Cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice
IntroductionThyroid hormones (THs) are known to have various effects on the cardiovascular system. However, the impact of TH levels on preexisting cardiac diseases is still unclear. Pressure overload due to arterial hypertension or aortic stenosis and aging are major risk factors for the development...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2024.1339741/full |
| _version_ | 1797300391265697792 |
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| author | Helena Kerp Janina Gassen Susanne Camilla Grund Georg Sebastian Hönes Stefanie Dörr Jens Mittag Nina Härting Frank Kaiser Lars Christian Moeller Kristina Lorenz Kristina Lorenz Dagmar Führer |
| author_facet | Helena Kerp Janina Gassen Susanne Camilla Grund Georg Sebastian Hönes Stefanie Dörr Jens Mittag Nina Härting Frank Kaiser Lars Christian Moeller Kristina Lorenz Kristina Lorenz Dagmar Führer |
| author_sort | Helena Kerp |
| collection | DOAJ |
| description | IntroductionThyroid hormones (THs) are known to have various effects on the cardiovascular system. However, the impact of TH levels on preexisting cardiac diseases is still unclear. Pressure overload due to arterial hypertension or aortic stenosis and aging are major risk factors for the development of structural and functional abnormalities and subsequent heart failure. Here, we assessed the sensitivity to altered TH levels in aged mice with maladaptive cardiac hypertrophy and cardiac dysfunction induced by transverse aortic constriction (TAC).MethodsMice at the age of 12 months underwent TAC and received T4 or anti-thyroid medication in drinking water over the course of 4 weeks after induction of left ventricular pressure overload.ResultsT4 excess or deprivation in older mice had no or only very little impact on cardiac function (fractional shortening), cardiac remodeling (cardiac wall thickness, heart weight, cardiomyocyte size, apoptosis, and interstitial fibrosis), and mortality. This is surprising because T4 excess or deprivation had significantly changed the outcome after TAC in young 8-week-old mice. Comparing the gene expression of deiodinases (Dio) 2 and 3 and TH receptor alpha (TRα) 1 and the dominant-negative acting isoform TRα2 between young and aged mice revealed that aged mice exhibited a higher expression of TRα2 and Dio3, while expression of Dio2 was reduced compared with young mice. These changes in Dio2 and 3 expressions might lead to reduced TH availability in the hearts of 12-month-old mice accompanied by reduced TRα action due to higher TRα2.DiscussionIn summary, our study shows that low and high TH availability have little impact on cardiac function and remodeling in older mice with preexisting pressure-induced cardiac damage. This observation seems to be the result of an altered expression of deiodinases and TRα isoforms, thus suggesting that even though cardiovascular risk is increasing with age, the response to TH stress may be dampened in certain conditions. |
| first_indexed | 2024-03-07T23:07:31Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-07T23:07:31Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-d63a415a73d242b091129ce12f56a6f12024-02-22T04:51:30ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-02-011510.3389/fendo.2024.13397411339741Cardiac recovery from pressure overload is not altered by thyroid hormone status in old miceHelena Kerp0Janina Gassen1Susanne Camilla Grund2Georg Sebastian Hönes3Stefanie Dörr4Jens Mittag5Nina Härting6Frank Kaiser7Lars Christian Moeller8Kristina Lorenz9Kristina Lorenz10Dagmar Führer11Department 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, GermanyDepartment of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyCardiovascular Pharmacology, Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, GermanyInstitute of Endocrinology and Diabetes and Center for Brain, Behavior and Metabolism, University Hospital Schleswig-Holstein (UKSH), University of Lübeck, Lübeck, GermanyInstitute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyCardiovascular Pharmacology, Leibniz-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, GermanyIntroductionThyroid hormones (THs) are known to have various effects on the cardiovascular system. However, the impact of TH levels on preexisting cardiac diseases is still unclear. Pressure overload due to arterial hypertension or aortic stenosis and aging are major risk factors for the development of structural and functional abnormalities and subsequent heart failure. Here, we assessed the sensitivity to altered TH levels in aged mice with maladaptive cardiac hypertrophy and cardiac dysfunction induced by transverse aortic constriction (TAC).MethodsMice at the age of 12 months underwent TAC and received T4 or anti-thyroid medication in drinking water over the course of 4 weeks after induction of left ventricular pressure overload.ResultsT4 excess or deprivation in older mice had no or only very little impact on cardiac function (fractional shortening), cardiac remodeling (cardiac wall thickness, heart weight, cardiomyocyte size, apoptosis, and interstitial fibrosis), and mortality. This is surprising because T4 excess or deprivation had significantly changed the outcome after TAC in young 8-week-old mice. Comparing the gene expression of deiodinases (Dio) 2 and 3 and TH receptor alpha (TRα) 1 and the dominant-negative acting isoform TRα2 between young and aged mice revealed that aged mice exhibited a higher expression of TRα2 and Dio3, while expression of Dio2 was reduced compared with young mice. These changes in Dio2 and 3 expressions might lead to reduced TH availability in the hearts of 12-month-old mice accompanied by reduced TRα action due to higher TRα2.DiscussionIn summary, our study shows that low and high TH availability have little impact on cardiac function and remodeling in older mice with preexisting pressure-induced cardiac damage. This observation seems to be the result of an altered expression of deiodinases and TRα isoforms, thus suggesting that even though cardiovascular risk is increasing with age, the response to TH stress may be dampened in certain conditions.https://www.frontiersin.org/articles/10.3389/fendo.2024.1339741/fullmaladaptive cardiac hypertrophythyroid hormonetransverse aortic constrictionagingthyroid hormone receptordeiodinase |
| spellingShingle | Helena Kerp Janina Gassen Susanne Camilla Grund Georg Sebastian Hönes Stefanie Dörr Jens Mittag Nina Härting Frank Kaiser Lars Christian Moeller Kristina Lorenz Kristina Lorenz Dagmar Führer Cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice Frontiers in Endocrinology maladaptive cardiac hypertrophy thyroid hormone transverse aortic constriction aging thyroid hormone receptor deiodinase |
| title | Cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice |
| title_full | Cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice |
| title_fullStr | Cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice |
| title_full_unstemmed | Cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice |
| title_short | Cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice |
| title_sort | cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice |
| topic | maladaptive cardiac hypertrophy thyroid hormone transverse aortic constriction aging thyroid hormone receptor deiodinase |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1339741/full |
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