Plasma concentrations predict aortic expression of growth-arrest-specific protein 6 in patients undergoing coronary artery bypass grafting.

Abstract

The tyrosine kinase receptor Axl is expressed in the vasculature, and growth arrest-specific protein 6 (Gas6) is its ligand. Plasma Gas6 levels have been shown to be associated with endothelial dysfunction markers and cardiovascular events. We set out to determine the plasma Gas6 levels in patients undergoing coronary artery bypass grafting (CABG) and investigate the expression of Gas6 and Axl in the aorta.Immunoassays were used to investigate plasma Gas6 levels in CABG patients (n = 19) and control subjects (n = 20). The expression of Gas6 and Axl in the injured aorta were examined by reverse transcription-polymerase chain reactions, real-time reverse transcription-polymerase chain reactions, western blotting, and immunohistochemical staining. Plasma Gas6 levels were significantly lower in CABG patients than in matched control subjects. In CABG patients, plasma Gas6 levels were negatively correlated with fasting glucose, E-selectin, and vascular cell adhesion molecule-1 levels. The levels predicted the operative mortality rate and were positively correlated with plasma soluble Axl (sAxl) levels and Gas6 expression in the aorta. Moreover, Gas6 expression was positively correlated with Axl expression in the aorta.We concluded that plasma Gas6 is associated with fasting glucose, endothelial dysfunction markers, sAxl values, and vascular Gas6 expression in CABG patients, and it predicts the operative mortality of these patients. These findings suggest that the Gas6/Axl system is crucial in vascular biology.