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A role for galectin-3 in the development of early molecular alterations in short-term aortic stenosis.
Clin Sci (Lond) 2017; 131(10):935-949CS

Abstract

Aortic stenosis (AS) is characterized by pressure overload and causes left ventricular (LV) fibrosis and inflammation, two mechanisms that eventually lead to cardiac dysfunction. Galectin-3 (Gal-3), a β-galactoside-binding lectin, promotes cardiac remodelling. In the present study, we investigated the role of Gal-3 in LV remodelling in patients with AS and the effects of Gal-3 blockade in rats subjected to short-term (6-week) supravalvular aortic banding (AS group). Myocardial biopsies were obtained from 25 patients with severe AS referred for aortic valve replacement and from necropsies of 11 cardiovascular disease-free control individuals. Gal-3 was up-regulated in myocardial biopsies from AS patients compared with controls. Gal-3 directly correlated with parameters assessing myocardial fibrosis and inflammation in AS patients. Normotensive AS animals presented decreased LV diastolic diameter compared with controls. At the histological level, AS rats exhibited a slight increase in LV cross-sectional area and LV wall thickness, and augmented cardiomyocyte width and cross-sectional area. AS animals presented enhanced cardiac Gal-3 expression, which paralleled higher myocardial fibrosis and inflammation. Cardiac Gal-3 was associated with fibrosis and inflammatory markers. Gal-3 pharmacological inhibition prevented the increase in cardiac Gal-3 and normalized histological and molecular alterations in AS rats. In short-term AS, the increase in myocardial Gal-3 expression was associated with cardiac fibrosis and inflammation, alterations that were prevented by Gal-3 blockade. These data suggest that Gal-3 inhibition could be a novel therapeutic approach in the prevention of AS-associated early pathological cardiac remodelling.

Authors+Show Affiliations

Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Ciber de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III. Av. Compltense s.n. Madrid, Spain.INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT. 9 avenue de la forêt de Haye, 54500 Nancy, France.Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain natalia.lopez.andres@navarra.es. INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT. 9 avenue de la forêt de Haye, 54500 Nancy, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28360193

Citation

Arrieta, Vanessa, et al. "A Role for Galectin-3 in the Development of Early Molecular Alterations in Short-term Aortic Stenosis." Clinical Science (London, England : 1979), vol. 131, no. 10, 2017, pp. 935-949.
Arrieta V, Martinez-Martinez E, Ibarrola J, et al. A role for galectin-3 in the development of early molecular alterations in short-term aortic stenosis. Clin Sci. 2017;131(10):935-949.
Arrieta, V., Martinez-Martinez, E., Ibarrola, J., Alvarez, V., Sádaba, R., Garcia-Peña, A., ... López-Andrés, N. (2017). A role for galectin-3 in the development of early molecular alterations in short-term aortic stenosis. Clinical Science (London, England : 1979), 131(10), pp. 935-949. doi:10.1042/CS20170145.
Arrieta V, et al. A Role for Galectin-3 in the Development of Early Molecular Alterations in Short-term Aortic Stenosis. Clin Sci. 2017 May 1;131(10):935-949. PubMed PMID: 28360193.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A role for galectin-3 in the development of early molecular alterations in short-term aortic stenosis. AU - Arrieta,Vanessa, AU - Martinez-Martinez,Ernesto, AU - Ibarrola,Jaime, AU - Alvarez,Virginia, AU - Sádaba,Rafael, AU - Garcia-Peña,Amaia, AU - Fernández-Celis,Amaya, AU - Cachofeiro,Victoria, AU - Rossignol,Patrick, AU - López-Andrés,Natalia, Y1 - 2017/03/30/ PY - 2017/02/12/received PY - 2017/03/28/revised PY - 2017/03/28/accepted PY - 2017/4/1/pubmed PY - 2017/7/28/medline PY - 2017/4/1/entrez KW - aortic stenosis KW - fibrosis KW - galectin-3 KW - inflammation KW - pressure overload SP - 935 EP - 949 JF - Clinical science (London, England : 1979) JO - Clin. Sci. VL - 131 IS - 10 N2 - Aortic stenosis (AS) is characterized by pressure overload and causes left ventricular (LV) fibrosis and inflammation, two mechanisms that eventually lead to cardiac dysfunction. Galectin-3 (Gal-3), a β-galactoside-binding lectin, promotes cardiac remodelling. In the present study, we investigated the role of Gal-3 in LV remodelling in patients with AS and the effects of Gal-3 blockade in rats subjected to short-term (6-week) supravalvular aortic banding (AS group). Myocardial biopsies were obtained from 25 patients with severe AS referred for aortic valve replacement and from necropsies of 11 cardiovascular disease-free control individuals. Gal-3 was up-regulated in myocardial biopsies from AS patients compared with controls. Gal-3 directly correlated with parameters assessing myocardial fibrosis and inflammation in AS patients. Normotensive AS animals presented decreased LV diastolic diameter compared with controls. At the histological level, AS rats exhibited a slight increase in LV cross-sectional area and LV wall thickness, and augmented cardiomyocyte width and cross-sectional area. AS animals presented enhanced cardiac Gal-3 expression, which paralleled higher myocardial fibrosis and inflammation. Cardiac Gal-3 was associated with fibrosis and inflammatory markers. Gal-3 pharmacological inhibition prevented the increase in cardiac Gal-3 and normalized histological and molecular alterations in AS rats. In short-term AS, the increase in myocardial Gal-3 expression was associated with cardiac fibrosis and inflammation, alterations that were prevented by Gal-3 blockade. These data suggest that Gal-3 inhibition could be a novel therapeutic approach in the prevention of AS-associated early pathological cardiac remodelling. SN - 1470-8736 UR - https://www.unboundmedicine.com/medline/citation/28360193/A_role_for_galectin_3_in_the_development_of_early_molecular_alterations_in_short_term_aortic_stenosis_ L2 - http://clinsci.org/cgi/pmidlookup?view=long&pmid=28360193 DB - PRIME DP - Unbound Medicine ER -