Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Inhibition of platelet aggregation and expression of alpha granule membrane protein 140 and thromboxane B2 with pravastatin therapy for hypercholesterolemia. 1185 67

It is becoming increasingly recognized that the beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-Co-A) reductase inhibitors (statins) on reducing clinically important cardiovascular events (myocardial infarction and stroke) are not only attributable to their hypocholesterolemic effect but also to non-lipid mechanisms of action. The nonlipid factors may include the stabilization of arterial plaques, endothelial normalization, anti-inflammatory effects and inhibition of platelet thrombus formation. The inhibition of platelet thrombus formation has not been adequately studied in man and the results are often contradictory. It is the objective of this review to discuss the effects of statins on platelet aggregation in the context of relatively new and specific techniques for the measurement of platelet function as reported by Ma and coinvestigators in this issue of JAAMP. Ma et al. examined the effect of pravastatin given for 8 to 12 weeks on platelet function and low density lipoprotein-cholesterol (LDL-C) in 21 Chinese patients with primary hypercholesterolemia. Platelet function was evaluated by adenosine diphosphate (ADP)-induced aggregation, thromboxane B2 (TXB2) and the expression of alpha granule membrane protein-140 (GMP-140). GMP-140 is considered one of the most sensitive indicators of the state of platelet function. As expected, pravastatin treatment significantly reduced LDL-C and inhibited ADP-induced platelet aggregation, TXB2 synthesis and the expression of GMP-140--all such parameters can lead to thrombus formation and subsequent cardiovascular events. Using the test methods of Ma et al., additional dose-response studies with several statins and standard antiplatelet drugs are needed to confirm their effects on platelet aggregation, if any. Furthermore, we need to determine whether the antiplatelet effect of the statins, if present, is independent of their hypocholesterolemic action. The additional studies could provide important clues toward the development of new and specific antithrombotic drugs.
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PMID:Statins, platelet aggregation and coronary heart disease. 1185 68