Statins inhibit pulmonary artery smooth muscle cell proliferation by upregulation of HO-1 and p21WAF1

被引：0
作者：
Manxiang Li
Yuan Liu
Hongyang Shi
Yonghong Zhang
Guizuo Wang
Jing Xu
Jiamei Lu
Dexin Zhang
Xinming Xie
Dong Han
Yuanyuan Wu
Shaojun Li
机构：
[1] Xi’an Jiaotong University,Respiratory Diseases Research Center, The Second Affiliated Hospital of Medical College
[2] Xi’an Jiaotong University,Respiratory Diseases Research Center, The Second Affiliated Hospital of Medical College
来源：
Naunyn-Schmiedeberg's Archives of Pharmacology | 2012年 / 385卷
关键词：
Simvastatin; HO-1; p21; Pulmonary artery smooth muscle cells; Proliferation;
D O I：
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学科分类号：
摘要：
Simvastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, which has been shown to ameliorate the development of pulmonary hypertension in animal model by suppression of pulmonary artery smooth muscle cells (PASMCs) proliferation, yet its underlying molecular mechanisms are not completely understood. In this study, we show that simvastatin dose-dependently inhibited serotonin-stimulated PASMCs proliferation. This was accompanied with the parallel induction of heme oxyganase-1 (HO-1) and upregulation of p21WAF1. More importantly, we found that Tin-protoporphyrin (SnPP), a selective inhibitor of HO-1, could block the effect of simvastatin on inhibition of cell proliferation in response to serotonin and abolish simvastatin-induced p21WAF1 expression. The inhibitive effect of simvastatin on cell proliferation was also significantly suppressed by silencing p21WAF1 with siRNA transfection. The extent of effect of SnPP on inhibition of cell proliferation was similar to that of lack of p21WAF1 by siRNA transfection. Taken together, our study suggests that simvastatin inhibits PASMCs proliferation by sequential upregulation of HO-1 and p21WAF1 to benefit pulmonary hypertension.
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页码：961 / 968
页数：7
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