Galectin-3,a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis

Background-galectin-3 (gal-3) participates in different mechanisms involved in atherothrombosis,such as inflammation,proliferation,or macrophage chemotaxis. thus,there have been committed intensive efforts to elucidate the function of gal-3 in cardiovascular (cv) diseases. the role of gal-3 as a circulating biomarker has been demonstrated in patients with heart failure,but its importance as a biomarker in atherothrombosis is still unknown. methods and results-because gal-3 is involved in monocyte-to-macrophage transition,we used fresh isolated monocytes and the in vitro model of macrophage differentiation of thp-1 cells stimulated with phorbol myristate acetate (pma). gal-3 release is increased by pma in human monocytes and macrophages,a process involving exosomes and regulated by reactive oxygen species/nadph oxidase activity. in asymptomatic subjects (n=199),gal-3 plasma levels are correlated with nadph oxidase activity in peripheral blood mononuclear cells (r=0.476; p<0.001) and carotid intima-media thickness (r=0.438; p<0.001),a surrogate marker of atherosclerosis. accordingly,gal-3 plasma concentrations are increased in patients with carotid atherosclerosis (n=158),compared to control subjects (n=115; 14.3 [10.7 to 16.9] vs. 10.4 [8.6 to 12.5] ng/ml; p<0.001). finally,on a 5-year follow-up study in patients with peripheral artery disease,gal-3 concentrations are significantly and independently associated with an increased risk for cv mortality (hazard ratio=2.24,95% confidence interval: 1.06 to 4.73,p<0.05). conclusions-gal-3 extracellular levels could reflect key underlying mechanisms involved in atherosclerosis etiology,development,and plaque rupture,such as inflammation,infiltration of circulating cells and oxidative stress. moreover,circulating gal-3 concentrations are associated with clinical outcomes in patients with atherothrombosis. © 2014 the authors.