Carl Ekman1, Anders Gottsäter, Bengt Lindblad, Björn Dahlbäck. 1. Lund University, Department of Laboratory Medicine, Clinical Chemistry, Wallenberg Laboratory, Entrance 46, Floor 6, University Hospital, SE-20502 Malmö, Sweden. Carl.ekman@med.lu.se
Abstract
INTRODUCTION: Critical limb ischemia (CLI) is a severe peripheral arterial disease, characterized by rest pain, ulcers and gangrene in the legs. Gas6 is a vitamin K-dependent protein, which binds and activates the tyrosine kinase receptor Axl. Gas6-mediated Axl-signaling influences endothelial activation, neointima formation and immune regulation. Axl can be cleaved and soluble Axl (sAxl) is detectable in circulation. DESIGN AND METHODS: We quantified plasma concentrations of Gas6 and sAxl in 189 CLI patients and 204 controls. RESULTS: Gas6 and sAxl concentrations were increased in the CLI patients (p<0.0001) and correlated to C-reactive protein, interleukin-6, tumor necrosis factor alpha and neopterin. Patients who died within 3years of sampling (n=84) had increased concentrations of Gas6 and sAxl as compared to survivors (p=0.0009 and p=0.0011). CONCLUSIONS: Plasma concentrations of Gas6 and sAxl correlate to inflammation and predict survival. This indicates that Gas6 and sAxl have a role in CLI, presumably connected to the inflammatory process. Copyright 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
INTRODUCTION:Critical limb ischemia (CLI) is a severe peripheral arterial disease, characterized by rest pain, ulcers and gangrene in the legs. Gas6 is a vitamin K-dependent protein, which binds and activates the tyrosine kinase receptor Axl. Gas6-mediated Axl-signaling influences endothelial activation, neointima formation and immune regulation. Axl can be cleaved and soluble Axl (sAxl) is detectable in circulation. DESIGN AND METHODS: We quantified plasma concentrations of Gas6 and sAxl in 189 CLI patients and 204 controls. RESULTS:Gas6 and sAxl concentrations were increased in the CLI patients (p<0.0001) and correlated to C-reactive protein, interleukin-6, tumor necrosis factor alpha and neopterin. Patients who died within 3years of sampling (n=84) had increased concentrations of Gas6 and sAxl as compared to survivors (p=0.0009 and p=0.0011). CONCLUSIONS: Plasma concentrations of Gas6 and sAxl correlate to inflammation and predict survival. This indicates that Gas6 and sAxl have a role in CLI, presumably connected to the inflammatory process. Copyright 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
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