In the present study, we focused on the endogenous angiogenetic response upon the myocardial ischemia and identified the regulatory effect of KMT2D on angiogenesis in the cardiomyocytes and the vascular endothelial cells by using KMT2D cardiomyocyte-specific knockout mice and cell culture system with CRISPR/Cas9 gene-edited or siRNA-mediated KMT2D knockdown cells. This evidence concerns the gene KMT2D and myocardial ischemia.