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

Julio Madrigal-Matute, Jes Sandal Lindholt, Carlos Ernesto Fernandez-Garcia, Alberto Benito-Martin, Elena Burillo, Guillermo Zalba, Oscar Beloqui, Patricia Llamas-Granda, Alberto Ortiz, Jesus Egido, Luis Miguel Blanco-Colio, Jose Luis Martin-Ventura

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere000785
JournalJournal of the American Heart Association
Volume3
Issue number4
DOIs
StatePublished - 2014

Keywords

  • Atherothrombosis
  • Biomarkers
  • Inflammation
  • Mortality
  • Oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Madrigal-Matute, J., Lindholt, J. S., Fernandez-Garcia, C. E., Benito-Martin, A., Burillo, E., Zalba, G., Beloqui, O., Llamas-Granda, P., Ortiz, A., Egido, J., Blanco-Colio, L. M., & Martin-Ventura, J. L. (2014). Galectin-3, a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis. Journal of the American Heart Association, 3(4), [e000785]. https://doi.org/10.1161/JAHA.114.000785