title: Thrombin peptide, TP508, stimulates angiogenic responses in animal models of dermal wound healing, in chick chorioallantoic membranes, and in cultured human aortic and microvascular endothelial cells.
abstract: The alpha-thrombin peptide, TP508, accelerates the healing of full-thickness wounds in both normal and ischemic skin. In wounds treated with TP508, a pattern of increased vascularization is consistently observed both grossly and microscopically when compared to wounds treated with saline. One possible mechanism by which the peptide accelerates wound healing is by promoting revascularization of granulation tissue at the injured site. To evaluate the angiogenic potential of TP508, the peptide was tested in the chick embryo chorioallantoic membrane (CAM), where it increased the density and size of CAM blood vessels relative to controls. Additionally, TP508 stimulated chemokinesis and chemotaxis in a dose-dependent fashion in cultured human aortic and human microvascular endothelial cells. Taken together, these in vivo and in vitro data support an angiogenic role for TP508 in wound healing. A working model is presented to explain how this 23-amino-acid peptide, which lacks proteolytic activity, is generated during wound healing and contributes to the nonproteolytic functions associated with alpha-thrombin during tissue repair.
authors.affiliation: Chrysalis BioTechnology, Inc., 2200 Market Street, Suite 600, Galveston, TX 77550, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Norfleet
authors.forename: J S
authors.initials: JS
authors.lastname: Bergmann
authors.forename: D H
authors.initials: DH
authors.lastname: Carney
mesh_terms: D000482:Allantois / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001011:Aorta; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D008833:Microcirculation / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D023421:Models, Animal; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply*; D013917:Thrombin / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D010446:Peptide Fragments; C412222:rusalatide acetate; D013917:Thrombin