期刊
JOURNAL OF HYPERTENSION
卷 32, 期 6, 页码 1293-1299出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HJH.0000000000000157
关键词
arteries; cellular senescence; hypertension; telomere
资金
- NIH: National Institute of Aging [AG040297]
- National Institute of Aging [AG029337, AG033196, AG033755]
- NIH Heart, Lung, and Blood Institute [HL09183]
- Department of Veterans Affairs Merit Grant [E6910R]
- University of Utah Center on Aging Grant
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 -H2A.X (-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, (2)(p)=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.
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