Statins in atherothrombosis.
Clinical studies have shown that hydroxy-methyl glutaryl coenzyme A reductase inhibitors (statins) may favorably affect atherothrombosis. In addition to their potent cholesterol-lowering properties, statins reduce atheroma progression as well as the incidence of acute thrombosis-related vascular events and their dreadful clinical consequences. Available data indicate that statins exert significant antithrombotic effects in clinical practice by reducing the occurrence of vascular atherothrombotic events, with a more prominent effect in high-risk patients. The mechanisms by which statins inhibit thrombosis have been extensively investigated, and several pathways appear to be involved. In particular, statins have been proposed to reduce platelet activation and to exert favorable effects on fibrinolysis, but no clear-cut conclusion can be drawn from available studies. Moreover, statins do not consistently influence fibrinogen or factor VII levels in plasma. In contrast, in vitro and in vivo data indicate that these compounds profoundly affect thrombin generation driven by tissue factor/factor VII pathway. In vitro studies indicate that this effect is not dependent on plasma cholesterol lowering but, rather, on the inhibition of isoprenoid biosynthesis. The relative contribution of reduced levels of prenylated proteins and of cholesterol pathway to the modulation of tissue factor expression is, however, hardly to be established in clinical settings.
Colli
Susanna
S
E. Grossi Paoletti Center, Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy.
Werba
José Pablo
JP
Tremoli
Elena
E
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015539:Platelet Activation / Q000187:drug effects; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors