1. Secretoneurin, an angiogenic neuropeptide, induces postnatal vasculogenesis.
- Author
-
Kirchmair R, Egger M, Walter DH, Eisterer W, Niederwanger A, Woell E, Nagl M, Pedrini M, Murayama T, Frauscher S, Hanley A, Silver M, Brodmann M, Sturm W, Fischer-Colbrie R, Losordo DW, Patsch JR, and Schratzberger P
- Subjects
- Androstadienes pharmacology, Animals, Apoptosis drug effects, Bone Marrow Transplantation, Cells, Cultured cytology, Cells, Cultured drug effects, Chemotaxis drug effects, Flavonoids pharmacology, Flow Cytometry, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells drug effects, Humans, Lac Operon, MAP Kinase Signaling System drug effects, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells drug effects, Mice, Mice, Inbred Strains, Mice, Transgenic, Neuropeptides pharmacology, Phosphoinositide-3 Kinase Inhibitors, Protein Serine-Threonine Kinases physiology, Proto-Oncogene Proteins physiology, Proto-Oncogene Proteins c-akt, Radiation Chimera, Rats, Receptor, TIE-2 genetics, Secretogranin II, Signal Transduction drug effects, Vascular Endothelial Growth Factor A pharmacology, Wortmannin, Corneal Neovascularization drug therapy, Neuropeptides physiology
- Abstract
Background: Induction of postnatal vasculogenesis, the mobilization of bone marrow-derived endothelial progenitor cells and incorporation of these cells into sites of blood vessel formation, is a well-known feature of angiogenic cytokines such as vascular endothelial growth factor. We hypothesized that the angiogenic neuropeptide secretoneurin induces this kind of neovascularization., Methods and Results: Secretoneurin induced mobilization of endothelial progenitor cells to sites of vasculogenesis in vivo in the cornea neovascularization assay. Progenitor cells were incorporated into vascular structures or were located adjacent to them. Systemic injection of secretoneurin led to increase of circulating stem cells and endothelial progenitor cells. In vitro secretoneurin induced migration, exerted antiapoptotic effects, and increased the number of these cells. Furthermore, secretoneurin stimulated the mitogen-activated protein kinase system, as shown by phosphorylation of extracellular signal-regulated kinase, and activated the protein kinase B/Akt pathway. Activation of mitogen-activated protein kinase was necessary for increase of cell number and migration, whereas Akt seemed to play a role in migration of endothelial progenitor cells., Conclusions: These data show that the angiogenic neuropeptide secretoneurin stimulates postnatal vasculogenesis by mobilization, migration, and incorporation of endothelial progenitor cells.
- Published
- 2004
- Full Text
- View/download PDF