Cardiac hypertrophy is one of the major pathogeneses of heart failure. In cardiac hypertrophy, dead cardiomyocytes are supposed to be promptly engulfed by phagocytic cells. However, the cells and molecules responsible for removing dead cardiomyocytes in cardiac hypertrophy have not yet been revealed.
We performed transverse aortic constriction (TAC) operation on wild-type (WT) mice to generate mouse models of cardiac hypertrophy. Among the several molecules mediating engulfment, the expression level of MFG-E8, a molecule that promotes engulfment, in the heart was significantly increased after TAC operation. MFG-E8 was specifically expressed in myofibroblasts. We revealed that myofibroblasts have the ability to engulf dead cells via MFG-E8. Consistent with these results, the cardiac conditions of TAC-operated MFG-E8 KO mice were markedly worse compared with those of WT mice. In addition, exogenous expression of MFG-E8 in hearts of WT mice by the adeno-associated virus significantly improved the cardiac condition after TAC operation. In conclusion, we identified cardiac myofibroblasts and MFG-E8 are responsible for the removal of dead cardiomyocytes in cardiac hypertrophy.
