Antithrombotic Effects of Hypolipidaemic Agents

Overview

Hypolipidemic drugs (statins, flbrates) have signiflcant pleiotropic effects. In the present review, we discuss the current knowledge on the non-lipid related effects of statins and flbrates, with special emphasis on their potential beneflts in different diseases, such as atherosclerosis, cardiovascular diseases, stroke and other diseases. The mechanism(s) responsible for their favourable properties are also reviewed. More recently statins have shown to have pleiotropic effects, not related to lipid lowering but dependent upon the inhibition of mevalonic acid synthesis and the formation of isoprenoids (geranylgeranyl and farnesyl) which inhibit the cell multiplication, secretion metalloproteinases (MMPases) and protect the cardiovascular walls at the level of endothelium, smooth muscles cells and monocytes macrophages. A stimulating effect of statins on eNOs (nitrit oxide synthase) has been shown to protect against brain ischemia. Since 1998 the effects of statins on isoprenoids formation have been shown to have a fundamental importance in non cardiovascular diseases, such as osteoporosis, antiproliferative effects (e.g. colon center and glioma) and chronic inflammatory diseases (pulmonary flbrosis). The effects of statins and related compounds on LDL lowering and the pleiotropic effects represent now one of the most rapidly growing areas of prevention and therapy of cardiovascular and other chronic diseases. The clinical beneflts of flbrates are explained by its antiatherogenic effects, which are the result of its effects on lipid and lipoprotein metabolism, coagulation and flbrinolysis, and anti-inflammatory action at the arterial wall level. The potential effects of flbrates on coagulation and flbrinolysis have an importem bearing on occlusive arterial clinical events. Plasma flbrinogen levels may be reduced 10 - 25 % by some (not all) flbrates, and these changes do not seem to be related to changes in plasma lipids or lipoproteins. Other potential anti-atherothrombotic effects include the inhibition of inflammatory mediators involved in atherogenesis. Fibrates have been shown to decrease the production of H.-6 and IL-1, an effect probably mediated by suppression of nuclear factor-KB.

Key words:
arterial smooth muscle cell proliferation, atherosclerosis, cholesterol accumulation, endothelial function, inflammation, macrophages, migration, statins, flbrates, homocysteine, thrombosis