Myocardial Aldosterone Receptor and Aquaporin 1 Up-Regulation Is Associated with Cardiomyocyte Remodeling in Human Heart Failure

Background: Abnormal aldosterone signaling is a recognized source of cardiovascular damage. Its influence on cardiomyocyte structure, function, and hormonal receptors when associated with heart failure is still unreported. Methods: Twenty-six consecutive patients with heart failure (LVEF < 40%) a...

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Autores principales:	Andrea Frustaci, Claudio Letizia, Cristina Chimenti, Romina Verardo, Maria Alfarano, Rossella Scialla, Giulia Bagnato, Fabio Miraldi, Luigi Sansone, Matteo Antonio Russo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hyperaldosteronism myocardial damage aldosterone receptor vacuolar degeneration cellular and molecular rehabilitation Medicine R
Acceso en línea:	https://doaj.org/article/242cf9251b404d2db7c3a8cd1b80e747
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spelling	oai:doaj.org-article:242cf9251b404d2db7c3a8cd1b80e7472021-11-11T17:31:04ZMyocardial Aldosterone Receptor and Aquaporin 1 Up-Regulation Is Associated with Cardiomyocyte Remodeling in Human Heart Failure10.3390/jcm102148542077-0383https://doaj.org/article/242cf9251b404d2db7c3a8cd1b80e7472021-10-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/21/4854https://doaj.org/toc/2077-0383Background: Abnormal aldosterone signaling is a recognized source of cardiovascular damage. Its influence on cardiomyocyte structure, function, and hormonal receptors when associated with heart failure is still unreported. Methods: Twenty-six consecutive patients with heart failure (LVEF < 40%) and normal coronaries and valves underwent left ventricular endomyocardial biopsy (EMB) for evaluation of myocardial substrate. Biopsy samples were processed for histology, electron microscopy, immunohistochemistry, and Western blot analysis of myocardial aldosterone receptor and aquaporin-1 correlated with plasma aldosterone (AD) and renin activity (PRA). Eight patients with virus-negative inflammatory cardiomyopathy (ICM) had a control EMB after 6 months of immunosuppressive therapy and recovery of cardiac function with re-evaluation of cardiomyocyte structure and receptor expression. Results: EMB in addition to the diagnosis of myocarditis (15 cases), dilated cardiomyopathy CM (6), alcohol CM (2), and diabetic CM (3) showed vacuolar degeneration and cloudy swelling of cardiomyocytes corresponding at electron microscopy to ions and water accumulation into cytosol, membrane-bound vesicles, nucleus, and other organelles, and was associated with an increased AD, PRA, and myocardial expression of aldosterone receptor (2.6 fold) and aquaporin 1 (2.7 fold). In the 8 patients recovered from ICM, cardiomyocyte diameter reduced with disappearance of intracellular vacuoles and normalization of cytosol, nucleus, and cell organelles’ electron-density, along with down-regulation of aldosterone receptor and aquaporin-1. Conclusion: Human heart failure is associated with overexpression of myocardial aldosterone receptor and aquaporin-1. These molecular changes are paralleled by intracellular water overloading and cardiomyocyte swelling and dysfunction. Cardiac recovery is accompanied by down-regulation of hormonal receptors and normalization of cell structure and composition.Andrea FrustaciClaudio LetiziaCristina ChimentiRomina VerardoMaria AlfaranoRossella SciallaGiulia BagnatoFabio MiraldiLuigi SansoneMatteo Antonio RussoMDPI AGarticlehyperaldosteronismmyocardial damagealdosterone receptorvacuolar degenerationcellular and molecular rehabilitationMedicineRENJournal of Clinical Medicine, Vol 10, Iss 4854, p 4854 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hyperaldosteronism myocardial damage aldosterone receptor vacuolar degeneration cellular and molecular rehabilitation Medicine R
spellingShingle	hyperaldosteronism myocardial damage aldosterone receptor vacuolar degeneration cellular and molecular rehabilitation Medicine R Andrea Frustaci Claudio Letizia Cristina Chimenti Romina Verardo Maria Alfarano Rossella Scialla Giulia Bagnato Fabio Miraldi Luigi Sansone Matteo Antonio Russo Myocardial Aldosterone Receptor and Aquaporin 1 Up-Regulation Is Associated with Cardiomyocyte Remodeling in Human Heart Failure
description	Background: Abnormal aldosterone signaling is a recognized source of cardiovascular damage. Its influence on cardiomyocyte structure, function, and hormonal receptors when associated with heart failure is still unreported. Methods: Twenty-six consecutive patients with heart failure (LVEF < 40%) and normal coronaries and valves underwent left ventricular endomyocardial biopsy (EMB) for evaluation of myocardial substrate. Biopsy samples were processed for histology, electron microscopy, immunohistochemistry, and Western blot analysis of myocardial aldosterone receptor and aquaporin-1 correlated with plasma aldosterone (AD) and renin activity (PRA). Eight patients with virus-negative inflammatory cardiomyopathy (ICM) had a control EMB after 6 months of immunosuppressive therapy and recovery of cardiac function with re-evaluation of cardiomyocyte structure and receptor expression. Results: EMB in addition to the diagnosis of myocarditis (15 cases), dilated cardiomyopathy CM (6), alcohol CM (2), and diabetic CM (3) showed vacuolar degeneration and cloudy swelling of cardiomyocytes corresponding at electron microscopy to ions and water accumulation into cytosol, membrane-bound vesicles, nucleus, and other organelles, and was associated with an increased AD, PRA, and myocardial expression of aldosterone receptor (2.6 fold) and aquaporin 1 (2.7 fold). In the 8 patients recovered from ICM, cardiomyocyte diameter reduced with disappearance of intracellular vacuoles and normalization of cytosol, nucleus, and cell organelles’ electron-density, along with down-regulation of aldosterone receptor and aquaporin-1. Conclusion: Human heart failure is associated with overexpression of myocardial aldosterone receptor and aquaporin-1. These molecular changes are paralleled by intracellular water overloading and cardiomyocyte swelling and dysfunction. Cardiac recovery is accompanied by down-regulation of hormonal receptors and normalization of cell structure and composition.
format	article
author	Andrea Frustaci Claudio Letizia Cristina Chimenti Romina Verardo Maria Alfarano Rossella Scialla Giulia Bagnato Fabio Miraldi Luigi Sansone Matteo Antonio Russo
author_facet	Andrea Frustaci Claudio Letizia Cristina Chimenti Romina Verardo Maria Alfarano Rossella Scialla Giulia Bagnato Fabio Miraldi Luigi Sansone Matteo Antonio Russo
author_sort	Andrea Frustaci
title	Myocardial Aldosterone Receptor and Aquaporin 1 Up-Regulation Is Associated with Cardiomyocyte Remodeling in Human Heart Failure
title_short	Myocardial Aldosterone Receptor and Aquaporin 1 Up-Regulation Is Associated with Cardiomyocyte Remodeling in Human Heart Failure
title_full	Myocardial Aldosterone Receptor and Aquaporin 1 Up-Regulation Is Associated with Cardiomyocyte Remodeling in Human Heart Failure
title_fullStr	Myocardial Aldosterone Receptor and Aquaporin 1 Up-Regulation Is Associated with Cardiomyocyte Remodeling in Human Heart Failure
title_full_unstemmed	Myocardial Aldosterone Receptor and Aquaporin 1 Up-Regulation Is Associated with Cardiomyocyte Remodeling in Human Heart Failure
title_sort	myocardial aldosterone receptor and aquaporin 1 up-regulation is associated with cardiomyocyte remodeling in human heart failure
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/242cf9251b404d2db7c3a8cd1b80e747
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Myocardial Aldosterone Receptor and Aquaporin 1 Up-Regulation Is Associated with Cardiomyocyte Remodeling in Human Heart Failure

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