the management of the cardiovascular complications of Marfan Syndrome. This includes a multi-team approach to this multi-system disease and improvements in the standard of research.
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Xu, Dong. "Genetic factors and phenotypic variability in Marfan syndrome and abdominal aortic aneurysm /." [St. Lucia, Qld.], 1999. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16256.pdf.

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43

Kim, Andrew. "Targeted macrophage depletion is protective against heart valve disease in Marfan syndrome." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1562059861013629.

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44

Sellers, Stephanie Leigh. "Vascular biology of marfan syndrome : angiotensin II receptors, losartan, and nitric oxide." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/62489.

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The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.
Medicine, Faculty of
Anesthesiology, Pharmacology and Therapeutics, Department of
Graduate
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45

Lepreux, Sébastien. "Syndrome de Marfan et syndromes marfanoi͏̈des. Expression de la fibrilline-1 et de l'élastine au niveau des biopsies cutanées : à propos de 12 cas." Bordeaux 2, 1999. http://www.theses.fr/1999BOR23094.

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46

Egana, Isabel. "Specific features of the aortic endothelium in a murine model of Marfan Syndrome." Thesis, Bordeaux 2, 2013. http://www.theses.fr/2013BOR22052/document.

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La formation de podosomes dans les cellules endothéliales (Ces) aortiques en réponse au TGFβ est bien décrite in vitro (dans des boîtes de culture) et ex vivo (dans des segments de vaisseaux aortiques vivants). Le projet de cette thèse était de franchir l’étape suivante en démontrant la présence de podosomes in vivo en réponse à du TGFβ d’origine endogène. Pour ce faire, nous avons choisi d’utiliser un modèle de souris génétiquement modifiées présentant spontanément des niveaux de TGFβ élevés dans la paroi aortique, raisonnant que cet environnement devrait être propice à l’apparition des structures. La souris Marfan (FbnC1039G/+) constitue le modèle murin de la maladie humaine appelée « syndrome de Marfan ». Chez la souris comme chez l’homme, une mutation dans le gène codant pour la fibrilline-1 conduit à une augmentation des niveaux de TGFβ dans la paroi aortique et dans le sang circulant. Nous avons utilisé ce modèle pour rechercher la présence de podosomes dans l'endothélium aortique. La visualisation « en face » de l'endothélium marqué pour l’actine fibrillaire, la cortactine, la protéine adaptatrice Tks5 et la metalloprotéase MT1-MMP, a révélé des rosettes de podosomes semblables à celles détectées ex vivo en réponse à du TGFβ d’origine exogène. Ces rosettes peuvent être trouvées dans l'endothélium de l'aorte ascendante ou descendante. L’analyse du tissu sous-jacent révèle une détérioration de la lame basale qui apparait parsemée de zones dépourvues d’un de ses constituants majeurs, le collagène IV. Nous émettons l'hypothèse que les rosettes de podosomes sont impliquées dans la formation de ces zones de dégradation du collagène IV. Pour examiner les conséquences du déficit en fibrilline-1 pour les CEs et confirmer les données in vivo concernant la souris Marfan, nous avons utilisé deux approches in vitro. D’abord, nous avons mis au point un protocole pour isoler les CEs aortiques à partir des souris Marfan. Ensuite, nous avons, par la stratégie des siRNA, procédé à la déplétion en fibrilline-1 de CEs aortiques d’origine bovine (BAEc). Les cellules endothéliales aortiques isolées des souris Marfan conservent in vitro le phénotype « TGFβ » et forment podosomes capables de dégrader la matrice extracellulaire sans aucune stimulation exogène. Dans le modèle des cellules BAE, le dosage du TGFβ indique que, in vitro, la déplétion de ces cellules en fibrilline-1 provoque une augmentation de TGFβ biologiquement actif associé à la fraction cellulaire. Ce TGFβ conduit alors à la formation de podosomes dans les CEs. Nous avons observé d’autres conséquences du déficit en fibriline-1 dans l’endothélium in situ. L’analyse topologique de la surface de l’endothélium aortique de la souris Marfan révèle des phénomènes de « blebbing », des filopodes, des anomalies des jonctions cellules-cellules. L’analyse ultrastructurale en microscopie électronique à transmission révèle que l’endothélium de la souris Marfan a une apparence radicalement distincte de celui observé chez les témoins sauvages. La lame élastique, fragilisée par le déficit en fibrilline-1, disparaît comme digérée, par endroits. On observe une sécrétion anormale de matrice extracellulaire. Les cellules présentent un phénotype activé ou des signes d’apoptose. Ces études fournissent la première démonstration de l'apparition de podosomes endothéliaux in vivo et suggèrent leur implication en physiopathologie vasculaire. Elles fournissent également la première démonstration que l’endothelium aortique est profondément modifié dans le modèle murin de la maladie de Marfan
Podosome formation in aortic endothelial cells exposed to TGFβ has been well described in vitro (in tissue culture dishes) and ex vivo (in living aortic vessel segments). The aim of the project was to go to the next step and demonstrate the occurrence of podosomes in vivo in response to endogenous TGFβ. For this purpose, we chose to use a genetically engineered mouse model, which spontaneously presents high TGFβ levels in the aorta, reasoning that this would be a favorable environment for these structures to appear. Marfan mice represent the murine model of the human disease Marfan syndrome. Similar to the human disease, a mutation in the fibrillin-1 gene (C1039G/+) leads to enhanced TGFβ levels in the aortic wall as well as in circulating blood. We therefore used the Marfan mouse model in search of podosomes in the aortic endothelium. “En face” viewing of the endothelium stained for filamentous actin, cortactin, Tks5 adaptator protein and MT1-MMP metalloprotease detected podosome rosettes with features similar to those detected in the ex vivo situation. Podosome rosettes were found in both descending and ascending aorta. Analysis of the underlying tissue with collagen IV staining revealed a basement membrane scattered with staining-free patches, most likely corresponding to collagen IV degradation. We propose that podosome rosettes are involved in basement membrane degradation in this mouse. To examine the consequences of fibrillin-1 deficiency in endothelial cells and confirm the data obtained in vivo in Marfan mouse aorta, we used two in vitro approaches. First, we set up a protocol to isolate aortic endothelial cells from Marfan aortas, second, we depleted fibrillin-1 from BAE cells by siRNA silencing. Isolated Marfan aortic endothelial cells retained in vitro the TGFβ activated phenotype and formed functional podosomes without any exogenous stimulation. TGFβ levels measurements in fibrillin-1 depleted aortic endothelial cells confirmed that fibrillin-1 deficiency triggers an increase in active, cell associated TGFβ, which in turns, leads to podosome formation in endothelial cells. Finally we studied other alterations caused by the fibrillin-1 defect at the endothelial cell level in situ. Topological analysis of the Marfan mouse aortic endothelium monolayer revealed cell blebbing, numerous filopodia and showed altered cell-cell junctions. At the ultrastructural level, transmission electronic microscopy revealed that the Marfan mouse endothelium had an appearance dramatically distinct from that observed in control littermates. The elastic lamina, weakened by fibrillin-1 deficit, disappeared in some places. The vessel wall also showed abundant extracellular matrix proteins. Endothelial cells presented an activated or apoptotic phenotype. These studies provide the first demonstration for the occurrence of endothelial podosomes in vivo and suggest their involvement in vascular physiopathology. In addition, they provide evidence that the aortic endothelium is profoundly altered in the murine model of Marfan syndrome
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47

Pons, Cots Ramon Maria. "Computational analysis of fluid dynamics at the asceding thoracic aorta in Marfan syndrome patients." Doctoral thesis, Universitat Ramon Llull, 2020. http://hdl.handle.net/10803/669234.

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Els aneurismes aòrtics són una dilatació progressiva i irreversible de la paret aòrtica, que pot causar la ruptura o dissecció dels vasos, el que resulta en una pèrdua catastròfica de sang que condueix a la mort. El tractament farmacològic inicial se centra en aturar el creixement per prevenir la ruptura, però requereix una reparació invasiva oberta o una reparació endovascular en pacients en risc. El maneig del pacient i l'estratificació de risc després del diagnòstic són crítics, especialment en l'aorta ascendent, ja que actualment no hi ha tractaments endovasculars disponibles. Segons les directrius actuals, el diàmetre aòrtic màxim és l'únic criteri geomètric o fluidodinàmic específic del pacient acceptat com a predictor clínic del risc de ruptura. No obstant això, l'anormal fluidodinàmica en l'aorta ascendent s'ha reportat àmpliament com una possible font d'aneurismes aòrtics i la seva comprensió podria millorar l'avaluació del risc del pacient. En aquest estudi, es va avaluar la fluidodinàmica en aortes de controls sans i pacients amb síndrome de Marfan. Per fer això, hem comparat el rendiment de les simulacions de dinàmica de fluids computacional i d'interacció fluid-estructura utilitzant imatges clíniques com a condicions específiques del pacient. També hem dissenyat un sistema in vitro que podria exposar les cèl·lules endotelials aòrtiques humanes a un entorn fluidodinàmic que imita el de les simulacions aòrtiques. L'estudi ha revelat, en pacients Marfan, que considerà l'elasticitat de la paret en les simulacions és essencial per obtenir amb precisió els valors fluidodinàmics que tenen el potencial d'estratificar aquests pacients. En aquest sentit, les simulacions d'interacció fluid-estructura han superat la fluidodinàmica computacional clàssica a un cost computacional moderat. Com a resultat d'aquest estudi, un paràmetre adimensional, la relació d'esforç tallant, ha determinat el seu potencial com a marcador de progressió d'aneurisma en pacients amb Marfan.
Los aneurismas aórticos son una dilatación progresiva e irreversible de la pared aórtica, que puede causar la ruptura o disección de los vasos, lo que resulta en una pérdida catastrófica de sangre que conduce a la muerte. El tratamiento farmacológico inicial se centra en detener el crecimiento para prevenir la ruptura, pero se requiere una reparación invasiva abierta o una reparación endovascular en pacientes en riesgo. El manejo del paciente y la estratificación del riesgo después del diagnóstico son críticos, especialmente en la aorta ascendente, ya que actualmente no hay tratamientos endovasculares disponibles. Según las directrices actuales, el diámetro aórtico máximo es el único criterio geométrico o fluidodinámico específico del paciente aceptado como predictor clínico del riesgo de ruptura. Sin embargo, la anormal fluidodinámica en la aorta ascendente se ha reportado ampliamente como una posible fuente de aneurismas aórticos y su comprensión podría mejorar la evaluación del riesgo del paciente. En este estudio, se evaluó la fluidodinámica en aortas de controles sanos y pacientes con síndrome de Marfan. Para hacer esto, hemos comparado el rendimiento de las simulaciones de dinámica de fluidos computacional y de interacción fluido-estructura utilizando imágenes clínicas como condiciones específicas del paciente. También hemos diseñado un sistema in vitro que podría exponer las células endoteliales aórticas humanas a un entorno fluidodinámico que imita el de las simulaciones aórticas. El estudio ha revelado, en pacientes Marfan, que considerar la elasticidad de la pared en las simulaciones es esencial para obtener con precisión los valores dinámicos de los fluidos que tienen el potencial de estratificar a estos pacientes. En este sentido, las simulaciones de interacción fluido-estructura han superado la fluidodinámica computacional clásica a un costo computacional moderado. Como resultado de este estudio, un parámetro adimensional, la relación de esfuerzo cortante, ha demostrado su potencial como marcador de progresión de aneurisma en pacientes con Marfan.
Aortic aneurysms are a progressive and irreversible dilation of the aortic wall, which can lead to vessel rupture or dissection, resulting in catastrophic blood loss leading to death. Initial pharmacological treatment is focused on growth arrest to prevent rupture, but invasive open repair or endovascular repair are required in patients at risk. Patient management and risk stratification after diagnosis are critical, especially in the ascending aorta since no endovascular treatments are currently available. According to current guidelines, maximum aortic diameter is the only patient-specific geometrical or fluidodynamic criterion accepted as clinical rupture risk predictor. However, abnormal fluid dynamics at the ascending aorta have been widely reported as potential origin of aortic aneurysms and their understanding could improve the risk assessment of patients. In this study, the fluid dynamics of aortae from healthy controls and patients with Marfan syndrome have been evaluated. To do so, we have compared the performance of computational fluid dynamics and fluid-structure interaction simulations using clinical imaging as patient-specific inputs. We have also designed an in vitro system that could expose human aortic endothelial cells to a fluidodynamic environment that mimics that of aortic simulations. The study has revealed, in Marfan patients, that considering the wall elasticity in simulations is critical to derive precisely fluid dynamic values that hold the potential to stratify such patients. In this sense, fluid-structure interaction simulations have outperformed classic computational fluid dynamics at a moderate computational cost. As a result of this study, a dimensionless parameter, the shear stress ratio, has shown its potential as marker of aneurysm progression in Marfan patients.
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48

Gehle, Petra [Verfasser]. "NT-pro BNP und diastolische linksventrikuläre Funktion bei Patienten mit Marfan Syndrom / Petra Gehle." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2016. http://d-nb.info/1102933414/34.

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49

Berry, Karen L. (Karen Louise) 1972. "The structural basis of arterial stiffness and its relationship to cardiovascular outcome." Monash University, Dept. of Medicine, 2003. http://arrow.monash.edu.au/hdl/1959.1/7919.

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50

Touat, Ziad. "Anévrysmes des aortes ascendante et abdominale chez l'homme : rôle des plaquettes dans ces pathologies." Paris 7, 2007. http://www.theses.fr/2007PA077069.

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Les anévrysmes se définissent par une dilatation de l'artère qui conduit à une perte de parallélisme des berges vasculaires. L'implication de la composante sanguine a longtemps été négligée dans ces pathologies. Mon travail de thèse s'est concentré sur l'étude d'un lien entre les anévrysmes de l'aorte chez l'homme et le sang. Les anévrysmes de l'aorte abdominale s'accompagnent d'un thrombus non occlusif qui forme une interface active entre le sang et la paroi. Nous avons montré le rôle actif de ce thrombus dans les AAA. Les thrombi forment un réservoir de protéases qui agressent la paroi et empêchent la cicatrisation du thrombus. J'ai également montré que le renouvellement de ces thrombi est responsable de l'enrichissement en PMN via l'exposition constante de P-sélectines par les plaquettes. Ces résultats ont été validés in vivo sur un modèle expérimental d'anévrysmes. J'ai ensuite montré pour la première fois une activation plaquettaire et une génération de thrombine chez les porteurs d'un anévrysme de l'aorte ascendante, par dosage et détection de biomarqueurs. Le développement de ces anévrysmes ne s'accompagne pas de la formation d'ur thrombus. Ces résultats originaux suggèrent un rôle pour l'activation plaquettaire et de Ia prothrombine sur l'évolution de cette maladie. En conclusion, mes travaux mettent en évidence pour la 1ere fois, le rôle des plaquettes et de Ia coagulation dans les maladies anévrysmales. Mes résultats conduisent à une meilleun compréhension des mécanismes de cette pathologie dont l'évolution inéluctable est la rupture permettant d'envisager de nouvelles applications cliniques, en thérapeutique et en imageriefonctionnelle
Aneurysms are defined by a dilation of the artery which leads to a loss of parallelism of the vascular wall. The implication of the blood component was neglected a long time in these pathologies. My work during my PhD concentrated on the study of a bond between aortic aneurysms of the aorta and the blood components. The abdominal aortic aneurysms are accompanied by a nonocclusive thrombus which forms an active interface between blood and arterial wall. We showed the active role for this thrombus in the AAA. The thrombi form a tank of proteases which attack the wall and prevent the cicatrization of the thrombus. I also showed that the renewal of these thrombi is responsible for enrichment in PMI1 via the constant exposure of P-selectin by activated platelets. These results were validated in vivo on an experimental model of aneurisms. I then showed for the first time a state of platelet activation and a generation of thrombin in patient with thoracic ascending aortic aneurysm, by detection of biomarkers. The development of these aneurisms is not accompanied by the formation of a thrombus. These original results suggest ; role for platelet activation and of the prothrombin on the evolution of this disease. In conclusion, my work highlights for the 1st time, the role of the platelets and coagulation cascade in the aneurysmal diseases. My results lead to a better understanding of this pathology whose inescapable evolution is the rupture, allowing to consider new clinical applications, into therapeutic and functional imagery
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