![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CARDIOVASCULAR
Laboratory of Cellular Tissue Engineering, School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania (J.-P.D., A.R., F.D.A., P.L., P.I.L.); and Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (P.L.)
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 
0.5 ng/ml). Recombinant human bFGF was significantly more efficacious than either viper NGF or rhVEGF, both of which stimulated HAEC migration by 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.
Address correspondence to: Dr. Peter I. Lelkes, Calhoun Chair Professor of Cellular Tissue Engineering, School of Biomedical Engineering, Science and Health Systems, Drexel University, 3141 Chestnut St., Philadelphia, PA 19104. E-mail: pil22{at}drexel.edu
This article has been cited by other articles:
|
|
 |
|
  A. Caporali and C. Emanueli Cardiovascular Actions of Neurotrophins Physiol Rev, January 1, 2009; 89(1): 279 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zheng, L. P. Christensen, and R. J. Tomanek Differential effects of cyclic and static stretch on coronary microvascular endothelial cell receptors and vasculogenic/angiogenic responses Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H794 - H800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Uttayarat, M. Chen, M. Li, F. D. Allen, R. J. Composto, and P. I. Lelkes Microtopography and flow modulate the direction of endothelial cell migration Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H1027 - H1035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. G Sengers, C. P Please, and R. O.C Oreffo Experimental characterization and computational modelling of two-dimensional cell spreading for skeletal regeneration J R Soc Interface, December 22, 2007; 4(17): 1107 - 1117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Nascent Transcripts Mol. Interv., December 1, 2005; 5(6): 334 - 334. [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
