Chen et al. used a rat model of cardiopulmonary bypass followed by 30-min ischemia (induced by ascending aorta blockage) and 15-min reperfusion [1]. They reported that pyruvate dehydrogenase E1α subunit (PDHA1) overexpression attenuated myocardial ischemia reperfusion injury (MIRI), while PDHA1 interference exacerbated MIRI [1]. PDHA1 controlled the expression of glucose transporter 4 (GLUT4). They claimed that GLUT4 controlled the uptake and utilization of myocardial glucose, influencing the development of myocardial insulin resistance, and ultimately modulating MIRI [1].

The concept that PDHA1 and GLUT4 are involved in MIRI is not new. Liang et al. reported that the expression of myocardial total GLUT4 was reduced and the translocation of GLUT4 from the cytoplasm to surface membrane was attenuated in canine hearts exposed to MIRI [2]. Sun et al. reported that cardiac-specific deletion of Pdha1resulted in a larger infarct size in mice exposed to MIRI. Dichloroacetate, a pyruvate dehydrogenase activator, increased glucose oxidation in wild-type mouse hearts during MIRI and attenuated myocardial infarct size in wild-type mice, but not in PDH E1α-deficient mouse hearts [3]. Deletion of the PDH E1α impaired AMP-activated protein kinase activation, leading to the increased susceptibility to MIRI [3]. Pan et al. showed that PDHA1 suppresses the expression of pyrin domain-containing protein 3 (NLRP3), and thus suppresses pyroptosis and attenuates MIRI in the rat heart. They suggested that insulin attenuates MIRI via inducing PDHA1 dephosphorylation