2026-06-30T01:54:34Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
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
funder
Asociación Española Contra el Cáncer
funder
Complutense University of Madrid (España)
funder
Fundación ProCNIC
funder
Ministerio de Ciencia e Innovación (España)
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Instituto de Salud Carlos III
funder
Comunidad de Madrid (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
2021-06-23T07:41:28Z
2021-06-23T07:41:28Z
2020-10
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
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.
eng
Aging-Associated miR-217 Aggravates Atherosclerosis and Promotes Cardiovascular Dysfunction.
journal article
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