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Simvastatin attenuates pulmonary vascular remodelling by down-regulating matrix metalloproteinase-1 and -9 expression in a carotid artery-jugular vein shunt pulmonary hypertension model in rats.
MedLine Citation:
PMID:  23087098     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVES: It remains controversial as to whether simvastatin has a beneficial effect on pulmonary artery hypertension. This study aimed to explore the efficacy of simvastatin on haemodynamic changes, pulmonary vascular remodelling and expression of matrix metalloproteinase-1 and -9 (MMP-1,9) in a carotid artery-jugular vein (CA-JV) shunt pulmonary artery hypertension (PAH) model in rats.
METHODS: Thirty-six Sprague-Dawley rats were randomized into three groups: Control group, CA-JV group, and Treatment group. A pre-tricuspid systemic-pulmonary shunt from the left common carotid artery to the external jugular vein was established on the CA-JV and Treatment groups, but only ligations of both vessels were performed in Control group. Simvastatin (4 mg/kg/d) was administered to the Treatment group, and placebo to the CA-JV group. Twelve weeks later, the animals underwent a haemodynamic evaluation, followed by pulmonary tissue sampling for morphometry, quantitative real-time PCR and Western blot analysis.
RESULTS: By week 12, rats in the CA-JV group had higher right ventricular systolic pressure (RVSP), medial area/total area (MA/TA) and percentage of fibrous tissue (F%) than those in the Control group. These changes were associated with up-regulation of MMP-1,9 mRNA and increased expression of MMP-1,9 proteins. Pretreatment with simvastatin decreased the shunt-induced RVSP, MA/TA and F% in pulmonary arteries. In addition, lung MMP-1,9 mRNA and proteins levels decreased toward normal levels in simvastatin-treated rats.
CONCLUSIONS: Simvastatin ameliorated the structural and functional derangements of pulmonary arterioles caused by the CA-JV shunt, partly associated with the suppression of up-regulated MMP-1, as well as MMP-9. Simvastatin may play a role in the treatment of systemic-pulmonary shunt-induced PAH diseases, such as congenital heart disease.
Authors:
Jianping Yao; Mai Xiong; Bing Tang; Guangxian Chen; Mengya Liang; Xiaofan Ma; Zhiping Wang; Zhongkai Wu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery     Volume:  42     ISSN:  1873-734X     ISO Abbreviation:  Eur J Cardiothorac Surg     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804069     Medline TA:  Eur J Cardiothorac Surg     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  e121-7     Citation Subset:  IM    
Affiliation:
Department of Paediatric and Congenital Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
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