Tetrandrine downregulates TRPV2 expression to ameliorate myocardial ischemia/reperfusion injury in rats via regulation of cardiomyocyte apoptosis, calcium homeostasis and mitochondrial function.

Our previous study has indicated that tetrandrine (TET) can target miR-202-5p to repress the activation of transient receptor potential vanilloid type 2 (TRPV2), eventually ameliorating the progression of myocardial ischemia/reperfusion injury (MI/RI). This study is aimed to further ascertain the detailed mechanisms between TET and TRPV2 in MI/RI pathogenesis. Here, a myocardial I/R injury rat model and a hypoxia-reoxygenation (H/R) model in rat myocardial cell line (H9C2 cells) were established. We reported that pronounced upregulation of TRPV2 was observed in I/R rats and H/R-induced H9C2 cells. Silencing of TRPV2 could improve cardiac function and myocardial injury, reduced infarction size, and promoted cardiomyocyte proliferation in I/R rats. In I/R rats or H/R-induced H9C2 cells, cardiomyocyte apoptosis was inhibited by knocking-down TRPV2. Meanwhile, the silenced TRPV2 or TET treatment ameliorated the damaged mitochondrial structure, mitigated ROS generation, restored the impaired ΔΨM, inhibited mPTP opening and alleviated Ca overload in H/R-induced H9C2 cells. The results obtained from the overexpression of TRPV2 were contrary to those depicted above. Moreover, TET could downregulate TRPV2 expression, while the overexpression of TRPV2 could reverse the above protective effects of TET in H/R-induced H9C2 cells. The results indicated that TET may function as a TRPV2 blocking agent, thereby attenuating the progression of MI/RI through modulation of cardiomyocyte apoptosis, calcium homeostasis and mitochondrial function. These findings offer a theoretical foundation for potential clinical application of TET therapy in patients with MI/RI.