The impact of galectin-3 inhibition on aldosterone-induced cardiac and renal injuries

Laurent Calvier, Ernesto Martinez-Martinez, Maria Miana, Victoria Cachofeiro, Elodie Rousseau, J. Rafael Sádaba, Faiez Zannad, Patrick Rossignol, Natalia López-Andrés

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100 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)59-67
Number of pages9
JournalJACC: Heart Failure
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Aldosterone
  • Biomarker
  • Cardiorenal injury
  • Collagen
  • Galectin-3

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Calvier, L., Martinez-Martinez, E., Miana, M., Cachofeiro, V., Rousseau, E., Sádaba, J. R., Zannad, F., Rossignol, P., & López-Andrés, N. (2015). The impact of galectin-3 inhibition on aldosterone-induced cardiac and renal injuries. JACC: Heart Failure, 3(1), 59-67. https://doi.org/10.1016/j.jchf.2014.08.002