The Impact of Galectin-3 Inhibition on Aldosterone-Induced Cardiac and Renal Injuries

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.
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Submitted on : Wednesday, April 4, 2018 - 5:19:05 PM
Last modification on : Thursday, April 5, 2018 - 1:31:22 AM

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Laurent Calvier, Ernesto Martinez-Martinez, Maria Miana, Victoria Cachofeiro, Elodie Rousseau, et al.. The Impact of Galectin-3 Inhibition on Aldosterone-Induced Cardiac and Renal Injuries. JACC: Heart Failure, Elsevier/American College of Cardiology, 2015, 3 (1), pp.59 - 67. ⟨10.1016/j.jchf.2014.08.002⟩. ⟨hal-01758739⟩

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