Pleiotropic vascular effects of PPARγ ligands
Pleiotropic vascular effects of PPARγ ligands
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DOI：
10.1358/dnp.2003.16.4.829330
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发表时间：
2003-05-01
影响因子：
--
通讯作者：
Collins, AR
中科院分区：
文献类型：
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作者：
Collins, AR
过氧化物酶体增殖物激活受体-γ (PPARγ) 配体多年来一直被用作胰岛素敏感性和葡萄糖代谢的调节剂。大量研究的最新数据表明，PPARgamma 配体对脉管系统具有多种有益作用。它们已被证明可以调节血管平滑肌细胞的增殖和迁移以及改善内皮细胞功能。它们通过抵抗动脉和肾脏的作用来改善血压。临床试验表明，PPARgamma 配体可以最大程度地减少动脉粥样硬化的发展并调节其他血管炎症。 PPARγ 已在血管壁中发现的所有细胞以及与血管病理生理学相关的细胞中检测到。在单核细胞/巨噬细胞中，PPARγ 配体下调炎症细胞因子的产生和迁移。此外，PPARgamma 配体调节 SR-A 和 CD36 受体的表达，这些受体吸收巨噬细胞中的脂质。 PPARgamma 也被证明可以通过肝脏 X 受体 a 发挥作用。增加这些细胞中胆固醇反向转运的活性。在树突状细胞和 T 细胞中，PPARgamma 配体已被证明可以抑制炎症的激活和引发。在给予 PPARgamma 配体的动物模型中，炎症细胞因子被下调，从而减少动脉粥样硬化。虽然 PPARgamma 配体已可用于治疗 2 型糖尿病，但这些化合物引起的重要血管保护作用可能在未来具有更大的益处。 (C) 2003 年《Prous Science》。版权所有。
Peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands have been used for several years as modulators of insulin sensitivity and glucose metabolism. Recent data from numerous studies have shown that PPARgamma ligands have numerous beneficial effects in the vasculature. They have been shown to regulate proliferation and migration of vascular smooth muscle cells as well as improving endothelial cell function. They improve blood pressure by actions at the resistance arteries and kidneys. Clinical trials have indicated that PPARgamma ligands can minimize the development of atherosclerosis as well as regulating other vascular inflammation. PPARgamma has been detected in all the cells found in the vessel wall as well as those cells associated with vascular pathophysiologies. In the monocyte/macrophage, PPARgamma ligands downregulate production of inflammatory cytokines and migration. Also, PPARgamma ligands regulate the expression of SR-A and CD36 receptors that take up lipids in the macrophage. PPARgamma has also been demonstrated to act through the liver X receptor a. to increase the activity of reverse cholesterol transport in these cells. In dendritic cells and T-cells, PPARgamma ligands have been shown to inhibit activation and the initiation of inflammation. Inflammatory cytokines are downregulated in animal models administered PPARgamma ligands, leading to decreased atherosclerosis. While PPARgamma ligands have been useful in the treatment of type 2 diabetes, the important vasculoprotection elicited by these compounds could prove to be of greater benefit in the future. (C) 2003 Prous Science. All rights reserved.