Formyl Peptide Receptor 2 Is Involved in Cardiac Repair After Myocardial Infarction Through Mobilization of Circulating Angiogenic Cells.

Abstract

Increasing evidence suggests that circulating angiogenic cells (CACs) promote repair of ischemic tissues. Activation of formyl peptide receptor 2 (Fpr2) has been reported to stimulate repair of ischemic heart. This study was conducted to investigate the role of Fpr2 on CAC mobilization and cardiac protection in myocardial infarction (MI). WKYMVm, a strong agonist for Fpr2, was administered in a murine model of acute MI, and mobilization of CACs including endothelial progenitor cells (CD34+ Flk1+ or Sca1+ Flk1+ cells) in peripheral blood was monitored. CAC mobilization by daily injection of WKYMVm for the first 4 days after MI was as efficient as granulocyte colony-stimulating factor and provided myocardial protection from apoptosis with increased vascular density and preservation of cardiac function. Transplantation of bone marrow (BM) from green fluorescent protein mice showed that BM-derived cells homed to ischemic heart after WKYMVm treatment and contributed to tissue protection. Transplantation of BM from Fpr2 knockout mice showed that Fpr2 in BM cells is critical in mediation of WKYMVm-stimulated myocardial protection and neovascularization after MI. These results suggest that activation of Fpr2 in BM after WKYMVm treatment provides cardiac protection through mobilization of CACs after MI, which may lead to the development of a new clinical protocol for treating patients with ischemic heart conditions. Stem Cells 2017;35:654-665.

• Authors: Soon Chul Heo, Yang Woo Kwon, Il Ho Jang, Geun Ok Jeong, Tae Wook Lee, Jung Won Yoon, Ho Jin Shin, Hae Chang Jeong, Youngkeun Ahn, Tae Hee Ko, Sang Chul Lee, Jin Han, Jae Ho Kim
• Journal: Stem cells (Dayton, Ohio) (Stem Cells) Vol. 35 Issue 3 Pg. 654-665 (03 2017) ISSN: 1549-4918 [Electronic] England
• PMID: 27790799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 AlphaMed Press.

Chemical References

• Cardiotonic Agents
• Oligopeptides
• Receptors, Formyl Peptide
• Trp-Lys-Tyr-Met-Val-Met

Topics

• Animals
• Bone Marrow Cells (drug effects, metabolism)
• Cardiotonic Agents (pharmacology)
• Endothelial Progenitor Cells (cytology, drug effects, metabolism)
• Heart Function Tests
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Myocardial Infarction (metabolism, pathology, physiopathology)
• Neovascularization, Physiologic (drug effects)
• Oligopeptides (pharmacology)
• Receptors, Formyl Peptide (metabolism)
• Regeneration (drug effects)