Inhibition of TRPA1 Promotes Cardiac Repair in Mice After Myocardial Infarction.

Abstract

Recent studies have shown that TRPA1, a nonselective cation channel with high permeability to calcium, is expressed in many tissues of the cardiovascular system and is involved in the pathogenesis of many cardiovascular diseases. However, the role of TRPA1 in cardiac repair after myocardial infarction (MI) has not been clearly defined. The aim of this study was to confirm whether inhibition of TRPA1 could attenuate MI-induced cardiac ischemia injury. The C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery and treated with TRPA1-specific inhibitor HC-030031 (HC) for 4 weeks. Echocardiography was performed to assess cardiac function. The results showed that HC significantly attenuated MI-induced cardiac dysfunction 4 weeks after MI. Similarly, HC reduced cardiac fibrosis and cell apoptosis after MI and significantly increased angiogenesis in the border zone of the infarct. In vitro, we found that HC promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs). Importantly, HC treatment decreased phosphatase and tensin homolog expression and augmented the expression of phosphorylated Akt in the myocardium post MI and HUVECs. However, treatment of HUVECs with a PI3K inhibitor, LY294002, before HC administration almost completely abolished HC-induced migration in HUVECs. In conclusion, we demonstrate that the inhibition of TRPA1 promotes angiogenesis after MI, thereby alleviating myocardial ischemia injury via mechanisms involving inhibition of phosphatase and tensin homolog expression and subsequent activation of the PI3K/Akt signaling.