Vascular mineralocorticoid receptor regulates microRNA-155 to promote vasoconstriction and rising blood pressure with aging

• DOI: 10.1172/jci.insight.88942
• Publication Date: 2016-09-07T15:01:49Z
• Authors: Jennifer J. DuPont; Amy McCurley; Ana P. Davel; Joseph McCarthy; Shawn B. Bender; Kwangseok Hong; Yan Yang; Jeung-Ki Yoo; Mark Aronovitz; Wendy E. Baur; Demetra D. Christou; Michael A. Hill; Iris Z. Jaffe
• Keywords: 0303 health sciences; 03 medical and health sciences; 3. Good health

Hypertension is nearly universal yet poorly controlled in the elderly despite proven benefits of intensive treatment. Mice lacking mineralocorticoid receptors smooth muscle cells (SMC-MR-KO) are protected from rising blood pressure (BP) with aging, normal renal function. Vasoconstriction attenuated aged SMC-MR-KO mice, thus they were used to explore vascular mechanisms that may contribute hypertension aging. MicroRNA (miR) profiling identified miR-155 as most down-regulated miR aging MR-intact but not mice. The aging-associated decrease mesenteric resistance vessels was associated increased mRNA abundance MR and predicted targets Cav1.2 (L-type calcium channel (LTCC) subunit) angiotensin type-1 receptor (AgtR1). mice lacked these gene expression changes. In HEK293 cells, repressed promoter activity. cultured SMCs, decreased AgtR1 mRNA. Compared littermates, had systolic BP, myogenic tone, SMC LTCC current, vessel influx, LTCC-induced vasoconstriction II-induced oxidative stress. Restoration specifically SMCs LTCC-mediated Finally, a trial blockade humans, changes serum BP treatment response. Thus, SMC-MR regulation miR-155, impacts This novel mechanism identifies potential new strategies biomarkers improve individualize antihypertensive therapy elderly.