Regulation of iodothyronine deiodinase and roles of thyroid hormones in human coronary artery smooth muscle cells
Regulation of iodothyronine deiodinase and roles of thyroid hormones in human coronary artery smooth muscle cells
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DOI：
10.1016/j.atherosclerosis.2005.07.018
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发表时间：
2006-05-01
期刊：
影响因子：
5.3
通讯作者：
Murakami, M
中科院分区：
文献类型：
--
作者：
Kasahara, T;Tsunekawa, K;Murakami, M
据报道，甲状腺激素对外周血管系统有显著影响，包括舒张血管平滑肌细胞和预防动脉粥样硬化。为了发挥其生物活性，甲状腺素（T-4）需要通过1型和2型碘甲状腺原氨酸脱碘酶转化为3，5，3 '-三碘甲状腺原氨酸（T-3）。我们在体外培养的人冠状动脉平滑肌细胞（human coronary artery smooth muscle cells，hCASMCs）中发现了2型碘甲状腺原氨酸脱碘酶（type 2 iodothyronine deiodinase，D2）的表达，在本研究中，我们观察了稳定的前列环素类似物贝前列素钠（berprost sodium，BPS）和血小板衍生生长因子（platelet derived growth factor，PDGF）对hCASMCs中D2表达的调控，以及甲状腺激素在hCASMCs功能中的作用。BPS增加D2表达，而PDGF抑制BPS刺激的D2表达，而不影响hCASMC中cAMP的产生。PDGF促进hCASMC DNA合成，而BPS、T-3或T-4抑制PDGF刺激的DNA合成。3，3 '，5'-三碘甲状腺原氨酸（rT（3））抑制D2活性部分恢复了T-4对PDGF刺激的hCASMC DNA合成的抑制。PDGF可增强hCASMCs的迁移活性，而BPS、T-3或T-4可抑制PDGF对hCASMCs迁移活性的促进作用，提示BPS可增强hCASMCs D2的表达，而PDGF可抑制hCASMCs D2的表达，提示细胞内甲状腺激素的激活可能参与了hCASMCs DNA合成和迁移活性的抑制。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
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 (T-4) needs to be converted to 3,5,3'-triiodothyronine (T-3) 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, T-3 or T-4 suppressed PDGF stimulated DNA synthesis in hCASMCs. Inhibition of D2 activity by 3,3',5'-triiodothyronine (rT(3)) partially restored T-4 suppression of PDGF stimulated DNA synthesis in hCASMCs. PDGF increased migration activity, whereas BPS, T-3 or T-4 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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.