Adiponectin-based therapeutics show strong promise for mitigating myocardial ischemia-reperfusion injury via metabolic rebalancing

Myocardial ischemia-reperfusion injury (MIRI) remains a critical unmet need in contemporary ST-segment-elevation myocardial infarction (STEMI) care. While reperfusion is vital for limiting ischemic myocardial necrosis, it paradoxically induces deleterious effects such as impaired carbohydrate oxidation, excessive fatty-acid oxidation, intracellular acidosis, calcium (Ca2+) overload, oxidative/nitrative stress, and mitochondrial fragmentation. These processes expand infarct size, worsen microvascular obstruction, and fuel adverse ventricular remodeling. Adiponectin, an adipocyte-derived hormone, circulates at high levels in healthy individuals but is reduced in obesity, diabetes, and cardiovascular disease. Low adiponectin concentrations are strongly associated with coronary artery disease, myocardial infarction, MIRI, and heart failure. The activation of the adiponectin-adiponectin receptor (AdipoR) axis directly counteracts these MIRI processes, offering a promising therapeutic target.