Lovastatin, the inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, is widely used in treatments of coronary artery diseases. Lovastatin induces apoptosis in nucleate cells, such as macrophages, cancer cells, and skeletal muscle cells. Lovastatin has side effects of thrombocytopenia and hemorrhage, however, the possible pathogenesis of the side effects have still remained unknown.

Methods and Results

In this study, we found that collagen and thrombin-induced platelet aggregation was obviously reduced in platelets treated by lovastatin, while platelet activation (expression of P-selectin or PAC-1 binding on platelet surface) was not detected. The apoptosis markers in both intrinsic mitochondrial pathway (ΔΨm changes, PS exposure, Bax/Bak and Bcl-XL expression, and caspase9/3 activation) and extrinsic pathway (caspase 8) were detected in platelets treated with lovastatin. Apoptosis decreased in platelets after being pretreated by tetrapeptide arginine-glycine-aspartic acid-serine (RGDS) peptide (the GPIIb/IIIa antagonist). Lovastatin was

intraperitoneally injected into C57 mice at a dose of 5 mg/kg for four hours. The circulating platelets were significantly decreased by lovastatin compared with that of vehicle control.


Lovastatin induced platelet apoptosis by both intrinsic mitochondrial and extrinsic pathways, which might be the possible pathogenesis of thrombocytopenia or hemorrhage in patients treated with lovastatin.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.

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