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

OBJECTIVES This study investigated whether gatectin (Gal)-3 inhibition could block aldosterone-induced cardiac and renal fibrosis and improve cardiorenal dysfunction. BACKGROUND Atdosterone 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 beta-gatactoside-binding lectin, is increased in heart failure and kidney injury. METHODS Rats were treated with aldosterone-salt combined with spironotactone (a mineralocorticoid receptor antagonist) or modified citrus pectin (a Gat-3 inhibitor), for 3 weeks. Wild-type and Gal-3 knockout mice were treated with atdosterone 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 atdosterone-salt treatment. Spironotactone or modified citrus pectin treatment reversed all of these effects. In wild-type mice, atdosterone did not alter blood pressure levels but increased cardiac and renal Gal-3 expression, fibrosis, and renal epithelial-mesenchymat 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 rote for Gal-3 in cardiorenal remodeling and dysfunction induced by aldosterone. Gal-3 could be used as a new biotarget for specific pharmacological interventions. (C) 2015 by the American College of Cardiology Foundation.