Transcriptional Control of Vascular Smooth Muscle Cell Proliferation by Peroxisome Proliferator-Activated Receptor-gamma: Therapeutic Implications for Cardiovascular Diseases.
Transcriptional Control of Vascular Smooth Muscle Cell Proliferation by Peroxisome Proliferator-Activated Receptor-gamma: Therapeutic Implications for Cardiovascular Diseases.
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过氧化物体增殖物激活受体伽玛对血管平滑肌细胞增殖的转录控制：对心血管疾病的治疗意义。
DOI：
10.1155/2008/429123
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发表时间：
2008
期刊：
影响因子：
2.9
通讯作者：
Bruemmer, Dennis
中科院分区：
文献类型：
--
作者：
Gizard, Florence;Bruemmer, Dennis
血管平滑肌细胞（SMC）的增殖是动脉粥样硬化和用于治疗动脉粥样硬化疾病的程序的并发症（包括血管成形术后再狭窄、静脉移植失败和移植血管病）发展的关键过程。过氧化物酶体增殖物激活受体（Peroxisome proliferator-activated receptor，PPAR）是核激素受体超家族的成员，是噻唑烷二酮类药物（thiazolidinediones，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。除了改善胰岛素敏感性的功效外，TZD对血管基因表达程序发挥广谱的多效性有益作用。在SMC中，PPAR在新生内膜形成过程中显著上调，并抑制对动脉壁损伤的增殖反应。在SMC中受PPAR调节的分子靶基因中，有编码参与细胞周期进程、细胞衰老和凋亡调节的蛋白质的基因。这种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。本文就平滑肌细胞中受PPAR调控的转录靶基因及其激活对动脉粥样硬化及其并发症的治疗意义进行综述。
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) 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, PPAR is prominently upregulated during neointima formation and suppresses the proliferative response to injury of the arterial wall. Among the molecular target genes regulated by PPAR 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 PPAR in SMCs and outline the therapeutic implications of PPAR activation for the treatment and prevention of atherosclerosis and its complications.
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