Nerve growth factor–endothelial cell interaction leads to angiogenesis in vitro and in vivo

• Published in: The FASEB journal 2002-08, Vol.16 (10), p.1307-1309
• Main Authors: Cantarella, Giuseppina, Lempereur, Laurence, Presta, Marco, Ribatti, Domenico, Lombardo, Gabriella, Lazarovici, Philip, Zappalà, Giovanna, Pafumi, Carlo, Bernardini, Renato
• Format: Article
• Language: English
• Subjects: Animals; Autocrine Communication; blood vessels; Blood Vessels - anatomy & histology; Blood Vessels - embryology; Cell Division; Cells, Cultured; Chick Embryo; endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - growth & development; Endothelium, Vascular - metabolism; Extraembryonic Membranes - anatomy & histology; Extraembryonic Membranes - blood supply; Extraembryonic Membranes - drug effects; growth factors; Humans; Models, Biological; Neovascularization, Physiologic; Nerve Growth Factor - pharmacology; Nerve Growth Factor - physiology; proliferation; Receptor, Nerve Growth Factor - biosynthesis; Receptor, Nerve Growth Factor - genetics; Receptor, trkA - biosynthesis; Receptor, trkA - genetics; RNA, Messenger - biosynthesis; trkANGFR
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.01-1000fje

ABSTRACT Nerve growth factor (NGF) has important functions during embryonic development and on various tissues and organs under normal and pathological conditions during the extrauterine life. RT‐PCR analysis and immunological methods demonstrate that human umbilical vein endothelial cells (HUVECs) express the NGF receptors trkANGFR and p75NTR. NGF treatment caused a rapid phosphorylation of trkANGFR in HUVECs, determining a parallel increase of phosphorylated ERK1/2. Accordingly, NGF induced a significant increase in HUVEC proliferation that was abolished by the trkANGFR inhibitor K252a. Also, HUVECs express significant levels of NGF under standard culture conditions that were up‐regulated during serum starvation. Endogenous NGF was responsible for the basal levels of trkANGFR and ERK1/2 phosphorylation observed in untreated HUVEC cultures. Finally, NGF exerted a potent, direct, angiogenic activity in vivo when delivered onto the chorioallantoic membrane of the chicken embryo. The data indicate that NGF may play an important role in blood vessel formation in the nervous system and in several pathological processes, including tumors and inflammatory diseases. Unraveling mechanisms of NGF‐dependent angiogenesis could provide valuable tools for novel therapeutic approaches in antiangiogenic therapy.