Thiazolidinedione regulation of smooth muscle cell proliferation
Thiazolidinedione regulation of smooth muscle cell proliferation
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DOI：
10.1016/j.amjmed.2003.09.014
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发表时间：
2003-12-08
影响因子：
5.9
通讯作者：
Law, RE
中科院分区：
文献类型：
--
作者：
Bruemmer, D;Law, RE
成人动脉中膜的血管平滑肌细胞(VSMCs)通常处于静止状态，以低频率增殖，并被阻止在细胞周期的G(0)/G(1)期。VSMCs的增殖是对动脉损伤的反应，在动脉粥样硬化过程和再狭窄的发病机制中起着至关重要的作用。2型糖尿病患者血管成形术后再狭窄的风险增加，这是由于过度的内膜增生引起的。噻唑烷二酮(TZD)类胰岛素增敏剂通过减弱重要的细胞周期调节因子的活性来抑制VSMC的生长。TZD通过阻断生长因子诱导的视网膜母细胞瘤肿瘤抑制蛋白(Rb)的磷酸化，抑制细胞周期中从G(1)期到S期的进展。在再狭窄动物模型中，TZDS可抑制胰岛素敏感型和胰岛素抵抗型血管机械损伤后的内膜增生。使用曲格列酮的初步临床研究表明，在2型糖尿病患者中，使用这种TZD的患者植入冠状动脉支架后，内膜增生较少。还需要进一步的大型试验来证实TZD治疗可以预防血管成形术后的再狭窄。(C)2003年，由Excerpta Medica，Inc.
Vascular smooth muscle cells (VSMCs) in the media of adult arteries are normally quiescent, proliferate at low frequency, and are arrested in the G(0)/G(1) phase of the cell cycle. Proliferation of VSMCs occurs in response to arterial injury and plays a crucial role in the atherosclerotic process and in the pathogenesis of restenosis. Patients with type 2 diabetes mellitus are at increased risk for postangioplasty restenosis, which results from excessive intimal hyperplasia. Insulin sensitizers of the thiazolidinedione (TZD) class inhibit growth of VSMCs by attenuating the activity of important cell-cycle regulators. The TZDs inhibit progression from G(1) to S phase in the cell cycle by blocking growth factor-induced phosphorylation of retinoblastoma tumor suppressor protein (Rb). In animal models of restenosis, TZDs inhibit intimal hyperplasia after mechanical injury in both insulin-sensitive and insulin-resistant vessels. Preliminary clinical studies using troglitazone demonstrate less intimal hyperplasia with this TZD after implantation of coronary stents; in individuals with type 2 diabetes. Further large trials are needed to confirm that treatment with a TZD can protect against postangioplasty restenosis. (C) 2003 by Excerpta Medica, Inc.