title: Homocysteine accelerates endothelial cell senescence.
abstract: In this study we demonstrate that exposure of cultured endothelial cells to homocysteine significantly accelerates the rate of endothelial senescence. Examination of telomere length demonstrates that homocysteine increases the amount of telomere length lost per population doubling. The effects of homocysteine on both senescence and telomere length are inhibited by treatment with the peroxide scavenger catalase. Chronic exposure of endothelial cells to homocysteine also increases the expression of two surface molecules linked to vascular disease, intracellular adhesion molecule-1 (ICAM-1) and plasminogen activator inhibitor-1 (PAI-1). Interestingly, the level of expression of both ICAM-1 and PAI-1 correlates with the degree of endothelial senescence. Taken together, these results suggest that homocysteine accelerates the rate of cellular senescence through a redox-dependent pathway. In addition, it suggests that chronic oxidative stress in the vessel wall may hasten the rate of senescence and that the senescent endothelial cell may in turn be pro-atherogenic.
authors.affiliation: Laboratory of Molecular Biology, NHLBI, NIH, Bldg 10/7B-15, 10 Center Drive, Bethesda, MD 20892-1650, USA.
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.forename: R
authors.initials: R
authors.lastname: Neville
authors.forename: T
authors.initials: T
authors.lastname: Finkel
mesh_terms: D001161:Arteriosclerosis / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D006710:Homocysteine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D016615:Telomere / Q000187:drug effects; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D006710:Homocysteine; D018799:Intercellular Adhesion Molecule-1; D006861:Hydrogen Peroxide; D002374:Catalase; D001616:beta-Galactosidase