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03-02-2025 | Heart Failure | Original Article

Targeting KDM4C Prevents Heart Failure after Acute Myocardial Infarction Via Activation of SOS2

Authors: Caiping Tan, Xiaoqi Chen, Lingqi Xu, Jiaping Chen, Yingbing Tu

Published in: Journal of Cardiovascular Translational Research

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Abstract

Here, we focused on the function of SOS2 in heart failure (HF) after acute myocardial infarction (AMI) and investigated the mechanism. An oxygen–glucose deprivation (OGD) model in HL-1 cardiomyocytes and the ligation of the left anterior descending coronary artery in mice were conducted for MI modeling. SOS2 was downregulated in the heart tissues of mice with AMI. SOS2 activated the PI3K/Akt signaling, thereby alleviating cardiomyocyte apoptosis and inflammatory response, which were compromised by PI3K/Akt signaling inhibitor LY294002. Lysine-specific demethylase 4C (KDM4C) levels were downregulated in the heart tissue of AMI mice and OGD-induced HL-1 cells, accompanied by a reduction in H3K9Me3, while KDM4C overexpression triggered SOS2 expression by removing H3K9Me3 modification from its promoter. Knockdown of SOS2 abated the effects of KDM4C overexpression, thereby accentuating HF in mice. This study revealed that KDM4C protected mice against HF following AMI by restoration of SOS2 and the PI3K/Akt signaling.

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Metadata
Title
Targeting KDM4C Prevents Heart Failure after Acute Myocardial Infarction Via Activation of SOS2
Authors
Caiping Tan
Xiaoqi Chen
Lingqi Xu
Jiaping Chen
Yingbing Tu
Publication date
03-02-2025
Publisher
Springer US
Published in
Journal of Cardiovascular Translational Research
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI
https://doi.org/10.1007/s12265-025-10594-2

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