Inhibitory activity of clinical thiazolidinedione peroxisome proliferator activating receptor-γ ligands toward internal mammary artery, radial artery, and saphenous vein smooth muscle cell proliferation
Inhibitory activity of clinical thiazolidinedione peroxisome proliferator activating receptor-γ ligands toward internal mammary artery, radial artery, and saphenous vein smooth muscle cell proliferation
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DOI：
10.1161/01.cir.0000074040.31731.96
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发表时间：
2003-05-27
期刊：
影响因子：
37.8
通讯作者：
Little, PJ
中科院分区：
文献类型：
--
作者：
de Dios, ST;Bruemmer, D;Little, PJ
背景-血管平滑肌细胞（VSMC）的增殖是已知的对动脉损伤的反应，是再狭窄和动脉粥样硬化过程的重要组成部分。糖尿病患者由于冠状动脉粥样硬化加速而增加了心血管疾病的风险。治疗2型糖尿病的最新药物是噻唑烷二酮类，它是胰岛素增敏过氧化物酶体增殖物激活受体-γ（PPARgamma）配体。我们研究了曲格列酮，罗格列酮和吡格列酮对VSMCs的抗增殖作用来自三个血管床用于冠状动脉旁路移植术：内乳和桡动脉和隐静脉。方法和结果，三个血管产生的增殖细胞形态略有不同。细胞增殖的抑制作用通过细胞计数和细胞周期研究进行了评估，通过Western印迹磷酸化视网膜母细胞瘤蛋白。所有三种噻唑烷二酮均显示出对细胞增殖的抑制效力，曲格列酮>罗格列酮近似于托吡格列酮，并且这种效力特征对视网膜母细胞瘤蛋白的生长因子和胰岛素刺激的磷酸化保持不变，控制细胞周期进程。结论-临床噻唑烷二酮对不同血管来源的抑制效力取决于个体噻唑烷二酮，而对血管来源的抑制效力很小。源头
Background-The proliferation of vascular smooth muscle cells (VSMCs) is a known response to arterial injury that is an important part of the process of restenosis and atherosclerosis. People with diabetes have an increased risk of cardiovascular disease resulting from accelerated coronary atherosclerosis. The newest drugs for Type 2 diabetes are thiazolidinediones, which are insulin-sensitizing peroxisome proliferator activating receptor-gamma (PPARgamma) ligands. We investigated the antiproliferative effects of troglitazone, rosiglitazone, and pioglitazone on VSMCs derived from the three vascular beds used for coronary artery by-pass grafting: the internal mammary and radial artery and saphenous veins.Methods and Results-The three vessels yielded proliferating cells of slightly differing morphology. Inhibition of cell proliferation was assessed by cell counting and cell cycle studies by Western blotting for phosphorylated retinoblastoma protein. All three thiazolidinediones showed inhibitory potency toward cell proliferation with a potency troglitazone>rosiglitazoneapproximate topioglitazone, and this potency profile was maintained toward the growth factor and insulin-stimulated phosphorylation of the retinoblastoma protein, which controls cell cycle progression.Conclusion-The inhibitory potency of clinical thiazolidinediones toward different vascular sources is dependent on the individual thiazolidinedione and very little on the vascular source.