title: Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction.
abstract: Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6Clowand Ly6Chigh) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E2is 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 Ly6ClowMos/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 Ly6ClowMos/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 Ly6ClowMos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.
authors.affiliation: Key Laboratory of Food Safety Research, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.|Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Guilin
authors.initials: G
authors.lastname: Chen
authors.affiliation: Key Laboratory of Food Safety Research, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Qiangyou
authors.initials: Q
authors.lastname: Wan
authors.affiliation: Key Laboratory of Food Safety Research, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Key Laboratory of Food Safety Research, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.|Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, 5 Sassoon Road, Hong Kong, SAR 999077, China.|School of Life Science, Chinese University of Hong Kong, Hong Kong, SAR 999077, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.affiliation: Key Laboratory of Food Safety Research, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Guizhu
authors.initials: G
authors.lastname: Liu
authors.affiliation: Key Laboratory of Food Safety Research, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shengkai
authors.initials: S
authors.lastname: Zuo
authors.affiliation: Key Laboratory of Food Safety Research, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tao
authors.affiliation: Key Laboratory of Food Safety Research, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Center for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, 5 Sassoon Road, Hong Kong, SAR 999077, China.|Division of Biomedical Statistics and Informatics, Center for Individualized Medicine, Mayo Clinic, Scottsdale, Arizona 85259, USA.|Department of Biomedical Informatics, Arizona State University, Scottsdale, Arizona 85259, USA.
authors.forename: Junwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba City, Ibaraki 305-8575, Japan.
authors.forename: Michael
authors.identifier: 0000-0003-3863-4474
authors.initials: M
authors.lastname: Lazarus
authors.affiliation: Key Laboratory of Food Safety Research, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.|Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1 / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D015870:Gene Expression; D008264:Macrophages / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000235:genetics / Q000378:metabolism*; D020127:Recovery of Function; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D058308:Receptors, Prostaglandin E, EP3 Subtype; D042461:Vascular Endothelial Growth Factor A