Abstract 17248: The role of microRNA-21 in regulating the coronary microcirculation in diabetes

Title

Abstract 17248: The role of microRNA-21 in regulating the coronary microcirculation in diabetes

Creator

Juguilon C; Wang Z; Gadd J;Ohanyan VA; Anurag J; Molly E; Wang T; Kolz C; William MC; Yin L

Publisher

Circulation

Date

2020
2020-11-17

Description

Introduction: Coronary microvascular dysfunction is prevalent among diabetics and intersects with deficits in endothelial-dependent vasodilation. These deficits occur early in the progression of the disease, but the mechanisms remain incompletely understood. Nitric oxide (NO) is the major endothelial-dependent mediator of vasodilation in the healthy coronary circulation, but the mediator switches to hydrogen peroxide (H2O2) in coronary artery disease (CAD) patients. Diabetes is a risk factor for CAD, so we hypothesized that a similar switch would occur.Methods: Coronary arteries were isolated and endothelial-dependent vasodilation was assessed using myography. Quantitative polymerase chain reaction (qPCR) was performed for gene expression analysis and myocardial blood flow (MBF) was measured by contrast echocardiography.Results: Nitric oxide synthase inhibitor (L-NAME) inhibited vasodilation in wild type (WT) mice, but the H2O2 scavenger (PEG-catalase) had no effect. In contrast, vasodilation in diabetic mice was blunted by PEG-catalase, but not L-NAME. This suggests that the mediator of coronary vasodilation switched from NO to H2O2 in diabetes. Importantly, we found that microRNA-21 (miR-21) is upregulated in diabetes and the deficiency modulates the mediator switch from NO to H2O2 in diabetic mice.Conclusions: The switch in the mediator of coronary vasodilation from NO to H2O2 contributes to microvascular dysfunction in diabetes and miR-21 regulates this switch. Further genetic profiling will elucidate the pathways and mechanisms converging with miR-21 to regulate microvascular function in diabetes. This is the first mouse model that recapitulates the switch in mediator of coronary vasodilation from NO to H2O2 seen in CAD patients.

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Format

journalArticle

Search for Full-text

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Pages

A17248-A17248

Issue

Suppl 3

Volume

142

ISSN

0009-7322

NEOMED College

NEOMED College of Medicine Student
NEOMED College of Medicine

NEOMED Department

Department of Integrative Medical Sciences
NEOMED Student Publications

Update Year & Number

December 2020 List

Citation

Juguilon C; Wang Z; Gadd J;Ohanyan VA; Anurag J; Molly E; Wang T; Kolz C; William MC; Yin L, “Abstract 17248: The role of microRNA-21 in regulating the coronary microcirculation in diabetes,” NEOMED Bibliography Database, accessed June 15, 2021, https://neomed.omeka.net/items/show/11484.

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