Importance des mouvements calciques au cours de l'activite des plaquettes sanguines

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 78936 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

STRESS OXYDANT ET GLYCATION (ETUDE DE L'ALBUMINE ET DES APOLIPOPROTEINES AI ET B ; BIOSYNTHESES PAR L'HEPATOCYTE HUMAIN EN CULTURE ET IMPORTANCE CHEZ LE DIABETIQUE (DOCTORAT : BIOCHIMIE))

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Activated platelets contribute to oxidized low-density lipoproteins and dysfunctional high-density lipoproteins through a phospholipase A2-dependent mechanism

Plasma activity of secretory phospholipase A2 (sPLA2) increases in patients with cardiovascular disease. The present study investigated whether platelet-released sPLA2 induces low-density lipoprotein (LDL) and high-density lipoprotein (HDL) modifications that translate into changes in lipoprotein function. Activated but not resting platelets induced oxidative modifications of human native LDLs and HDLs, which render these particles dysfunctional. Platelet-incubated LDLs stimulated the incorporation of cholesterol oleate into macrophages, and modified HDLs lost their cholesterol efflux capacity and antioxidant properties. In vitro and ex vivo experiments showed that lysophophatidylcholine accumulated in the platelet-modified LDLs and HDLs of mice expressing sPLA2 (Balb/c and transgenic C57Bl/6 mice expressing human sPLA2) but not in the lipoproteins of naturally sPLA2-deficient mice (C57Bl/6). Unlike C57Bl/6 mice, Balb/c mice injected with leptin (67 mu g/mouse, i.p.) as an in vivo prothrombotic agent displayed increased plasma sPLA2 activity, reduced clotting time, higher plasma levels of oxidation products, increased production of nonesterified fatty acids, and more substantial platelet-mediated modification of lipoproteins. These effects were blocked completely by injection of the platelet inhibitor ticlopidine (5 mg/kg, i.p.) or by a sPLA2 inhibitor (LY311727, 3 mg/kg, i.p.). These results demonstrate that stimulated platelets are major contributors to plasma sPLA2 activity in vivo and account to a large extent for the adverse modification of circulating lipoproteins.-Blache, D., Gautier, T., Tietge, U.J.F., Lagrost, L. Activated platelets contribute to oxidized low-density lipoproteins and dysfunctional high-density lipoproteins through a phospholipase A2-dependent mechanism. FASEB J. 26, 927-937 (2012). www.fasebj.or

MINIREVIEW Impaired Homocysteine Metabolism and Atherothrombotic Disease Homocysteine Metabolism and Its Regulation

SUMMARY: Based on recent retrospective, prospective, and experimental studies, mild to moderate elevation of fasting or postmethionine-load plasma homocysteine is accepted as an independent risk factor for cardiovascular disease and thrombosis in both men and women. Hyperhomocysteinemia results from an inhibition of the remethylation pathway or from an inhibition or a saturation of the transsulfuration pathway of homocysteine metabolism. The involvement of a high dietary intake of methionine-rich animal proteins has not yet been investigated and cannot be ruled out. However, folate deficiency, either associated or not associated with the thermolabile mutation of the N 5,10 -methylenetetrahydrofolate reductase, and vitamin B 6 deficiency, perhaps associated with cystathionine ␤-synthase defects or with methionine excess, are believed to be major determinants of the increased risk of cardiovascular disease related to hyperhomocysteinemia. Recent experimental studies have suggested that moderately elevated homocysteine levels are a causal risk factor for atherothrombotic disease because they affect both the vascular wall structure and the blood coagulation system. The oxidant stress that results from impaired homocysteine metabolism, which modifies the intracellular redox status, might play a central role in the molecular mechanisms underlying moderate hyperhomocysteinemia-mediated vascular disorders. Because folate supplementation can efficiently reduce plasma homocysteine levels, both in the fasting state and after methionine loading, results from further prospective cohort studies and from on-going interventional trials will determine whether homocysteine-lowering therapies can contribute to the prevention and reduction of cardiovascular risk. Additionally, these studies will provide unequivocal arguments for the independent and causal relationship between hyperhomocysteinemia and atherothrombotic disease. (Lab Invest 2001, 81:645-672). C ardiovascular diseases remain the leading cause of mortality in Western populations. Hyperlipoproteinemia, hypertension, diabetes, obesity, and tobacco smoking are the main risk factors for atherosclerosis and its thrombotic complications. However, these factors alone cannot account for all of the deaths caused by vascular pathologies. As early as 1969, clinical studies conducted in homocystinuric children revealed the importance of severe hyperhomocysteinemia in premature development of atherosclerosis and thromboembolism In the present review, we describe homocysteine metabolism and its regulation by tissue folate and S-adenosylmethionine levels. We also discuss the metabolic abnormalities leading to hyperhomocysteinemia and the importance of moderate hyperhomocysteinemia in the incidence of cardiovascular pathologies. Specific attention is given to understanding the inconsistencies in the prospective studies. Finally, we focus on the potential mechanisms involved in vascular disorders caused by hyperhomocysteinemia and we describe the possible vitamin treatments

Système de caractérisation de type load-pull temporel pour l'optimisation des classes de fonctionnement des transistors de puissance et pour l'étude de l'intermodulation

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