2026-06-08T01:06:26Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/924182024-01-12T02:23:00Zcom_20.500.14352_14col_20.500.14352_15

Aging-Associated miR-217 Aggravates Atherosclerosis and Promotes Cardiovascular Dysfunction García-Yébenes Mena, Virginia Pilar Ramiro, Almudena R. Objective:microRNAs are master regulators of gene expression with essential roles in virtually all biological processes. miR-217 has been associated with aging and cellular senescence, but its role in vascular disease is not understood. Approach and Results:We have used an inducible endothelium-specific knock-in mouse model to address the role of miR-217 in vascular function and atherosclerosis. miR-217 reduced NO production and promoted endothelial dysfunction, increased blood pressure, and exacerbated atherosclerosis in proatherogenic apoE−/− mice. Moreover, increased endothelial miR-217 expression led to the development of coronary artery disease and altered left ventricular heart function, inducing diastolic and systolic dysfunction. Conversely, inhibition of endogenous vascular miR-217 in apoE−/− mice improved vascular contractility and diminished atherosclerosis. Transcriptome analysis revealed that miR-217 regulates an endothelial signaling hub and downregulates a network of eNOS (endothelial NO synthase) activators, including VEGF (vascular endothelial growth factor) and apelin receptor pathways, resulting in diminished eNOS expression. Further analysis revealed that human plasma miR-217 is a biomarker of vascular aging and cardiovascular risk. Conclusions:Our results highlight the therapeutic potential of miR-217 inhibitors in aging-related cardiovascular disease. 2024-01-11T08:18:04Z 2024-01-11T08:18:04Z 2024-01-11T08:18:04Z 2020-10-03 journal article https://hdl.handle.net/20.500.14352/92418 XXXX-XXXX 10.1161/ATVBAHA.120.314333 eng RYC-2009-04503 INVES18013GARC http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 International American Heart Association