In addition to this, macrophages in the early stages of MI highly express Lgr4, which leads to inflammatory macrophage activation by promoting cAMP response element binding protein(CREB) mediated c-Fos, Fosl1 and FosB trans activation, further leading to reduced cardiac function, increased myocardial infarct size and poor ventricular remodeling (65). This evidence concerns the gene CREB1 and myocardial infarction.