Abstract
Mitochondrial ATP-sensitive potassium channel (mitoKATP) is a common end effector of many protective stimuli in myocardial ischemia-reperfusion injury (MIRI). However, the specific molecular mechanism underlying its myocardial protective effect is not well elucidated. We characterized an anoxia/reoxygenation (A/R) model using freshly isolated adult rat cardiomyocytes. MitoKATP status was interfered with its specific opener diazoxide (DZ) or blocker 5-hydroxydecanote (5-HD). Digital gene expression (DGE) and bioinformatic analysis were deployed. Three energy metabolism related genes (MT-ND6, Idh2, and Acadl) were upregulated when mitoKATP opened. In addition, as many as 20 differentially expressed genes (DEGs) were significantly enriched in five energy homeostasis correlated pathways (PPAR, TCA cycle, fatty acid metabolism, and peroxisome). These findings indicated that mitoKATP opening in MIRI resulted in energy mobilization, which was confirmed by measuring ATP content in cardiomyocytes. These causal outcomes could be a molecular mechanism of myocardial protection of mitoKATP and suggested that the mitoKATP opening plays a physiologic role in triggering cardiomyocytes' energy homeostasis during MIRI. Strategies of modulating energy expenditure during myocardial ischemia-reperfusion may be promising approaches to reduce MIRI.
Highlights
Myocardial infarction has been a leading cause of death worldwide
We have reported that mitoKATP opening was cardioprotective in myocardial ischemia-reperfusion injury (MIRI) [12,13,14], but our understanding of its specific mechanism remained quite preliminary
We developed an A/R model using freshly isolated adult rat cardiomyocytes, which are more relevant to the in vivo IR conditions
Summary
Myocardial infarction has been a leading cause of death worldwide. The prognosis of acute myocardial infarction has been dramatically improved due to the advances of both catheterization techniques and reperfusion therapy by coronary mechanical and pharmacological intervention methods. Strategies to limit myocardial ischemia-reperfusion injury (MIRI), reducing infarct size, have not been well applied in clinical settings. Myocardial ischemia-reperfusion (IR) induces lethal injury in the heart, after some artificial interventions, the cardiomyocytes and the heart tissue therein have powerful endogenous mechanisms to protect themselves from oxidative stress, energy deficiency, protein aggregation, and organelle malfunction, thereby minimizing MIRI [1]. Murry et al in 1990 [2, 3] first proposed that ischemic preconditioning (IPC) may protect the heart by reducing myocardial energy demand during myocardial ischemia and decreasing cell death by preserving ATP content and/or reducing catabolite accumulation. It is demonstrated that the pharmacological inhibition of the mitoKATP in early reperfusion abolished the infarct-limiting effects of IPost [9,10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
