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 periph eral vascular system, including relaxation of vascular smooth muscle cells and antiatherosclerotic effects. To exert its biological activity, thyroxin e, which is a major secretory product of thyroid gland, needs to be convert ed to 3,5,3'-triiodothyronine (T-3) by iodothyronine deiodinase. Type I iod othyronine deiodinase (DI) is widely distributed and maintains circulating T-3 level, whereas type II iodothyronine deiodinase (DII) is present in a l imited number of tissues to provide local intracellular T-3. In the present study, we have identified iodothyronine deiodinase in cultured human coron ary artery smooth muscle cells (hASMCs) and human aortic smooth muscle cell s (hASMCs). All of the characteristics of the deiodinating activity in hCAS MCs and hASMCs were compatible with DII, Northern analysis demonstrated tha t 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 forskol in. These data demonstrate, for the first time, the expression of DII in hu man vascular smooth muscle cells, which is regulated by a cAMP-mediated mec hanism. The present results suggest a previously unrecognized role of local T-3 production by DII in the pathophysiology of human vascular smooth musc le cells.