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Metabolic Adaptations and Therapies in Cardiac Hypoxia

Huili Li, Fei Xiao, Chenghui Zhou, Tao Zhu, Sheng Wang

2025JACC Basic to Translational Science13 citationsDOIOpen Access PDF

Abstract

Cardiac hypoxia triggers a cascade of responses and functional changes in myocardial and non-myocardial cells, profoundly affecting cellular metabolism, oxygen-sensing mechanisms, and immune responses. Myocardial cells, being the primary cell type in cardiac tissue, undergo significant alterations in energy metabolism, including glycolysis, fatty acid metabolism, ketone body utilization, and branched-chain amino acid metabolism, to maintain cardiac function under hypoxic conditions. Non-myocardial cells, such as fibroblasts, endothelial cells, and immune cells, although fewer in number, play crucial roles in regulating cardiac homeostasis, maintaining structural integrity, and responding to injury. This review discusses the metabolic reprogramming of immune cells, particularly macrophages, during ischemia-reperfusion injury and explores various therapeutic strategies that modulate these metabolic pathways to protect the heart during hypoxia. Understanding these interactions provides valuable insights and potential therapeutic targets for heart disease treatment.

Topics & Concepts

Hypoxia (environmental)MedicineCardiologyInternal medicineIntensive care medicineChemistryOxygenOrganic chemistryMitochondrial Function and PathologyCancer, Hypoxia, and MetabolismAdipose Tissue and Metabolism