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1

Macchi, Chiara, Nicola Ferri, Chiara Favero, et al. "Long-term exposure to air pollution raises circulating levels of proprotein convertase subtilisin/kexin type 9 in obese individuals." European Journal of Preventive Cardiology 26, no. 6 (2018): 578–88. http://dx.doi.org/10.1177/2047487318815320.

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Aims Exposure to airborne particulate matter has been consistently associated with early death and increased morbidity, particularly raising the risk of cardiovascular disease. Obesity, one of the leading cardiovascular disease risk factors, increases susceptibility to the adverse effects of particulate matter exposure. Proprotein convertase subtilisin/kexin type 9 has been related to a large number of cardiovascular risk factors, e.g. atherogenic lipoproteins, arterial stiffness and platelet activation. Thus, the present study was aimed at evaluating, in a series of obese individuals, the eff
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2

Stoekenbroek, Robert M., and John J. P. Kastelein. "Proprotein convertase subtilisin/kexin type 9." Current Opinion in Cardiology 33, no. 3 (2018): 269–75. http://dx.doi.org/10.1097/hco.0000000000000517.

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3

Sahebkar, Amirhossein. "Proprotein Convertase Subtilisin/Kexin Type 9." Angiology 65, no. 3 (2013): 243. http://dx.doi.org/10.1177/0003319713512016.

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4

Sinan, Umit Yasar. "Proprotein Convertase Subtilisin/Kexin Type 9." Angiology 65, no. 3 (2013): 244. http://dx.doi.org/10.1177/0003319713512558.

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5

Bergeron, Nathalie, Binh An P. Phan, Yunchen Ding, Aleyna Fong, and Ronald M. Krauss. "Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition." Circulation 132, no. 17 (2015): 1648–66. http://dx.doi.org/10.1161/circulationaha.115.016080.

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6

Farnier, Michel. "Proprotein convertase subtilisin kexin type 9 inhibitors." Current Opinion in Lipidology 27, no. 6 (2016): 597–604. http://dx.doi.org/10.1097/mol.0000000000000356.

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7

Marais, David A., Dirk J. Blom, Francine Petrides, Yann Gouëffic, and Gilles Lambert. "Proprotein convertase subtilisin/kexin type 9 inhibition." Current Opinion in Lipidology 23, no. 6 (2012): 511–17. http://dx.doi.org/10.1097/mol.0b013e3283587563.

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8

Zenti, Maria G., Anna Altomari, Maria G. Lupo, et al. "From lipoprotein apheresis to proprotein convertase subtilisin/kexin type 9 inhibitors: Impact on low-density lipoprotein cholesterol and C-reactive protein levels in cardiovascular disease patients." European Journal of Preventive Cardiology 25, no. 17 (2018): 1843–51. http://dx.doi.org/10.1177/2047487318792626.

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In this observational study, we compared the effect of lipoprotein apheresis and evolocumab or alirocumab on levels of lipoprotein cholesterol, triglycerides and inflammatory markers (C reactive protein and interleukin 6) in cardiovascular patients ( n = 9). Patients were monitored during the last year of lipoprotein apheresis followed by six months of treatment with proprotein convertase subtilisin/kexin type 9 inhibitors. The biochemical parameters were determined pre- and post- every apheresis procedure for 12 months and then after one, three and six months of treatment with evolocumab (140
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9

Hess, Gregory P., Pradeep Natarajan, Kamil F. Faridi, Anna Fievitz, Linda Valsdottir, and Robert W. Yeh. "Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Therapy." Circulation 136, no. 23 (2017): 2210–19. http://dx.doi.org/10.1161/circulationaha.117.028430.

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10

Leong, Derek, and Peter E. Wu. "Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors." Canadian Medical Association Journal 191, no. 32 (2019): E894. http://dx.doi.org/10.1503/cmaj.190107.

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11

Hoang, Van Bac, Vadim V. Tyrenko, Oksana V. Shcherbatyuk, Sergey G. Bologov, and Nikolay Yu Demyanenko. "The effect of proprotein convertase subtilisin kexin type 9 inhibitors on the survival of patients at extreme cardiovascular risk in real clinical practice." HERALD of North-Western State Medical University named after I.I. Mechnikov 16, no. 4 (2024): 35–44. https://doi.org/10.17816/mechnikov634428.

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BACKGROUND: Among non-communicable diseases, cardiovascular diseases occupy a leading position in terms of mortality rate in developed countries, including Russia. In the clinical practice of the Russian Federation, almost all modern methods and means of treating patients with cardiovascular diseases are used. In particular, innovative lipid-lowering drugs are used, such as proprotein convertase inhibitors subtilisin/kexin type 9 — alirocumab and evolocumab. However, at the moment there is no complete information on how these drugs affect the survival of patients at extreme cardiovascular risk
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12

Hanton, Sally L., and Charles Van Heyningen. "Proprotein convertase subtilisin/kexin type 9 related familial hypercholesterolaemia." British Journal of Diabetes & Vascular Disease 12, no. 5 (2012): 256–59. http://dx.doi.org/10.1177/1474651412463256.

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13

Schmit, David, Danilo Fliser, and Thimoteus Speer. "Proprotein convertase subtilisin/kexin type 9 in kidney disease." Nephrology Dialysis Transplantation 34, no. 8 (2019): 1266–71. http://dx.doi.org/10.1093/ndt/gfz122.

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Abstract Chronic kidney disease (CKD) is associated with a substantially increased risk for the development of atherosclerotic cardiovascular (CV) disease. Accordingly, CV mortality is increased even in the earliest stages of CKD. In the general population and in CKD patients, high plasma levels of low-density lipoprotein cholesterol (LDL-C) are crucially involved in the initiation and progression of atherosclerotic vascular lesions. Lowering LDL-C by use of statins and/or ezetimibe represents the gold standard of lipid-lowering therapy, with a great body of evidence from several large clinica
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14

Macchi, Chiara, Maria Francesca Greco, Margherita Botta, et al. "Leptin, Resistin, and Proprotein Convertase Subtilisin/Kexin Type 9." American Journal of Pathology 190, no. 11 (2020): 2226–36. http://dx.doi.org/10.1016/j.ajpath.2020.07.016.

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15

Spolitu, Stefano, Wen Dai, John A. Zadroga, and Lale Ozcan. "Proprotein convertase subtilisin/kexin type 9 and lipid metabolism." Current Opinion in Lipidology 30, no. 3 (2019): 186–91. http://dx.doi.org/10.1097/mol.0000000000000601.

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16

Pavlicek, Valérie, Daniel Urban, and Ulrich Laufs. "Hemmung der Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)." CardioVasc 13, no. 6 (2013): 44–48. http://dx.doi.org/10.1007/s15027-013-0271-z.

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17

Simonen, Piia, Ulf-Håkan Stenman, and Helena Gylling. "Serum proprotein convertase subtilisin/kexin type 9 concentration is not increased by plant stanol ester consumption in normo- to moderately hypercholesterolaemic non-obese subjects. The BLOOD FLOW intervention study." Clinical Science 129, no. 5 (2015): 439–46. http://dx.doi.org/10.1042/cs20150193.

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The present randomized, controlled clinical intervention demonstrated that plant stanol ester consumption does not affect serum proprotein convertase subtilisin/kexin type 9 concentration thus offering an effective dietary means to lower LDL cholesterol concentration.
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18

LI, ChangYong, Yuan BAI, and YongWen QIN. "Research advances in proprotein convertase subtilisin/kexin type 9 inhibitors." Pharmaceutical Care and Research 13, no. 4 (2013): 241–44. http://dx.doi.org/10.5428/pcar20130401.

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19

Ali, Ali, Pierluigi Costanzo, and Angela Hoye. "Proprotein Convertase Subtilisin/kexin type 9 Inhibition in Cardiovascular Prevention." Current Pharmaceutical Design 24, no. 4 (2018): 442–50. http://dx.doi.org/10.2174/1381612824666180111105201.

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Elevated levels of Low Density Lipoprotein cholesterol (LDL-C) are directly associated with increased risk for atherosclerotic cardiovascular and cerebrovascular events. Statins have been used to control serum LDLC and this has translated into reduction in cardiovascular and cerebrovascular events. However, despite high dose statin therapy, LDL-C control may remain inadequate in some patients, particularly those with familial hypercholesterolemia. A new therapeutic approach has emerged in recent years with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. In this review, we des
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20

Blumenthal, Roger S., Khurram Nasir, and Seth S. Martin. "Realizing Value With Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors." Circulation 138, no. 8 (2018): 767–69. http://dx.doi.org/10.1161/circulationaha.118.035156.

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21

Koutagiar, I., C. Vlachopoulos, D. Terentes-Printzios, et al. "Proprotein convertase subtilisin/ kexin type 9 levels and arterial function." Atherosclerosis 275 (August 2018): e132. http://dx.doi.org/10.1016/j.atherosclerosis.2018.06.385.

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22

Filippatos, Theodosios D., Eliza C. Christopoulou, and Moses S. Elisaf. "Pleiotropic effects of proprotein convertase subtilisin/kexin type 9 inhibitors?" Current Opinion in Lipidology 29, no. 4 (2018): 333–39. http://dx.doi.org/10.1097/mol.0000000000000523.

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23

Chan, Dick C. "Regulation of proprotein convertase subtilisin/kexin type 9: Therapeutical perspectives." Atherosclerosis 217, no. 1 (2011): 77–79. http://dx.doi.org/10.1016/j.atherosclerosis.2011.02.040.

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24

Julius, U., S. Tselmin, U. Schatz, S. Fischer, and S. R. Bornstein. "Lipoprotein(a) and proprotein convertase subtilisin/kexin type 9 inhibitors." Clinical Research in Cardiology Supplements 14, S1 (2019): 45–50. http://dx.doi.org/10.1007/s11789-019-00099-z.

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25

Noel, Zachary R., and Craig J. Beavers. "Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors: A Brief Overview." American Journal of Medicine 130, no. 2 (2017): 229.e1–229.e4. http://dx.doi.org/10.1016/j.amjmed.2016.09.021.

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26

Dua, Pamila, and KH Reeta. "PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9): A Narrative Review." Journal of the Practice of Cardiovascular Sciences 6, no. 3 (2020): 226. http://dx.doi.org/10.4103/jpcs.jpcs_3_20.

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27

Huang, Ya-Ping, Yun-Shan Wang, Bi-Wen Liu, et al. "Dammarane-type saponins with proprotein convertase subtilisin/kexin type 9 inhibitory activity from Gynostemma pentaphyllum." Phytochemistry 194 (February 28, 2022): 1–11. https://doi.org/10.1016/j.phytochem.2021.113005.

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Huang, Ya-Ping, Wang, Yun-Shan, Liu, Bi-Wen, Song, Zhe, Liang, Xiao-Shuang, Teng, Yuan, Zhang, Jian, Yin, Zhi-Qi, Pan, Ke (2022): Dammarane-type saponins with proprotein convertase subtilisin/kexin type 9 inhibitory activity from Gynostemma pentaphyllum. Phytochemistry (113005) 194: 1-11, DOI: 10.1016/j.phytochem.2021.113005, URL: http://dx.doi.org/10.1016/j.phytochem.2021.113005
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28

Filippatos, Theodosios D., Anastazia Kei, Christos V. Rizos, and Moses S. Elisaf. "Effects of PCSK9 Inhibitors on Other than Low-Density Lipoprotein Cholesterol Lipid Variables." Journal of Cardiovascular Pharmacology and Therapeutics 23, no. 1 (2017): 3–12. http://dx.doi.org/10.1177/1074248417724868.

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Low-density lipoprotein cholesterol (LDL-C) is a major cardiovascular risk factor, but other lipid variables such as triglycerides (TRGs), high-density lipoprotein cholesterol (HDL-C) and lipoprotein a [Lp(a)] also affect cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly lower LDL-C concentration but also modestly improve the concentrations of TRGs and HDL-C and more robustly decrease Lp(a) levels. The review presents the associated mechanisms of the beneficial effects of PCSK9 inhibitors on the other than LDL-C lipid variables, including the e
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29

Stein, Evan A. "Proprotein Convertase Subtilisin/kexin Type 9 Inhibitors in Clinical Practice: A Focused Update." US Cardiology Review 11, no. 2 (2017): 105. http://dx.doi.org/10.15420/usc.2017:23:1.

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This article provides an updated review of the LDL-cholesterol efficacy, safety, and cardiovascular benefits of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. It focuses on evidence from numerous clinical trials and provides clinicians with a basis for understanding, assessing, and selecting these agents for clinical practice. It also provides some perspective on other potential agents in development that target PCSK9.
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30

Shapiro, Michael D., Joshua Miles, Hagai Tavori, and Sergio Fazio. "Diagnosing Resistance to a Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor." Annals of Internal Medicine 168, no. 5 (2017): 376. http://dx.doi.org/10.7326/m17-2485.

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31

Shahreyar, Muhammed, Salem A. Salem, Mannu Nayyar, Lekha K. George, Nadish Garg, and Santhosh K. G. Koshy. "Hyperlipidemia: Management with Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors." Journal of the American Board of Family Medicine 31, no. 4 (2018): 628–34. http://dx.doi.org/10.3122/jabfm.2018.04.170447.

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32

Farnier, Michel. "The Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Hyperlipidemia." American Journal Cardiovascular Drugs 11, no. 3 (2011): 145–52. http://dx.doi.org/10.2165/11590330-000000000-00000.

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33

Kotani, Kazuhiko, and Maciej Banach. "Lipoprotein(a) and inhibitors of proprotein convertase subtilisin/kexin type 9." Journal of Thoracic Disease 9, no. 1 (2017): E78—E82. http://dx.doi.org/10.21037/jtd.2017.01.40.

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34

Sklar, Michael C., Claudia C. dos Santos, and Patrick R. Lawler. "Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition and Survival in Sepsis." Critical Care Medicine 47, no. 3 (2019): 489–91. http://dx.doi.org/10.1097/ccm.0000000000003609.

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35

Bittner, Vera. "Pleiotropic Effects of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibitors?" Circulation 134, no. 22 (2016): 1695–96. http://dx.doi.org/10.1161/circulationaha.116.023687.

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36

Pihtili Taş, Nevsun, Rabia Aydogan Baykara, Ayhan Kamanli, et al. "Proprotein convertase subtilisin/kexin type 9 and apelin in fibromyalgia syndrome." Archives of Rheumatology 39, no. 3 (2024): 375–83. http://dx.doi.org/10.46497/archrheumatol.2024.10462.

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Objectives: This study aimed to investigate the potential roles of proprotein convertase subtilisin/ kexin type 9 (PCSK9) and apelin in the etiology of fibromyalgia syndrome (FS). Patients and methods: The retrospective study was conducted between May 2022 and February 2023. Fifty-eight female FS patients (mean age: 45.2±9.9 years; range, 25 to 66 years) and 30 age- and body mass index-matched control subjects (mean age: 43.1±9.9 years; range, 26 to 67 years) were included in the study. Apelin and PCSK9 levels of all individuals were measured using appropriate methods. Results: The levels of P
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37

Schmidt, Robert J., Youyan Zhang, Yang Zhao, et al. "A Novel Splicing Variant of Proprotein Convertase Subtilisin/Kexin Type 9." DNA and Cell Biology 27, no. 4 (2008): 183–89. http://dx.doi.org/10.1089/dna.2007.0667.

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38

Koutagiar, Losif, Charalambos Vlachopoulos, Dimitrios Terentes-Printzios, et al. "P8 PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 LEVELS AND ARTERIAL FUNCTION." Artery Research 20, no. C (2017): 63. http://dx.doi.org/10.1016/j.artres.2017.10.061.

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39

Wang, Ya, Murong Ma, Jian-An Wang, Alan Daugherty, and Hong S. Lu. "Targeting proprotein convertase subtilisin/kexin type 9 in mice and monkeys." Current Opinion in Lipidology 30, no. 2 (2019): 154–55. http://dx.doi.org/10.1097/mol.0000000000000583.

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40

Rakipovski, Günaj, G. Kees Hovingh, and Michael Nyberg. "Proprotein convertase subtilisin/kexin type 9 inhibition as the next statin?" Current Opinion in Lipidology 31, no. 6 (2020): 340–46. http://dx.doi.org/10.1097/mol.0000000000000718.

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41

Alberts, Mark J., and Paul D. Thompson. "PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) Inhibition and Stroke Prevention." Stroke 51, no. 5 (2020): 1361–62. http://dx.doi.org/10.1161/strokeaha.120.028567.

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42

Vekić, Jelena, Dragana Bojanin, and Vesna Spasojević-Kalimanovska. "The role of proprotein convertase subtilisin/kexin type 9 in atherosclerosis." Biologia Serbica 41, no. 2 (2019): 9–14. https://doi.org/10.5281/zenodo.3532045.

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<strong>Summary. </strong>Dyslipidemia is one of the predominant causes of atherosclerosis and cardiovascular disease (CVD) development. Accordingly, lifestyles approaches and therapeutic targeting of low-density lipoprotein (LDL)-cholesterol remain the main strategies for CVD prevention and treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serin-protease with important roles in lipoprotein metabolism. In particular, PCSK9 promotes degradation of hepatic LDL-receptors, leading to reduced clearance of LDL particles and increased plasma LDL-cholesterol levels. To da
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43

Safaeian, Leila, Golnaz Vaseghi, Hedieh Jabari, and Nasim Dana. "Evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, promotes angiogenesis in vitro." Canadian Journal of Physiology and Pharmacology 97, no. 5 (2019): 352–58. http://dx.doi.org/10.1139/cjpp-2018-0542.

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The proprotein convertases family is involved in several physiological processes such as cell growth, migration, and angiogenesis, and also in different pathological conditions. Evolocumab, an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9), has recently been approved for treatment of hypercholesterolemia. This study aimed to investigate the effect of evolocumab on angiogenesis in human umbilical vein endothelial cells (HUVECs). Cell proliferation and migration were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell methods. In vitro a
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44

Chaulin, A., L. Karslyan, A. Aleksandrov, A. Mazaev, E. Grigorieva, and D. Nurbaltaeva. "The Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Atherosclerosis Development." Bulletin of Science and Practice 5, no. 5 (2019): 112–20. http://dx.doi.org/10.33619/2414-2948/42/15.

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Elevated plasma low-density lipoprotein cholesterol (LDL-C) is an important risk factor for cardiovascular diseases. Statins are the most widely used therapy for patients with hyperlipidemia. However, a significant residual cardiovascular risk remains in some patients even after maximally tolerated statin therapy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new promising therapeutic target for decreasing LDL-C. PCSK9 reduces LDL intake from circulation by enhancing low-density lipoprotein receptors (LDLR) degradation and preventing LDLR recirculation to the cell surface. In addi
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45

Sun, Xiaowei, Rachid Essalmani, Robert Day, Abdel M. Khatib, Nabil G. Seidah, and Annik Prat. "Proprotein Convertase Subtilisin/Kexin Type 9 Deficiency Reduces Melanoma Metastasis in Liver." Neoplasia 14, no. 12 (2012): 1122—IN5. http://dx.doi.org/10.1593/neo.121252.

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46

de Dios García-Díaz, Juan, Iraida M. Corral-Bueno, José María Mesa-Latorre, Cristina Lozano-Durán, and Concepción Hernández-Ahijado. "Proprotein Convertase Subtilisin/Kexin Type 9 Antibody and Statin-Associated Autoimmune Myopathy." Annals of Internal Medicine 171, no. 1 (2019): 68. http://dx.doi.org/10.7326/l18-0705.

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47

Navarese, Eliano P., Michalina Kolodziejczak, Dean J. Kereiakes, Udaya S. Tantry, Christopher O'Connor, and Paul A. Gurbel. "Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies for Acute Coronary Syndrome." Annals of Internal Medicine 164, no. 9 (2016): 600. http://dx.doi.org/10.7326/m15-2994.

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48

Shafiq, Muhammad, Timothy Walmann, Venkat Nutalapati, Cheryl Gibson, and Yousaf Zafar. "Effects of proprotein convertase subtilisin/kexin type-9 inhibitors on fatty liver." World Journal of Hepatology 12, no. 12 (2020): 1258–167. http://dx.doi.org/10.4254/wjh.v12.i12.1258.

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49

Turgeon, Ricky D., and Glen J. Pearson. "Proprotein convertase subtilisin/kexin type 9 inhibitors for reduction of cardiovascular events." American Journal of Health-System Pharmacy 75, no. 11 (2018): 747–54. http://dx.doi.org/10.2146/ajhp170707.

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50

Mangata, S. Ramin, and G. Lambert. "Proprotein convertase subtilisin kexin type 9 in human pancreatic beta cells physiology." Atherosclerosis 331 (August 2021): e44. http://dx.doi.org/10.1016/j.atherosclerosis.2021.06.126.

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