The Impact of Galectin-3 Inhibition on Aldosterone-Induced Cardiac and Renal Injuries
| Autor: | Laurent Calvier, Natalia López-Andrés, J. Rafael Sadaba, Elodie Rousseau, María Miana, Patrick Rossignol, Faiez Zannad, Ernesto Martínez-Martínez, Victoria Cachofeiro |
|---|---|
| Přispěvatelé: | Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Fundación Miguel Servet, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Complejo Hospitalario de Navarra, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy] |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
collagen Renal Hypertrophy Galectin 3 030204 cardiovascular system & hematology Spironolactone MESH: Mice Knockout chemistry.chemical_compound Mice 0302 clinical medicine Mineralocorticoid receptor Fibrosis MESH: Animals Mineralocorticoid Receptor Antagonists Mice Knockout 0303 health sciences Aldosterone MESH: Enzyme-Linked Immunosorbent Assay cardiorenal injury Acute Kidney Injury Hyperaldosteronism Immunohistochemistry 3. Good health Galectin-3 MESH: Spironolactone biomarker Cardiology and Cardiovascular Medicine medicine.medical_specialty MESH: Rats MESH: Acute Kidney Injury Enzyme-Linked Immunosorbent Assay MESH: Mineralocorticoid Receptor Antagonists 03 medical and health sciences [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system MESH: Mice Inbred C57BL Internal medicine galectin-3 medicine Renal fibrosis Animals Rats Wistar MESH: Mice 030304 developmental biology Heart Failure aldosterone business.industry MESH: Aldosterone MESH: Immunohistochemistry MESH: Rats Wistar medicine.disease MESH: Galectin 3 MESH: Male Rats Mice Inbred C57BL Disease Models Animal Endocrinology chemistry MESH: Heart Failure MESH: Disease Models Animal business |
| Zdroj: | JACC: Heart Failure JACC: Heart Failure, Elsevier/American College of Cardiology, 2015, 3 (1), pp.59-67. ⟨10.1016/j.jchf.2014.08.002⟩ |
| ISSN: | 2213-1779 |
| DOI: | 10.1016/j.jchf.2014.08.002⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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