%0 Journal Article
%A García-Yébenes Mena, Virginia Pilar
%A Ramiro, Almudena R.
%T Aging-Associated miR-217 Aggravates Atherosclerosis and Promotes Cardiovascular Dysfunction
%D 2020
%U https://hdl.handle.net/20.500.14352/92418
%X 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.
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