Molecular defects in cardiac myofibrillar proteins due to thyroid hormone imbalance and diabetes.
The heart very often becomes a victim of endocrine abnormalities such as thyroid hormone imbalance and insulin deficiency, which are manifested in a broad spectrum of cardiac dysfunction from mildly compromised function to severe heart failure. These functional changes in the heart are largely independent of alterations in the coronary arteries and instead reside at the level of cardiomyocytes. The status of cardiac function reflects the net of underlying subcellular modifications induced by an increase or decrease in thyroid hormone and insulin plasma levels. Changes in the contractile and regulatory proteins constitute molecular and structural alterations in myofibrillar assembly, called myofibrillar remodeling. These alterations may be adaptive or maladaptive with respect to the functional and metabolic demands on the heart as a consequence of the altered endocrine status in the body. There is a substantial body of information to indicate alterations in myofibrillar proteins including actin, myosin, tropomyosin, troponin, titin, desmin, and myosin-binding protein C in conditions such as hyperthyroidism, hypothyroidism, and diabetes. The present article is focussed on discussion how myofibrillar proteins are altered in response to thyroid hormone imbalance and lack of insulin or its responsiveness, and how their structural and functional changes explain the contractile defects in the heart.
Machackova
Jarmila
J
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada.
Barta
Judit
J
Dhalla
Naranjan S
NS
D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D013959:Thyroid Diseases / Q000378:metabolism* / Q000473:pathology; D013963:Thyroid Hormones / Q000378:metabolism*
D009124:Muscle Proteins; D013963:Thyroid Hormones