Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28256515.
- Also identified by DOI 10.1038/ncomms14656 and PMC identifier 5338035.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C<sup>low</sup> and Ly6C<sup>high</sup>) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E<sub>2</sub> 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<sup>low</sup> 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<sup>low</sup> Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE<sub>2</sub>/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6C<sup>low</sup> Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.
Medical subject headings
- Macrophages
- Myocardial Infarction
- Myocardium
- Receptors, Prostaglandin E, EP3 Subtype