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

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C(low) and Ly6C(high)) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E(2) is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing r...

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Autores principales: Tang, Juan, Shen, Yujun, Chen, Guilin, Wan, Qiangyou, Wang, Kai, Zhang, Jian, Qin, Jing, Liu, Guizhu, Zuo, Shengkai, Tao, Bo, Yu, Yu, Wang, Junwen, Lazarus, Michael, Yu, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338035/
https://www.ncbi.nlm.nih.gov/pubmed/28256515
http://dx.doi.org/10.1038/ncomms14656
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author Tang, Juan
Shen, Yujun
Chen, Guilin
Wan, Qiangyou
Wang, Kai
Zhang, Jian
Qin, Jing
Liu, Guizhu
Zuo, Shengkai
Tao, Bo
Yu, Yu
Wang, Junwen
Lazarus, Michael
Yu, Ying
author_facet Tang, Juan
Shen, Yujun
Chen, Guilin
Wan, Qiangyou
Wang, Kai
Zhang, Jian
Qin, Jing
Liu, Guizhu
Zuo, Shengkai
Tao, Bo
Yu, Yu
Wang, Junwen
Lazarus, Michael
Yu, Ying
author_sort Tang, Juan
collection PubMed
description Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C(low) and Ly6C(high)) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E(2) 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 PGE(2)/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.
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spelling pubmed-53380352017-03-09 Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction Tang, Juan Shen, Yujun Chen, Guilin Wan, Qiangyou Wang, Kai Zhang, Jian Qin, Jing Liu, Guizhu Zuo, Shengkai Tao, Bo Yu, Yu Wang, Junwen Lazarus, Michael Yu, Ying Nat Commun Article Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C(low) and Ly6C(high)) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E(2) 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 PGE(2)/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. Nature Publishing Group 2017-03-03 /pmc/articles/PMC5338035/ /pubmed/28256515 http://dx.doi.org/10.1038/ncomms14656 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Tang, Juan
Shen, Yujun
Chen, Guilin
Wan, Qiangyou
Wang, Kai
Zhang, Jian
Qin, Jing
Liu, Guizhu
Zuo, Shengkai
Tao, Bo
Yu, Yu
Wang, Junwen
Lazarus, Michael
Yu, Ying
Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction
title Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction
title_full Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction
title_fullStr Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction
title_full_unstemmed Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction
title_short Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction
title_sort activation of e-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338035/
https://www.ncbi.nlm.nih.gov/pubmed/28256515
http://dx.doi.org/10.1038/ncomms14656
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