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

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1349-1353
Number of pages5
JournalEnvironmental Health Perspectives
Volume113
Issue number10
DOIs
Publication statusPublished - Oct 2005
Externally publishedYes

Fingerprint

CD95 Antigens
Death Domain Receptors
Tobacco Smoke Pollution
Mitochondria
mitochondrion
Initiator Caspases
Smoke
smoke
Rats
Heart Diseases
Fibrosis
Somatomedins
Tobacco Products
Messenger RNA
Tobacco
Somatomedin Receptors
Caspase 9
Caspase 8
cardiovascular disease
Environmental Exposure

Keywords

  • Cardiac survival IGF-1 signalling
  • Caspases
  • Death-receptor-dependent pathway
  • Mitochondria-dependent pathway
  • Second-hand smoke (SHS)

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

Cite this

Second-hand smoke-induced cardiac fibrosis is related to the fas death receptor apoptotic pathway without mitochondria-dependent pathway involvement in rats. / Kuo, Wei Wen; Wu, Chieh Hsi; Lee, Shin Da; Lin, James A.; Chu, Chia Yih; Hwang, Jin Ming; Ueng, Kwo Chang; Chang, Mu Hsin; Yeh, Yu Lan; Wang, Chau Jong; Liu, Jer Liu; Huang, Chih Yang.

In: Environmental Health Perspectives, Vol. 113, No. 10, 10.2005, p. 1349-1353.

Research output: Contribution to journalArticle

Kuo, Wei Wen ; Wu, Chieh Hsi ; Lee, Shin Da ; Lin, James A. ; Chu, Chia Yih ; Hwang, Jin Ming ; Ueng, Kwo Chang ; Chang, Mu Hsin ; Yeh, Yu Lan ; Wang, Chau Jong ; Liu, Jer Liu ; Huang, Chih Yang. / Second-hand smoke-induced cardiac fibrosis is related to the fas death receptor apoptotic pathway without mitochondria-dependent pathway involvement in rats. In: Environmental Health Perspectives. 2005 ; Vol. 113, No. 10. pp. 1349-1353.
@article{1fd93067e9ee49cca15bc847022b4333,
title = "Second-hand smoke-induced cardiac fibrosis is related to the fas death receptor apoptotic pathway without mitochondria-dependent pathway involvement in rats",
abstract = "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.",
keywords = "Cardiac survival IGF-1 signalling, Caspases, Death-receptor-dependent pathway, Mitochondria-dependent pathway, Second-hand smoke (SHS)",
author = "Kuo, {Wei Wen} and Wu, {Chieh Hsi} and Lee, {Shin Da} and Lin, {James A.} and Chu, {Chia Yih} and Hwang, {Jin Ming} and Ueng, {Kwo Chang} and Chang, {Mu Hsin} and Yeh, {Yu Lan} and Wang, {Chau Jong} and Liu, {Jer Liu} and Huang, {Chih Yang}",
year = "2005",
month = "10",
doi = "10.1289/ehp.7479",
language = "English",
volume = "113",
pages = "1349--1353",
journal = "Environmental Health Perspectives",
issn = "0091-6765",
publisher = "Public Health Services, US Dept of Health and Human Services",
number = "10",

}

TY - JOUR

T1 - Second-hand smoke-induced cardiac fibrosis is related to the fas death receptor apoptotic pathway without mitochondria-dependent pathway involvement in rats

AU - Kuo, Wei Wen

AU - Wu, Chieh Hsi

AU - Lee, Shin Da

AU - Lin, James A.

AU - Chu, Chia Yih

AU - Hwang, Jin Ming

AU - Ueng, Kwo Chang

AU - Chang, Mu Hsin

AU - Yeh, Yu Lan

AU - Wang, Chau Jong

AU - Liu, Jer Liu

AU - Huang, Chih Yang

PY - 2005/10

Y1 - 2005/10

N2 - 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.

AB - 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.

KW - Cardiac survival IGF-1 signalling

KW - Caspases

KW - Death-receptor-dependent pathway

KW - Mitochondria-dependent pathway

KW - Second-hand smoke (SHS)

UR - http://www.scopus.com/inward/record.url?scp=27244443037&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27244443037&partnerID=8YFLogxK

U2 - 10.1289/ehp.7479

DO - 10.1289/ehp.7479

M3 - Article

VL - 113

SP - 1349

EP - 1353

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

SN - 0091-6765

IS - 10

ER -