Future treatments need to target both immune cell metabolic adaptations and endothelial repair mechanisms to break the vicious cycle of inflammation, achieve plaque stabilization or even reversal, and modulate immune metabolism: inhibiting glycolysis (e.g., 2DG, metformin) or enhancing OXPHOS (e.g., PPARγ agonists), However, due to systemic side effects such as hepatic steatosis and heart failure, the treatment of AS with PPARγ agonists remains challengingto promote anti-inflammatory phenotypes (Sandhu et al., 2024). The gene discussed is PPARG; the disease is heart failure.