The main objective of this study was to determine whether or not monocyte infiltration occurs in the diabetic heart and its role in diabetic cardiomyopathy. We hypothesize that the diabetic heart is significantly populated with monocytes and that bone morphogenetic protein (BMP)-7, a novel mediator of monocyte polarization, activates infiltrated monocytes into anti-inflammatory M2 macrophages, thereby inhibiting apoptosis and fibrosis and improving cardiac function. C57Bl6 mice were assigned to control, D (diabetic), or D+BMP-7 groups. D and D+BMP-7 groups were administered STZ (50 mg/kg) whereas control animals received sodium citrate buffer. Afterwards, the D+BMP-7 group were administered BMP-7 (200 µg/ kg) for three days. Our data show significantly increased infiltrated monocytes and associated pro-inflammatory cytokines, adverse cardiac remodeling, and heart dysfunction in the D group (p<0.05). Interestingly, increase in M2 macrophage differentiation and associated anti-inflammatory cytokines were enhanced, reduced adverse cardiac remodeling, and improved cardiac function in the D+BMP-7 group (p<0.05). In conclusion, our data suggest, that diabetic cardiomyopathy is associated with increased monocyte infiltration, released of pro-inflammatory cytokines, which contributes to adverse cardiac remodeling, and cardiac dysfunction. Moreover, we report that BMP-7 possesses novel therapeutic potential in its ability to differentiate monocytes into M2 macrophages and confer cardiac protection in the diabetic heart.
- Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology