Abstract
Overexpression of the catalytic subunit of telomerase (hTERT) immortalizes healthy human endothelial cells (EC) but its effect on senescence in pathological conditions is unknown. Our objective was to investigate whether hTERT overexpression would prevent senescence in EC isolated from patients with coronary artery disease (CAD). EC isolated from discarded internal mammary arteries of 11 patients undergoing CABG were infected or not with a lentivirus expressing hTERT and cultured in vitro. We quantified senescence by cytochemical detection of senescence‐associated b‐galactosidase, hTERT activity by real‐time TRAPassay, telomere length by Southern blotting, mRNA levels (p21 and ATM, a DNA damage response protein) by qPCR and oxidative stress by immunostaining of lipid peroxidation (HNE). Compared to control EC, lentiviral infection increased hTERT activity (p<0.05), elongated telomeres (p<0.05), decreased ATM and p21 mRNA levels (p<0.05), increased EC replicative potential (p<0.05) but only delayed the onset of senescence (p<0.05). HNE levels increased in both groups, with time (p<0.05). In conclusion, since no immortalization was observed, we hypothesize that hTERT overexpression delays replicative senescence but cannot bypass stress‐induced senescence associated with CAD.This study was supported by the Canadian Institutes of Health Research and the Fonds de la Recherche en Santé du Québec.
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