Ghrelin inhibits FGF-2-mediated angiogenesis in vitro and in vivo

被引:69
作者
Conconi, MT
Nico, B
Guidolin, D
Baiguera, S
Spinazzi, R
Rebuffat, P
Malendowicz, LK
Vacca, A
Carraro, G
Parnigotto, PP
Nussdorfer, GG
Ribatti, D
机构
[1] Univ Bari, Sch Med, Dept Human Anat & Histol, I-70124 Bari, Italy
[2] Univ Padua, Dept Pharmaceut Sci, I-35121 Padua, Italy
[3] Univ Padua, Sch Med, Dept Human Anat & Physiol, I-35121 Padua, Italy
[4] Poznan Univ Med Sci, Dept Histol & Embryol, PL-60781 Poznan, Poland
[5] Univ Bari, Sch Med, Dept Biomed Sci & Human Oncol, I-70124 Bari, Italy
关键词
angiogenesis; antiangiogenesis; FGF-2; ghrelin; vinblastine;
D O I
10.1016/j.peptides.2004.08.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-LyS(3)-growth hormone releasing peptide-6. FGF-2 stimulated HUVEC cult-wed 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. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:2179 / 2185
页数:7
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