Inhibition of platelet aggregation and expression of alpha granule membrane protein 140 and thromboxane B2 with pravastatin therapy for hypercholesterolemia.

ABSTRACT

The drugs in the group of the "statins" lower blood lipids, especially cholesterol, thereby reducing a risk factor for, and diminishing the incidence of, clinically important cerebrocardiovascular events. Cardiovascular events and stroke are significant causes of morbidity and mortality in China and the United States. Statins reduce platelet-mediated thrombus formation and atherosclerotic progression through mechanisms not completely elucidated. While important, the lipid-lowering action of statins does not completely explain their multifaceted benefits. Nonlipid related mechanisms are essential to such effects. The authors explore these nonlipid related mechanisms of action of pravastatin that may translate into clinically relevant benefits. This study was conducted in Guangzhou, China. Twenty-one hypercholesterolemic patients were treated with pravastatin--10-20 mg/day for 12 weeks. Blood for tests was obtained at baseline and after 8 and 12 weeks of pravastatin therapy. After 8- and 12-weeks of therapy, significant decreases were observed in the following (1) total blood cholesterol and low density lipoprotein-C (P < 0.01), (2) ADP-induced maximum platelet aggregation (P < 0.01), (3) TXB2 or thromboxane B2 in platelets (P < 0.01), and (4) expression of GMP-140 or granule membrane protein-140 (P < 0.01). The therapeutic effects of the drug did not vary significantly with length of therapy. Pravastatin induces inhibition of platelet aggregation and expression of TXB2 and GMP-140, the likely causes of thrombus formation, atherosclerotic progression, and subsequently cardiovascular events. These potential beneficial events occur within 8 weeks of pravastatin therapy.