Qiliqiangxin Improves Cardiac Glucose Metabolism After Myocardial Infarction Through a HIF-1α/MIF/AMPK Axis

Cardiac glucose metabolism is critically involved in the pathophysiology of myocardial infarction. This study investigated whether Qiliqiangxin (QL), a traditional Chinese medicine, improves myocardial glucose uptake and aerobic oxidation after myocardial infarction (MI) and explored the underlying mechanisms. QL treatment significantly increased LVEF, enhanced myocardial glucose uptake, reduced fibrosis, apoptosis, ROS production and elevated ATP generation along with activity of pyruvate dehydrogenase (PDH) and citrate synthase (CS). These effects were abolished by HIF-1α-shRNA transduction. QL also upregulated the expression of HIF-1α, MIF, p-AMPKα, GLUT-4, hexokinase 2 (HK2), PDH and CS, which were similarly attenuated by HIF-1α knockdown. In conclusion, our study demonstrated that QL enhances myocardial glucose uptake and aerobic oxidation in a murine model of post-MI heart failure. Genetic inhibition of HIF-1α reverses these beneficial effects, suggesting the involvement of the HIF-1α/MIF/AMPK signalling axis.