TRPV1 activation mitigates hypoxic injury in mouse cardiomyocytes by inducing autophagy through the AMPK signaling pathway.

Autophagy as a kind of highly conservative self-protection mechanism plays a crucial role in cardiovascular diseases. Transient receptor potential vanilloid 1 ion channel (TRPV1) is a nonselective cation channel and play an important role in the regulation of heart function. Here, we investigated the effects and mechanisms of the TRPV1 on autophagy in hypoxic cardiomyocytes. In this study, primary cardiomyocytes isolated from C57 mice were subjected to hypoxic stress, the expressions of TRPV1 and AMPK were regulated, Then Western blotting and immunofluorescence staining were performed to assess autophagic flux, CCK8 and an LDH assay were utilized to determine cell viability. In addition, the calcium influx were examined after up the TRPV1 expression in cardiomyocyte. We found that autophagosome was elevated in cardiomyocytes under hypoxic stress, and blocking of autophagy flux aggravated hypoxic damage to cardiomyocytes. Meanwhile, expression of TRPV1 was induced under hypoxic stress, and its upregulation by capsaicin improved autophagy flux and protected cardiomyocytes from hypoxic damage, while silencing of TRPV1 significantly attenuated autophagy. Moreover, our observations revealed that Adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling was activated in cardiomyocytes under hypoxic stress and involved in the TRPV1-induced autophagy in cardiomyocytes under hypoxic stress. On the whole, this study provides evidences that activation of TRPV1 mitigates hypoxic injury in cardiomyocytes by improving autophagy flux through the AMPK signaling pathway and highlights TRPV1 as a novel therapeutic target for the treatment of ischemic cardiac disease.