2026-06-30T01:54:25Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/131772024-09-27T08:24:33Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc de Yebenes, Virginia G author Briones, Ana M author Martos-Folgado, Inmaculada author Mur, Sonia M. author Oller, Jorge author Bilal, Faiz author González-Amor, María author Mendez-Barbero, Nerea author Silla-Castro, Juan Carlos author Were, Felipe author Jimenez-Borreguero, Luis J author Sanchez-Cabo, Fatima author Bueno, Hector author Salaices, Mercedes author Redondo, Juan Miguel author Ramiro, Almudena R author 2020-10 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. Our results highlight the therapeutic potential of miR-217 inhibitors in aging-related cardiovascular disease. Arterioscler Thromb Vasc Biol. 2020; 40(10):2408-2424 10.1161/ATVBAHA.120.314333 1524-4636 Arteriosclerosis, thrombosis, and vascular biology 32847388 http://hdl.handle.net/20.500.12105/13177 Aging-Associated miR-217 Aggravates Atherosclerosis and Promotes Cardiovascular Dysfunction.