Thyroid hormone receptor expression in cardiovascular disease and pharmacology
Author: Shahrara, Shiva
Date: 1999-12-10
Location: Föreläsningssalen R64, Huddinge sjukhus
Time: 9.00
Department: Institutionen för medicin, Huddinge Sjukhus / Department of Medicine at Huddinge University Hospital
Abstract
The heart is a major target organ for thyroid hormone actions. Thyroid hormone exerts effects on the myocardium, which are mediated by specific nuclear receptors. The thyroid hormone receptors (TR) are members of the steroid hormone receptor superfamily. These receptors regulate gene expression by binding to the promotor region of target genes as monomers, homodimers or heterodimers depending on the thyroid hormone response element (TRE) and the presence or absence of thyroid hormone.
Aims of the study: 1. To evaluate the organ specific expression of TR rnRNA and protein distribution in different human tissues in relation to the levels in the heart; 2. To investigate if TR rnRNA expression is affected in heart failure that is due to dilated cardiomyopathy (DCM) or chronic valvular disease (CVD); 3. To investigate if TR subtype rnRNA expression is affected by amiodarone treatment; 4. To clarify whether AT-1 cardiomyocytes express TR rnRNA and protein; and 5. To determine if propranolol may affect TR subtype rnRNA expression in mouse myocardium as well as in AT-1 cardiomyocytes.
Conclusions: 1. Specific patterns of TR [alpha]1, [alpha]2, ß1, and ß2 mRNA and protein in heart and other tissues suggest tissue-specific expression of TR subtypes. The TR mRNA and protein concentration were rather high in heart compared to the other tissues. There is also a correlation between the pattern of TR rnRNA and protein distribution in heart; 2. TR 8, and ß2 mRNA show increased expression in the failing canine heart with DCM or CVD; 3. In mouse heart, amiodarone downregulated the levels of TR [alpha]1 and ß mRNA dose-dependently in comparison to the control. There were however no differences in the TR[alpha]2 and TR62 rnRNA levels; 4. The AT-1 cardiomyocyte, like the mouse heart, expresses ligand-binding TR protein and TR [alpha]1 [alpha]2, ß1 and ß2 mRNA, although in lower quantities. This suggests a highly differentiated state of the AT-1 cardiomyocyte. This cell line can thus be suitable for studies of cellular effects of T3 on cardiac cells; and 5. Propranolol downregulated the levels of TR[alpha]1 and ß1 rnRNA in mouse heart and of TRß1 rnRNA in AT-1 cardiomyocytes in comparison to control.
Aims of the study: 1. To evaluate the organ specific expression of TR rnRNA and protein distribution in different human tissues in relation to the levels in the heart; 2. To investigate if TR rnRNA expression is affected in heart failure that is due to dilated cardiomyopathy (DCM) or chronic valvular disease (CVD); 3. To investigate if TR subtype rnRNA expression is affected by amiodarone treatment; 4. To clarify whether AT-1 cardiomyocytes express TR rnRNA and protein; and 5. To determine if propranolol may affect TR subtype rnRNA expression in mouse myocardium as well as in AT-1 cardiomyocytes.
Conclusions: 1. Specific patterns of TR [alpha]1, [alpha]2, ß1, and ß2 mRNA and protein in heart and other tissues suggest tissue-specific expression of TR subtypes. The TR mRNA and protein concentration were rather high in heart compared to the other tissues. There is also a correlation between the pattern of TR rnRNA and protein distribution in heart; 2. TR 8, and ß2 mRNA show increased expression in the failing canine heart with DCM or CVD; 3. In mouse heart, amiodarone downregulated the levels of TR [alpha]1 and ß mRNA dose-dependently in comparison to the control. There were however no differences in the TR[alpha]2 and TR62 rnRNA levels; 4. The AT-1 cardiomyocyte, like the mouse heart, expresses ligand-binding TR protein and TR [alpha]1 [alpha]2, ß1 and ß2 mRNA, although in lower quantities. This suggests a highly differentiated state of the AT-1 cardiomyocyte. This cell line can thus be suitable for studies of cellular effects of T3 on cardiac cells; and 5. Propranolol downregulated the levels of TR[alpha]1 and ß1 rnRNA in mouse heart and of TRß1 rnRNA in AT-1 cardiomyocytes in comparison to control.
List of papers:
I. Shahrara S, Drvota V, Sylvén C (1999). Organ specific expression of thyroid hormone receptor mRNA and protein in different human tissues. Biol Pharm Bull. 22(10):1027-1033.
Pubmed
II. Shahrara S, Tidholm A, Drvota V, Häggström J, Sylvén C (1998). Upregulation of thyroid hormone receptor beta 1 and beta 2 messenger RNA in the myocardium of dogs with dilated cardiomyopathy or chronic valvular disease. Am J Vet Res. 60(7):848-852.
Pubmed
III. Shahrara S, Drvota V (1999). Thyroid hormone alpha1 and beta1 receptor mRNA are downregulated by amiodarone in mouse myocardium. J Cardiovasc Pharmacol. 34(2):261-267.
Pubmed
IV. Shahrara S, Drvota V, Blange I, Törmä H, Sylvén C (1997). Characterization of AT-1 cardiomyocytes as a model for studies of T3 effects on cardiac cells. Biochem Biophys Res Commun. 237(2):303-306.
Pubmed
V. Shahrara S, Drvota V, Sylvén S. Subtype specific downregulation of thyroid hormone receptor mRNA by propranolol in mouse myocardium and AT-1 cardiomyocytes. [Submitted]
I. Shahrara S, Drvota V, Sylvén C (1999). Organ specific expression of thyroid hormone receptor mRNA and protein in different human tissues. Biol Pharm Bull. 22(10):1027-1033.
Pubmed
II. Shahrara S, Tidholm A, Drvota V, Häggström J, Sylvén C (1998). Upregulation of thyroid hormone receptor beta 1 and beta 2 messenger RNA in the myocardium of dogs with dilated cardiomyopathy or chronic valvular disease. Am J Vet Res. 60(7):848-852.
Pubmed
III. Shahrara S, Drvota V (1999). Thyroid hormone alpha1 and beta1 receptor mRNA are downregulated by amiodarone in mouse myocardium. J Cardiovasc Pharmacol. 34(2):261-267.
Pubmed
IV. Shahrara S, Drvota V, Blange I, Törmä H, Sylvén C (1997). Characterization of AT-1 cardiomyocytes as a model for studies of T3 effects on cardiac cells. Biochem Biophys Res Commun. 237(2):303-306.
Pubmed
V. Shahrara S, Drvota V, Sylvén S. Subtype specific downregulation of thyroid hormone receptor mRNA by propranolol in mouse myocardium and AT-1 cardiomyocytes. [Submitted]
Issue date: 1999-11-19
Publication year: 1999
ISBN: 91-628-3766-4
Statistics
Total Visits
Views | |
---|---|
Thyroid ...(legacy) | 531 |
Thyroid ... | 142 |
Total Visits Per Month
October 2023 | November 2023 | December 2023 | January 2024 | February 2024 | March 2024 | April 2024 | |
---|---|---|---|---|---|---|---|
Thyroid ... | 1 | 0 | 2 | 1 | 1 | 0 | 0 |
Top country views
Views | |
---|---|
United States | 147 |
Germany | 83 |
China | 60 |
Sweden | 45 |
Japan | 16 |
South Korea | 10 |
Russia | 9 |
Canada | 8 |
France | 7 |
Switzerland | 6 |
Top cities views
Views | |
---|---|
Sunnyvale | 32 |
Nürnberg | 27 |
Kiez | 25 |
Shenzhen | 21 |
Beijing | 17 |
Tokyo | 15 |
Mountain View | 11 |
Seoul | 9 |
Ashburn | 8 |
University Park | 7 |