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Updated: Apr 15, 2026
Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs
Published on: April 17, 2021
MCP-1-induced protein attenuates post-infarct cardiac remodeling and dysfunction through mitigating NF-κB activation
Jianli Niu1, Zhuqing Jin, Hyunbae Kim
1Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 4000 Central Florida Boulevard, Orlando, FL, 32816, USA, Jianli.Niu@ucf.edu.
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-κB 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-κB-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-κB signaling and suppressing inflammation-associated microRNA expression.
Insights
Monocyte chemoattractant protein-1-induced protein (MCPIP) overexpression in the heart reduces inflammation and improves outcomes after myocardial infarction (MI). This finding suggests MCPIP as a potential therapeutic target for heart failure.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Inflammation Research
Background:
- Monocyte chemoattractant protein-1-induced protein (MCPIP, ZC3H12A) is a known negative regulator of inflammation.
- MCPIP expression is elevated in the hearts of patients with ischemic heart failure.
- The specific role of MCPIP in post-myocardial infarction (MI) cardiac inflammation and remodeling remains unclear.
Purpose of the Study:
- To investigate the inhibitory effect of MCPIP on cardiac inflammation and adverse remodeling following myocardial infarction (MI).
- To determine the potential of MCPIP as a therapeutic target for mitigating post-MI cardiac dysfunction.
Main Methods:
- Mice with cardiomyocyte-specific MCPIP overexpression were subjected to permanent coronary artery ligation (MI).
- Cardiac function, infarct size, fibrosis, cellular infiltration, and inflammatory markers were assessed post-MI.
- NF-κB signaling pathway activation and microRNA expression were analyzed in vivo and in vitro.
Main Results:
- MCPIP overexpression improved survival rates, reduced cardiac hypertrophy, fibrosis, and improved cardiac performance 28 days post-MI.
- MCPIP significantly decreased monocytic cell infiltration, cytokine expression, and apoptosis in the ischemic myocardium.
- MCPIP attenuated NF-κB signaling activation and suppressed inflammation-associated microRNA expression.
Conclusions:
- MCPIP expression in the ischemic myocardium protects against adverse cardiac remodeling and dysfunction after MI.
- MCPIP exerts its protective effects by modulating myocardial inflammation, likely through inhibiting NF-κB signaling and inflammation-associated microRNAs.
- MCPIP represents a promising therapeutic target for managing post-infarct heart failure.
