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

被引：0

作者：

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

Ying Yu

机构：

[1] Key Laboratory of Food Safety Research,Department of Pharmacology

[2] CAS Center for Excellence in Molecular Cell Science,Division of Biomedical Statistics and Informatics

[3] Institute for Nutritional Sciences,Department of Biomedical Informatics

[4] Shanghai Institutes for Biological Sciences,undefined

[5] Chinese Academy of Sciences,undefined

[6] University of Chinese Academy of Sciences,undefined

[7] School of Basic Medical Sciences,undefined

[8] Tianjin Medical University,undefined

[9] Center for Genomic Sciences,undefined

[10] LKS Faculty of Medicine,undefined

[11] The University of Hong Kong,undefined

[12] School of Life Science,undefined

[13] Chinese University of Hong Kong,undefined

[14] Center for Individualized Medicine,undefined

[15] Mayo Clinic,undefined

[16] Arizona State University,undefined

[17] Scottsdale,undefined

[18] International Institute for Integrative Sleep Medicine (WPI-IIIS),undefined

[19] University of Tsukuba,undefined

来源：

Nature Communications | / 8卷

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摘要：

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.

引用

共 104 条

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