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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-9941

Largiadèr, T; Masato, E; Payeli, S K; Greutert, H; Viswambharan, H; Lachat , M; Zünd, G; Yang, Z; Tanner, F C; Lüscher, T F (2008). Endothelial nitric oxide synthase gene transfer inhibits human smooth muscle cell migration via inhibition of Rho A. Journal of Cardiovascular Pharmacology, 52(4):369-374.

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Abstract

Smooth muscle cell (SMC) migration contributes to vascular remodeling. Nitric oxide (NO) produced via endothelial NO synthase (eNOS) inhibits SMC migration. This study analyzes signal transduction mechanisms of SMC migration targeted by NO. SMCs were cultured from human saphenous veins, and cell migration was studied using Boyden chambers. PDGF-BB (0.1 to 10 ng/ml) stimulated SMC migration in a concentration-dependent manner, which was inhibited by adenoviral-mediated overexpression of eNOS and by the NO donor diethylentriamine NONOate (DETANO, 10 to 10 mol/L). NO release was enhanced in eNOS-transduced SMCs, and L-NAME blunted the effect of eNOS overexpression on migration. PDGF-BB (10 ng/ml) activated Rho A, which was inhibited by the overexpression of eNOS by DETANO and by 8 bromo-cGMP. The inhibitory effect of DETANO on Rho A activity was prevented by the cGMP-dependant kinase inhibitor. Furthermore, inhibition of Rho A by C3 exoenzyme and inhibition of ROCK by Y-27632 diminished cell migration stimulated by PDGF-BB. Finally, in the cells overexpressing constitutively active ROCK mutant (CAT), DETANO failed to prevent PDGF-BB-induced SMC migration. In conclusion, NO inhibits human SMC migration via blockade of the Rho A pathway.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiovascular Surgery
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:October 2008
Deposited On:09 Jan 2009 17:04
Last Modified:27 Nov 2013 18:33
Publisher:Lippincott Wiliams & Wilkins
ISSN:0160-2446
Funders:Swiss National Foundation (4037-055166/1 and 32-67202.01), Postgraduate Course of the Medical Faculty, University of Zurich, ADUMED Foundation, Max Cloetta Foundation, Hartmann-Müller Stiftung
Publisher DOI:10.1097/FJC.0b013e31818953d0
PubMed ID:18841072
Citations:Web of Science®. Times Cited: 10
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