Induction of thyroid hormone-degrading deiodinase in cardiac hypertrophy and failure
The similarities between the changes in cardiac gene expression in pathological ventricular hypertrophy and hypothyroidism suggest a role of impaired cardiac thyroid hormone (TH) action in the development of contractile dysfunction during chronic cardiac pressure overload. Here we studied the possible involvement of altered cardiac TH metabolism using a rat model of right-ventricular (RV) hypertrophy induced by pressure-overload. Pathological RV hypertrophy was indicated by decreased mRNA levels of sarcoplasmic reticulum(SR) Ca2-ATPase type 2a (SERCA2a) and myosin heavy chain a (MHCalpha), and increased levels of MHCbeta mRNA. Enzyme activity of type HI deiodinase (D3), which converts T4 and T3 to the inactive compounds rT3 and 3,3'-T2, respectively, was identified in ventricular tissue. This activity was stimulated up to five fold in hypertrophic RV, but remained unaltered in the non-hypertrophic left ventricle (LV). A low level of type Ideiodinase activity was also detected, which decreased significantly in both RV and LV. Stimulation of RV D3 activity was significantly higher in those animals in which hypertrophy progressed to heart failure, compared to animals that developed compensatory hypertrophy. The induction of a cardiac TR-degrading deiodinase maybe expected to result in reduced cellular levels of T3 and thereby contribute to a local hypothyroid state in the hypertrophic and, particularly, in the failing ventricle.
|Animals, Body Weight/physiology, Cardiomegaly/*enzymology, Gene Expression Regulation, Enzymologic, Heart Failure, Congestive/*enzymology, Heart Ventricles/enzymology, Iodide Peroxidase/*biosynthesis/genetics, Male, Organ Size/physiology, RNA, Messenger/biosynthesis/genetics, Rats, Rats, Wistar, Research Support, Non-U.S. Gov't, Thyroid Hormones/blood, Up-Regulation/genetics|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Wassen, F.W.J.S, Schiel, A.E, Kaptein, E, Bakker, O, Visser, T.J, Simonides, W.S, & Kuiper, G.G.J.M. (2002). Induction of thyroid hormone-degrading deiodinase in cardiac hypertrophy and failure. Endocrinology. Retrieved from http://hdl.handle.net/1765/9922