Thyroid hormone activation in human vascular smooth muscle cells: expression of type II iodothyronine deiodinase

Thyroid hormone has been reported to have significant effects on the peripheral vascular system, including relaxation of vascular smooth muscle cells and antiatherosclerotic effects. To exert its biological activity, thyroxine, which is a major secretory product of thyroid gland, needs to be converted to 3,5,3'-triiodothyronine (T(3)) by iodothyronine deiodinase. Type I iodothyronine deiodinase (DI) is widely distributed and maintains circulating T(3) level, whereas type II iodothyronine deiodinase (DII) is present in a limited number of tissues to provide local intracellular T(3). In the present study, we have identified iodothyronine deiodinase in cultured human coronary artery smooth muscle cells (hCASMCs) and human aortic smooth muscle cells (hASMCs). All of the characteristics of the deiodinating activity in hCASMCs and hASMCs were compatible with DII. Northern analysis demonstrated that DII mRNA was expressed in both hCASMCs and hASMCs, and DII mRNA levels as well as DII activities were rapidly increased by dibutyryl-cAMP or forskolin. These data demonstrate, for the first time, the expression of DII in human vascular smooth muscle cells, which is regulated by a cAMP-mediated mechanism. The present results suggest a previously unrecognized role of local T(3) production by DII in the pathophysiology of human vascular smooth muscle cells.