Atherosclerosis is a chronic inflammatory disease driven by persistent immune activation within the vascular wall. While anti-inflammatory therapies have been shown to reduce cardiovascular events, their non-specific immunosuppressive effects underscore the urgent need for targeted approaches that resolve vascular inflammation without impairing host immunity.
Plaque-resident macrophages exhibit remarkable plasticity and can adopt a spectrum of phenotypes ranging from pro-inflammatory to reparative. Emerging evidence suggests that these phenotypic transitions are strongly influenced by local metabolic cues. Metabolic reprogramming can modulate macrophage function, promoting inflammation resolution and tissue repair. Preliminary data from our lab demonstrates that under low-inflammatory conditions, a subset of macrophages expressing smooth muscle cell (SMC) markers such as ACTA2 emerges within stable plaque regions. These cells display enhanced collagen production and express metabolic enzymes involved in energy metabolism, suggesting a role for energy metabolism in driving a reparative, myofibroblast-like phenotype.
