THIAZOLIDINEDIONES AND VASCULAR MYOCYTE METABOLISM

动脉粥样硬化性缺血性心脏病是死亡的主要原因， 西方工业化国家。尽管失败率为30-50%， 再狭窄，冠状动脉血管成形术正在成为治疗的选择。 动脉粥样硬化和再狭窄的病理学基础是一种 炎症-纤维增生性重塑过程中，血管 平滑肌（VSMC）细胞不适当地去分化、迁移 增殖和合成细胞外基质（ECM）蛋白， 多种生长调节因子的作用。结果是 冠状血管中阻塞性新生内膜病变的形成。 我们的长期目标是研究人VSMC的功能调节， 在基础和“合成”条件下的PDGF和TGF-β 1。在 合成表型，VSMC表现出过度增殖、趋化性 蛋白质合成特性与动脉粥样硬化和 再狭窄病变这些生长因子对指数的影响 增殖（3 H-胸苷掺入、c-myc和c-myb表达）， 细胞迁移和蛋白质的定量和定性方面 将使用合成人VSMC中的合成作为定量估计 在体内的病理损伤的潜在过程。 目前还没有有效的药物可以治疗或预防 动脉粥样硬化或再狭窄。噻唑烷二酮类是一类 胰岛素增敏、抗血脂异常、抗高血压药物 在这些适应症的人体试验中。这些分子抑制 啮齿类动物VSMC的体外增殖。我们建议扩展这些研究 培养的人主动脉VSMC（HAVSMC）测量所述参数 以上

Atherosclerotic ischemic heart disease is the major cause of death in western industrialized countries. Despite a failure rate of 30-50% due to restenosis, coronary angioplasty is emerging as the treatment of choice. The pathology underlying atherosclerosis and restenosis is an inflammatory-fibroproliferative remodeling process in which vascular smooth muscle (VSMC) cells inappropriately de-differentiate, migrate, proliferate and synthesize extracellular matrix (ECM) proteins in response to multiple growth regulatory factors released locally. The result is formation of obstructive neointimal lesions in the coronary vessels. Our long term goal is to study the functional modulation of human VSMC by PDGF and TGF-beta1 under basal and "synthetic" conditions. In the synthetic phenotype, VSMC exhibit hyper-proliferative, chemotactic and protein synthetic properties similar to those seen in atherosclerotic and restenotic lesions. The effects of these growth factors on indices of proliferation (3H-thymidine incorporation, c-myc and c-myb expression), cell migration and quantitative and qualitative aspects of protein synthesis in synthetic human VSMC will be used as a quantitative estimate of the processes underlying the pathological lesion in vivo. There is no efficacious drug presently available to treat or prevent atherosclerosis or restenosis. The thiazolidinediones are a class on insulin-sensitizing, anti-dyslipidemic, antihypertensive drugs presently in human trials for these indications. These molecules inhibit proliferation of rodent VSMC in vitro. We propose to extend these studies to cultured human aortic VSMC (HAVSMC) measuring the parameters described above.