Title
Role of Arterial Telomere Dysfunction in Hypertension: Relative Contributions of Telomere Shortening and Telomere Uncapping
Document Type
Article
Publication Date
2014
Embargo Period
5-17-2017
Keywords
Arteries, cellular senescence, hypertension, telomere
Abstract
OBJECTIVE: Telomere shortening in arteries could lead to telomere uncapping and cellular senescence, which in turn could promote the development of hypertension.
METHODS AND 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).
CONCLUSION: 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.
Published In
Journal of Hypertension
Volume
32
Issue
6
Pages
1293-1299
Recommended Citation
Morgan RG, Ives SJ, Walker AE, Cawthon RM, Andtbacka RH, Noyes D, Lesniewski LA, Richardson RS, Donato AJ. Role of arterial telomere dysfunction in hypertension: relative contributions of telomere shortening and telomere uncapping. J Hypertens. 2014 Jun;32(6):1293-9. doi: 10.1097/HJH.0000000000000157. PubMed PMID: 24686009; PubMed Central PMCID: PMC4198301.
DOI
10.1097/HJH.0000000000000157