Atherosclerosis and thrombosis. Old and new drugs.
Thanks to the increasing knowledge of the pathogenesis of atherosclerosis, much effort has been made in the last years to develop new drugs aimed at controlling risk factors correlated with the disease as well as to investigate more deeply their mechanism of action. In particular, this brief review will describe some new aspects of the mechanism of action of drugs widely used in the control of risk factors like hyperlipemia, hypertension and blood viscosity. Among drugs active on plasma lipid profile, HMG-CoA reductase inhibitor are, at present, under study for their promising activity in the modulation of the interaction between the cells of the arterial wall and circulating blood elements. Indeed, these compounds have been found to control the proliferation of smooth muscle cells and other events related to the formation of atheroma. As far as antithrombotic drugs are concerned, the efficacy of low doses of aspirin has emerged by recent clinical trials. The successful use of low doses of aspirin has been possible following the comprehension of the mechanism by which this compound inhibits TXA-dependent platelet function, thus allowing a dose-dependent dissociation of the antithrombotic activity from other undesirable effects. Also for calcium antagonist an antiatherogenic effect which deserves further investigations has been recently clarified. Indeed it has been demonstrated that calcium antagonists have a protective effect against vascular lesions because they inhibit smooth muscle cell proliferation, lipid uptake by macrophages and the production of collagen and elastin. Another class of drugs which represents a new approach in the control of some risk factors is represented by n-3 fatty acids. Besides their activity on triglycerides, these compounds exert a positive effect on hemostatic and thromboembolic event, by reducing platelet aggregation and blood viscosity. Also for those molecules which appear to exert promising antiatherosclerotic and antithrombotic action, further studies will define their exact mechanism of action.
Paoletti
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R
Institute of Pharmacological Sciences, University of Milan, via Balzaretti, 9, 20133 Milan, Italy.
Bruno
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F
Colli
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S