IKKε-deficient macrophages impede cardiac repair after myocardial infarction by enhancing the macrophage-myofibroblast transition.

ABSTRACT: The regulatory role of the inhibitor of NF-kB kinase ε (IKKε) in postmyocardial infarction (MI) inflammation remains uncertain. Using an MI mouse model, we examined the cardiac outcomes of IKKε knockout (KO) mice and wild-type mice. We employed single-cell RNA sequencing (scRNA-seq) and phosphorylated protein array techniques to profile cardiac macrophages. IKKε KO mice exhibited compromised survival, heightened inflammation, pronounced cardiac fibrosis, and a reduced ejection fraction. A distinct cardiac macrophage subset in IKKε KO mice exhibited increased fibrotic marker expression and decreased phosphorylated p38 (p-p38) levels, indicating an enhanced macrophage-myofibroblast transition (MMT) post-MI. While cardiac inflammation is crucial for initiating compensatory pathways, the timel

SUBMITTER: Cho HH 

PROVIDER: S-EPMC11446912 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature