title: Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension.
abstract: Hypertensive cardiac remodeling is accompanied by molecular inflammation and fibrosis, 2 mechanisms that finally affect cardiac function. At cardiac level, aldosterone promotes inflammation and fibrosis, although the precise mechanisms are still unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, is associated with inflammation and fibrosis in the cardiovascular system. We herein investigated whether Gal-3 inhibition could block aldosterone-induced cardiac inflammation and fibrosis and its potential role in cardiac damage associated with hypertension. Aldosterone-salt-treated rats presented hypertension, cardiac inflammation, and fibrosis that were prevented by the pharmacological inhibition of Gal-3 with modified citrus pectin. Cardiac inflammation and fibrosis presented in spontaneously hypertensive rats were prevented by modified citrus pectin treatment, whereas Gal-3 blockade did not modify blood pressure levels. In the absence of blood pressure modifications, Gal-3 knockout mice were resistant to aldosterone-induced cardiac inflammation. In human cardiac fibroblasts, aldosterone increased Gal-3 expression via its mineralocorticoid receptor. Gal-3 and aldosterone enhanced proinflammatory and profibrotic markers, as well as metalloproteinase activities in human cardiac fibroblasts, effects that were not observed in Gal-3-silenced cells treated with aldosterone. In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac inflammation and fibrosis, alterations that were prevented by Gal-3 blockade independently of blood pressure levels. These data suggest that Gal-3 could be a new molecular mechanism linking cardiac inflammation and fibrosis in situations with high-aldosterone levels, such as hypertension.
authors.affiliation: From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., A.F.-C., N.L.-A.); INSERM, Centre d'Investigations Cliniques- Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), French-Clinical Research Infrastructure Network (F-CRIN), Nancy, France (L.C., E.R., F.J., F.Z., P.R., N.L.-A.); Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil (L.V.R.); and INSERM UMR 872 Team 1, Centre de Recherche des Cordeliers, University Pierre and Marie Curie, Paris, France (F.J.).
authors.forename: Ernesto
authors.initials: E
authors.lastname: Martínez-Martínez
authors.affiliation: From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., A.F.-C., N.L.-A.); INSERM, Centre d'Investigations Cliniques- Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), French-Clinical Research Infrastructure Network (F-CRIN), Nancy, France (L.C., E.R., F.J., F.Z., P.R., N.L.-A.); Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil (L.V.R.); and INSERM UMR 872 Team 1, Centre de Recherche des Cordeliers, University Pierre and Marie Curie, Paris, France (F.J.).
authors.forename: Laurent
authors.initials: L
authors.lastname: Calvier
authors.affiliation: From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., A.F.-C., N.L.-A.); INSERM, Centre d'Investigations Cliniques- Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), French-Clinical Research Infrastructure Network (F-CRIN), Nancy, France (L.C., E.R., F.J., F.Z., P.R., N.L.-A.); Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil (L.V.R.); and INSERM UMR 872 Team 1, Centre de Recherche des Cordeliers, University Pierre and Marie Curie, Paris, France (F.J.).
authors.forename: Amaya
authors.initials: A
authors.lastname: Fernández-Celis
authors.affiliation: From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., A.F.-C., N.L.-A.); INSERM, Centre d'Investigations Cliniques- Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), French-Clinical Research Infrastructure Network (F-CRIN), Nancy, France (L.C., E.R., F.J., F.Z., P.R., N.L.-A.); Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil (L.V.R.); and INSERM UMR 872 Team 1, Centre de Recherche des Cordeliers, University Pierre and Marie Curie, Paris, France (F.J.).
authors.forename: Elodie
authors.initials: E
authors.lastname: Rousseau
authors.affiliation: From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., A.F.-C., N.L.-A.); INSERM, Centre d'Investigations Cliniques- Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), French-Clinical Research Infrastructure Network (F-CRIN), Nancy, France (L.C., E.R., F.J., F.Z., P.R., N.L.-A.); Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil (L.V.R.); and INSERM UMR 872 Team 1, Centre de Recherche des Cordeliers, University Pierre and Marie Curie, Paris, France (F.J.).
authors.forename: Raquel
authors.initials: R
authors.lastname: Jurado-López
authors.affiliation: From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., A.F.-C., N.L.-A.); INSERM, Centre d'Investigations Cliniques- Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), French-Clinical Research Infrastructure Network (F-CRIN), Nancy, France (L.C., E.R., F.J., F.Z., P.R., N.L.-A.); Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil (L.V.R.); and INSERM UMR 872 Team 1, Centre de Recherche des Cordeliers, University Pierre and Marie Curie, Paris, France (F.J.).
authors.forename: Luciana V
authors.initials: LV
authors.lastname: Rossoni
authors.affiliation: From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., A.F.-C., N.L.-A.); INSERM, Centre d'Investigations Cliniques- Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), French-Clinical Research Infrastructure Network (F-CRIN), Nancy, France (L.C., E.R., F.J., F.Z., P.R., N.L.-A.); Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil (L.V.R.); and INSERM UMR 872 Team 1, Centre de Recherche des Cordeliers, University Pierre and Marie Curie, Paris, France (F.J.).
authors.forename: Frederic
authors.initials: F
authors.lastname: Jaisser
authors.affiliation: From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., A.F.-C., N.L.-A.); INSERM, Centre d'Investigations Cliniques- Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), French-Clinical Research Infrastructure Network (F-CRIN), Nancy, France (L.C., E.R., F.J., F.Z., P.R., N.L.-A.); Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil (L.V.R.); and INSERM UMR 872 Team 1, Centre de Recherche des Cordeliers, University Pierre and Marie Curie, Paris, France (F.J.).
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., A.F.-C., N.L.-A.); INSERM, Centre d'Investigations Cliniques- Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), French-Clinical Research Infrastructure Network (F-CRIN), Nancy, France (L.C., E.R., F.J., F.Z., P.R., N.L.-A.); Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil (L.V.R.); and INSERM UMR 872 Team 1, Centre de Recherche des Cordeliers, University Pierre and Marie Curie, Paris, France (F.J.).
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.affiliation: From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., A.F.-C., N.L.-A.); INSERM, Centre d'Investigations Cliniques- Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), French-Clinical Research Infrastructure Network (F-CRIN), Nancy, France (L.C., E.R., F.J., F.Z., P.R., N.L.-A.); Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil (L.V.R.); and INSERM UMR 872 Team 1, Centre de Recherche des Cordeliers, University Pierre and Marie Curie, Paris, France (F.J.).
authors.forename: Victoria
authors.initials: V
authors.lastname: Cachofeiro
authors.affiliation: From the Cardiovascular Translational Research, Navarrabiomed (Fundación Miguel Servet), Pamplona, Spain (E.M.-M., A.F.-C., N.L.-A.); INSERM, Centre d'Investigations Cliniques- Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, and INI-CRCT (Cardiovascular and Renal Clinical Trialists), French-Clinical Research Infrastructure Network (F-CRIN), Nancy, France (L.C., E.R., F.J., F.Z., P.R., N.L.-A.); Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain (R.J.-L., V.C.); Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil (L.V.R.); and INSERM UMR 872 Team 1, Centre de Recherche des Cordeliers, University Pierre and Marie Curie, Paris, France (F.J.). natalia.lopez.andres@navarra.es.
authors.forename: Natalia
authors.initials: N
authors.lastname: López-Andrés
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis / Q000209:etiology / Q000473:pathology; D037502:Galectin 3 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009205:Myocarditis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D013148:Spironolactone / Q000627:therapeutic use*
chemical_list: D037502:Galectin 3; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone
keywords: aldosterone; fibrosis; galectin 3; hypertension; inflammation