BACKGROUND: Neointimal fibroproliferative lesions after balloon angioplasty remain a major clinical problem, frequently leading to restenosis of initially successfully dilated coronary arteries. The cGMP-dependent protein kinase type I (cGMP-PK I) and its substrate vasodilator-stimulated phosphoprotein (VASP), molecular targets of the atrial natriuretic factor (ANF) and nitric oxide (NO) signalling pathways, are likely to be involved in various aspects of vascular wall regulation and restenosis formation. METHODS: To investigate the occurrence of cGMP-PK I and VASP in neointimal cells in situ, we performed immunohistochemistry and immunoblotting experiments on denuded rat carotid arteries. RESULTS: Although the soluble cGMP-PK I showed a homogeneous distribution throughout the neointima, VASP apparently was more concentrated in smooth muscle cells (SMCs) lining the artery lumen, possibly reflecting enhanced growth factor stimulation of luminal SMCs. The membrane-associated cGMP-PK type II could not be detected in both the non-injured vessel wall and the restenotic tissue. CONCLUSION: The presence of both cGMP-PK I and VASP, major regulators of the actin cytoskeleton and cell motility, in neointimal tissue suggest that this emerging signal transduction pathway could be a target for the regulation and control of restenosis.
BACKGROUND: Neointimal fibroproliferative lesions after balloon angioplasty remain a major clinical problem, frequently leading to restenosis of initially successfully dilated coronary arteries. The cGMP-dependent protein kinase type I (cGMP-PK I) and its substrate vasodilator-stimulated phosphoprotein (VASP), molecular targets of the atrial natriuretic factor (ANF) and nitric oxide (NO) signalling pathways, are likely to be involved in various aspects of vascular wall regulation and restenosis formation. METHODS: To investigate the occurrence of cGMP-PK I and VASP in neointimal cells in situ, we performed immunohistochemistry and immunoblotting experiments on denuded rat carotid arteries. RESULTS: Although the soluble cGMP-PK I showed a homogeneous distribution throughout the neointima, VASP apparently was more concentrated in smooth muscle cells (SMCs) lining the artery lumen, possibly reflecting enhanced growth factor stimulation of luminal SMCs. The membrane-associated cGMP-PK type II could not be detected in both the non-injured vessel wall and the restenotic tissue. CONCLUSION: The presence of both cGMP-PK I and VASP, major regulators of the actin cytoskeleton and cell motility, in neointimal tissue suggest that this emerging signal transduction pathway could be a target for the regulation and control of restenosis.
Authors: A Aszódi; A Pfeifer; M Ahmad; M Glauner; X H Zhou; L Ny; K E Andersson; B Kehrel; S Offermanns; R Fässler Journal: EMBO J Date: 1999-01-04 Impact factor: 11.598
Authors: Robert Lukowski; Pascal Weinmeister; Dominik Bernhard; Susanne Feil; Michael Gotthardt; Joachim Herz; Steffen Massberg; Alma Zernecke; Christian Weber; Franz Hofmann; Robert Feil Journal: Arterioscler Thromb Vasc Biol Date: 2008-04-17 Impact factor: 8.311