title: The impact of galectin-3 inhibition on aldosterone-induced cardiac and renal injuries.
abstract: OBJECTIVE
  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.
authors.affiliation: INSERM, Université de Lorraine UMR 1116, Vandoeuvre-Lès-Nancy, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Calvier
authors.affiliation: Universidad Complutense de Madrid, Madrid, Spain; Navarrabiomed-Fundación Miguel Servet, Pamplona, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Martinez-Martinez
authors.affiliation: Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Miana
authors.affiliation: Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Cachofeiro
authors.affiliation: INSERM, Université de Lorraine UMR 1116, Vandoeuvre-Lès-Nancy, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Rousseau
authors.affiliation: Navarrabiomed-Fundación Miguel Servet, Pamplona, Spain; Department of Cardiac Surgery, Complejo Hospitalario de Navarra, Pamplona, Spain.
authors.forename: J Rafael
authors.initials: JR
authors.lastname: Sádaba
authors.affiliation: 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.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: 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.
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.affiliation: INSERM, Université de Lorraine UMR 1116, Vandoeuvre-Lès-Nancy, France; Navarrabiomed-Fundación Miguel Servet, Pamplona, Spain. Electronic address: natalia.lopez.andres@navarra.es.
authors.forename: Natalia
authors.initials: N
authors.lastname: López-Andrés
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000450:Aldosterone / Q000633:toxicity; D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D037502:Galectin 3 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000627:therapeutic use*
chemical_list: D037502:Galectin 3; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone
keywords: aldosterone; biomarker; cardiorenal injury; collagen; galectin-3