Cellular senescence in endothelial cells from atherosclerotic patients is accelerated by oxidative stress associated with cardiovascular risk factors

被引:125
作者
Voghel, Guillaume [1 ]
Thorin-Trescases, Nathalie [1 ]
Farhat, Nada [1 ]
Nguyen, Albert [1 ]
Villeneuve, Louis [1 ]
Mamarbachi, Aida M. [1 ]
Fortier, Annik [2 ]
Perrault, Louis P. [1 ]
Carrier, Michel [1 ]
Thorin, Eric [1 ]
机构
[1] Univ Montreal, Montreal Heart Inst, Res Ctr, Dept Surg, Montreal, PQ H1T 1C8, Canada
[2] Univ Montreal, Montreal Heart Inst, Coordinating Ctr, Dept Biostat, Montreal, PQ H1T 1C8, Canada
基金
加拿大健康研究院;
关键词
endothelium; cellular senescence; telomere; oxidative stress; caveolin-1;
D O I
10.1016/j.mad.2007.09.006
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Risk factors for cardiovascular diseases (CVD) increase oxidative stress, and they are proposed to hasten endothelial cell (EC) damage and dysfunction. Our objective was to elucidate the impact of chronic exposure to risk factors for CVD on senescence of EC isolated and cultured from internal mammary arterial segments of patients with severe coronary artery disease. Senescence induced by serial passages resulted in progressive telomere shortening, and short initial telomeres predicted early appearance of senescence in culture. Neither time course of senescence nor telomere length was age-dependent, suggesting that biological age, rather than chronological age, determined the dynamics. Senescence appeared earlier in patients with longer history of risk factor for CVD, and multivariate analysis suggested that hypertension hastened the onset of senescence. Risk factors for CVD override the effects of chronological aging likely by generating stress-dependent damage: senescent EC exhibited oxidative stress (increase in lipid peroxydation and caveolin-1 gene expression) and cell damage markers (loss of eNOS expression and increase in Cox2 mRNA, lower TRF1 protein level). Thus, cell senescence was triggered both by telomere-dependent and -independent pathways. In conclusion, chronic exposure to risk factors for CVD accelerated the development of endothelial senescence that could contribute to the pathogenesis of CVD. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:662 / 671
页数:10
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