Macrophage-Specific IκB Kinase α Contributes to Ventricular Remodelling and Dysfunction After Myocardial Infarction

Abstract Background The IκB kinase (IKK) complex has been found to have critical functions in cancer and the immune system. In particular, IKKα, which is a member of the IKK complex, has been shown to influence the inflammatory response and malignant diseases. However, the role of IKKα in macrophages after myocardial infarction (MI) remains largely unknown. Methods Sham or myocardial infarction (MI) operations were performed on macrophage-specific IKKɑ knockout (mIKKɑ -/- ) mice and IKKɑ flox/flox littermates. We ligated the left anterior descending (LAD) coronary artery of the MI group and observed the results at 3 days, 7 days and 30 days after MI. Results We discovered more severe cardiac dysfunction with reduced angiogenesis, fibrosis and collagen deposition in mIKKɑ -/- than in IKKɑ flox/flox . Additionally, we also observed that macrophages in mIKKɑ -/- were easier to polarize to the M1 phenotype and expressed more pro-inflammatory factors than IKKɑ flox/flox . Mechanistically, IKKα deficiency in macrophages inhibited the alternative NF-κB/RelB pathway and enhanced the MEK1/2/ERK1/2 pathway. Conclusion Overall, our data identifies IKKɑ in the heart as a novel mediator that protected the heart from a severe inflammatory response and attenuated ventricular remodeling after MI by negatively regulating macrophage polarization to the M1 phenotype. Therefore, IKKα may serve as a potential therapeutic target for treatment after MI.