Vasohibin inhibits angiogenic sprouting in vitro and supports vascular maturation processes in vivo.
BACKGROUND
The murine homologue of human vasohibin (mVASH1), a putative antiangiogenic protein, was investigated for its effects on in vitro and in vivo angiogenesis.


METHODS
Cell growth and migration were analyzed in murine fibroblasts, smooth muscle cells and endothelial cells. Angiogenic sprouting was studied in human umbilical vein endothelial cells (HUVECs) in the spheroid sprouting assay. In vivo effects on blood vessel formation were investigated in the chorioallantoic membrane (CAM) assay and in the C57BL/6 melanoma xenograft model.


RESULTS
Purified murine and human VASH1 protein induced apoptosis of murine fibroblasts in vitro, but not of vascular aortic smooth muscle cells (AoSMC) or endothelial cells. Adenoviral overexpression of murine and human VASH1 inhibited capillary sprouting of HUVECs in the spheroid assay. Administration of recombinant murine and human VASH1 inhibited growth of large vessels in the CAM assay and promoted the formation of a dense, fine vascular network. Murine VASH1-overexpressing B16F10 melanomas displayed a reduction in large vessels and vascular area. Moreover, tumors showed more microvessels that stained positive for the mural cell markers alpha-smooth muscle cell actin (ASMA) and proteoglycan (NG2).


CONCLUSIONS
Our data imply that murine VASH1 causes angiogenic remodelling by inhibiting angiogenic sprouting and large vessel growth, thereby supporting the formation of a vascular bed consisting predominantly of mature microvessels.
Kern
Johann
J
Division of Internal Medicine V, Tumor Biology & Angiogenesis Laboratory, Medical University Innsbruck, Innrain 66, A-6020 Innsbruck, Austria. johann.kern@i-med.ac.at
Steurer
Michael
M
Gastl
Günther
G
Gunsilius
Eberhard
E
Untergasser
Gerold
G
D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001808:Blood Vessels / Q000254:growth & development* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply* / Q000378:metabolism; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000254:growth & development / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D018874:Spheroids, Cellular; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D018797:Cell Cycle Proteins; C493181:VASH1 protein, human
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