Circulating Gas6 is associated with reduced human carotid atherosclerotic plaque burden in high risk cardiac patients

Abstract

ObjectivePre-clinical studies suggest that growth arrest-specific protein 6 (Gas6), a member of the vitamin K dependent family of proteins, is implicated in atherosclerosis. A role for Gas6 in stabilizing atherosclerotic plaque has been suggested. Our aim was to determine the association between Gas6 and measures of carotid artery atherosclerosis in humans undergoing elective coronary angiography. Secondary aims were to determine the association between Gas6 and sex, diabetes, and obesity. MethodsIn 204 outpatients referred for coronary angiography, EDTA plasma was collected and a focused carotid ultrasound performed. Degree of angiographic coronary artery disease was scored. Carotid intima media thickness as well as maximum plaque height, plaque area, and grayscale median were measured by vascular sonography. Gas6 was assessed by enzyme-linked immunosorbent assay. ResultsWe found that Gas6 concentrations were lower in males and were associated with diabetes, obesity, and lower kidney function. After adjustment for age, sex, kidney function, BMI and traditional cardiac risk factors; diabetes was associated with higher levels of Gas6, whilst there was a significant inverse relationship between Gas6 and total plaque area. Gas6 was inversely associated with maximum plaque height and total plaque area in adjusted multi-variable models. ConclusionsWe observed higher levels of Gas6 in participantswith adverse cardiovascular risk profiles (e.g. diabetes, obesity) yet Gas6 was independently associated with reduced plaque height and total plaque area. These findings suggest that Gas6 may play a role in human atherosclerotic plaque remodeling.