(1) Background: The activation of sequential processes for the formation of permanent fibrotic tissue following myocardial infarction (MI) is pivotal for optimal healing of heart tissue. M1 and M2 macrophages are known to play essential roles in wound healing by the activation of cardiac fibroblasts after an episode of MI. However, the molecular and cellular mechanisms mediated by these macrophages in cellular proliferation, fibrosis, and wound healing remain unclear. (2) Methods: In the present study, we aimed to explore the mechanisms by which M1 and M2 macrophages contribute to cellular proliferation, fibrosis, and wound healing. Using both in vivo and cellular models, we examined the remodeling effects of M1 and M2 macrophages on infarcted cardiac fibroblasts and their role in promoting cardiac healing post-MI. (3) Results: Our findings indicate that M1 macrophages induce a proliferative effect on infarcted cardiac fibroblasts by exerting an anti-apoptotic effect, thereby preventing cell death. Moreover, M1 macrophages were found to activate the mechanism of epithelial-to-mesenchymal transition (EMT), resulting in wound healing and inducing the fibrotic process. The present findings suggest that M1 macrophages play a crucial role in promoting cardiac remodeling post-MI, as they activate the EMT pathway and contribute to increased collagen production and fibrotic changes. (4) Conclusions: The present study provides insights into molecular and cellular mechanisms mediated by M1 and M2 macrophages in cellular proliferation, fibrosis, and wound healing post-MI. Our findings highlight the critical role of M1 macrophages in promoting cardiac remodeling by activating the EMT pathway. Understanding these mechanisms can potentially result in the development of targeted therapies aimed at enhancing the healing process and improving outcomes following MI.
Keywords: M1 macrophages; M2 macrophages; cardiovascular disease; epithelial-to-mesenchymal transition; myocardial infarction.