title: A role for galectin-3 in the development of early molecular alterations in short-term aortic stenosis.
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.affiliation: Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Arrieta
authors.affiliation: Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Martinez-Martinez
authors.affiliation: Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Ibarrola
authors.affiliation: Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Alvarez
authors.affiliation: Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Sádaba
authors.affiliation: Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.
authors.forename: Amaia
authors.initials: A
authors.lastname: Garcia-Peña
authors.affiliation: Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA). C/ Irunlarrea 3, 31008 Pamplona, Spain.
authors.forename: Amaya
authors.initials: A
authors.lastname: Fernández-Celis
authors.affiliation: 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.
authors.forename: Victoria
authors.initials: V
authors.lastname: Cachofeiro
authors.affiliation: 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.
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.affiliation: 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.
authors.forename: Natalia
authors.initials: N
authors.lastname: López-Andrés
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001024:Aortic Valve Stenosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling
chemical_list: D037502:Galectin 3
keywords: aortic stenosis; fibrosis; galectin-3; inflammation; pressure overload