Protective Effects of Thyroid Hormone Deprivation on Progression of Maladaptive Cardiac Hypertrophy and Heart Failure
Purpose: Thyroid hormones (TH) play a central role for cardiac function. TH influence heart rate and cardiac contractility, and altered thyroid function is associated with increased cardiovascular morbidity and mortality. The precise role of TH in onset and progression of heart failure still require...
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2021-07-01
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doaj-5c8f5d3052414b1fa1475ecb7c3370522021-07-30T06:11:25ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-07-01810.3389/fcvm.2021.683522683522Protective Effects of Thyroid Hormone Deprivation on Progression of Maladaptive Cardiac Hypertrophy and Heart FailureHelena Kerp0Georg Sebastian Hönes1Elen Tolstik2Judith Hönes-Wendland3Janina Gassen4Lars Christian Moeller5Kristina Lorenz6Kristina Lorenz7Dagmar Führer8Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyLeibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, GermanyDepartment of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyLeibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, GermanyInstitute of Pharmacology and Toxicology, University of Würzburg, Würzburg, GermanyDepartment of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyPurpose: Thyroid hormones (TH) play a central role for cardiac function. TH influence heart rate and cardiac contractility, and altered thyroid function is associated with increased cardiovascular morbidity and mortality. The precise role of TH in onset and progression of heart failure still requires clarification.Methods: Chronic left ventricular pressure overload was induced in mouse hearts by transverse aortic constriction (TAC). One week after TAC, alteration of TH status was induced and the impact on cardiac disease progression was studied longitudinally over 4 weeks in mice with hypo- or hyperthyroidism and was compared to euthyroid TAC controls. Serial assessment was performed for heart function (2D M-mode echocardiography), heart morphology (weight, fibrosis, and cardiomyocyte cross-sectional area), and molecular changes in heart tissues (TH target gene expression, apoptosis, and mTOR activation) at 2 and 4 weeks.Results: In diseased heart, subsequent TH restriction stopped progression of maladaptive cardiac hypertrophy and improved cardiac function. In contrast and compared to euthyroid TAC controls, increased TH availability after TAC propelled maladaptive cardiac growth and development of heart failure. This was accompanied by a rise in cardiomyocyte apoptosis and mTOR pathway activation.Conclusion: This study shows, for the first time, a protective effect of TH deprivation against progression of pathological cardiac hypertrophy and development of congestive heart failure in mice with left ventricular pressure overload. Whether this also applies to the human situation needs to be determined in clinical studies and would infer a critical re-thinking of management of TH status in patients with hypertensive heart disease.https://www.frontiersin.org/articles/10.3389/fcvm.2021.683522/fullthyroid hormonesmaladaptive cardiac hypertrophypressure-overloadheart failuremice |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Helena Kerp Georg Sebastian Hönes Elen Tolstik Judith Hönes-Wendland Janina Gassen Lars Christian Moeller Kristina Lorenz Kristina Lorenz Dagmar Führer |
spellingShingle |
Helena Kerp Georg Sebastian Hönes Elen Tolstik Judith Hönes-Wendland Janina Gassen Lars Christian Moeller Kristina Lorenz Kristina Lorenz Dagmar Führer Protective Effects of Thyroid Hormone Deprivation on Progression of Maladaptive Cardiac Hypertrophy and Heart Failure Frontiers in Cardiovascular Medicine thyroid hormones maladaptive cardiac hypertrophy pressure-overload heart failure mice |
author_facet |
Helena Kerp Georg Sebastian Hönes Elen Tolstik Judith Hönes-Wendland Janina Gassen Lars Christian Moeller Kristina Lorenz Kristina Lorenz Dagmar Führer |
author_sort |
Helena Kerp |
title |
Protective Effects of Thyroid Hormone Deprivation on Progression of Maladaptive Cardiac Hypertrophy and Heart Failure |
title_short |
Protective Effects of Thyroid Hormone Deprivation on Progression of Maladaptive Cardiac Hypertrophy and Heart Failure |
title_full |
Protective Effects of Thyroid Hormone Deprivation on Progression of Maladaptive Cardiac Hypertrophy and Heart Failure |
title_fullStr |
Protective Effects of Thyroid Hormone Deprivation on Progression of Maladaptive Cardiac Hypertrophy and Heart Failure |
title_full_unstemmed |
Protective Effects of Thyroid Hormone Deprivation on Progression of Maladaptive Cardiac Hypertrophy and Heart Failure |
title_sort |
protective effects of thyroid hormone deprivation on progression of maladaptive cardiac hypertrophy and heart failure |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cardiovascular Medicine |
issn |
2297-055X |
publishDate |
2021-07-01 |
description |
Purpose: Thyroid hormones (TH) play a central role for cardiac function. TH influence heart rate and cardiac contractility, and altered thyroid function is associated with increased cardiovascular morbidity and mortality. The precise role of TH in onset and progression of heart failure still requires clarification.Methods: Chronic left ventricular pressure overload was induced in mouse hearts by transverse aortic constriction (TAC). One week after TAC, alteration of TH status was induced and the impact on cardiac disease progression was studied longitudinally over 4 weeks in mice with hypo- or hyperthyroidism and was compared to euthyroid TAC controls. Serial assessment was performed for heart function (2D M-mode echocardiography), heart morphology (weight, fibrosis, and cardiomyocyte cross-sectional area), and molecular changes in heart tissues (TH target gene expression, apoptosis, and mTOR activation) at 2 and 4 weeks.Results: In diseased heart, subsequent TH restriction stopped progression of maladaptive cardiac hypertrophy and improved cardiac function. In contrast and compared to euthyroid TAC controls, increased TH availability after TAC propelled maladaptive cardiac growth and development of heart failure. This was accompanied by a rise in cardiomyocyte apoptosis and mTOR pathway activation.Conclusion: This study shows, for the first time, a protective effect of TH deprivation against progression of pathological cardiac hypertrophy and development of congestive heart failure in mice with left ventricular pressure overload. Whether this also applies to the human situation needs to be determined in clinical studies and would infer a critical re-thinking of management of TH status in patients with hypertensive heart disease. |
topic |
thyroid hormones maladaptive cardiac hypertrophy pressure-overload heart failure mice |
url |
https://www.frontiersin.org/articles/10.3389/fcvm.2021.683522/full |
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