Regulation of iodothyronine deiodinase and roles of thyroid hormones in human coronary artery smooth muscle cells.
Thyroid hormones have been reported to have significant effects on the peripheral vascular system, including relaxation of vascular smooth muscle cells and prevention of atherosclerosis. To exert its biological activity, thyroxine (T4) needs to be converted to 3,5,3'-triiodothyronine (T3) by type 1 and type 2 iodothyronine deiodinases. We have previously identified type 2 iodothyronine deiodinase (D2) expression in cultured human coronary artery smooth muscle cells (hCASMCs). In the present study, we have characterized the regulation of D2 expression in hCASMCs by stable prostacyclin analogue beraprost sodium (BPS) and platelet derived growth factor (PDGF), and the roles of thyroid hormones in the functions of hCASMCs. BPS increased D2 expression, whereas PDGF suppressed BPS stimulated D2 expression without affecting cAMP production in hCASMCs. PDGF increased DNA synthesis, while BPS, T3 or T4 suppressed PDGF stimulated DNA synthesis in hCASMCs. Inhibition of D2 activity by 3,3',5'-triiodothyronine (rT3) partially restored T4 suppression of PDGF stimulated DNA synthesis in hCASMCs. PDGF increased migration activity, whereas BPS, T3 or T4 suppressed PDGF stimulated migration activity of hCASMCs. These results suggest that D2 expression is increased by BPS and suppressed by PDGF in hCASMCs, and that intracellular thyroid hormone activation may be involved in the suppression of DNA synthesis and migration activity of hCASMCs.
Kasahara
Takayuki
T
Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi 371-8511, Japan.
Tsunekawa
Katsuhiko
K
Seki
Koji
K
Mori
Masatomo
M
Murakami
Masami
M
D015152:Blotting, Northern; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism / Q000517:prevention & control; D003331:Coronary Vessels / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D000242:Cyclic AMP / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D007453:Iodide Peroxidase / Q000096:biosynthesis / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics*; D013963:Thyroid Hormones / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D000097564:Iodothyronine Deiodinase Type II
D000242:Cyclic AMP; D011464:Epoprostenol; D007453:Iodide Peroxidase; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014665:Vasodilator Agents; D000097564:Iodothyronine Deiodinase Type II; C048081:beraprost