Role of cardiac myocyte CXCR4 expression in development and left ventricular remodeling after acute myocardial infarction.

Rationale:Stromal cell–derived factor (SDF)-1/CXCR4 axis has an instrumental role during cardiac development and has been shown to be a potential therapeutic target for optimizing ventricular remodeling after acute myocardial infarction (AMI) and in ischemic cardiomyopathy. Although a therapeutic target, the specific role of cardiac myocyte CXCR4 (CM-CXCR4) expression following cardiogenesis and survival of cardiac myocyte and left ventricular remodeling after AMI is unknown. Objective:We hypothesized that cardiac myocyte derived CXCR4 is critical for cardiac development, but it may have no role in adulthood secondary to the short transient expression of SDF-1 and the delayed expression of CM-CXCR4 following AMI. To address this issue, we developed congenital and conditional CM-CXCR4−/− mouse models. Methods and Results:Two strains of CM-CXCR4flox/flox mice were generated by crossing CXCR4flox/flox mice with MCM-Cre+/− mouse and MLC2v-Cre+/− mouse on the C57BL/6J background, yielding CXCR4flox/flox MCM-Cr...