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

    Authors

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

    Comments

    Authors: contact us about adding a copy of your work at STARS@ucf.edu

    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

    Share

    COinS