Abstract
Elevated thyroid-stimulating hormone (TSH) levels often accompany impaired LV diastolic function and subtle systolic dysfunction in subclinical hypothyroidism (sHT). These cardiac dysfunctions are characterized by increases in mean aortic acceleration and pre-ejection/ejection time ratios. To explore the mechanism underlying these pathologies, we investigated the effects of TSH on sarcoplasmic reticulum calcium ATPase (SERCA2a) activity and expression in neonatal rat cardiomyocytes. TSH inhibited SERCA2a activity and expression by binding to TSH receptors in cardiomyocyte membranes and inhibiting the protein kinase A/phoshpolamban (PKA/PLN) signaling pathway. These results suggest that increases in serum TSH levels contribute to the development of cardiac diastolic and systolic dysfunction.
Highlights
Hypothyroidism is characterized by elevated serum thyroid stimulating hormone (TSH) concentrations and reduced concentrations of free T4
Conventional echocardiography and videodensitometric analysis confirmed that myocardial contractility is reduced and both the active and passive phases of diastole are dysregulated in subclinical hypothyroidism (sHT), as indicated by the following: (a) a lower cyclic variation index (CVI) in sHT indicated altered myocardial intrinsic contractility; (b) lower systolic strain and strain rate revealed an impairment of myocardial regional deformability; (c) an increase in peak A and decrease in peak E mitral flow velocity that resulted in a decline in left ventricular diastolic function [8]
A distinct TSH receptor (TSHR) protein band was present in western blots from neonatal rat cardiomyocytes (NRCM) cells, the TSHR protein level was lower in NRCM cells than in positive control FRTL-5 cells; the TSHR band was not present in negative control CHO cells (Figure 2b)
Summary
Hypothyroidism is characterized by elevated serum thyroid stimulating hormone (TSH) concentrations and reduced concentrations of free T4. Several studies show that hypothyroidism changes myocardial oxygen consumption, cardiac output, and cardiac contractility, resulting in decreased heart output along with a prolonged isovolumic relaxation phase. Some of these cardiovascular symptoms result from the impact of thyroid hormone on the cardiovascular system [1]. We found that the risk of these cardiovascular events is increased in subclinical hypothyroidism (sHT), which is defined by elevated serum TSH with normal free thyroid hormone levels. Conventional echocardiography and videodensitometric analysis confirmed that myocardial contractility is reduced and both the active and passive phases of diastole are dysregulated in sHT, as indicated by the following: (a) a lower cyclic variation index (CVI) in sHT indicated altered myocardial intrinsic contractility; (b) lower systolic strain and strain rate revealed an impairment of myocardial regional deformability; (c) an increase in peak A and decrease in peak E mitral flow velocity that resulted in a decline in left ventricular diastolic function [8]
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