Simvastatin inhibits cigarette smoking-induced emphysema and pulmonary hypertension in rat lungs.
BACKGROUND
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.


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.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Pochon CHA University, Seongnam, Korea.
Ji-Hyun
JH
Lee
Dong-Soon
DS
Lee
Eun-Kyung
EK
Kim
Kang-Hyeon
KH
Choe
Yeon-Mock
YM
Oh
Tae-Sun
TS
Shim
Sang-Eun
SE
Kim
Yun-Song
YS
Lee
Sang-Do
SD
Lee
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001706:Biopsy; D002908:Chronic Disease; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000517:prevention & control*; D007249:Inflammation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000187:drug effects / Q000276:immunology; D019278:Matrix Metalloproteinase 3 / Q000032:analysis / Q000187:drug effects / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000276:immunology; D011651:Pulmonary Artery / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D011656:Pulmonary Emphysema / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D012907:Smoking / Q000009:adverse effects* / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D019001:Nitric Oxide Synthase; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2