In:
Nature Communications, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2017-03-03)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2041-1723
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2017
detail.hit.zdb_id:
2553671-0
