Txnip/PDK4-Mediated Hyperdependence on Fatty-Acid Oxidation Amplifies Susceptibility of Diabetic Myocardium to Ischemia-Reperfusion Damage.

BACKGROUND

Undergoing perioperative ischemia-reperfusion injury (I/RI), the prevalence of adverse cardiac events is high due to increased myocardial vulnerability in diabetic patients. However, the specific mechanisms of increased myocardial vulnerability in diabetes are still unknown.

OBJECTIVE

To investigate the specific mechanisms underlying increased myocardial vulnerability in diabetes and to explore potential myocardial protective strategies.

METHODS

In this study, we repeatedly verified through single-cell sequencing, fluorescence in situ staining, metabonomics, and animal experiments.

RESULTS

Here we show for the first time that the cardiomyocyte subtype (C6 cardiomyocyte) is a cardiomyocyte characterized by myocardial contraction, and the reduction of its number and metabolic heterogeneity is the basis of myocardial ischemia-reperfusion injury in diabetes. Among them, TXNIP/PDK4 mediated metabolic reprogramming is an important reason for myocardial vulnerability in diabetes, and through regulating TXNIP/PDK4, we optimize myocardial energy metabolism. It can significantly improve the vulnerability of diabetes myocardium, play a good role in myocardial protection, and has clinical transformation potential.