title: Telomerase activation causes vascular smooth muscle cell proliferation in genetic hypertension.
abstract: Although abnormal cell growth in arterial vessel walls underpins vascular remodeling in high blood pressure, the molecular basis of the abnormality in hypertension has not been fully defined. Here, we report that in the aorta of spontaneously hypertensive rats, telomerase is selectively activated and telomeres are lengthened, in vivo and in vitro. Down-regulation of telomerase, the ribonucleoprotein complex responsible for the maintenance and elongation of telomeres (the ends of chromosomes) arrests the increased proliferation of spontaneously hypertensive rat vascular smooth muscle cells and induces apoptosis. This apoptosis is reversible by overexpressing telomerase and is prevented by increasing p53 tumor suppressor protein expression and worsened by lowering p53. Telomerase activation, telomere maintenance, and the p53 checkpoint appear to be critical for increased vascular smooth muscle proliferation, thus they represent potential novel therapeutic targets in hypertension.
authors.affiliation: Molecular Signaling Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cao
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.forename: Fi-Tjen
authors.initials: FT
authors.lastname: Mu
authors.forename: Osamu
authors.initials: O
authors.lastname: Ebisui
authors.forename: John W
authors.initials: JW
authors.lastname: Funder
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Liu
mesh_terms: D000818:Animals; D001011:Aorta / Q000201:enzymology; D017209:Apoptosis; D002455:Cell Division; D002478:Cells, Cultured; D015536:Down-Regulation; D004789:Enzyme Activation; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007700:Kinetics; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D009928:Organ Specificity; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D019098:Telomerase / Q000378:metabolism* / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D016159:Tumor Suppressor Protein p53; D019098:Telomerase