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

被引：45

作者：

Tang, Juan ^{[1
,2
]}

Shen, Yujun ^{[2
]}

Chen, Guilin ^{[2
]}

Wan, Qiangyou ^{[1
]}

Wang, Kai ^{[1
]}

Zhang, Jian ^{[1
,2
]}

Qin, Jing ^{[3
,4
]}

Liu, Guizhu ^{[1
]}

Zuo, Shengkai ^{[1
]}

Tao, Bo ^{[1
]}

Yu, Yu ^{[1
]}

Wang, Junwen ^{[3
,5
,6
]}

Lazarus, Michael ^{[7
]}

Yu, Ying ^{[1
,2
]}

机构：

[1] Univ Chinese Acad Sci, Chinese Acad Sci, Key Lab Food Safety Res, Inst Nutr Sci,Shanghai Inst Biol Sci,CAS Ctr Exce, Shanghai 200031, Peoples R China

[2] Tianjin Med Univ, Sch Basic Med Sci, Dept Pharmacol, Tianjin 300070, Peoples R China

[3] Univ Hong Kong, Ctr Genom Sci, LKS Fac Med, 5 Sassoon Rd, Hong Kong 999077, Hong Kong, Peoples R China

[4] Chinese Univ Hong Kong, Sch Life Sci, Hong Kong 999077, Hong Kong, Peoples R China

[5] Mayo Clin, Ctr Individualized Med, Div Biomed Stat & Informat, Scottsdale, AZ 85259 USA

[6] Arizona State Univ, Dept Biomed Informat, Scottsdale, AZ 85259 USA

[7] Univ Tsukuba, Int Inst Integrat Sleep Med WPI IIIS, Tsukuba, Ibaraki 3058575, Japan

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

中国国家自然科学基金;

关键词：

PROSTAGLANDIN E-2 SYNTHASE-1; GENE-EXPRESSION; CELLS IMPAIRS; MONOCYTES; SIZE; INCREASES; ISCHEMIA; INJURY; MICE; OVEREXPRESSION;

D O I：

10.1038/ncomms14656

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 TGFb1 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.

引用

页数：14

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