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Role of Rho kinase signalling in healthy and varicose human saphenous veins
Author(s) -
CarioToumaniantz Chrystelle,
Evellin Sandrine,
Maury Séverine,
Baron Olivier,
Pacaud Pierre,
Loirand Gervaise
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704849
Subject(s) - rho associated protein kinase , rhoa , contraction (grammar) , varicose veins , actin cytoskeleton , myosin light chain kinase , rho kinase inhibitor , microbiology and biotechnology , muscle contraction , cytoskeleton , actin , fibronectin , kinase , extracellular matrix , biology , anatomy , medicine , chemistry , endocrinology , signal transduction , biochemistry , cell , surgery
The present study was performed to determine the role of Rho‐Rho kinase signalling pathway in smooth muscle cells from both healthy and varicose human saphenous vein. The Rho kinase inhibitor Y‐27632 inhibited the noradrenaline (NA)‐induced contraction in human saphenous veins with IC 50 corresponding to 0.5 μ M and 10.9 μ M in control and varicose veins, respectively. The maximal amplitude of the NA‐induced contraction was smaller in varicose vein compared to control (1263±172 mg versus 1974±245 mg, P <0.05). In β‐escin permeabilized strips, GTPγS induced a rise in tension that was inhibited by Y‐27632. The amplitude of the GTPγS‐induced contraction was smaller in varicose compared to control veins (23.1±2.4% versus 41.3±2.2%, P <0.002). In smooth muscle cells, Y‐27632 induced disassembly of both actin cytoskeleton and extracellular fibronectin matrix. In comparison to control cells, varicose vein smooth muscle cells show decreased actin cytoskeleton organization and reduction of fibronectin matrix deposition. The Rho proteins Rnd1 and RhoA, and Rho kinase 1 are expressed in human saphenous veins. A 2.6 fold reduction of Rho kinase expression was found in varicose veins. These results indicate that RhoA‐Rho kinase mediated Ca 2+ sensitization of the contraction and regulated actin cytoskeleton and extracellular fibronectin matrix assembly in human saphenous smooth muscle. The decrease of Rho kinase expression and Rho kinase‐dependent functions detected in smooth muscle from varicose veins supports a role of this signalling pathway in the functional alterations of the vein wall occurring in the course of the disease.British Journal of Pharmacology (2002) 137 , 205–212. doi: 10.1038/sj.bjp.0704849

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