In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 129, No. Suppl_1 ( 2021-09-03)
Abstract:
Rationale: Myocardial infarction (MI) is a major cause of death and inflammation mainly contributes to pathological progress. Expression of IKKe is induced in inflammatory macrophages, but the pathophysiological roles in cardiac injury remain unclear. Objective: We aimed to investigate the role of IKKe in macrophages in the IKKe knockout (KO) MI mouse model. Methods and Results: MI was induced by coronary artery ligation, then cardiac macrophages and bone marrow-derived macrophages were isolated for further comparison studies.The IKKe KO group showed poor survival rate, high circulating IL-6 level, large cardiac fibrosis (14.7±4.8% vs. 31.1±10.2%, p 〈 0.05), and low ejection fraction (34.02±5.5% vs. 30.33±5.3% vs. p 〈 0.05) compared with the wild type (WT) group.Next, we investigated the inflammatory and fibrotic responses to understand the relevant mechanism. Flow cytometry and phosphorylated protein array showed that IKKe-deficient macrophages exhibited lower phosphorylated p38 and higher inflammatory markers.Moreover, we identified macrophage-myofibroblast transition (MMT) by detecting aSMA expression in macrophages, and found that the number of cells under MMT was 2.0-fold higher in the IKKe KO group than in the WT group.In parallel to the increase in MMT, the transition of CD206(+) anti-inflammatory macrophages to myofibroblasts was 2.16-fold greater in the IKKe KO mice.Macrophages with chemical or genetic interfering of p38 displayed the remarkable increases in both MMT and inflammatory phenotype. Conclusions: Our results suggest that IKKe-p38 axis may potentially induce the inflammation resolution and limit MMT in macrophages in response to MI. Mechanistical understanding of IKKe signaling offers novel therapeutic pathways to treat MI.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/res.129.suppl_1.P444
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2021
detail.hit.zdb_id:
1467838-X
