Role of prostaglandin E2 in macrophage polarization: Insights into atherosclerosis

Atherosclerosis, a trigger of cardiovascular disease, poses grave threats to human health. Although atherosclerosis depends on lipid accumulation and vascular wall inflammation, abnormal phenotypic regulation of macrophages is considered the pathological basis of atherosclerosis. Macrophage polarization mainly refers to the transformation of macrophages into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, which has recently become a much-discussed topic. Increasing evidence has shown that M2 macrophage polarization can alleviate atherosclerosis progression. PGE₂ is a bioactive lipid that has been observed to be elevated in atherosclerosis and to play a pro-inflammatory role, yet recent studies have reported that PGE₂ promotes anti-inflammatory M2 macrophage polarization and mitigates atherosclerosis progression. However, the mechanisms by which PGE₂ acts remain unclear. This review summarizes current knowledge of PGE₂ and macrophages in atherosclerosis. Additionally, we discuss potential PGE₂ mechanisms of macrophage polarization, including CREB, NF-κB, and STAT signaling pathways, which may provide important therapeutic strategies based on targeting PGE₂ pathways to modulate macrophage polarization for atherosclerosis treatment.