Sirtuins regulate macrophage polarization in heart failure: Metabolic reprogramming, epigenetic regulation, and immune cell interactions

ABSTRACT Heart failure (HF) is an end-stage cardiovascular syndrome caused by structural or functional cardiac abnormalities. Its high morbidity and mortality underscore the urgent need for novel therapeutic strategies. In recent years, the dynamic regulatory mechanisms underlying macrophage polarization in the onset and progression of HF have attracted widespread attention. The Sirtuin family, as NAD + -dependent deacetylases, has emerged as a key regulatory factor in reshaping the macrophage polarization phenotype by integrating metabolic reprogramming, epigenetic regulation, and immune cell interactions. This paper systematically elaborates the molecular mechanisms by which Sirtuins (SIRT1-SIRT7) regulate metabolic reprogramming (e.g., glucose metabolism, lipid metabolism, and glutamine metabolism), coordinate epigenetic modifications (e.g., DNA methylation, histone modifications, and non-coding RNA regulation), and mediate interactions between immune cells to dynamically balance macrophage polarization. Furthermore, this review summarizes recent advances in the active components of phytomedicines, such as resveratrol, pterostilbene, astragaloside IV, quercetin, dihydromyricetin, berberine, honokiol, ginsenoside Rc, ginsenoside Rg1, and ginsenoside Rg3, in targeting the Sirtuin–macrophage polarization axis for the prevention and treatment of HF. This review aims to provide a theoretical framework and translational guidance for developing HF-targeted therapeutic strategies based on Sirtuin-mediated macrophage polarization, as well as for the research and development of related natural products.