[Diabetes, coagulation and vascular events].
Excessive oxidative stress due to hyperglycemia and glycoxidation leads to an increased production of F2-isoprostanes, one of which, 8-iso-PGF2 alpha, reaches high concentrations in plasma and urine in both insulin-dependent and non-insulin-dependent diabetics. This is associated with an increase in platelet activation, reflected by an increased urinary excretion of platelet-derived TxB2. Improved metabolic control or vitamin E supplementation reduces urinary 8-iso-PGF2 alpha and TxB2, whereas aspirin or indobufen reduces TxB2 but not 8-iso-PGF2 alpha. Since TxB2 in the urine seems to represent the common link between diabetes (as well as other risk factors) and the thrombotic complications of vascular disease, platelet activation due to lipid-glycoxidation is an important aspect in the pathogenesis of vascular complications of diabetes mellitus. Among the various plasma coagulation and fibrinolysis factors that are found to be altered in diabetes, the increased level of plasminogen activator inhibitor (PAI-1) in the plasma and in the vessel wall is of the utmost importance. Indeed, it is suspected that the atherosclerotic plaques formed in the presence of high concentrations of PAI-1 are more prone to rupture and ensuing thrombosis. The thrombosis-oriented modifications of blood platelets, coagulation and fibrinolysis are an important cause behind the high prevalence of vascular events in diabetes.
Nenci
G G
GG
Dipartimento di Medicina Interna, Università, Perugia. medvasc@unipg.it
Paliani
U
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D001779:Blood Coagulation Factors; D002318:Cardiovascular Diseases / Q000209:etiology*; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000209:etiology*; D005342:Fibrinolysis; D006031:Glycosylation; D006801:Humans; D018384:Oxidative Stress; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000378:metabolism; D015539:Platelet Activation; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology*; D013929:Thromboxane B2 / Q000652:urine
D001779:Blood Coagulation Factors; D017395:Plasminogen Activator Inhibitor 1; D013929:Thromboxane B2