The Regulatory Role of miR‐21 in Coronary Microcirculation

Abstract

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.

The cardiovascular changes underlying a low cardiac output with exercise in patients with type 2 diabetes mellitus

“…with ischemic heart disease including pts. with T2DM, nitric oxide production switches to hydrogen peroxide production lowering flow-mediated vasodilation (Juguilon et al, 2022). Additionally, and perhaps even more important, the perivascular fibrosis that results in vascular rarefaction, and as shown from combined endomyocardial biopsy and angiography perivascular fibrosis vascular rarefaction, perivascular fibrosis is responsible for microvascular dysfunction, i.e., lowering of myocardial blood flow during stress (Dai et al, 2012).…”