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Neural driven angiogenesis by overexpression of nerve growth factor

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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.

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Abbreviations

NGF:

Nerve growth factor

VEGF:

Vascular endothelial growth factor

VD:

Vascular density

BFR:

Blood flow rate

RBC:

Red blood cell velocity

LEI:

Leukocyte–endothelial interaction

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Acknowledgments

This work was supported by a Werner Otto Stiftung research grant to N.H-A. and P.A., N.H-A., L.W., C.J., and C.S., were members of the DFG Graduate Kolleg [GRK476], P.A. and A.H., were members of the DFG Graduate Kolleg [GRK336]. We thank Rakesh K. Jain and Dai Fukumura for fruitful discussions. We thank M. Ammelt for help with the image processing analysis.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany

    N. Hansen-Algenstaedt, C. Schaefer, B. Schwarzloh, L. Wiesner & W. Rüther

  2. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany

    P. Algenstaedt & N. Kilic

  3. Department of Anatomy, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany

    G. Cingöz, N. Kilic & S. Ergün

  4. Center of Biomechanics, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany

    N. Hansen-Algenstaedt, C. Schaefer, L. Wolfram, M. Schroeder, C. Joscheck & W. Rüther

  5. Department of Internal Medicine I, University Medical Center Heidelberg, 69115, Heidelberg, Germany

    A. Hamann

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  1. N. Hansen-Algenstaedt
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  2. P. Algenstaedt
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  3. C. Schaefer
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Correspondence to N. Hansen-Algenstaedt.

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Hansen-Algenstaedt, N., Algenstaedt, P., Schaefer, C. et al. Neural driven angiogenesis by overexpression of nerve growth factor. Histochem Cell Biol 125, 637–649 (2006). https://doi.org/10.1007/s00418-005-0111-z

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