title: Role of arterial telomere dysfunction in hypertension: relative contributions of telomere shortening and telomere uncapping.
abstract: OBJECTIVE
  Telomere shortening in arteries could lead to telomere uncapping and cellular senescence, which in turn could promote the development of hypertension.
  
  
  RESULTS
  To assess the novel role of arterial telomere dysfunction in hypertension, we compared mean telomere length (qPCR), telomere uncapping (serine 139 phosphorylated histone γ-H2A.X (γ-H2) localized to telomeres: ChIP), and tumor suppressor protein p53 (P53)/cyclin-dependent kinase inhibitor 1A (P21)-induced senescence (P53 bound to P21 gene promoter: ChIP) in arteries from 55 age-matched hypertensive and nonhypertensive individuals. Arterial mean telomere length was not different in hypertensive patients compared with nonhypertensive individuals (P = 0.29). Arterial telomere uncapping and P53/P21-induced senescence were two-fold greater in hypertensive patients compared with nonhypertensive individuals (P = 0.04 and P = 0.02, respectively). Arterial mean telomere length was not associated with telomere uncapping or P53/P21-induced senescence (r = -0.02, P = 0.44 and r = 0.01, P = 0.50, respectively), but telomere uncapping was a highly influential covariate for the hypertension group difference in P53/P21-induced senescence (r = 0.62, P < 0.001, η(p)(2) = 0.35). Finally, telomere uncapping was a significant predictor of hypertension status (P = 0.03), whereas mean telomere length was not (P = 0.68).
  
  
  CONCLUSIONS
  Collectively, these findings demonstrate that arterial telomere uncapping and P53/P21-induced senescence are linked to hypertension independently of mean telomere length, and telomere uncapping influences hypertension status more than mean telomere length.
authors.affiliation: aGeorge E. Wahlen Department of Veterans Affairs Medical Center bGeriatric Research Education and Clinical Center, Salt Lake City Geriatrics Research, Education, and Clinical Center (182), Veterans Administration Salt Lake City Health Care System cDivision of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine dDepartment of Human Genetics, Eccles Institute of Human Genetics eDepartment of Surgery, University of Utah Health Sciences Center fDepartment of Exercise and Sports Science, College of Health, University of Utah, Salt Lake City, Utah, USA.
authors.forename: R Garrett
authors.initials: RG
authors.lastname: Morgan
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Walker
authors.forename: Richard M
authors.initials: RM
authors.lastname: Cawthon
authors.forename: Robert H I
authors.initials: RH
authors.lastname: Andtbacka
authors.forename: Dirk
authors.initials: D
authors.lastname: Noyes
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lesniewski
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
mesh_terms: D000368:Aged; D001158:Arteries / Q000473:pathology*; D001706:Biopsy; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D012044:Regression Analysis; D016615:Telomere / Q000473:pathology; D059506:Telomere Shortening; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53