title: Ghrelin inhibits FGF-2-mediated angiogenesis in vitro and in vivo.
abstract: Recent evidence indicates that ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), is highly expressed in the cardiovascular system, and in this study we addressed the possibility that ghrelin may affect angiogenesis in vitro and in vivo. Reverse transcription-polymerase chain reaction showed that human umbilical vein endothelial cells (HUVECs) express ghrelin and GHS-R mRNAs. Ghrelin inhibited FGF-2-induced proliferation of HUVECs cultured in vitro, the maximal effective concentration being 10(-8) M, and this effect was annulled by the GHS-R antagonist D-Lys3-growth hormone releasing peptide-6. FGF-2 stimulated HUVEC cultured on Matrigel to form capillary-like structures, and ghrelin (10(-8) M) suppressed this effect. In the chick embryo chorioallantoic membrane in vivo assay, FGF-2 induced a strong angiogenic response, which was counteracted by ghrelin (500 ng). Taken together, these findings suggest that ghrelin acts as an angiostatic molecule and indicate that its activity is comparable to that of a well-known angiostatic agent, i.e., vinblastine. The antiangiogenic activity of ghrelin deserves further investigations, alone or together with other antiangiogenic agents, for the treatment of pathological conditions characterized by enhanced angiogenesis.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padua, I-35121 Padua, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Conconi
authors.forename: Beatrice
authors.initials: B
authors.lastname: Nico
authors.forename: Diego
authors.initials: D
authors.lastname: Guidolin
authors.forename: Silvia
authors.initials: S
authors.lastname: Baiguera
authors.forename: Raffaella
authors.initials: R
authors.lastname: Spinazzi
authors.forename: Piera
authors.initials: P
authors.lastname: Rebuffat
authors.forename: Ludwik K
authors.initials: LK
authors.lastname: Malendowicz
authors.forename: Angelo
authors.initials: A
authors.lastname: Vacca
authors.forename: Gianni
authors.initials: G
authors.lastname: Carraro
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Parnigotto
authors.forename: Gastone G
authors.initials: GG
authors.lastname: Nussdorfer
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
mesh_terms: D000818:Animals; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D054439:Ghrelin; D006801:Humans; D008858:Microscopy, Phase-Contrast; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D036361:Peptide Hormones / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054439:Ghrelin; D036361:Peptide Hormones; D016222:Fibroblast Growth Factor 2