Metabolic Perspective on Atherosclerosis: Macrophage Reprogramming and Novel Therapeutic Targets

Atherosclerosis is a chronic inflammatory disease driven by metabolic disorders, and macrophages play a central role in their occurrence and development. Macrophages are not static; their functional polarization and fate decisions are highly regulated by metabolic signals from the microenvironment, a process known as metabolic reprogramming. This review systematically reviews the latest progress in the metabolic reprogramming of glucose, lipids, and mitochondria in atherosclerosis, focusing on how key metabolites such as glycolysis, pentose phosphate pathway, cholesterol/sphingolipid metabolism, gut microbiota derivatives, and oxaloacetate dynamically regulate the inflammatory phenotype, foam cell formation, and immune response of macrophages. This review also delves into new concepts such as trained immunity and analyzes the therapeutic potential of targeting these metabolic pathways, aiming to comprehensively reveal the core role of metabolic-immune cross-talk in atherosclerosis and provide a theoretical basis for developing new strategies for diagnosing and treating atherosclerosis based on macrophage metabolic reprogramming.