Dynamic regulation of the ‘mitochondria‑immune axis’ in myocardial infarction: Molecular mechanisms driving macrophage polarization through energy metabolism disorders (Review)

The pathological process of myocardial infarction (MI), an acute cardiovascular event that has a high global death and disability rate, includes not only widespread cardiomyocyte necrosis but also intricate reactions like immune system activation and problems with mitochondrial energy metabolism. An increasing body of evidence in recent years has shown that mitochondria are essential for maintaining metabolic homeostasis in cardiomyocytes and for regulating the immune system. After MI, ATP production is impaired, and metabolites such as reactive oxygen species and mitochondrial DNA are released in excess due to mitochondrial structural damage, kinetic imbalance [such as overactivation of dynamin‑related protein 1 (Drp1)], and disruption of the sirtuin (SIRT)3 ‑ AMP‑activated protein kinase ‑ peroxisome proliferative activated receptor γ (PPARγ) coactivator 1α (PGC‑1α) pathway. These factors drive macrophage polarization toward the M1 proinflammatory phenotype via signaling pathways such as Toll‑like receptor 9/NLR family pyrin domain containing 3, thereby aggravating secondary injury to myocardial tissue. However, repair‑phase macrophages can remodel mitochondrial oxidative phosphorylation via the PPARγ/PGC‑1α axis, shifting to an M2‑type phenotype to promote tissue repair, thereby forming a closed loop of ‘metabolic‑immune’ regulation. To improve energy metabolism and the immune microenvironment simultaneously, targeted regulation of the ‘mitochondria‑immunity axis’ (e.g., inhibition of Drp1 hypersegmentation and activation of the SIRT3 antioxidant pathway) may offer a fresh perspective on the accurate treatment of MI. In this review, the key mechanism underlying mitochondrial energy metabolism disorder in cardiomyocytes after MI is described, and the signaling roles and functional shifts of metabolites in macrophage polarization are examined, thereby providing a theoretical basis and targeted new ideas for the precise treatment of MI.