Activation of E-Prostanoid 3 Receptor in Macrophages Facilitates Cardiac Healing After Myocardial Infarction
Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6Clow and Ly6Chi) 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 signaling 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.
- Author (aut): Tang, Juan
- Author (aut): Shen, Yujun
- Author (aut): Chen, Guilin
- Author (aut): Wan, Qiangyou
- Author (aut): Wang, Kai
- Author (aut): Zhang, Jian
- Author (aut): Qin, Jing
- Author (aut): Liu, Guizhu
- Author (aut): Zuo, Shengkai
- Author (aut): Tao, Bo
- Author (aut): Yu, Yu
- Author (aut): Wang, Junwen
- Author (aut): Lazarus, Michael
- Author (aut): Yu, Ying
- Contributor (ctb): College of Health Solutions