(548.7) The Regulatory Role of miR-21 in Coronary Microcirculation

Poster Board Number: E23

Cody Juguilon (Northeast Ohio Medical University), Yang Wang (Northeast Ohio Medical University), Zhiyuan Wang (Northeast Ohio Medical University), Molly Enrick (Northeast Ohio Medical University), James Gadd (Northeast Ohio Medical University), Alyssa Clark (Northeast Ohio Medical University), William Chilian (Northeast Ohio Medical University), Liya Yin (Northeast Ohio Medical University)

Introduction: Coronary microvascular dysfunction is characterized by impaired endothelial-dependent vasodilation. These impairments are seen in diabetic cardiomyopathy (DCM), coronary artery disease (CAD) and ischemia with non-obstructive coronary artery (INOCA), Takotsubo cardiomyopathy, myocardial infarction with non-obstructive coronary artery disease (MINOCA), and heart failure with preserved ejection fraction (HFpEF), but detailed mechanisms have yet to be elucidated.

Methods:  microRNA-21 (miR-21) global and conditional knockout mice were used to study how miR-21 regulates coronary microcirculation in pathological conditions like DCM. Both genetic (db/db) and diet-induced diabetic models were used. Coronary arteries were isolated, and endothelial-dependent vasodilation was assessed using myography (DMT). In vivo myocardial blood flow (MBF) under stress was measured by contrast echocardiography or doppler after the treatment with different dosages of norepinephrine. Quantitative polymerase chain reaction (qPCR) was performed for gene expression analysis. Trichrome staining and histology were performed for structural changes of the hearts.

Results:  Our preliminary data show that miR-21 is upregulated in DCM and the deficiency of miR-21 restores the endothelial-dependent vasodilation in isolated diabetic coronary arterioles and coronary blood flow under stress in DCM through the mechanism that miR-21 prevents the mediator of coronary vasodilation switching from NO to H2O2 in diabetes.

Conclusions:   miR-21 regulates microvascular dysfunction in DCM. Further genetic profiling will elucidate the pathways and mechanisms converging with miR-21 to regulate microvascular function.

This research is funded by National Institutes of Health grant 2R01HL103227-05 (YZ, LY), 1R01HL135110-01 (WMC, LY), 1 R01 HL137008-01A1 (LY), 1F31HL156726-01A1 (CJ)