Key result
Activating the macrophage PGE2/Ep3 axis promotes post-MI cardiac healing via reparative macrophage recruitment and angiogenesis.
Why the study?
The role of prostaglandin E2 receptors in monocytes/macrophages in cardiac healing after myocardial infarction remains to be determined.
Does targeted overexpression of Ep3 receptors in macrophages improve cardiac healing after myocardial infarction in mice?
Does targeted overexpression of Ep3 receptors in macrophages improve cardiac healing after myocardial infarction in mice?
Activation of the Ep3 receptor in macrophages promotes cardiac healing and angiogenesis after myocardial infarction in mice, suggesting a potential therapeutic target.
Ep3 inhibition remains investigational post-MI; leaves open whether targeting it improves human cardiac recovery.
Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6Clow and Ly6Chigh) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E2 is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6Clow Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signalling and subsequently inhibits Ly6Clow Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE2/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6Clow Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.
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Tang et al. (2017) studied Myocardial infarction. Ep3 receptor activation/overexpression or deletion vs. Wild-type or Ep3F/F controls was evaluated on Cardiac healing (neovascularization, infarct size, and cardiac function) and Ly6Clow macrophage infiltration. Activation of the PGE2/Ep3 axis in macrophages promotes cardiac healing after myocardial infarction by enhancing TGFβ1-mediated recruitment of reparative Ly6Clow macrophages and angiogenesis.
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