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

Research output: Contribution to journalArticle

96 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Galectin 3
Aldosterone
Kidney
Wounds and Injuries
Fibrosis
Spironolactone
Salts
Knockout Mice
Pharmacology
Mineralocorticoid Receptor Antagonists
Galactosides
Hyperaldosteronism
Epithelial-Mesenchymal Transition
Cardiomegaly
Lectins
Heart Failure
Hemodynamics

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., ... 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

The impact of galectin-3 inhibition on aldosterone-induced cardiac and renal injuries. / Calvier, Laurent; Martinez-Martinez, Ernesto; Miana, Maria; Cachofeiro, Victoria; Rousseau, Elodie; Sádaba, J. Rafael; Zannad, Faiez; Rossignol, Patrick; López-Andrés, Natalia.

In: JACC: Heart Failure, Vol. 3, No. 1, 01.01.2015, p. 59-67.

Research output: Contribution to journalArticle

Calvier, L, Martinez-Martinez, E, Miana, M, Cachofeiro, V, Rousseau, E, Sádaba, JR, Zannad, F, Rossignol, P & López-Andrés, N 2015, 'The impact of galectin-3 inhibition on aldosterone-induced cardiac and renal injuries', JACC: Heart Failure, vol. 3, no. 1, pp. 59-67. https://doi.org/10.1016/j.jchf.2014.08.002
Calvier, Laurent ; Martinez-Martinez, Ernesto ; Miana, Maria ; Cachofeiro, Victoria ; Rousseau, Elodie ; Sádaba, J. Rafael ; Zannad, Faiez ; Rossignol, Patrick ; López-Andrés, Natalia. / The impact of galectin-3 inhibition on aldosterone-induced cardiac and renal injuries. In: JACC: Heart Failure. 2015 ; Vol. 3, No. 1. pp. 59-67.
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