García-Yébenes Mena, Virginia PilarRamiro, Almudena R.2024-01-112024-01-112020-10-0310.1161/ATVBAHA.120.314333https://hdl.handle.net/20.500.14352/92418Objective: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.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://www.ahajournals.org/doi/full/10.1161/ATVBAHA.120.314333?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.orghttps://pubmed.ncbi.nlm.nih.gov/32847388/open access616.12-005Endothelial cellMicroRNAsCardiovascular diseaseAgingCiencias Biomédicas24 Ciencias de la Vida