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

IntroductionCritical 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 methodsWe quantified plasma concentrations of Gas6 and sAxl in 189 CLI patients and 204 controls.ResultsGas6 and sAxl concentrations were increased in the CLI patients (p < 0.0001) and correlated to C-reactive protein, interleukin-6, tumor necrosis factor α and neopterin. Patients who died within 3 years of sampling (n = 84) had increased concentrations of Gas6 and sAxl as compared to survivors (p = 0.0009 and p = 0.0011).ConclusionsPlasma 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.