Title

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

Authors

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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