Prostaglandin E 2 Receptor 2 Modulates Macrophage Activity for Cardiac Repair

Background-—Prostaglandin E2 has long been known to be an immune modulator. It is released after tissue injury and plays a role in modulating macrophage activities, which are essential for tissue regeneration. However, the involvement of prostaglandin E2 receptor 2 (EP2)–dependent regulation of macrophages in postischemic heart is unclear. This study aims to evaluate the role of EP2 in damaged heart. Methods and Results-—The effect of EP2 in postischemic heart was evaluated using EP2-deficient transgenic mice. We demonstrated that cardiac function was worse after myocardial injury on loss of EP2. Furthermore, EP2 deficiency also altered proinflammatory response and resulted in a defect in macrophage recruitment to the injured myocardium. Transcriptome analysis revealed that the expression of erythroid differentiation regulator 1 (Erdr1) was significantly induced in EP2-deficient macrophages. Knocking down Erdr1 expression restored migration ability of EP2-deficient cells both in vitro and in vivo. By using a genetic fate- mapping approach, we showed that abolishment of EP2 expression effectively attenuated cell replenishment. Conclusions-—The EP2-dependent signaling pathway plays a critical role in regulating macrophage recruitment to the injured myocardium, thereby exerting a function in modulating the inflammatory microenvironment for cardiac repair.