Littérature scientifique sur le sujet « Blood lipoproteins Oxidation »

Air pollution is a leading global risk factor for cardiovascular disease. Experimental animal models and short-term studies in humans are consistent with systemic effects of particulate matter smaller than 2.5 microns. Exposure to fine as well as ultrafine particles (<0.1 microns) have been shown to be consistently associated with a number of risk factors including hypertension, diabetes, and abnormalities in lipoproteins. The size of particles and the chemical composition are key determinants of propensity for systemic effects. While direct chemical translocation of smaller particles across the alveolar–capillary membrane is possible, oxidative modification of phospholipids in entities such as lipoproteins and other plasma proteins may represent additional mechanisms by which exposure may transduce systemic effects. Studies in susceptible disease models have been particularly informative as exposure to air pollution appears to aggravate a number of risk factors such as hypertension and diabetes. Collectively, these studies seem to suggest that chronic exposure to air pollution may potentiate the risk factors and may represent a convergent pathway through which air pollution may mediate susceptibility to cardiovascular disease. Air pollution exposure also exerts acute effects through mechanisms that include alterations in vascular tone, coagulation abnormalities, and changes in blood pressure. Collectively, these findings argue for the recognition of air pollution as an independent risk factor for the pathogenesis of cardiovascular disease.

Aspirin, considered the prototypic platelet antagonist, has been available for over a century and currently represents a mainstay both in the prevention and treatment of vascular events that include stroke, myocardial infarction, peripheral vascular occlusion, and sudden death. Aspirin irreversibly acetylates cyclooxygenase (COX), impairing prostaglandin metabolism and thromboxane A2 (TXA2) synthesis. As a result, platelet aggregation in response to collagen, adenosine diphosphate (ADP), and thrombin (in low concentrations) is attenuated (Roth and Majerus, 1975). Because aspirin more selectively inhibits COX-1 activity (found predominantly in platelets) than COX-2 activity (expressed in tissues following an inflammatory stimulus), its ability to prevent platelet aggregation is seen at relatively low doses, compared with the drug’s potential antiinflammatory effects, which require much higher doses (Patrono, 1994). Several alternative mechanisms of platelet inhibition by aspirin have been proposed, including: (1) inhibition of platelet activation by neutrophils and (2) enhanced nitric oxide production. In addition, aspirin may prevent the progression of atherosclerosis by protecting low-density lipoprotein (LDL) cholesterol from oxidation and scavenging hydroxyl radicals. Following oral ingestion, aspirin is promptly absorbed in the proximal gastrointestinal (GI) tract (stomach, duodenum), achieving peak serum levels within 15 to 20 minutes and platelet inhibition within 40 to 60 minutes. Enteric-coated preparations are less well absorbed, causing an observed delay in peak serum levels and platelet inhibition to 60 and 90 minutes, respectively. The antiplatelet effect occurs even before acetylsalicylic acid is detectable in peripheral blood, probably from platelet exposure in the portal circulation. The plasma concentration of aspirin decays rapidly with a circulating half-life of approximately 20 minutes. Despite the drug’s rapid clearance, platelet inhibition persists for the platelet’s life span (7 ± 2 days) due to aspirin’s irreversible inactivation of COX-1. Because 10% of circulating platelets are replaced every 24 hours, platelet activity (bleeding time, primary hemostasis) returns toward normal (≥50% activity) within 5 to 6 days of the last aspirin dose (O’Brien, 1968). A single dose of 100 mg of aspirin effectively reduces the production of TXA2 in many (but not all) individuals.