title: Lovastatin induces platelet apoptosis.
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 patients treated with statins.
authors.affiliation: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Soochow University, SanXiang Road 1055, Suzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Mengxing
authors.initials: M
authors.lastname: Chen
authors.affiliation: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Renping
authors.initials: R
authors.lastname: Hu
authors.affiliation: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yan
authors.affiliation: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China. Electronic address: kesdai@hotmail.com.
authors.forename: Kesheng
authors.initials: K
authors.lastname: Dai
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001792:Blood Platelets; D016466:CHO Cells; D053148:Caspase 3 / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation; D008148:Lovastatin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation; D015854:Up-Regulation
chemical_list: D000924:Anticholesteremic Agents; D019007:P-Selectin; D008148:Lovastatin; D053148:Caspase 3
keywords: Apoptosis; Hemorrhage; Lovastatin; Platelets; Thrombocytopenia