Myeloid receptor CD36 is required for early phagocytosis of myocardial infarcts and induction of Nr4a1-dependent mechanisms of cardiac repair.

Phagocytosis after myocardial infarction (MI) is a prerequisite to cardiac repair. Recruited monocytes clear necrotic cardiomyocytes and differentiate into cardiac macrophages. Some studies have linked apoptotic cell receptors on cardiac macrophages to tissue repair; however, the contribution of precursor monocyte phagocytic receptors, which are the first to interact with the cardiac parenchyma, is unclear. The scavenger receptor cluster of differentiation (CD)36 protein was detected on cardiac Ly6cHI monocytes, and bone marrow-derived Cd36 was essential for both early phagocytosis of dying cardiomyocytes and for smaller infarct sizes in female and male mice after permanent coronary ligation. Cd36 deficiency led to reduced expression of phagocytosis receptor Mertk and nuclear receptor Nr4a1 in cardiac macrophages, the latter previously shown to be required for phagocyte survival. Nr4a1 was required for phagocytosis-induced Mertk expression, and Nr4a1 protein directly bound to Mertk gene regulatory elements. To test the overall contribution of the Cd36-Mertk axis, MI was induced in Cd36-/- Mertk-/- double-knockout mice and led to increases in myocardial rupture. These data implicate monocyte CD36 in the mitigation of early infarct size and transition to Mertk- dependent macrophage function. Increased myocardial rupture in the absence of both Cd36 and Mertk underscore the physiologic significance of phagocytosis during tissue injury.-Dehn, S., Thorp, E. B. Myeloid receptor CD36 is required for early phagocytosis of myocardial infarcts and induction of Nr4a1-dependent mechanisms of cardiac repair.