Laurent Calvier1, Ernesto Martinez-Martinez2, Maria Miana3, Victoria Cachofeiro3, Elodie Rousseau1, J Rafael Sádaba4, Faiez Zannad5, Patrick Rossignol5, Natalia López-Andrés6. 1. INSERM, Université de Lorraine UMR 1116, Vandoeuvre-Lès-Nancy, France. 2. Universidad Complutense de Madrid, Madrid, Spain; Navarrabiomed-Fundación Miguel Servet, Pamplona, Spain. 3. Universidad Complutense de Madrid, Madrid, Spain. 4. Navarrabiomed-Fundación Miguel Servet, Pamplona, Spain; Department of Cardiac Surgery, Complejo Hospitalario de Navarra, Pamplona, Spain. 5. INSERM, Université de Lorraine UMR 1116, Vandoeuvre-Lès-Nancy, France; CHU Nancy, INSERM Clinical Investigation Center, CIC 9501, Vandoeuvre-Lès-Nancy, France; F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. 6. INSERM, Université de Lorraine UMR 1116, Vandoeuvre-Lès-Nancy, France; Navarrabiomed-Fundación Miguel Servet, Pamplona, Spain. Electronic address: natalia.lopez.andres@navarra.es.
Abstract
OBJECTIVES: This study investigated whether galectin (Gal)-3 inhibition could block aldosterone-induced cardiac and renal fibrosis and improve cardiorenal dysfunction. BACKGROUND: Aldosterone is involved in cardiac and renal fibrosis that is associated with the development of cardiorenal injury. However, the mechanisms of these interactions remain unclear. Gal-3, a β-galactoside-binding lectin, is increased in heart failure and kidney injury. METHODS: Rats were treated with aldosterone-salt combined with spironolactone (a mineralocorticoid receptor antagonist) or modified citrus pectin (a Gal-3 inhibitor), for 3 weeks. Wild-type and Gal-3 knockout mice were treated with aldosterone for 3 weeks. Hemodynamic, cardiac, and renal parameters were analyzed. RESULTS: Hypertensive aldosterone-salt-treated rats presented cardiac and renal hypertrophy (at morphometric, cellular, and molecular levels) and dysfunction. Cardiac and renal expressions of Gal-3 as well as levels of molecular markers attesting fibrosis were also augmented by aldosterone-salt treatment. Spironolactone or modified citrus pectin treatment reversed all of these effects. In wild-type mice, aldosterone did not alter blood pressure levels but increased cardiac and renal Gal-3 expression, fibrosis, and renal epithelial-mesenchymal transition. Gal-3 knockout mice were resistant to aldosterone effects. CONCLUSIONS: In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac and renal fibrosis and dysfunction but was prevented by pharmacological inhibition (modified citrus pectin) or genetic disruption of Gal-3. These data suggest a key role for Gal-3 in cardiorenal remodeling and dysfunction induced by aldosterone. Gal-3 could be used as a new biotarget for specific pharmacological interventions.
OBJECTIVES: This study investigated whether galectin (Gal)-3 inhibition could block aldosterone-induced cardiac and renal fibrosis and improve cardiorenal dysfunction. BACKGROUND:Aldosterone is involved in cardiac and renal fibrosis that is associated with the development of cardiorenal injury. However, the mechanisms of these interactions remain unclear. Gal-3, a β-galactoside-binding lectin, is increased in heart failure and kidney injury. METHODS:Rats were treated with aldosterone-salt combined with spironolactone (a mineralocorticoid receptor antagonist) or modified citrus pectin (a Gal-3 inhibitor), for 3 weeks. Wild-type and Gal-3 knockout mice were treated with aldosterone for 3 weeks. Hemodynamic, cardiac, and renal parameters were analyzed. RESULTS:Hypertensivealdosterone-salt-treated rats presented cardiac and renal hypertrophy (at morphometric, cellular, and molecular levels) and dysfunction. Cardiac and renal expressions of Gal-3 as well as levels of molecular markers attesting fibrosis were also augmented by aldosterone-salt treatment. Spironolactone or modified citrus pectin treatment reversed all of these effects. In wild-type mice, aldosterone did not alter blood pressure levels but increased cardiac and renal Gal-3 expression, fibrosis, and renal epithelial-mesenchymal transition. Gal-3 knockout mice were resistant to aldosterone effects. CONCLUSIONS: In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac and renal fibrosis and dysfunction but was prevented by pharmacological inhibition (modified citrus pectin) or genetic disruption of Gal-3. These data suggest a key role for Gal-3 in cardiorenal remodeling and dysfunction induced by aldosterone. Gal-3 could be used as a new biotarget for specific pharmacological interventions.
Authors: Anahita Ghorbani; Vijeta Bhambhani; Robert H Christenson; Wouter C Meijers; Rudolf A de Boer; Daniel Levy; Martin G Larson; Jennifer E Ho Journal: J Am Coll Cardiol Date: 2018-12-25 Impact factor: 24.094
Authors: Rabea Asleh; Maurice Enriquez-Sarano; Allan S Jaffe; Sheila M Manemann; Susan A Weston; Ruoxiang Jiang; Véronique L Roger Journal: J Am Coll Cardiol Date: 2019-05-14 Impact factor: 24.094
Authors: E Martínez-Martínez; L Calvier; P Rossignol; E Rousseau; A Fernández-Celis; R Jurado-López; M Laville; V Cachofeiro; N López-Andrés Journal: Int J Obes (Lond) Date: 2016-02-08 Impact factor: 5.095
Authors: Casey M Rebholz; Elizabeth Selvin; Menglu Liang; Christie M Ballantyne; Ron C Hoogeveen; David Aguilar; John W McEvoy; Morgan E Grams; Josef Coresh Journal: Kidney Int Date: 2017-08-31 Impact factor: 10.612