INTRODUCTION: Simvastatin was predicted to be a potential inhibitor to pulmonary vascular remodeling. This novel reversion induced by simvastatin has remained an uncertain mechanism.
OBJECTIVE: Our goal was to explore the role of simvastatin as a potential inhibitor of pulmonary vascular remodeling.
METHODS: We established a neointimal pulmonary hypertensive rat model receiving monocrotaline after pneumonectomy. Simvastatin was administered after the operation. Hemodynamic and vascular remodeling corresponding indices were detected. GATA-6, a gene transcription factor, was evaluated in vivo. Proliferation and the cellular cycle were assessed in cultured vascular smooth muscle cells (VSMCs). α-SM-actin, F-actin, and paxillin were detected to evaluate the phenotype changes.
RESULTS: Neointimal changes developed in 88.5% of right lung intraacinar arteries after pneumonectomy and monocrotaline administration. Mean pulmonary artery pressure, the right ventricle/(left ventricle + S) ratio, and media wall thickness significantly increased in rats that had pneumonectomy and were treated with monocrotaline but decreased significantly in simvastatin-treated rats. The expression of GATA-6 markedly decreased in these rats and was significantly upregulated after receiving simvastatin. In vitro, the proliferation was significantly downregulated in VSMCs with simvastatin compared to that with platelet-derived growth factor. α-SM-actin increased significantly, and F-actin or paxillin was downregulated in simvastatin-treated rats.
CONCLUSIONS: Our data indicate that simvastatin is most likely a pulmonary vascular remodeling inhibitor, which may reverse the proliferation of VSMCs and phenotype changes. Simvastatin can also upregulate GATA-6 expression in lung tissue.
Submitted by Hanmin Liu
- Copyright © 2008 by the American Academy of Pediatrics