Secretoneurin, an angiogenic neuropeptide, induces postnatal vasculogenesis.
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.


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.
Clinical Department of Internal Medicine, Clinical Division of General Internal Medicine, Innsbruck Medical University, Innsbruck, Austria.
Rudolf
R
Kirchmair
Margot
M
Egger
Dirk H
DH
Walter
Wolfgang
W
Eisterer
Andreas
A
Niederwanger
Ewald
E
Woell
Markus
M
Nagl
Michael
M
Pedrini
Toshinori
T
Murayama
Silke
S
Frauscher
Allison
A
Hanley
Marcy
M
Silver
Marianne
M
Brodmann
Wolfgang
W
Sturm
Reiner
R
Fischer-Colbrie
Douglas W
DW
Losordo
Josef R
JR
Patsch
Peter
P
Schratzberger
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D016510:Corneal Neovascularization / Q000188:drug therapy; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007763:Lac Operon; D020935:MAP Kinase Signaling System / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D011828:Radiation Chimera; D051381:Rats; D042787:Receptor, TIE-2 / Q000235:genetics; D053381:Secretogranin II; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D005419:Flavonoids; D009479:Neuropeptides; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D053381:Secretogranin II; D042461:Vascular Endothelial Growth Factor A; C081159:secretoneurin; D042787:Receptor, TIE-2; C494918:AKT1 protein, human; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin