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Nerve growth factor-induced migration of endothelial cells
Journal article   Peer reviewed

Nerve growth factor-induced migration of endothelial cells

Jean-Pierre Dollé, Amir Rezvan, Fred D Allen, Philip Lazarovici and Peter I Lelkes
The Journal of pharmacology and experimental therapeutics, v 315(3), pp 1220-1227
Dec 2005
DOI: https://doi.org/10.1124/jpet.105.093252
PMID: 16123305
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Adrenal Medulla - cytology Animals Aorta - cytology Carbazoles - pharmacology Cell Line Cell Movement - drug effects Dose-Response Relationship, Drug Drug Interactions Endothelial Cells - cytology Endothelial Cells - drug effects Endothelium, Vascular - cytology Enzyme Inhibitors - pharmacology Fibroblast Growth Factor 2 - genetics Fibroblast Growth Factor 2 - pharmacology Humans Indole Alkaloids Indoles - pharmacology Mice Models, Biological Nerve Growth Factor - analysis Nerve Growth Factor - genetics Nerve Growth Factor - pharmacology Pyrroles - pharmacology Rats Receptor, Nerve Growth Factor - drug effects Receptor, trkA - antagonists & inhibitors Recombinant Proteins - pharmacology Reproducibility of Results Time Factors Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - pharmacology Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors Viperidae
Nerve growth factor (NGF) is a well known neurotropic and neurotrophic agonist in the nervous system, which recently was shown to also induce angiogenic effects in endothelial cells (ECs). To measure NGF effects on the migration of cultured ECs, an important step in neoangiogenesis, we optimized an omnidirectional migration assay using human aortic endothelial cells (HAECs) and validated the assay with human recombinant basic fibroblast growth factor (rhbFGF) and human recombinant vascular endothelial growth factor (rhVEGF). The potencies of nerve growth factor purified from various species (viper, mouse, and recombinant human) to stimulate HAEC migration was similar to that of VEGF and basic fibroblast growth factor (bFGF) (EC50 of approximately 0.5 ng/ml). Recombinant human bFGF was significantly more efficacious than either viper NGF or rhVEGF, both of which stimulated HAEC migration by approximately 30% over basal spontaneous migration. NGF-mediated stimulation of HAEC migration was completely blocked by the NGF/TrkA receptor antagonist K252a [(8R*,9S*,11S*)-(/)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,-8H,11H-2,7b,11a-triazadibenzo(a,g)cycloocta(c,d,e)trindene-1-one] (30 nM) but not by the VEGF/Flk receptor antagonist SU-5416 [3-[(2,4-dimethylpyrrol-5-yl) methylidenyl]-indolin-2-one] (250 nM), indicating a direct effect of NGF via TrkA receptor activation on HAEC migration. Viper NGF stimulation of HAEC migration was additively increased by either rhVEGF or rhbFGF, suggesting a potentiating interaction between their tyrosine kinase receptor signaling pathways. Viper NGF represents a novel pharmacological tool to investigate possible TrkA receptor subtypes in endothelial cells. The ability of NGF to stimulate migration of HAEC cells in vitro implies that this factor may play an important role in the cardiovascular system besides its well known effects in the nervous system.

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63 citations in Web of Science
69 citations in Scopus

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Web of Science research areas
Pharmacology & Pharmacy
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