Targeting ALDH2 for Therapeutic Interventions in Chronic Pain-Related Myocardial Ischemic Susceptibility

Theranostics
Chen LiHeng Ma

Abstract

Clinical observations have demonstrated a link between chronic pain and increased ischemic heart disease mortality, but the mechanisms remain elusive. Reactive aldehydes have recently been confirmed as a new player in pain pathologies, while our previous study demonstrated that reactive aldehydes (4-HNE) induced carbonyl stress contributing to myocardial ischemic intolerance. The aim of this study was to explore whether chronic pain increases susceptibility to myocardial ischemia/reperfusion (MI/R) injury and to investigate the underlying mechanisms focusing on toxic aldehyde and carbonyl stress. Methods: Chronic pain was induced by chronic compression of the dorsal root ganglion (CCD). After 2 weeks CCD, aldehyde dehydrogenase (ALDH2) KO or wild-type (WT) littermate mice were then subjected to in vivo MI/R. Results: In CCD-WT mice, heightened nociception paralleled circulating aldehyde (4-HNE) accumulation and cardiac protein carbonylation. Mechanistically, CCD-induced 4-HNE overload provoked cardiac Sirtuin 1 (SIRT1) carbonylative inactivation and inhibited Liver kinase B1 (LKB1) - AMP-activated protein kinase (LKB1-AMPK) interaction, which resulted in exacerbated MI/R injury and higher mortality compared with non-CCD WT mice...Continue Reading

Citations

Feb 26, 2019·International Heart Journal·Boyuan FanQiangsun Zheng
Dec 24, 2019·Molecular Aspects of Medicine·Luiz H M BoziJulio C B Ferreira
Jan 11, 2019·Chemical Research in Toxicology·José Salud Rodríguez-ZavalaBelem Yoval-Sánchez
Nov 13, 2021·Circulation Research·Lu GanYajing Wang

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Datasets Mentioned

BETA
BC005476

Methods Mentioned

BETA
carbonylation
acetylation
fluorescence microscopy
transgenic
ELISA
electrophoresis
dissection
immunoprecipitation
Co-Immunoprecipitation

Software Mentioned

GraphPad Prism
GraphPad
ImageJ

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