Ghrelin inhibits FGF-2-mediated angiogenesis in vitro and in vivo.
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.
Conconi
Maria Teresa
MT
Department of Pharmaceutical Sciences, University of Padua, I-35121 Padua, Italy.
Nico
Beatrice
B
Guidolin
Diego
D
Baiguera
Silvia
S
Spinazzi
Raffaella
R
Rebuffat
Piera
P
Malendowicz
Ludwik K
LK
Vacca
Angelo
A
Carraro
Gianni
G
Parnigotto
Pier Paolo
PP
Nussdorfer
Gastone G
GG
Ribatti
Domenico
D
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
D054439:Ghrelin; D036361:Peptide Hormones; D016222:Fibroblast Growth Factor 2