Endogenous oxidative stress prevents telomerase-dependent immortalization of human endothelial cells |
| |
Authors: | Guillaume Voghel Nathalie Thorin-Trescases Aida M Mamarbachi Frédérick A Mallette Nada Farhat Michel Carrier |
| |
Institution: | a Department of Surgery, Research Center, Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada b Department of Biochemistry, Université de Montréal, Montréal, Québec, Canada |
| |
Abstract: | IntroductionWith aging, oxidative stress accelerates vascular endothelial cell (EC) telomere shortening-induced senescence, and may promote atherosclerosis in humans. Our aim was to investigate whether an antioxidant treatment combined with telomerase (hTERT) over-expression would prevent senescence of EC isolated from patients with severe atherosclerosis.MethodsCells were isolated from internal mammary arteries (n = 11 donors), cultured until senescence with or without N-acetylcystein (NAC) and infected, or not, with a lentivirus over-expressing hTERT.ResultsCompared to control EC, hTERT-NAC cells had increased telomerase activity, longer telomeres and underwent more cell divisions. According to the donor, hTERT-NAC either delayed (n = 5) or prevented (n = 4) EC senescence, the latter leading to cell immortalization. Lack of cell immortalization by hTERT-NAC was accompanied by an absence of beneficial effect of NAC alone in paired EC. Accordingly, lack of EC immortalization by hTERT-NAC was associated with high endogenous susceptibility to oxidation. In EC where hTERT-NAC did not immortalize EC, p53, p21 and p16 expression increased with senescence, while oxidative-dependent DNA damage associated with senescence was not prevented.ConclusionOur data suggest that irreversible oxidative stress-dependent damages associated with cardiovascular risk factors are responsible for senescence of EC from atherosclerotic patients. |
| |
Keywords: | Telomerase Endothelium Oxidative stress Cellular senescence Coronary artery disease |
本文献已被 ScienceDirect 等数据库收录! |
|