Background Transient receptor potential canonical (TRPC) channels play a role in angiogenesis. However, the involvement of TRPC1 in myocardial infarction (MI) remains unclear. The present study was aimed at investigating whether TRPC1 can improve the recovery of cardiac function via prompting angiogenesis following MI. Methods and Results In vitro, coronary artery endothelial cells from floxed TRPC1 mice and endothelial cell-specific TRPC1 channel knockout mice were cultured to access EC angiogenesis. Both EC tube formation and migration were significantly suppressed in mouse coronary artery endothelial cells from endothelial cell-specific TRPC1 channel knockout mice. In vivo, coronary artery endothelial cells from floxed TRPC1 and endothelial cell-specific TRPC1 channel knockout mice were subjected to MI, then echocardiography, triphenyltetrazolium chloride staining and immunofluorescence were performed to assess cardiac repair on day 28. Endothelial cell-specific TRPC1 channel knockout mice had higher ejection fraction change, larger myocardial infarct size, and reduced capillary density in the infarct area compared with coronary artery endothelial cells from floxed TRPC1 mice. Furthermore, we found underlying regulation by HIF-1α (hypoxic inducible factor-1α) and MEK-ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase) that could be the mechanism for the angiogenetic action of TRPC1. Significantly, treatment with dimethyloxaloylglycine, an activator of HIF-1α, induced cardiac improvement via the HIF-1α-TRPC1-MEK/ERK pathway in MI mice. Conclusions Our study demonstrated TRPC1 improves cardiac function after MI by increasing angiogenesis via the upstream regulator HIF-1α and downstream MEK/ERK, and dimethyloxaloylglycine treatment has protective effect on MI through the HIF-1α-TRPC1-MEK/ERK pathway.
Keywords: angiogenesis; hypoxia‐inducible factor; myocardial infarction; transient receptor potential channels; vascular biology.