Title

MCP-1-induced protein attenuates post-infarct cardiac remodeling and dysfunction through mitigating NF-kappa B activation and suppressing inflammation-associated microRNA expression

Authors

Authors

J. L. Niu; Z. Q. Jin; H. Kim;P. E. Kolattukudy

Comments

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Abbreviated Journal Title

Basic Res. Cardiol.

Keywords

Myocardial infarction; MCP-1-induced protein; Inflammation; Left; ventricular remodeling; MONOCYTE CHEMOATTRACTANT PROTEIN-1; HEART-FAILURE; MYOCARDIAL-INFARCTION; INNATE IMMUNITY; TRANSCRIPTION FACTOR; TNF-ALPHA; CARDIOMYOCYTE; MICE; OVEREXPRESSION; ISCHEMIA; Cardiac & Cardiovascular Systems

Abstract

MCP-1-induced protein (MCPIP, also known as ZC3H12A) has recently been uncovered to act as a negative regulator of inflammation. Expression of MCPIP was elevated in the ventricular myocardium of patients with ischemic heart failure. However, the role of MCPIP in the development of post-infarct cardiac inflammation and remodeling is unknown. The objective of the present study was to investigate whether MCPIP exerts an inhibitory effect on the cardiac inflammatory response and adverse remodeling after myocardial infarction (MI). Mice with cardiomyocyte-specific expression of MCPIP and their wild-type littermates (FVB/N) were subjected to permanent ligation of left coronary artery. The levels of MCPIP were significantly increased in the ischemic myocardium and sustained for 4 weeks after MI. Acute infarct size was comparable between groups. However, constitutive overexpression of MCPIP in the murine heart resulted in improved survival rate, decreased cardiac hypertrophy, less of fibrosis and scar formation, and better cardiac performance at 28 days after MI, along with a markedly reduced monocytic cell infiltration, less cytokine expression, decreased caspase-3/7 activities and apoptotic cell death compared to the wild-type hearts. Cardiomyocyte-specific expression of MCPIP also attenuated activation of cardiac NF-kappa B signaling and expression of inflammation-associated microRNAs (miR-126, -146a, -155, and -199a) when compared with the post-infarct wild-type hearts. In vitro, MCPIP expression suppressed hypoxia-induced NF-kappa B-luciferase activity in cardiomyocytes. In conclusion, MCPIP expression in the ischemic myocardium protects against adverse cardiac remodeling and dysfunction following MI by modulation of local myocardial inflammation, possibly through mitigating NF-kappa B signaling and suppressing inflammation-associated microRNA expression.

Journal Title

Basic Research in Cardiology

Volume

110

Issue/Number

3

Publication Date

1-1-2015

Document Type

Article

Language

English

First Page

15

WOS Identifier

WOS:000354607300006

ISSN

0300-8428

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