Neural driven angiogenesis by overexpression of nerve growth factor

N Hansen-Algenstaedt; P Algenstaedt; C Schaefer; A Hamann; L Wolfram; G Cingöz; N Kilic; B Schwarzloh; M Schroeder; C Joscheck; L Wiesner; W Rüther; S Ergün

doi:10.1007/s00418-005-0111-z

Neural driven angiogenesis by overexpression of nerve growth factor

Histochem Cell Biol. 2006 Jun;125(6):637-49. doi: 10.1007/s00418-005-0111-z. Epub 2005 Nov 29.

Authors

N Hansen-Algenstaedt¹, P Algenstaedt, C Schaefer, A Hamann, L Wolfram, G Cingöz, N Kilic, B Schwarzloh, M Schroeder, C Joscheck, L Wiesner, W Rüther, S Ergün

Affiliation

¹ Department of Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. nhansen@uke.uni-hamburg.de

PMID: 16315017
DOI: 10.1007/s00418-005-0111-z

Abstract

Mechanisms regulating angiogenesis are crucial in adjusting tissue perfusion on metabolic demands. We demonstrate that overexpression of nerve growth factor (NGF) in brown adipose tissue (BAT) of NGF-transgenic mice elevates both mRNA and protein levels of vascular endothelial growth factor (VEGF) and VEGF-receptors. Increased vascular permeability, leukocyte-endothelial interactions (LEI), and tissue perfusion were measured using intravital microscopy. NGF-stimulation of adipocytes and endothelial cells elevates mRNA expression of VEGF and its receptors, an effect blocked by NGF neutralizing antibodies. These data suggest an activation of angiogenesis as a result of both: stimulation of adipozytes and direct mitogenic effects on endothelial cells. The increased nerve density associated with vessels strengthened our hypothesis that tissue perfusion is regulated by neural control of vessels and that the interaction between the NGF and VEGF systems is the critical driver for the activated angiogenic process. The interaction of VEGF- and NGF-systems gives new insights into neural control of organ vascularization and perfusion.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes, Brown / chemistry
Adipocytes, Brown / metabolism
Adipose Tissue, Brown / blood supply*
Adipose Tissue, Brown / innervation
Adipose Tissue, Brown / metabolism*
Animals
Cell Proliferation
Endothelial Cells / cytology
Endothelial Cells / metabolism
Mice
Mice, Transgenic
Neovascularization, Physiologic* / genetics
Nerve Growth Factor / analysis
Nerve Growth Factor / genetics
Nerve Growth Factor / metabolism*
Neurotrophin 3 / analysis
Neurotrophin 3 / genetics
Neurotrophin 3 / metabolism*
RNA, Messenger / analysis
RNA, Messenger / metabolism
Up-Regulation
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism*
Vascular Endothelial Growth Factor Receptor-1 / genetics
Vascular Endothelial Growth Factor Receptor-1 / metabolism
Vascular Endothelial Growth Factor Receptor-2 / genetics
Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

Neurotrophin 3
RNA, Messenger
Vascular Endothelial Growth Factor A
Nerve Growth Factor
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2