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Thyroid hormone-induced alterations in phospholamban-deficient mouse hearts
1From the Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati; the 2nd Department of Medicine, Szent-Gyorgyi Medical University, Szeged, Hungary;
Circulation Research
|September 19, 1998
Summary
Thyroid hormone affects heart function by altering sarcoplasmic reticulum Ca2+-ATPase and phospholamban levels. Phospholamban deficiency impacts cardiac contractility, revealing its critical role in mammalian heart responses to thyroid states.
Area of Science:
- Cardiology
- Molecular Biology
- Endocrinology
Background:
- Thyroid hormones significantly influence cardiac function.
- Sarcoplasmic reticulum Ca2+-ATPase and phospholamban are key regulators of cardiac contractility.
- Alterations in these proteins are linked to thyroid hormone effects on the heart.
Purpose of the Study:
- To elucidate the specific role of phospholamban in mediating thyroid hormone's effects on cardiac function.
- To investigate cardiac contractility and protein expression in phospholamban-deficient mice under varying thyroid states.
Main Methods:
- Induction of hypothyroidism and hyperthyroidism in phospholamban-deficient and wild-type mice.
- Assessment of left ventricular contractility under different preload and afterload conditions.
- Quantification of cardiac sarcoplasmic reticulum Ca2+-ATPase and phospholamban expression levels.
Main Results:
- Hypothyroidism decreased contractility in both mouse types, while hyperthyroidism enhanced it in wild-types but not phospholamban-deficient mice.
- Thyroid hormone-induced changes in sarcoplasmic reticulum Ca2+-ATPase levels occurred similarly in both phospholamban-deficient and wild-type hearts.
- Phospholamban-deficient hearts showed preserved basal contractility even in hypothyroidism, comparable to stimulated hyperthyroid wild-type hearts.
Conclusions:
- Thyroid hormones regulate cardiac sarcoplasmic reticulum Ca2+-ATPase levels independently of phospholamban.
- Phospholamban is crucial for mediating the full extent of thyroid hormone-induced cardiac hyperdynamic function.
- Phospholamban levels critically determine cardiac contractile responses to altered thyroid states.