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Nerve growth factor–endothelial cell interaction leads to angiogenesis in vitro and in vivo
Author(s) -
Cantarella Giuseppina,
Lempereur Laurence,
Presta Marco,
Ribatti Domenico,
Lombardo Gabriella,
Lazarovici Philip,
Zappalà Giovanna,
Pafumi Carlo,
Bernardini Renato
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-1000fje
Subject(s) - nerve growth factor , tropomyosin receptor kinase a , angiogenesis , chorioallantoic membrane , neurotrophin , umbilical vein , trk receptor , in vivo , low affinity nerve growth factor receptor , endocrinology , biology , medicine , microbiology and biotechnology , cancer research , in vitro , receptor , biochemistry
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 trkA NGFR and p75 NTR . NGF treatment caused a rapid phosphorylation of trkA NGFR in HUVECs, determining a parallel increase of phosphorylated ERK1/2. Accordingly, NGF induced a significant increase in HUVEC proliferation that was abolished by the trkA NGFR 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 trkA NGFR 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.