Plasma concentrations of Gas6 and soluble Axl correlate with disease and predict mortality in patients with critical limb ischemia.

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.