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Role of miR-204 in segmental cardiac effects of phenylephrine and pressure overload
Journal article   Open access   Peer reviewed

Role of miR-204 in segmental cardiac effects of phenylephrine and pressure overload

Ravinder Reddy Gaddam, Veda Sudhir Amalkar, Veeresh Kumar Sali, Krishnamurthy Nakuluri, Julie S. Jacobs, Young Rae Kim, Quixia Li, Raman Bahal, Kaikobad Irani and Ajit Vikram
Biochemical and biophysical research communications, Vol.675, pp.85-91
10/2023
DOI: 10.1016/j.bbrc.2023.07.011
PMCID: PMC12050130
PMID: 37454401
url
https://pmc.ncbi.nlm.nih.gov/articles/PMC12050130/pdf/nihms-2072665.pdfView
Open Access

Abstract

Cardiotoxicity caused by adrenergic receptor agonists overdosing or stress-induced catecholamine release promotes cardiomyopathy, resembling Takotsubo cardiomyopathy (TC). TC is characterized by transient regional systolic dysfunction of the left ventricle. The animal models of TC and modalities for assessing regional wall motion abnormalities in animal models are lacking. We previously reported the protective role of a small noncoding microRNA-204-5p (miR-204) in cardiomyopathies, but its role in TC remains unknown. Here we compared the impact of miR-204 absence on phenylephrine (PE)-induced and transaortic constriction (TAC)-induced changes in cardiac muscle motion in the posterior and anterior apical, mid, and basal segments of the left ventricle using 2-dimensional speckle-tracking echocardiography (2-STE). Wildtype and miR-204−/− mice were subjected to cardiac stress in the form of PE for four weeks or TAC-induced pressure overload for five weeks. PE treatment increased longitudinal and radial motion in the apex of the left ventricle and shortened the peak motion time of all left ventricle segments. The TAC led to decreased longitudinal and radial motion in the left ventricle segments, and there was no difference in the peak motion time. Compared to wildtype mice, PE-induced peak cardiac muscle motion time in the anterior base of the left ventricle was significantly earlier in the miR-204−/− mice. There was no difference in TAC-induced peak cardiac muscle motion time between wildtype and miR-204−/− mice. Our findings demonstrate that PE and TAC induce regional wall motion abnormalities that 2-STE can detect. It also highlights the role of miR-204 in regulating cardiac muscle motion during catecholamine-induced cardiotoxicity. •Phenylephrine and trans-aortic constriction-induced pressure overload lead to regional wall motion abnormalities in mouse hearts.•2-dimensional speckle tracking echocardiography successfully measures regional wall motion abnormalities in mouse hearts.•miR-204 absence does not affect the timing of peak regional wall motion during pressure overload.•miR-204 regulates the timing of the longitudinal motion of the anterior base of the left ventricle during phenylephrine exposure.
Apical akinesia Basal hyperkinesia Broken heart disease Stress-induced cardiomyopathy Takotsubo cardiomyopathy

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