Objectives Atherosclerosis is currently considered to be a chronic inﬂammatory disease. Prostaglandin E receptors (EPs) are the G-protein-coupled receptors that respond to prostaglandin E2 (PGE2). Data has shown that PGE2 may function as an endogenous anti-inﬂammatory mediator by suppressing the production of cytokines. However, other studies have demonstrated that PGE2, a pro-inﬂammatory mediator produced by various cell types within the wounded vascular wall, plays a crucial role in atherosclerotic development. These contradictory results may be due to the versatility of EPs.
Methods Experimental data suggest an individual role for each PGE2 receptor in atherosclerosis.
Results The expression of EP1 was enhanced in the inﬂammatory region of human atherosclerotic plaques. Activation of the EP2 receptor and subsequent elevation of cAMP levels by PGE2 induces monocytes/macrophages to accumulate in the sub-endothelial space. By activating the EP3 receptors and subsequently inhibiting the cAMP-dependent pathway, pGE2 promotes platelet aggregation and contributes to atherothrombosis. PGE2-EP4 signalling crucially contributes to the anti-inﬂammatory function of macrophages by inhibiting the NF-κB and MAPK pathways. However, the activation of the EP4 receptor promotes macrophage survival through the PI3K/Akt and NF-κB signalling pathways.
Conclusions Regardless of the function of EPs as pro-inﬂammatory or anti-inﬂammatory mediators, pGE2 -EPs signalling has been indicated as a possible therapeutic strategy to modulate the development of atherosclerosis and plaque stability.
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