Title

Monocyte-specific Bcl-2 expression attenuates inflammation and heart failure in monocyte chemoattractant protein-1 (MCP-1)-induced cardiomyopathy

Authors

Authors

J. Niu; A. Azfer;P. E. Kolattukudy

Comments

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Abbreviated Journal Title

Cardiovasc. Res.

Keywords

inflammation; monocyte chemoattractant protein-1; apoptosis; cardiomyopathy; transgenic animal model; NF-KAPPA-B; APOPTOTIC CELLS; MYOCARDIAL-INFARCTION; DISEASE; INHIBITION; GENE; MICE; ATHEROSCLEROSIS; ACTIVATION; CHEMOKINES; Cardiac & Cardiovascular Systems

Abstract

Objective: Infiltrating inflammatory cells within the myocardium have been shown to be apoptotic, but the significance of apoptotic inflammatory cells to the development of cardiomyopathy remains undefined. Transgenic mice with cardiac-specific expression of MCP-1 exhibit extensive apoptosis of infiltrating mononuclear cells and develop heart failure. Here, we tested the hypothesis that in vivo selective inhibition of apoptosis of infiltrating mononuclear cells would preserve cardiac structure and function and improve survival in this murine model. Methods: Mice with cardiac-specific expression of MCP-1 and monocyte-specific expression of Bcl-2 were generated by cross-breeding MCP-1 transgenic mice with hMRP8-Bcl-2 mice that over-express Bcl-2 in the monocytes. Structural and functional parameters and the inflammatory response of the heart were evaluated and compared between the wild-type and transgenic mice. Results: Expression of Bcl-2 in monocytes results in superior preservation of myocardial structure, cardiac function and a significant prolongation of survival of MCP-1 transgenic mice. The beneficial effects of monocyte-specific Bcl-2 expression are associated with inhibition of apoptosis of infiltrating mononuclear cells, normalization of circulating C-reactive protein levels, attenuation of cellular infiltrates, macrophage activation and production of proinflammatory cytokines, tumor necrosis factor (TNF-(alpha), interleukin (IL)-1 beta and IL-6 in the hearts. Conclusions: These results demonstrate that apoptosis of infiltrating mononuclear cells plays a detrimental role in the development of heart failure in this murine model, suggesting that modulation of apoptosis of infiltrating mononuclear cells may be of clinical benefit in heart failure. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Journal Title

Cardiovascular Research

Volume

71

Issue/Number

1

Publication Date

1-1-2006

Document Type

Article; Proceedings Paper

Language

English

First Page

139

Last Page

148

WOS Identifier

WOS:000238881500018

ISSN

0008-6363

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