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Published on: February 10, 2013
Cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice
Helena Kerp1, Janina Gassen1, Susanne Camilla Grund1
1Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Insights
Altered thyroid hormone (TH) levels had minimal impact on cardiac function and remodeling in older mice with existing heart damage. This suggests a dampened response to TH stress in aged hearts due to changes in deiodinase and thyroid hormone receptor expression.
Area of Science:
- Cardiovascular physiology
- Endocrinology
- Aging research
Background:
- Thyroid hormones (THs) influence cardiovascular function, but their impact on pre-existing cardiac diseases, especially in aging, remains unclear.
- Pressure overload from conditions like hypertension or aortic stenosis, combined with aging, are key risk factors for heart failure.
- Understanding TH sensitivity in aged hearts with cardiac dysfunction is crucial for managing cardiovascular risk.
Purpose of the Study:
- To investigate the impact of altered thyroid hormone levels on aged mice with pressure-induced cardiac hypertrophy and dysfunction.
- To assess cardiac function, remodeling, and survival in response to thyroid hormone excess or deprivation in aged mice subjected to transverse aortic constriction (TAC).
Main Methods:
- 12-month-old mice underwent TAC to induce left ventricular pressure overload.
- Mice received T4 (thyroxine) or anti-thyroid medication for 4 weeks post-TAC.
- Cardiac function, remodeling markers (wall thickness, heart weight, cardiomyocyte size, apoptosis, fibrosis), mortality, and gene expression (deiodinases, TH receptors) were analyzed.
Main Results:
- Thyroid hormone excess or deprivation had minimal effects on cardiac function, remodeling, and mortality in aged mice post-TAC.
- These findings contrast with significant effects observed in younger mice subjected to similar conditions.
- Aged mice showed higher expression of TRα2 and Dio3, and reduced Dio2, potentially decreasing cardiac TH availability and action.
Conclusions:
- Altered thyroid hormone availability has limited impact on cardiac function and remodeling in older mice with pre-existing pressure-induced cardiac damage.
- This dampened response is likely due to altered expression of deiodinases and thyroid hormone receptor isoforms in aged hearts.
- Cardiovascular responses to thyroid hormone stress may be attenuated in aging, despite increasing cardiovascular risk with age.
Introduction:
Thyroid 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).
Methods:
Mice 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.
Results:
T4 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.
Discussion:
In 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.
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