title: Galectin-3, a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis.
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.
  
  
  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.
authors.affiliation: Vascular Research Lab, IIS Fundación Jiménez Díaz, Autónoma University, IRSIN, Madrid, Spain (J.M.M., C.E.F.G., A.B.M., E.B., P.L.G., A.O., J.E., L.M.B.C., J.L.M.V.) Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY (J.M.M.).
authors.forename: Julio
authors.initials: J
authors.lastname: Madrigal-Matute
authors.affiliation: Vascular Research Unit, Viborg Hospital, Viborg, Denmark (J.S.L.).
authors.forename: Jes Sandal
authors.initials: JS
authors.lastname: Lindholt
authors.affiliation: Vascular Research Lab, IIS Fundación Jiménez Díaz, Autónoma University, IRSIN, Madrid, Spain (J.M.M., C.E.F.G., A.B.M., E.B., P.L.G., A.O., J.E., L.M.B.C., J.L.M.V.).
authors.forename: Carlos Ernesto
authors.initials: CE
authors.lastname: Fernandez-Garcia
authors.affiliation: Vascular Research Lab, IIS Fundación Jiménez Díaz, Autónoma University, IRSIN, Madrid, Spain (J.M.M., C.E.F.G., A.B.M., E.B., P.L.G., A.O., J.E., L.M.B.C., J.L.M.V.).
authors.forename: Alberto
authors.initials: A
authors.lastname: Benito-Martin
authors.affiliation: Vascular Research Lab, IIS Fundación Jiménez Díaz, Autónoma University, IRSIN, Madrid, Spain (J.M.M., C.E.F.G., A.B.M., E.B., P.L.G., A.O., J.E., L.M.B.C., J.L.M.V.).
authors.forename: Elena
authors.initials: E
authors.lastname: Burillo
authors.affiliation: Division of Cardiovascular Sciences, CIMA University of Navarra, Pamplona, Spain (G.Z.) Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain (G.Z.).
authors.forename: Guillermo
authors.initials: G
authors.lastname: Zalba
authors.affiliation: University Clinic, University of Navarra, Pamplona, Spain (O.B.).
authors.forename: Oscar
authors.initials: O
authors.lastname: Beloqui
authors.affiliation: Vascular Research Lab, IIS Fundación Jiménez Díaz, Autónoma University, IRSIN, Madrid, Spain (J.M.M., C.E.F.G., A.B.M., E.B., P.L.G., A.O., J.E., L.M.B.C., J.L.M.V.).
authors.forename: Patricia
authors.initials: P
authors.lastname: Llamas-Granda
authors.affiliation: Vascular Research Lab, IIS Fundación Jiménez Díaz, Autónoma University, IRSIN, Madrid, Spain (J.M.M., C.E.F.G., A.B.M., E.B., P.L.G., A.O., J.E., L.M.B.C., J.L.M.V.).
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: Vascular Research Lab, IIS Fundación Jiménez Díaz, Autónoma University, IRSIN, Madrid, Spain (J.M.M., C.E.F.G., A.B.M., E.B., P.L.G., A.O., J.E., L.M.B.C., J.L.M.V.) Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain (J.E.).
authors.forename: Jesus
authors.initials: J
authors.lastname: Egido
authors.affiliation: Vascular Research Lab, IIS Fundación Jiménez Díaz, Autónoma University, IRSIN, Madrid, Spain (J.M.M., C.E.F.G., A.B.M., E.B., P.L.G., A.O., J.E., L.M.B.C., J.L.M.V.).
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Blanco-Colio
authors.affiliation: Vascular Research Lab, IIS Fundación Jiménez Díaz, Autónoma University, IRSIN, Madrid, Spain (J.M.M., C.E.F.G., A.B.M., E.B., P.L.G., A.O., J.E., L.M.B.C., J.L.M.V.).
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Martin-Ventura
mesh_terms: D000368:Aged; D015415:Biomarkers; D002340:Carotid Artery Diseases / Q000097:blood* / Q000000981:diagnostic imaging; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D005500:Follow-Up Studies; D037502:Galectin 3 / Q000097:blood* / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation; D008264:Macrophages; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000401:mortality; D011379:Prognosis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D037502:Galectin 3; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate
keywords: atherothrombosis; biomarkers; inflammation; mortality; oxidative stress
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