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The Regulatory Role of miR‐21 in Coronary Microcirculation
Author(s) -
Juguilon Cody,
Wang Yang,
Wang Zhiyuan,
Enrick Molly,
Gadd James,
Clark Alyssa,
Chilian William,
Yin Liya
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r3562
Subject(s) - medicine , cardiology , vasodilation , coronary artery disease , endothelial dysfunction , myocardial infarction , coronary arteries , microcirculation , artery
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 H 2 O 2 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.