(Chest. 2005;128:574S.)
© 2005
American College of Chest Physicians
Effects of Simvastatin on Cigarette Smoking-Induced Structural and Functional Changes in Rat Lungs
Sang Do Lee, MD;
Ji-Hyun Lee, MD;
Eun Kyung Kim, MD;
Kang-Hyun Choi, MD;
Yeon Mok Oh, MD and
Tae Sun Shim, MD
* From the Division of Pulmonary and Critical Care Medicine (Drs. S.D. Lee, Oh, and Shim), Asan Medical Center, University of Ulsan, Seoul, Korea; Department of Internal Medicine (Drs. J.H. Lee and Kim), Bundang CHA Hospital, Seoul, Korea; and the Department of Internal Medicine (Dr. Choi), College of Medicine, Chungbuk National University, Cheongju, Korea.
Correspondence to: Sang Do Lee, MD, Asan Medical Center, Internal Medicine, University of Ulsan, 388–1 Poongnab-dong SongpaGu, Seoul 138–736, South Korea; e-mail: sdlee{at}amc.seoul.kr
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Introduction
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Cigarette smoking-induced chronic inflammation is known to be the main cause of COPD, which is progressive and not fully reversible. Statins, particularly 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors, have been employed as lipid-lowering agents, but they can critically affect various cellular processes. Well-known functions of statins are antiinflammation, antioxidation, restoration of endothelial dysfunction, and antithrombogenesis, which act in opposition to the effects of cigarette smoking. Therefore, we hypothesized that simvastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, may attenuate structural and functional changes of rat lungs induced by cigarette smoking.
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Materials and Methods
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Male Sprague-Dawley rats were exposed to cigarette smoke (10 cigarettes per day for 16 weeks). Rats were divided into the following four groups: the SM group, exposed to smoke and received vehicle (n = 10); the SMST group, exposed to smoke and received simvastatin (5 mg/kg/d) [n = 10]; the CTL group, exposed to air and received vehicle (n = 10); and the ST group, exposed to air and received simvastatin (n = 5).
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Results
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Compared to the CTL group, the mean (± SD) pulmonary arterial pressure (21.0 ± 5.6 vs 14.6 ± 4.5 mm Hg, respectively), the proportion of vessels showing complete double-elastic lamina (32 ± 6% vs 10 ± 1%, respectively), and the mean linear intercept (116 ± 94 vs 67 ± 0.8 µm, respectively) were higher in the SM group (p < 0.01). The values for the SMST and ST groups were not significantly different compared to those for the CTL group in pulmonary hemodynamic and morphometric analyses of parenchyma and vessels. The SMST group showed increased eNOS expression and decreased endothelin-1 expression compared to the SM group (determined by reverse transcriptase polymerase chain reaction and immunohistochemical staining; p < 0.05). A zymogram showed increased matrix metalloprotease-9 activity in SM group compared to CTL and SMST group (p < 0.01).
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Conclusions
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Simvastatin prevented the development in rats of cigarette smoking-induced emphysema and pulmonary hypertension, which seem to be mediated by changes in the expression of eNOS, endothelin-1, and matrix metalloprotease-9.
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Footnotes
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Abbreviations: CoA = coenzyme A; CTL = exposed to air and received vehicle; SM = exposed to smoke and received vehicle; SMST = exposed to smoke and received simvastatin; ST = exposed to air and received simvastatin
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Introduction
Materials and Methods
