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

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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 - Jan 1 2014

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Galectin 3
Oxidative Stress
Biomarkers
Inflammation
Macrophages
Monocytes
NADPH Oxidase
Tetradecanoylphorbol Acetate
Atherosclerosis
Exosomes
Carotid Intima-Media Thickness
Carotid Artery Diseases
Peripheral Arterial Disease
Chemotaxis
Rupture
Reactive Oxygen Species
Blood Cells
Cardiovascular Diseases
Heart Failure
Confidence Intervals

Keywords

  • Atherothrombosis
  • Biomarkers
  • Inflammation
  • Mortality
  • Oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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

In: Journal of the American Heart Association, Vol. 3, No. 4, e000785, 01.01.2014.

Research output: Contribution to journalArticle

Madrigal-Matute, J, Lindholt, JS, Fernandez-Garcia, CE, Benito-Martin, A, Burillo, E, Zalba, G, Beloqui, O, Llamas-Granda, P, Ortiz, A, Egido, J, Blanco-Colio, LM & Martin-Ventura, JL 2014, 'Galectin-3, a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis', Journal of the American Heart Association, vol. 3, no. 4, e000785. https://doi.org/10.1161/JAHA.114.000785
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. / Galectin-3, a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis. In: Journal of the American Heart Association. 2014 ; Vol. 3, No. 4.
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AU - Benito-Martin, Alberto

AU - Burillo, Elena

AU - Zalba, Guillermo

AU - Beloqui, Oscar

AU - Llamas-Granda, Patricia

AU - Ortiz, Alberto

AU - Egido, Jesus

AU - Blanco-Colio, Luis Miguel

AU - Martin-Ventura, Jose Luis

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N2 - 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.

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