Neural driven angiogenesis by overexpression of nerve growth factor.
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.
Hansen-Algenstaedt
N
N
Department of Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. nhansen@uke.uni-hamburg.de
Algenstaedt
P
P
Schaefer
C
C
Hamann
A
A
Wolfram
L
L
Cingöz
G
G
Kilic
N
N
Schwarzloh
B
B
Schroeder
M
M
Joscheck
C
C
Wiesner
L
L
Rüther
W
W
Ergün
S
S
D052437:Adipocytes, Brown / Q000737:chemistry / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000098:blood supply* / Q000294:innervation / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics; D020932:Nerve Growth Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D020933:Neurotrophin 3; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D020932:Nerve Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2