BMP-7 attenuates adverse cardiac remodeling mediated through M2 macrophages in prediabetic cardiomyopathy

    Authors

    P. Urbina;D. K. Singla

    Comments

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    Abbreviated Journal Title

    Am. J. Physiol.-Heart Circul. Physiol.

    Keywords

    macrophages; monocytes; prediabetic cardiomyopathy; heart; apoptosis; bone morphogenetic protein-7; BONE MORPHOGENETIC PROTEIN-7; INDUCED DIABETIC-RATS; GLYCEMIC CONTROL; INHIBIT APOPTOSIS; CELLS; ATHEROSCLEROSIS; MELLITUS; MODEL; COMPLICATIONS; INTERLEUKIN-6; Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular; Disease

    Abstract

    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 mu g/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.

    Journal Title

    American Journal of Physiology-Heart and Circulatory Physiology

    Volume

    307

    Issue/Number

    5

    Publication Date

    1-1-2014

    Document Type

    Article

    Language

    English

    First Page

    H762

    Last Page

    H772

    WOS Identifier

    WOS:000341081200014

    ISSN

    0363-6135

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