Metabolic Reprogramming Intermediates of Glucose Regulate Macrophage Polarization: An Important Direction for Ameliorating Pulmonary Vascular Remodeling

Pulmonary vascular remodeling (PVR) is a key pathological basis for various lung diseases and is centered on macrophage-driven pathological vascular remodeling. Macrophage functional polarization is closely related to metabolic reprogramming, a process that not only encompasses energy supply but also dictates cellular function through metabolic intermediates. To bridge the knowledge gap between metabolic regulation and clinical translation in PVR, this review focuses on key metabolites produced during glucose metabolism: pyruvate, citrate, succinate, and itaconate. These intermediates are not merely metabolic byproducts; rather, they directly influence the pathological processes of vascular endothelial cells, smooth muscle cells, and the extracellular matrix by modulating the polarization of macrophages. This review systematically elucidates the precise regulatory mechanisms of these metabolic signals, with the aim of providing new diagnostic and therapeutic targets for PVR. It emphasizes the immense potential of targeting metabolic intermediates for future precision medicine, ultimately promoting a paradigm shift in PVR therapy from traditional anti-proliferative interventions to an innovative model based on metabolic reprogramming.