Skip to main content

Activation of the cGMP/cGKI signalling pathway in primary murine VSMCs accelerates growth

The endogenous signaling molecule nitric oxide (NO) exerts many of its actions via the cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase type I (cGKI) pathway. Recently, the analysis of an in vivo mouse model for atherosclerosis suggested that activation of cGKI in vascular smooth muscle cells (VSMCs) promotes the phenotypic modulation of medial VSMCs and, thus, vascular lesion formation. In contrast, many in vitro studies demonstrate an anti-proliferative role for cGKI. In the current study, primary and subcultured wild-type and cGKI-deficient VSMCs in response to the membrane permeable cGMP analogue 8-Br-cGMP were compared. In agreement with the common view an anti-proliferative effect of cGKI was found in repeatedly passaged VSMCs (P5–11). In contrast, the analysis of primary VSMCs revealed that activation of cGKI in primary VSMCs strongly promotes growth. Analysing proliferation, apoptosis, cytoskeletal dynamics and various signaling pathways indicated that an increase in cell adhesion is a major mechanism for cGKI-mediated "growth" in primary VSMCs. This pro-adhesive effect of cGKI might be mediated via an inhibition of Rho kinase (ROCK) and enhanced integrin signaling. These processes might contribute to inhibit anoïkis, the programmed cell death induced by the loss of cell/matrix interactions.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Pascal Weinmeister.

Rights and permissions

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

Reprints and Permissions

About this article

Cite this article

Weinmeister, P., Lukowski, R., Claudia Traidl-Hoffmann, C. et al. Activation of the cGMP/cGKI signalling pathway in primary murine VSMCs accelerates growth. BMC Pharmacol 7, P64 (2007). https://doi.org/10.1186/1471-2210-7-S1-P64

Download citation

Keywords

  • Nitric Oxide
  • Integrin Signaling
  • Cyclic Guanosine Monophosphate
  • Guanosine Monophosphate
  • cGMP Analogue