Dynamic Regulation of Macrophage Polarization in Acute Myocardial Infarction and Its Therapeutic Potential

Acute myocardial infarction (AMI) remains one of the leading causes of mortality and disability worldwide, involving complex immune and inflammatory responses. Among these, macrophages play a pivotal role as key immune cells. The polarization state of macrophages determines their function in both myocardial injury and repair. In the early phase of AMI, M1 macrophages promote inflammation and facilitate the clearance of necrotic tissue by releasing pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). However, excessive or prolonged M1 polarization may contribute to myocardial fibrosis and further deterioration of cardiac function. In contrast, M2 macrophages promote tissue repair and anti-inflammatory responses in the later phase by secreting anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), thereby reducing fibrosis and facilitating myocardial remodeling. This review summarizes the dynamic changes in macrophage polarization during AMI and elaborates on their roles in myocardial injury, inflammation, and tissue repair. Furthermore, it highlights recent advances in therapeutic strategies aimed at modulating macrophage polarization to improve AMI outcomes, including mTOR inhibitors, sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and gene-editing technologies such as CRISPR/Cas9. Overall, this review underscores the importance of regulating macrophage polarization, particularly the transition from M1 to M2, as a promising therapeutic target for AMI. Modulating macrophage function may provide novel insights into enhancing myocardial repair and preventing adverse cardiac events.