The histopathology and echocardiographic results revealed that the increases in cardiac diameter and volume and fibrosis that were observed in HDC−/− mice with MI could be attenuated by histamine administration; however, pre-treatment with H1R or H2R antagonists abrogated the protective effects of exogenous histamine on MI-induced cardiac remodeling and heart failure in HDC−/− mice (Fig. 5f,g and Supplementary Fig. S5c–h). This evidence concerns the gene HRH2 and myocardial infarction.