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


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.
Ekman
Carl
C
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
Gottsäter
Anders
A
Lindblad
Bengt
B
Dahlbäck
Björn
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016638:Critical Illness / Q000401:mortality*; D005260:Female; D006801:Humans; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D007511:Ischemia / Q000097:blood* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000097:blood*; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood*; D012044:Regression Analysis; D012995:Solubility; D016019:Survival Analysis; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C000722289:AXL protein, human