Second-hand smoke-induced cardiac fibrosis is related to the fas death receptor apoptotic pathway without mitochondria-dependent pathway involvement in rats

Wei Wen Kuo, Chieh Hsi Wu, Shin Da Lee, James A. Lin, Chia Yih Chu, Jin Ming Hwang, Kwo Chang Ueng, Mu Hsin Chang, Yu Lan Yeh, Chau Jong Wang, Jer Liu Liu, Chih Yang Huang

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26 引文 斯高帕斯(Scopus)

摘要

Exposure to environmental tobacco smoke has been epidemiologically linked to heart disease among nonsmokers. However, the molecular mechanism behind the pathogenesis of cardiac disease is unknown. In this study, we found that Wistar rats, exposed to tobacco cigarette smoke at doses of 5, 10, or 15 cigarettes for 30 min twice a day for 1 month, had a dose-dependently reduced heart weight to body weight ratio and enhanced interstitial fibrosis as identified by histopathologic analysis. The mRNA and activity of matrix metalloprotease-2 (MMP-2), representing the progress of cardiac remodeling, were also elevated in the heart. In addition, we used reverse-transcriptase polymerase chain reaction and Western blotting to demonstrate significantly increased levels of the apoptotic effecter caspase-3 in treated animal hearts. Dose-dependently elevated mRNA and protein levels of Fas, and promoted apoptotic initiator caspase-8 (active form), a molecule of a death-receptor-dependent pathway, coupled with unaltered or decreased levels of cytosolic cytochrome c and the apoptotic initiator caspase-9 (active form), molecules of mitochondria-dependent pathways, may be indicative of cardiac apoptosis, which is Fas death-receptor apoptotic-signaling dependent, but not mitochondria pathway dependent in rats exposed to second-hand smoke (SHS). With regard to the regulation of survival pathway, using dot blotting, we found cardiac insulin-like growth Factor-1 (IGF-1) and IGF-1 receptor mRNA levels to be significandy increased, indicating that compensative effects of IGF-1 survival signaling could occur. In conclusion, we found that the effects of SHS on cardiomyocyte are mediated by the Fas death-receptor-dependent apoptotic pathway and might be related to the epidemiologic incidence of cardiac disease of SHS-exposed non-smokers.

原文英語
頁(從 - 到)1349-1353
頁數5
期刊Environmental Health Perspectives
113
發行號10
DOIs
出版狀態已發佈 - 十月 2005
對外發佈

ASJC Scopus subject areas

  • 環境科學 (全部)
  • 環境化學
  • 公共衛生、環境和職業健康

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