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Increased expression of thyroid hormone receptor isoforms in end-stage human congestive heart failure
G d'Amati1, C R di Gioia, D Mentuccia
1Dipartimento di Medicina Sperimentale e Patologia, Università degli studi di Roma "La Sapienza," Rome 00161, Italy.
Abstract:
Thyroid hormone plays an important role on myocardial development and function. The local effects of thyroid hormone are mediated by the receptor isoforms ultimately driving the expression of cardiac-specific genes. Although overt and subclinical thyroid dysfunction causes well-known changes in the cardiovascular system, little is known about local thyroid hormone action in normal and failing human myocardium. With a newly developed multiplex competitive RT-PCR method, we evaluated the expression of thyroid hormone receptor (TR) isoforms alpha-1, alpha-2, and beta-1 in normal human hearts and in end-stage congestive heart failure. A statistically significant difference in the expression of all three TR isoforms was observed among samples from normal subjects, ischemic heart disease (IHD), and dilated cardiomyopathy (DCM). In DCM, compared with normal, the studied TR isoforms were significantly increased. In IHD, the increased expression was found significant only for alpha-1 and alpha-2 isoforms. No differences were observed between the pathologic groups. In conclusion, a coordinated increment in the expression of the TR isoforms was observed in both DCM and IHD by multiplex competitive RT-PCR. The observed changes could represent a compensatory mechanism to myocardial failure or to locally altered thyroid hormone action.
Insights
Thyroid hormone receptor (TR) isoforms increase in failing human hearts, suggesting a compensatory response. This study investigated TR isoform expression in normal and failing myocardium, revealing significant changes in dilated cardiomyopathy and ischemic heart disease.
Area of Science:
- Cardiology
- Endocrinology
- Molecular Biology
Background:
- Thyroid hormone is crucial for heart development and function.
- Local thyroid hormone effects are mediated by receptor isoforms.
- Thyroid dysfunction impacts the cardiovascular system, but local actions in heart failure are unclear.
Purpose of the Study:
- To evaluate thyroid hormone receptor (TR) isoform expression in normal and failing human myocardium.
- To compare TR isoform expression in dilated cardiomyopathy (DCM) and ischemic heart disease (IHD) with normal hearts.
Main Methods:
- Utilized a novel multiplex competitive RT-PCR method.
- Quantified expression of TR alpha-1, alpha-2, and beta-1 isoforms.
- Analyzed samples from normal subjects, IHD, and DCM patients.
Main Results:
- Significant differences in all three TR isoforms were found between normal, IHD, and DCM groups.
- TR isoforms were significantly increased in DCM compared to normal hearts.
- TR alpha-1 and alpha-2 isoforms were significantly increased in IHD compared to normal hearts.
Conclusions:
- A coordinated increase in TR isoform expression was observed in both DCM and IHD.
- These changes may represent a compensatory mechanism for myocardial failure.
- Altered local thyroid hormone action could be involved in heart failure pathophysiology.