Volume 14 Supplement 1

6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications

Open Access

The role of VASP in cGMP-mediated vascular smooth muscle relaxation

  • Staffan Hildebrand1, 2Email author,
  • Katrin Zimmermann1, 2,
  • Daniela Wenzel3,
  • Bernd K Fleischmann3 and
  • Alexander Pfeifer1, 2
BMC Pharmacology and Toxicology201314(Suppl 1):P28

https://doi.org/10.1186/2050-6511-14-S1-P28

Published: 29 August 2013

Background

Cyclic GMP (cGMP) is a major mediator of relaxation in the vascular system. cGMP is produced by the enzyme soluble Guanylyl Cyclase (sGC) in response to nitric oxide (NO) released from neighbouring endothelial cells. cGMP activates Protein Kinase G (PKG), which in turn mediates vascular relaxation through phosophorylation of various targets. One of the major substrates of PKG is the VAsodilator-Stimulated Phosphoprotein (VASP). The role of VASP in vascular smooth muscle relaxation is currently unknown. However, recent studies show that VASP-deficient brown adipocytes have an increased activity of the small GTPase Rac1 and elevated levels of sGC [1]. These data suggest a regulatory role for VASP in cGMP-mediated processes.

Results

Preliminary data acquired from the analysis of VASP-deficient (VASP-/-) mice provide evidence for the importance of VASP in the cGMP mediated relaxation pathway: VASP-/- aortas show higher levels of PKG and sGC compared to wild type (see Figure 1), and increased sensitivity to NO-induced relaxation. Additionally, cultured vascular smooth muscle cells (VSMCs) transduced with a constitutively active Rac1 mutant (RacL61) show elevated sGC and PKG expression as well as increased PKG activity. Cultured VSMCs from VASP-/- aortas also demonstrate decreased proliferation rates compared to wild-type cells in preliminary experiments.
Figure 1

Expression of PKGI and the ß1-subunit of sGC in VASP-/- and wild-type murine aortas as determined by western blotting N=3.

Authors’ Affiliations

(1)
Institute of Pharmacology and Toxicology, University of Bonn
(2)
NRW International Graduate School BIOTECH-PHARMA
(3)
Institute of Physiology I, University of Bonn

References

  1. Jennissen K, Siegel F, Liebig-Gonglach M, Hermann M-R, Kipschull S, van Dooren S, Kunz WS, Fässler R, Pfeifer A: A VASP-Rac-soluble guanylyl cyclase pathway controls cGMP production in adipocytes. Sci Signal. 2012, 5: ra62-10.1126/scisignal.2002867.View ArticlePubMedGoogle Scholar

Copyright

© Hildebrand et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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