PPARα activation attenuated heat-induced myocardial injury in mice

With climate change and global warming, extreme heatwaves occurred with more intense and higher frequency, significantly increasing the mortality rate associated with cardiovascular diseases. Using a mouse model of heat stress, the study aimed to clarify the adverse effects on heart, elucidate the underlying mechanism and explore the potential preventative strategies. Firstly, heat stress induced significant myocardial injury, which was further exacerbated even after termination of heat exposure. Next, PPARα (Peroxisome Proliferator-Activated Receptor Alpha) was screened and its downregulation in response to heat stress was confirmed at mRNA and protein levels. Then, pre-treatment with PPARα agonist fenofibrate significantly mitigated myocardial injury, accompanied with improved mitochondrial function in the myocardial tissues. In addition, PPARα activation may restore the mitochondrial homeostasis through enhancement of both antioxidation and mitophagy. These findings will highlight the pivotal role of PPARα in alleviating heat-induced myocardial injury and cardiovascular incidence, providing valuable target for drug development to prevent/treat heat stress-related diseases.