Division of Endocrinology and Molecular Medicine, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
PPAR Res. 2008;2008:429123. doi: 10.1155/2008/429123.
Proliferation of vascular smooth muscle cells (SMCs) is a critical process for the development of atherosclerosis and complications of procedures used to treat atherosclerotic diseases, including postangioplasty restenosis, vein graft failure, and transplant vasculopathy. Peroxisome proliferator-activated receptor (PPAR) gamma is a member of the nuclear hormone receptor superfamily and the molecular target for the thiazolidinediones (TZD), used clinically to treat insulin resistance in patients with type 2 diabetes. In addition to their efficacy to improve insulin sensitivity, TZD exert a broad spectrum of pleiotropic beneficial effects on vascular gene expression programs. In SMCs, PPARgamma is prominently upregulated during neointima formation and suppresses the proliferative response to injury of the arterial wall. Among the molecular target genes regulated by PPARgamma in SMCs are genes encoding proteins involved in the regulation of cell-cycle progression, cellular senescence, and apoptosis. This inhibition of SMC proliferation is likely to contribute to the prevention of atherosclerosis and postangioplasty restenosis observed in animal models and proof-of-concept clinical studies. This review will summarize the transcriptional target genes regulated by PPARgamma in SMCs and outline the therapeutic implications of PPARgamma activation for the treatment and prevention of atherosclerosis and its complications.
血管平滑肌细胞（SMC）的增殖是动脉粥样硬化发展和治疗动脉粥样硬化疾病（包括血管成形术后再狭窄、静脉移植物失败和移植血管病）所采用的方法的并发症的关键过程。过氧化物酶体增殖物激活受体（PPAR）γ是核激素受体超家族的成员，也是噻唑烷二酮（TZD）的分子靶点，临床上用于治疗 2 型糖尿病患者的胰岛素抵抗。除了提高胰岛素敏感性的功效外，TZD 还对血管基因表达谱发挥广泛的有益的多效性作用。在 SMC 中，PPARγ在新内膜形成过程中明显上调，并抑制动脉壁损伤后的增殖反应。在 SMC 中由 PPARγ调节的分子靶基因包括编码参与细胞周期进程、细胞衰老和细胞凋亡调节的蛋白质的基因。这种对 SMC 增殖的抑制可能有助于预防动物模型和概念验证临床研究中观察到的动脉粥样硬化和血管成形术后再狭窄。这篇综述将总结 PPARγ在 SMC 中调节的转录靶基因，并概述 PPARγ 激活在治疗和预防动脉粥样硬化及其并发症方面的治疗意义。
