Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/13177
Title
Aging-Associated miR-217 Aggravates Atherosclerosis and Promotes Cardiovascular Dysfunction.
Author(s)
de Yebenes, Virginia G CNIC | Briones, Ana M | Martos-Folgado, Inmaculada | Mur, Sonia M. CNIC | Oller, Jorge CNIC | Bilal, Faiz | González-Amor, María | Mendez-Barbero, Nerea CNIC | Silla-Castro, Juan Carlos CNIC | Were, Felipe CNIC | Jimenez-Borreguero, Luis J CNIC | Sanchez-Cabo, Fatima CNIC | Bueno, Hector CNIC | Salaices, Mercedes | Redondo, Juan Miguel CNIC | Ramiro, Almudena R CNIC
Date issued
2020-10
Citation
Arterioscler Thromb Vasc Biol. 2020; 40(10):2408-2424
Language
Inglés
Document type
journal article
Abstract
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.
MESH
Plaque, Atherosclerotic | Age Factors | Aged, 80 and over | Aging | Animals | Atherosclerosis | Case-Control Studies | Cells, Cultured | Coronary Artery Disease | Disease Models, Animal | Endothelial Cells | Female | Hemodynamics | Humans | Mice, Inbred C57BL | Mice, Knockout, ApoE | MicroRNAs | Middle Aged | Nitric Oxide | Nitric Oxide Synthase Type III | Signal Transduction | Ventricular Dysfunction, Left | Ventricular Function, Left
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