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Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension.
Hypertension 2015; 66(4):767-75H

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+Show Affiliations

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.).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.).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.).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.).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.).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.).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.).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.).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.).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.).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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26238446

Citation

Martínez-Martínez, Ernesto, et al. "Galectin-3 Blockade Inhibits Cardiac Inflammation and Fibrosis in Experimental Hyperaldosteronism and Hypertension." Hypertension (Dallas, Tex. : 1979), vol. 66, no. 4, 2015, pp. 767-75.
Martínez-Martínez E, Calvier L, Fernández-Celis A, et al. Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension. Hypertension. 2015;66(4):767-75.
Martínez-Martínez, E., Calvier, L., Fernández-Celis, A., Rousseau, E., Jurado-López, R., Rossoni, L. V., ... López-Andrés, N. (2015). Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension. Hypertension (Dallas, Tex. : 1979), 66(4), pp. 767-75. doi:10.1161/HYPERTENSIONAHA.115.05876.
Martínez-Martínez E, et al. Galectin-3 Blockade Inhibits Cardiac Inflammation and Fibrosis in Experimental Hyperaldosteronism and Hypertension. Hypertension. 2015;66(4):767-75. PubMed PMID: 26238446.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension. AU - Martínez-Martínez,Ernesto, AU - Calvier,Laurent, AU - Fernández-Celis,Amaya, AU - Rousseau,Elodie, AU - Jurado-López,Raquel, AU - Rossoni,Luciana V, AU - Jaisser,Frederic, AU - Zannad,Faiez, AU - Rossignol,Patrick, AU - Cachofeiro,Victoria, AU - López-Andrés,Natalia, Y1 - 2015/08/03/ PY - 2015/05/20/received PY - 2015/07/10/accepted PY - 2015/8/5/entrez PY - 2015/8/5/pubmed PY - 2015/12/15/medline KW - aldosterone KW - fibrosis KW - galectin 3 KW - hypertension KW - inflammation SP - 767 EP - 75 JF - Hypertension (Dallas, Tex. : 1979) JO - Hypertension VL - 66 IS - 4 N2 - 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. SN - 1524-4563 UR - https://www.unboundmedicine.com/medline/citation/26238446/Galectin_3_blockade_inhibits_cardiac_inflammation_and_fibrosis_in_experimental_hyperaldosteronism_and_hypertension_ L2 - http://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.115.05876?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -