Document Detail


Simvastatin inhibits cigarette smoking-induced emphysema and pulmonary hypertension in rat lungs.
MedLine Citation:
PMID:  16002570     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: In cigarette smoking-induced chronic obstructive pulmonary disease, structural and functional derangements are characterized by parenchymal destruction and pulmonary hypertension. Statins are 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase inhibitors that have been used as lipid-lowering agents. These drugs also have additional pharmacologic properties, including antiinflammation, scavenging reactive oxygen species, restoring endothelial function, and antithrombogenesis, all of which can counteract the harmful effects of cigarette smoking. OBJECTIVE: We performed assays to determine whether simvastatin could attenuate lung damage induced by chronic cigarette smoking in rats. METHODS: In Sprague-Dawley rats exposed to cigarette smoke for 16 weeks, morphologic changes in the lungs and pulmonary arterial pressure were examined. MAIN RESULTS: Simvastatin inhibited lung parenchymal destruction and development of pulmonary hypertension, and also inhibited peribronchial and perivascular infiltration of inflammatory cells and induction of matrix metalloproteinase-9 activity in lung tissue. Simvastatin additionally prevented pulmonary vascular remodeling and the changes in endothelial nitric oxide synthase expression induced by smoking. In human lung microvascular endothelial cells, simvastatin increased expression of endothelial nitric oxide synthase mRNA. CONCLUSIONS: Simvastatin ameliorated the structural and functional derangements of the lungs caused by cigarette smoking, partly by suppressing inflammation and matrix metalloproteinase-9 induction and preventing pulmonary vascular abnormality. These findings indicate that statins may play a role in the treatment of cigarette smoking-induced chronic obstructive pulmonary disease.
Authors:
Ji-Hyun Lee; Dong-Soon Lee; Eun-Kyung Kim; Kang-Hyeon Choe; Yeon-Mock Oh; Tae-Sun Shim; Sang-Eun Kim; Yun-Song Lee; Sang-Do Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-07-07
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  172     ISSN:  1073-449X     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-11     Completed Date:  2006-01-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  987-93     Citation Subset:  AIM; IM    
Affiliation:
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Pochon CHA University, Seongnam, Korea.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Analysis of Variance
Animals
Biopsy
Chronic Disease
Disease Models, Animal
Drug Evaluation, Preclinical
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology,  therapeutic use*
Hypertension, Pulmonary / etiology,  prevention & control*
Inflammation
Male
Matrix Metalloproteinase 2 / analysis,  drug effects,  immunology
Matrix Metalloproteinase 3 / analysis,  drug effects,  immunology
Nitric Oxide Synthase / drug effects,  immunology
Pulmonary Artery / drug effects,  immunology,  pathology
Pulmonary Emphysema / etiology,  prevention & control*
Rats
Rats, Sprague-Dawley
Risk Factors
Simvastatin / pharmacology,  therapeutic use*
Smoking / adverse effects*,  drug therapy,  immunology,  metabolism,  pathology
Time Factors
Chemical
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 79902-63-9/Simvastatin; EC 1.14.13.39/Nitric Oxide Synthase; EC 3.4.24.17/Matrix Metalloproteinase 3; EC 3.4.24.24/Matrix Metalloproteinase 2

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