The main objective of this study was to determine whether or not monocyte infiltration occurs in the prediabetic (PD) heart and its role in PD cardiomyopathy. We hypothesized that the PD 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, PD, or PD + BMP-7 groups. PD and PD + BMP-7 groups were administered streptozotocin (50 mg/kg), whereas control animals received sodium citrate buffer. Afterward, the PD + BMP-7 group was administered BMP-7 (200 μg/kg) for 3 days. Our data showed significantly increased infiltrated monocytes and associated pro-inflammatory cytokines, adverse cardiac remodeling, and heart dysfunction in the PD group (P < 0.05). Interestingly, M2 macrophage differentiation and associated anti-inflammatory cytokines were enhanced and there were reduced adverse cardiac remodeling and improved cardiac function in the PD + BMP-7 group (P < 0.05). In conclusion, our data suggest that PD cardiomyopathy is associated with increased monocyte infiltration and released proinflammatory 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 PD heart.

The purpose of this study was to determine the degree of infiltration of different cell subpopulations (tissue dendritic macrophages, T-helper cells, cytotoxic T lymphocytes, monocytes, neutrophils, and B cells) and the expression of the cytokines interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-␣) in inflamed and noninflamed resected tissues from Crohn's disease (CD) and non-CD patients. Twenty-one resected fullthickness intestinal tissue specimens representing 13 subjects (8 CD and 5 non-CD patients) were included in this study. Sections of 20 m in thickness were cut and then stained using immunohistochemistry. The sections were analyzed using confocal laser scanning microscopy (CLSM). Patterns of staining for inflamed CD and noninflamed CD tissues versus non-CD tissues demonstrated significant differences in the macrophage and T-helper subpopulations. Surprisingly, the T-helper subset was decreased significantly in the inflamed CD sections compared to the noninflamed CD and non-CD sections. The staining patterns also suggested differences in the expression of both IL-12 and TNF-␣ between the groups, with cytokine overexpression directly relating to the fistulizing state in CD patients. Cytokine expression is upregulated in chronic CD patients; therefore, the degree of inflammation and tissue damage in CD is dependent on the expression of specific cytokines within the tissue. Differentiation of cell subpopulations may be important for establishing a direct relationship with each state of CD (inflammatory, stricturing, and fistulizing states).