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

• Published in: JACC. Heart failure Vol. 3; no. 1; pp. 59 - 67
• Main Authors: Calvier, Laurent, Martinez-Martinez, Ernesto, Miana, Maria, Cachofeiro, Victoria, Rousseau, Elodie, Sádaba, J. Rafael, Zannad, Faiez, Rossignol, Patrick, López-Andrés, Natalia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2015; Elsevier/American College of Cardiology
• Subjects: Acute Kidney Injury; Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Acute Kidney Injury - metabolism; Aldosterone; Aldosterone - toxicity; Animals; biomarker; Cardiology and cardiovascular system; cardiorenal injury; Cardiovascular; collagen; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Galectin 3; Galectin 3 - antagonists & inhibitors; Galectin 3 - biosynthesis; Heart Failure; Heart Failure - chemically induced; Heart Failure - drug therapy; Heart Failure - metabolism; Human health and pathology; Immunohistochemistry; Life Sciences; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mineralocorticoid Receptor Antagonists; Mineralocorticoid Receptor Antagonists - therapeutic use; Rats; Rats, Wistar; Spironolactone; Spironolactone - therapeutic use; NGAL; KO; MR; aldosterone; SMA; collagen; Aldo; LV; biomarker; BP; Gal; cardiorenal injury; MCP; galectin-3; WT; HF; modified citrus pectin; left ventricular; knockout; blood pressure; heart failure; mineralocorticoid receptor; neutrophil gelatinase associated lipocalin; galectin; wild-type; smooth muscle actin
• ISSN: 2213-1779; 2213-1787; 2213-1787
• DOI: 10.1016/j.jchf.2014.08.002

This study investigated whether galectin (Gal)-3 inhibition could block aldosterone-induced cardiac and renal fibrosis and improve cardiorenal dysfunction. 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. 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. 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. 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.