Document Detail

Statins inhibit pulmonary artery smooth muscle cell proliferation by upregulation of HO-1 and p21(WAF1).
MedLine Citation:
PMID:  22820842     Owner:  NLM     Status:  Publisher    
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 p21(WAF1). 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 p21(WAF1) expression. The inhibitive effect of simvastatin on cell proliferation was also significantly suppressed by silencing p21(WAF1) with siRNA transfection. The extent of effect of SnPP on inhibition of cell proliferation was similar to that of lack of p21(WAF1) by siRNA transfection. Taken together, our study suggests that simvastatin inhibits PASMCs proliferation by sequential upregulation of HO-1 and p21(WAF1) to benefit pulmonary hypertension.
Manxiang Li; Yuan Liu; Hongyang Shi; Yonghong Zhang; Guizuo Wang; Jing Xu; Jiamei Lu; Dexin Zhang; Xinming Xie; Dong Han; Yuanyuan Wu; Shaojun Li
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-22
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  -     ISSN:  1432-1912     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Respiratory Diseases Research Center, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, People's Republic of China,
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