Lovastatin induces platelet apoptosis

Environmental Toxicology and Pharmacology
Qing ZhaoK Dai

Abstract

Statins are widely used in the prevention of atherosclerosis and treatment of coronary artery disease because of pleiotropic effects on thrombosis. Thrombocytopenia and hemorrhage occurred in some statin-treated patients, but the reason remains unclear. In the current study, we show that lovastatin dose-dependently induces depolarization of mitochondrial inner transmembrane potential, leading to up-regulation of Bak, down-regulation of Bcl-XL, and activation of caspase-3/8/9. Lovastatin treatment did not increase the surface expression of P-selectin or PAC-1 binding but led to strongly reduced collagen- and thrombin-induced platelet aggregation. The integrin αIIbβ3 antagonist, RGDS, inhibited lovastatin-induced apoptosis in both human platelets and Chinese hamster ovary (CHO) cells stably expressing integrin αIIbβ3. The number of circulating platelets in mice was significantly reduced after intraperitoneal injections with lovastatin. Taken together, these data indicate that lovastatin induced caspase-dependent platelet apoptosis. Lovastatin does not incur platelet activation, whereas impairs platelet function and reduces circulating platelets in vivo, suggesting the possible pathogenesis of thrombocytopenia and hemorrhage in pa...Continue Reading

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Citations

Sep 27, 2018·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Ashley I MartinezDaniela C Moga
Feb 11, 2021·BioMed Research International·Antonio NennaMassimo Chello
Feb 11, 2021·Curēus·Jasmine GhumanGurpreet Chahal

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