2026-06-08T02:42:27Zhttps://docta.ucm.es/rest/oai/requestoai:docta.ucm.es:20.500.14352/924182024-01-12T02:23:00Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense
author
García-Yébenes Mena, Virginia Pilar
author
Ramiro, Almudena R.
2024-01-11T08:18:04Z
2024-01-11T08:18:04Z
2020-10-03
10.1161/ATVBAHA.120.314333
https://hdl.handle.net/20.500.14352/92418
https://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.org
https://pubmed.ncbi.nlm.nih.gov/32847388/
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.
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
Aging-Associated miR-217 Aggravates Atherosclerosis and Promotes Cardiovascular Dysfunction
journal article
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URL
https://docta.ucm.es/bitstreams/d98ebe12-2385-4388-83e9-ea140aa9fab8/download
File
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de Yebenes VG ATVB.pdf
URL
https://docta.ucm.es/bitstreams/34e178c9-518a-49df-9a3f-5fe7ea4e0a4a/download
File
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de Yebenes VG ATVB.pdf.txt