Vascular mineralocorticoid receptor regulates microRNA-155 to promote vasoconstriction and rising blood pressure with aging
DC Field | Value | Language |
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dc.contributor.author | DuPont, Jennifer J. | - |
dc.contributor.author | McCurley, Amy | - |
dc.contributor.author | Davel, Ana P. | - |
dc.contributor.author | McCarthy, Joseph | - |
dc.contributor.author | Bender, Shawn B. | - |
dc.contributor.author | Hong, Kwangseok | - |
dc.contributor.author | Yang, Yan | - |
dc.contributor.author | Yoo, Jeung-Ki | - |
dc.contributor.author | Aronovitz, Mark | - |
dc.contributor.author | Baur, Wendy E. | - |
dc.contributor.author | Christou, Demetra D. | - |
dc.contributor.author | Hill, Michael A. | - |
dc.contributor.author | Jaffe, Iris Z. | - |
dc.date.accessioned | 2021-06-18T08:44:02Z | - |
dc.date.available | 2021-06-18T08:44:02Z | - |
dc.date.issued | 2016-09 | - |
dc.identifier.issn | 2379-3708 | - |
dc.identifier.issn | 2379-3708 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/45664 | - |
dc.description.abstract | Hypertension is nearly universal yet poorly controlled in the elderly despite proven benefits of intensive treatment. Mice lacking mineralocorticoid receptors in smooth muscle cells (SMC-MR-KO) are protected from rising blood pressure (BP) with aging, despite normal renal function. Vasoconstriction is attenuated in aged SMC-MR-KO mice, thus they were used to explore vascular mechanisms that may contribute to hypertension with aging. MicroRNA (miR) profiling identified miR-155 as the most down-regulated miR with vascular aging in MR-intact but not SMC-MR-KO mice. The aging-associated decrease in miR-155 in mesenteric resistance vessels was associated with increased mRNA abundance of MR and of predicted miR-155 targets Cav1.2 (L-type calcium channel (LTCC) subunit) and angiotensin type-1 receptor (AgtR1). SMC-MR-KO mice lacked these aging-associated vascular gene expression changes. In HEK293 cells, MR repressed miR-155 promoter activity. In cultured SMCs, miR-155 decreased Cav1.2 and AgtR1 mRNA. Compared to MR-intact littermates, aged SMC-MR-KO mice had decreased systolic BP, myogenic tone, SMC LTCC current, mesenteric vessel calcium influx, LTCC-induced vasoconstriction and angiotensin II-induced vasoconstriction and oxidative stress. Restoration of miR-155 specifically in SMCs of aged MR-intact mice decreased Cav1.2 and AgtR1 mRNA and attenuated LTCC-mediated and angiotensin II-induced vasoconstriction and oxidative stress. Finally, in a trial of MR blockade in elderly humans, changes in serum miR-155 predicted the BP treatment response. Thus, SMC-MR regulation of miR-155, Cav1.2 and AgtR1 impacts vasoconstriction with aging. This novel mechanism identifies potential new treatment strategies and biomarkers to improve and individualize antihypertensive therapy in the elderly. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | AMER SOC CLINICAL INVESTIGATION INC | - |
dc.title | Vascular mineralocorticoid receptor regulates microRNA-155 to promote vasoconstriction and rising blood pressure with aging | - |
dc.type | Article | - |
dc.identifier.doi | 10.1172/jci.insight.88942 | - |
dc.identifier.bibliographicCitation | JCI INSIGHT, v.1, no.14 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000387122400015 | - |
dc.citation.number | 14 | - |
dc.citation.title | JCI INSIGHT | - |
dc.citation.volume | 1 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordPlus | SMOOTH-MUSCLE-CELLS | - |
dc.subject.keywordPlus | SPONTANEOUSLY HYPERTENSIVE-RATS | - |
dc.subject.keywordPlus | ANGIOTENSIN-II | - |
dc.subject.keywordPlus | GLUCOCORTICOID-RECEPTOR | - |
dc.subject.keywordPlus | RESISTANT HYPERTENSION | - |
dc.subject.keywordPlus | GENE-TRANSCRIPTION | - |
dc.subject.keywordPlus | CALCIUM-CHANNELS | - |
dc.subject.keywordPlus | HEART-FAILURE | - |
dc.subject.keywordPlus | CA2+ CHANNELS | - |
dc.subject.keywordPlus | PROBE LEVEL | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.description.journalRegisteredClass | scie | - |
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