Macrophage trafficking and efferocytosis in atherosclerotic plaque regression: Molecular mechanisms and therapeutic perspectives.

Abstract

Atherosclerosis is characterized by the accumulation of plaques within arterial walls, with plaque progression and regression being dynamically influenced by macrophage behavior. This review examines the roles of macrophage trafficking and efferocytosis in atherosclerotic plaque regression, with particular emphasis on macrophage retention, egress, and the clearance of apoptotic cells. Retention of macrophages within plaques, mediated by regulators such as Netrin-1 and Semaphorin-3E, contributes to persistent inflammation and impaired plaque resolution. In contrast, macrophage egress through pathways involving CCR7 and CCL19 can promote inflammatory resolution and facilitate the removal of apoptotic cells. Effective efferocytosis is essential for maintaining tissue homeostasis, whereas its dysregulation contributes to continued inflammation and atherosclerosis progression. The review further discusses therapeutic strategies aimed at modulating macrophage behavior, including macrophage polarization, mTOR signaling, LXR activation, cholesterol efflux, and targeted approaches to enhance macrophage function. By integrating these mechanisms, this review highlights the interconnected roles of macrophage trafficking and efferocytosis in plaque regression and discusses their therapeutic potential for the development of strategies to promote atherosclerotic plaque resolution.