Published online January 2, 2008
PEDIATRICS Vol. 121 Supplement January 2008, pp. S95 (doi:10.1542/peds.2007-2022Q)
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ALLERGOLOGY


EXPERIMENTAL RESEARCH OF SIMVASTATIN IN REVERSING PULMONARY VASCULAR REMODELING IN VIVO AND IN VITRO

Hanmin Liu, Bin Liu, Yimin Hua, Xiaoqin Wang, Li Yu and Tongfu Zhou

West China Second University Hospital, Sichuan University, Chengdu, China

ABSTRACT

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). {alpha}-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. {alpha}-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