Galectin-3, a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis
Madrigal-Matute J (1), Lindholt JS (2), Fernandez-Garcia CE (3), Benito-Martin A (3), Burillo E (3), Zalba G (4), Beloqui O (5), Llamas-Granda P (3), Ortiz A (3), Egido J (6), Blanco-Colio LM (3), Martin-Ventura JL (3).
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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).
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.
CITA DEL ARTICULO J Am Heart Assoc. 2014 Aug 5;3(4). pii: e000785. doi: 10.1161/JAHA.114.000785.