title: Injectable PLGA microspheres encapsulating WKYMVM peptide for neovascularization.
abstract: Formyl peptide receptor-2 (FPR-2) is expressed in various cell types, such as phagocytes, fibroblasts, and endothelial cells. FPR-2 has been reported to play a significant role in inflammation and angiogenic response, and synthetic WKYMVm peptide has been identified as a novel peptide agonist for the FPR-2. In this study, we demonstrate that WKYMVm peptides stimulate the angiogenic potential of outgrowth endothelial cells (OECs). Upon WKYMVm peptide exposure, migration and proliferation of OECs were stimulated. WKYMVm effectively stimulated angiogenesis in tube formation assay and aortic ring assay. Furthermore, we fabricated injectable poly (lactide-co-glycolide) (PLGA) microspheres encapsulating WKYMVm peptides, which showed sustained release of cargo molecule. When WKYMVm peptide encapsulated microspheres were injected into the hind limb ischemia model, a single injection of microspheres was as effective as multiple injections of WKYMVm peptide in restoring blood flow from ischemic injury and promoting capillary growth. These results demonstrate that sustained release of WKYMVm peptide from microspheres in the application to ischemic hind limb extended angiogenic stimulation.
  
  
  CONCLUSIONS
  Formyl peptide receptor (FPR) has been reported to play an important role in inflammation and angiogenic response. A synthetic WKYMVm peptide has been identified as a novel peptide activating the FPR-2 that is expressed in a various cell types, such as phagocytes, fibroblasts, and endothelial cells. In this manuscript we explored a unique property of high-affinity ligand for formyl peptide receptors-2 (FPR-2) (i.e., WKYMVm). WKYMVm-induced activation of FPR2 has been reported to be crucial in host defense and inflammation by activation of phagocytes, monocytes, and lymphocytes. In this study, highlight the efficacy of WKYMVm peptide's role in inducing neovascularization in vivo hind limb ischemia model when the peptide was released from injected PLGA microspheres in sustained manner. Our results demonstrate that sustained release of WKYMVm peptide from microspheres have extended angiogenic stimulation capacity.
authors.affiliation: School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Young Hwan
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
authors.forename: Soon Chul
authors.initials: SC
authors.lastname: Heo
authors.affiliation: Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
authors.forename: Yang Woo
authors.initials: YW
authors.lastname: Kwon
authors.affiliation: School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Hwan D
authors.initials: HD
authors.lastname: Kim
authors.affiliation: School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Seung Hyun L
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
authors.forename: Il Ho
authors.initials: IH
authors.lastname: Jang
authors.affiliation: Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea. Electronic address: jhkimst@gmail.com.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 152-742, Republic of Korea; N-Bio Institute, Seoul National University, Seoul 152-742, Republic of Korea. Electronic address: nshwang@snu.ac.kr.
authors.forename: Nathaniel S
authors.initials: NS
authors.lastname: Hwang
mesh_terms: D000818:Animals; D001011:Aorta / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004655:Emulsions; D005786:Gene Expression Regulation / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D066298:In Vitro Techniques; D007267:Injections; D007511:Ischemia / Q000473:pathology; D019344:Lactic Acid / Q000737:chemistry*; D023821:Limb Salvage; D008297:Male; D008807:Mice, Inbred BALB C; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D009842:Oligopeptides / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D004655:Emulsions; D009842:Oligopeptides; C113617:Trp-Lys-Tyr-Met-Val-Met; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Drug delivery; Neovascularization; Outgrowth endothelial cells; PLGA microsphere; WKYMVm peptide