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Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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Related Experiment Video

Updated: Jul 6, 2026

In Vitro Model of Coronary Angiogenesis
08:03

In Vitro Model of Coronary Angiogenesis

Published on: March 10, 2020

VEGF promotes vascular sympathetic innervation.

Stephen B Marko1, Deborah H Damon

  • 1Department of Pharmacology, University of Vermont, Burlington, Vermont, USA.

American Journal of Physiology. Heart and Circulatory Physiology
|April 15, 2008
PubMed
Summary

Vascular endothelial growth factor (VEGF) from blood vessels promotes sympathetic nerve growth. This discovery reveals a new mechanism for how the sympathetic nervous system innervates cardiovascular targets.

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Area of Science:

  • Cardiovascular Biology
  • Neuroscience
  • Molecular Biology

Background:

  • The sympathetic nervous system regulates cardiovascular function through nerve innervation.
  • Mechanisms of sympathetic target innervation are not fully understood.

Purpose of the Study:

  • To investigate the role of target-derived vascular endothelial growth factor (VEGF) in promoting sympathetic innervation of blood vessels.

Main Methods:

  • Western blot and immunohistochemistry to detect VEGF and its receptors.
  • In vitro neurovascular coculture assays with vascular smooth muscle cells (VSMCs).
  • In vivo studies involving neutralization of VEGF in denervated arteries.

Main Results:

  • VEGF is produced by vascular cells and its receptors are on sympathetic nerve fibers.
  • VEGF and VSMCs inhibited semaphorin 3A-induced growth cone collapse in vitro.
  • VEGF increased sympathetic growth cone area in the absence of semaphorin 3A.
  • VEGF neutralization impaired arterial reinnervation in vivo.

Conclusions:

  • Target-derived VEGF promotes sympathetic axon growth.
  • VEGF acts via VEGF receptor 1 to modulate growth cone responses.
  • This study uncovers a novel role for VEGF in sympathetic neurovascular communication.