Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction

Ying Yu; Juan Tang; Yujun Shen; Guilin Chen; Qiangyou Wan; Kai Wang; Jian Zhang; Jing Qin; Guizhu Liu; Shengkai Zuo; Bo Tao; Yu Yu; Junwen Wang; Michael Lazarus

doi:10.1038/ncomms14656

Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction

Ying Yu, Juan Tang, Yujun Shen, Guilin Chen, Qiangyou Wan, Kai Wang, Jian Zhang, Jing Qin, Guizhu Liu, Shengkai Zuo, Bo Tao, Yu Yu, Junwen Wang, Michael Lazarus

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Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C_low and Ly6C_high) 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 Ly6C_low 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 Ly6C_low 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 Ly6C_low Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.

Original language	English (US)
Article number	14656
Journal	Nature communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms14656
State	Published - Mar 3 2017

ASJC Scopus subject areas

Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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10.1038/ncomms14656

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title = "Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction",

abstract = "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.",

author = "Ying Yu and Juan Tang and Yujun Shen and Guilin Chen and Qiangyou Wan and Kai Wang and Jian Zhang and Jing Qin and Guizhu Liu and Shengkai Zuo and Bo Tao and Yu Yu and Junwen Wang and Michael Lazarus",

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doi = "10.1038/ncomms14656",

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AU - Yu, Ying

AU - Tang, Juan

AU - Shen, Yujun

AU - Chen, Guilin

AU - Wan, Qiangyou

AU - Wang, Kai

AU - Zhang, Jian

AU - Qin, Jing

AU - Liu, Guizhu

AU - Zuo, Shengkai

AU - Tao, Bo

AU - Yu, Yu

AU - Wang, Junwen

AU - Lazarus, Michael

PY - 2017/3/3

Y1 - 2017/3/3

N2 - 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.

AB - 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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Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction

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