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

Authors :
Guillaume Voghel
Aida M. Mamarbachi
Michel Carrier
Nada Farhat
Louis P. Perrault
Albert Nguyen
Louis Villeneuve
Nathalie Thorin-Trescases
Eric Thorin
Annik Fortier
Source :
Mechanisms of Ageing and Development. 128:662-671
Publication Year :
2007
Publisher :
Elsevier BV, 2007.

Abstract

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.

Details

ISSN :
00476374
Volume :
128
Database :
OpenAIRE
Journal :
Mechanisms of Ageing and Development
Accession number :
edsair.doi.dedup.....7da963195959804f95cc895e5cf3b774