| First Author | Dong Q | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 42678 | PubMed ID | 28205608 |
| Mgi Jnum | J:326305 | Mgi Id | MGI:7310137 |
| Doi | 10.1038/srep42678 | Citation | Dong Q, et al. (2017) Blockage of transient receptor potential vanilloid 4 alleviates myocardial ischemia/reperfusion injury in mice. Sci Rep 7:42678 |
| abstractText | Transient receptor potential vanilloid 4 (TRPV4) is a Ca(2+)-permeable nonselective cation channel and can be activated during ischemia/reperfusion (I/R). This study tested whether blockade of TRPV4 can alleviate myocardial I/R injury in mice. TRPV4 expression began to increase at 1 h, reached statistically at 4 h, and peaked at 24-72 h. Treatment with the selective TRPV4 antagonist HC-067047 or TRPV4 knockout markedly ameliorated myocardial I/R injury as demonstrated by reduced infarct size, decreased troponin T levels and improved cardiac function at 24 h after reperfusion. Importantly, the therapeutic window for HC-067047 lasts for at least 12 h following reperfusion. Furthermore, treatment with HC-067047 reduced apoptosis, as evidenced by the decrease in TUNEL-positive myocytes, Bax/Bcl-2 ratio, and caspase-3 activation. Meanwhile, treatment with HC-067047 attenuated the decrease in the activation of reperfusion injury salvage kinase (RISK) pathway (phosphorylation of Akt, ERK1/2, and GSK-3beta), while the activation of survival activating factor enhancement (SAFE) pathway (phosphorylation of STAT3) remained unchanged. In addition, the anti-apoptotic effects of HC-067047 were abolished by the RISK pathway inhibitors. We conclude that blockade of TRPV4 reduces apoptosis via the activation of RISK pathway, and therefore might be a promising strategy to prevent myocardial I/R injury. |
