Thyroid hormone-regulated cardiac gene expression and cardiovascular disease

The effects of hypothyroidism on the cardiovascular system have been the subject of much research over the last several decades. The hypothyroid cardiac phenotype includes impaired contractile function, decreased cardiac output, and alterations in myocyte gene expression. In the setting of cardiac disease, as in other acute illnesses, alterations in thyroid hormone metabolism occur that result in decreased serum triiodothyronine (T(3)) levels. This is referred to as low T(3) syndrome. Similarities between the heart failure phenotype and the hypothyroid cardiac phenotype are numerous including changes in the expression of thyroid hormone regulated myocyte specific genes. The heart responds in a very sensitive manner to reduced circulating levels of T(3) with decreased expression of positively regulated genes and increased expression of negatively regulated genes. In the present paper we review data on thyroid hormone mediated cardiac specific gene transcriptional regulation. T(3) replacement therapy for hypothyroidism restores normal expression of these T(3) regulated genes and recent experiments suggest that the diseased human heart in congestive failure would benefit from similar T(3) replacement therapy.