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.

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.

• Authors: R Garrett Morgan, Stephen J Ives, Ashley E Walker, Richard M Cawthon, Robert H I Andtbacka, Dirk Noyes, Lisa A Lesniewski, Russell S Richardson, Anthony J Donato
• Journal: Journal of hypertension (J Hypertens) Vol. 32 Issue 6 Pg. 1293-9 (Jun 2014) ISSN: 1473-5598 [Electronic] England
• PMID: 24686009 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• TP53 protein, human
• Tumor Suppressor Protein p53

Topics

• Aged
• Arteries (pathology)
• Biopsy
• Cellular Senescence
• Cyclin-Dependent Kinase Inhibitor p21 (genetics)
• Female
• Gene Expression Regulation
• Humans
• Hypertension (genetics, pathology)
• Male
• Middle Aged
• Phosphorylation
• Regression Analysis
• Telomere (pathology)
• Telomere Shortening
• Tumor Suppressor Protein p53 (genetics)