Simvastatin Inhibits Proliferation and Migration of Pulmonary Artery Smooth Muscle Cells from Patients with Idiopathic Pulmonary Arterial Hypertension

Abstract

Background: Idiopathic pulmonary arterial hypertension (IPAH) is a progressive disease characterized by inappropriate increase of pulmonary artery smooth muscle cells (PASMCs) leading to occlusion of pulmonary arterioles. In this study, we assessed the inhibitory effects of simvastatin, an HMG-CoA reductase inhibitor, on proliferation and migration of PASMCs obtained from patients with IPAH. Methods and Results: PASMCs were obtained from 6 patients with IPAH who underwent lung transplantation. Platelet-derived growth factor (PDGF) (10 ng/mL) stimulation caused a significantly higher growth rate of PASMCs from patients with IPAH than that of control cells assessed by 3H-thymidine incorporation (P<0.05). Simvastatin at 0.1 μmol/L significantly inhibited PDGF-induced cell proliferation of PASMCs from IPAH patients but did not inhibit proliferation of control cells at the same concentration. Simvastatin at 1 μmol/L also inhibited PDGF-induced migration of PASMCs from IPAH patients assessed by a transwell migration assay (P<0.05) and a time-lapse microscopy assay with a dish that has micro-lithographed squared pattern (Kuraray, Japan) (P<0.0001). Conclusions: Simvastatin may be useful for treatment of patients with IPAH. [J Physiol Sci. 2008;58 Suppl:S189]