Tetrandrine has protective role in myocardial ischemia/reperfusion injury via the TRPV2/Ca/calcineurin/NFAT axis.

BACKGROUND

The protective function of the tetrandrine (TET)-mediated transient receptor potential vanilloid 2 (TRPV2) channel in myocardial ischemia/reperfusion injury (MI/RI) has been established in numerous investigations. The objective of the current study was to explain how TRPV2 further modulates downstream factors to influence the progression of MI/RI.

METHODS

To this end, an MI/RI model in rats and a hypoxia-reoxygenation (H/R) cell model in H9c2 cells were constructed. Based on western blotting analyses, the effects of TRPV2 on the levels of apoptosis-related proteins as well as calcineurin and nuclear factor of activated T cells (NFAT) were ascertained. Evans blue/triphenyltetrazolium chloride (TTC) double staining and H&E staining were, respectively, used to examine the pathological changes and infarction size of myocardial tissues in rats. Cardiomyocyte apoptosis was assessed with TUNEL assays and flow cytometry. Ca concentration and reactive oxygen species (ROS) production were determined using a calcium assay kit and dichlorodihydrofluorescein diacetate (DCFH-DA) staining, respectively.

RESULTS

Downregulated TRPV2 showed a significant ameliorative effect on cardiomyocyte histopathology and infarction area. Cardiomyocyte apoptosis, Ca concentration, and ROS amounts were also inhibited when TRPV2 was silenced. Furthermore, results indicated that TET could significantly decrease TRPV2, while knocking down TRPV2 markedly suppressed the expression of calcineurin and NFAT.

CONCLUSION

These findings shed light on the possible mechanisms behind the TET-mediated TRPV2 channel in MI/RI, indicating that TET has protective functions through downregulation of TRPV2 expression and suppression of the Ca/calcineurin/NFAT pathway.