期刊
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
卷 86, 期 11, 页码 761-769出版社
CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS
DOI: 10.1139/Y08-082
关键词
smoking; atherosclerosis; oxidative stress; caveolin-1; stress-induced senescence; telomere; replicative senescence
资金
- Foundation of the Montreal Heart Institute
- Heart and Stroke Foundation of Quebec
- Canadian Institutes of Health Research [MOP 14496]
- Canadian Institutes of Health Research
- Fonds de la Recherche en Sante du Quebec
Age-associated telomere shortening leads to replicative senescence of human endothelial cells (EC). Risk factors for cardiovascular disease (CVD) accelerate ageing, while there is a concomitant rise in oxidative stress known to promote stress-induced senescence (SIS) in vitro. Of all risk factors for CVD, smoking is most associated with the development of inflammation and accelerated atherosclerosis due to a prooxidant-antioxidant imbalance. We tested the hypothesis that SIS predominates in EC isolated from chronic smokers with premature atherosclerosis undergoing coronary artery bypass graft surgery (CABG). We isolated and cultured EC from segments of internal mammary arteries from smoker, former smoker, and nonsmoker coronary patients. Senescence of EC was induced by serial passage and quantified by the measurement of telomere length and senescence-associated beta-galactosidase activity. Compared with nonsmokers, smoker patients were 10 years younger at the time of CABG, evidence of premature atherosclerosis. Cellular senescence was independent of telomere length and directly related to oxidative damage. EC exhibited higher expression levels of markers of oxidative stress (lipid peroxydation level and caveolin-1 mRNA), inflammation (angiopoietin-like 2 mRNA), hypoxia (vascular endothelial growth factor (VEGF)-A mRNA), and cell damage (p53 mRNA). In conclusion, a high oxidative stress environment in EC isolated from atherosclerotic chronic smokers predisposes to SIS rather than replicative senescence.
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