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

Andrea Frustaci; Claudio Letizia; Cristina Chimenti; Romina Verardo; Maria Alfarano; Rossella Scialla; Giulia Bagnato; Fabio Miraldi; Luigi Sansone; Matteo Antonio Russo

doi:10.3390/jcm10214854

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

J Clin Med. 2021 Oct 22;10(21):4854. doi: 10.3390/jcm10214854.

Authors

Andrea Frustaci^{1

2}, Claudio Letizia³, Cristina Chimenti^{1

2}, Romina Verardo², Maria Alfarano¹, Rossella Scialla², Giulia Bagnato², Fabio Miraldi¹, Luigi Sansone⁴, Matteo Antonio Russo^{5

6}

Affiliations

¹ Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy.
² Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, 00149 Rome, Italy.
³ Department of Translation Medicine and Precision, Sapienza University, 00161 Rome, Italy.
⁴ Laboratory of Molecular and Cellular Pathology, IRCCS San Raffaele Pisana, 00163 Rome, Italy.
⁵ MEBIC Consortium, San Raffaele Open University, 00163 Rome, Italy.
⁶ IRCCS San Raffaele Pisana, 00163 Rome, Italy.

Abstract

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.

Keywords: aldosterone receptor; cellular and molecular rehabilitation; hyperaldosteronism; myocardial damage; vacuolar degeneration.