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(Circulation. 2004;110:1121-1127.)
© 2004 American Heart Association, Inc.

Original Articles

Secretoneurin, an Angiogenic Neuropeptide, Induces Postnatal Vasculogenesis

Rudolf Kirchmair, MD; Margot Egger; Dirk H. Walter, MD; Wolfgang Eisterer, MD; Andreas Niederwanger, MD; Ewald Woell, MD; Markus Nagl, MD; Michael Pedrini, MD; Toshinori Murayama, MD PhD; Silke Frauscher; Allison Hanley; Marcy Silver; Marianne Brodmann, MD; Wolfgang Sturm, MD; Reiner Fischer-Colbrie, PhD; Douglas W. Losordo, MD; Josef R. Patsch, MD; Peter Schratzberger, MD

From the Clinical Department of Internal Medicine, Clinical Division of General Internal Medicine (R.K., M.E., W.E., A.N., E.W., M.P., S.F., W.S., J.R.P., P.S.), Department of Pharmacology (R.F.-C.), and Institute of Hygiene and Social Medicine (M.N.), Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Division of Angiology, University Graz, Graz, Austria (M.B.); and Division of Cardiovascular Research (D.H.W., T.M., A.H., M.S., D.W.L.) and Vascular Medicine (D.W.L.), St Elizabeth’s Medical Center–Tufts University School of Medicine, Boston, Mass.

Correspondence to Rudolf Kirchmair, MD, or Peter Schratzberger, MD, Clinical Department of Internal Medicine, Innsbruck Medical University, Anichstr. 35, 6020 Innsbruck, Austria. E-mail rudolf.kirchmair{at}uibk.ac.at or peter.schratzberger@uibk.ac.at

Received December 30, 2003; revision received April 6, 2004; accepted April 8, 2004.

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.

Key Words: angiogenesis • endothelium • nervous system

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