title: Chronic treatment with N-acetyl-cystein delays cellular senescence in endothelial cells isolated from a subgroup of atherosclerotic patients.
abstract: Endothelial senescence may contribute to the pathogenesis of age-related vascular disorders. Furthermore, chronic exposure to risk factors for cardiovascular disease (CVD) accelerates the effects of chronological aging by generating stress-dependent damages, including oxidative stress, therefore promoting stress-induced premature senescence. Our objective was to determine whether a chronic treatment with an antioxidant (N-acetyl-cystein, NAC) could delay senescence of endothelial cells (EC) isolated and cultured from arterial segments of patients with severe coronary artery disease. If EC were considered as one population (n=26), chronic NAC treatment slightly shortened telomere attrition rate associated with senescence but did not significantly delay the onset of endothelial senescence. However, in a subgroup of NAC-treated EC (n=15) cellular senescence was significantly delayed, NAC decreased lipid peroxidation (HNE), activated the catalytic subunit of telomerase (hTERT) and inhibited telomere attrition. In contrast, in another subgroup of EC (n=11) characterized by initial short telomeres, no effect of NAC on HNE and high levels of DNA damages, the antioxidant was not beneficial on senescence, suggesting an irreversible stress-dependent damage. In conclusion, chronic exposure to NAC can delay senescence of diseased EC via hTERT activation and transient telomere stabilization, unless oxidative stress-associated cell damage has become irreversible.
authors.affiliation: Department of Surgery, Research Center, Montreal Heart Institute, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Voghel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Thorin-Trescases
authors.forename: Nada
authors.initials: N
authors.lastname: Farhat
authors.forename: Aida M
authors.initials: AM
authors.lastname: Mamarbachi
authors.forename: Louis
authors.initials: L
authors.lastname: Villeneuve
authors.forename: Annik
authors.initials: A
authors.lastname: Fortier
authors.forename: Louis P
authors.initials: LP
authors.lastname: Perrault
authors.forename: Michel
authors.initials: M
authors.lastname: Carrier
authors.forename: Eric
authors.initials: E
authors.lastname: Thorin
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008323:Mammary Arteries / Q000601:surgery; D008875:Middle Aged; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000187:drug effects; D019098:Telomerase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D019098:Telomerase; D000111:Acetylcysteine