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Journal of Hypertension:
doi: 10.1097/HJH.0000000000000157
ORIGINAL PAPERS: Ageing

Role of arterial telomere dysfunction in hypertension: relative contributions of telomere shortening and telomere uncapping

Morgan, R. Garretta,b; Ives, Stephen J.a,b,f; Walker, Ashley E.a,b,c; Cawthon, Richard M.d; Andtbacka, Robert H.I.e; Noyes, Dirke; Lesniewski, Lisa A.a,b,c,f; Richardson, Russell S.a,b,c,f; Donato, Anthony J.a,b,c,f

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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, ηp2 = 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.

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

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