Unknown

Dataset Information

0

Aging-Associated miR-217 Aggravates Atherosclerosis and Promotes Cardiovascular Dysfunction.


ABSTRACT: 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.

SUBMITTER: de Yebenes VG 

PROVIDER: S-EPMC7505150 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications


<h4>Objective</h4>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  ...[more]

Similar Datasets

| S-EPMC6005806 | biostudies-literature
| S-EPMC7381096 | biostudies-literature
| S-EPMC10564163 | biostudies-literature
| S-EPMC6786310 | biostudies-literature
| S-EPMC10742866 | biostudies-literature
| S-EPMC8376724 | biostudies-literature
| S-EPMC5319142 | biostudies-other
| S-EPMC8993617 | biostudies-literature
| S-EPMC8527036 | biostudies-literature
| S-EPMC7425207 | biostudies-literature