Selective Heart Irradiation Induces Cardiac Overexpression of the Pro-hypertrophic miR-212

Frontiers in Oncology
Márta SárközySándor Bátkai

Abstract

Background: A deleterious, late-onset side effect of thoracic radiotherapy is the development of radiation-induced heart disease (RIHD). It covers a spectrum of cardiac pathology including also heart failure with preserved ejection fraction (HFpEF) characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction. MicroRNA-212 (miR-212) is a crucial regulator of pathologic LVH via FOXO3-mediated pathways in pressure-overload-induced heart failure. We aimed to investigate whether miR-212 and its selected hypertrophy-associated targets play a role in the development of RIHD. Methods: RIHD was induced by selective heart irradiation (50 Gy) in a clinically relevant rat model. One, three, and nineteen weeks after selective heart irradiation, transthoracic echocardiography was performed to monitor cardiac morphology and function. Cardiomyocyte hypertrophy and fibrosis were assessed by histology at week 19. qRT-PCR was performed to measure the gene expression changes of miR-212 and forkhead box O3 (FOXO3) in all follow-up time points. The cardiac transcript level of other selected hypertrophy-associated targets of miR-212 including extracellular signal-regulated kinase 2 (ERK2), myocyte enhancer factor 2a (MEF2a), AMP-acti...Continue Reading

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Citations

May 30, 2020·International Journal of Molecular Sciences·Márton R SzabóTamás Csont
Feb 17, 2021·Clinical Research in Cardiology : Official Journal of the German Cardiac Society·Márta SárközyTamás Csont

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Methods Mentioned

BETA
electrophoresis
Protein Assay

Software Mentioned

Sigmaplot
TargetScan
Quantity One
EchoPac Dimension
Systat

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