The Bioinformatics Analysis of Publicly Available Datasets and Validation in a Mouse Model of Myocardial Infarction Through Coronary Artery Ligation

Background: Macrophages play a crucial role in the inflammatory response and fibrosis after myocardial infarction (MI). CMTM3 exerts important functions in the immune system and cardiovascular system. This study aims to explore the role and mechanism of CMTM3 in regulating macrophage-related inflammation after MI. Methods: mouse MI model was established. The effects of CMTM3 on MI and macrophage-related inflammation in mice were evaluated by TTC, Masson, echocardiography, flow cytometry and Elisa. In vitro, the effects of CMTM3 on primary macrophages were assessed by flow cytometry, RT-qPCR and Elisa. The mechanism of CMTM3 regulating macrophages was explored by Western blot. Results: In the mouse MI model, CMTM3 expression was mainly increased in macrophages. CMTM3 deficiency resulted in an enlarged infarct size, increased collagen deposition, and deteriorated cardiac function. Further studies revealed that CMTM3 deficiency promoted macrophage polarization toward M1 types, and increase the production and secretion of inflammatory factors IL-1β, IL-6 and TNF-α. In vitro studies also confirmed CMTM3 deficiency promoted M1 macrophage differentiation and upregulated the expression of inflammatory factors. Mechanistically, CMTM3 can interact with PPARα, CMTM3 deficiency can inhibit PPARα activity, and increase the phosphorylation of NF-κB, thereby promoting macrophage inflammation. Conclusion: CMTM3 inhibits macrophage-related inflammation after MI by activating PPARα and inhibiting NF-κB phosphorylation. This study highlights the anti-inflammatory effect of CMTM3 in MI, and holds that CMTM3 can serve as a new target for improving cardiac remodeling after MI.