1. Secretoneurin, an Angiogenic Neuropeptide, Induces Postnatal Vasculogenesis
- Author
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Marcy Silver, Allison Hanley, Toshinori Murayama, Ewald Woell, Michael T. Pedrini, Douglas W. Losordo, Marianne Brodmann, Wolfgang Sturm, Josef R. Patsch, Dirk H. Walter, Margot Egger, Markus Nagl, Rudolf Kirchmair, Peter Schratzberger, Silke Frauscher, Reiner Fischer-Colbrie, Andreas Niederwanger, and Wolfgang Eisterer
- Subjects
Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Endothelium ,MAP Kinase Signaling System ,Angiogenesis ,Apoptosis ,Mice, Inbred Strains ,Mice, Transgenic ,Protein Serine-Threonine Kinases ,Biology ,Mice ,chemistry.chemical_compound ,Vasculogenesis ,Proto-Oncogene Proteins ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Humans ,Corneal Neovascularization ,Progenitor cell ,Cells, Cultured ,Bone Marrow Transplantation ,Phosphoinositide-3 Kinase Inhibitors ,Flavonoids ,Secretoneurin ,Chemotaxis ,Neuropeptides ,Mesenchymal Stem Cells ,Flow Cytometry ,Hematopoietic Stem Cells ,Receptor, TIE-2 ,Rats ,Cell biology ,Androstadienes ,Endothelial stem cell ,Vascular endothelial growth factor ,medicine.anatomical_structure ,Endocrinology ,Lac Operon ,chemistry ,Secretogranin II ,Radiation Chimera ,Stem cell ,Wortmannin ,Cardiology and Cardiovascular Medicine ,Proto-Oncogene Proteins c-akt ,Signal Transduction - 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
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