Reversible cardiac fibrosis and heart failure induced by conditional expression of an antisense mRNA of the mineralocorticoid receptor in cardiomyocytes
| Autor: | Brigitte Escoubet, Stephane Cailmail, Claude Delcayre, Antoine Ouvrard-Pascaud, Vanessa Delage, Frederic Jaisser, Brigitte Bocchi, Ahmed T. Beggah, Michel Peuchmaur, Nicolette Farman, Stefania Puttini |
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| Přispěvatelé: | Hormones corticostéroïdes et protéines de transport ionique dans les cellules épithéliales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Transports épithéliaux: bases structurales, modulations, modèles pathologiques, Biologie et physiopathologie du système cardiovasculaire, Pathologie pédiatrique (EA_3102), Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-IFR02, IFR02-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré, Cailmail, Stéphane |
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Cardiac fibrosis
Gene Expression 030204 cardiovascular system & hematology Spironolactone MESH: Base Sequence chemistry.chemical_compound Mice 0302 clinical medicine Mineralocorticoid receptor Fibrosis MESH: Aldosterone Antagonists MESH: Animals MESH: RNA Antisense Mineralocorticoid Receptor Antagonists 0303 health sciences Multidisciplinary Aldosterone Ventricular Remodeling Heart Biological Sciences Hyperaldosteronism [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system MESH: Fibrosis medicine.medical_specialty DNA Complementary MESH: Myocardium MESH: Gene Expression MESH: Mice Transgenic Molecular Sequence Data Mice Transgenic Biology 03 medical and health sciences [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Internal medicine medicine Animals RNA Antisense RNA Messenger Ventricular remodeling MESH: Mice 030304 developmental biology MESH: RNA Messenger Heart Failure MESH: Molecular Sequence Data Base Sequence Myocardium MESH: Receptor MESH: DNA Complementary medicine.disease MESH: Heart Disease Models Animal Endocrinology Receptors Mineralocorticoid chemistry Heart failure MESH: Heart Failure Congestive MESH: Disease Models Animal |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2002, 99, pp.7160-5. ⟨10.1073/pnas.102673599⟩ ResearcherID |
| ISSN: | 0027-8424 1091-6490 |
| Popis: | Cardiac failure is a common feature in the evolution of cardiac disease. Among the determinants of cardiac failure, the renin–angiotensin–aldosterone system has a central role, and antagonism of the mineralocorticoid receptor (MR) has been proposed as a therapeutic strategy. In this study, we questioned the role of the MR, not of aldosterone, on heart function, using an inducible and cardiac-specific transgenic mouse model. We have generated a conditional knock-down model by expressing solely in the heart an antisense mRNA directed against the murine MR, a transcription factor with unknown targets in cardiomyocytes. Within 2–3 mo, mice developed severe heart failure and cardiac fibrosis in the absence of hypertension or chronic hyperaldosteronism. Moreover, cardiac failure and fibrosis were fully reversible when MR antisense mRNA expression was subsequently suppressed. |
| Databáze: | OpenAIRE |
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