Galectin‐3, a Biomarker Linking Oxidative Stress and Inflammation With the Clinical Outcomes of Patients With Atherothrombosis

• Published in: Journal of the American Heart Association Vol. 3; no. 4
• Main Authors: Madrigal‐Matute, Julio, Lindholt, Jes Sandal, Fernandez‐Garcia, Carlos Ernesto, Benito‐Martin, Alberto, Burillo, Elena, Zalba, Guillermo, Beloqui, Oscar, Llamas‐Granda, Patricia, Ortiz, Alberto, Egido, Jesus, Blanco‐Colio, Luis Miguel, Martin‐Ventura, Jose Luis
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 05.08.2014
• Subjects: Aged; atherothrombosis; Biomarkers; Carotid Artery Diseases - blood; Carotid Artery Diseases - diagnostic imaging; Carotid Intima-Media Thickness; Case-Control Studies; Cell Line; Female; Follow-Up Studies; Galectin 3 - blood; Galectin 3 - drug effects; Humans; In Vitro Techniques; Inflammation; Macrophages; Male; Middle Aged; Monocytes; mortality; NADPH Oxidases - metabolism; Original Research; Oxidative Stress; Peripheral Arterial Disease - blood; Peripheral Arterial Disease - mortality; Prognosis; Tetradecanoylphorbol Acetate - pharmacology; atherothrombosis; mortality; inflammation; biomarkers; oxidative stress
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.114.000785

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.