Role of the peroxisome proliferator-activated receptors (PPAR) in atherosclerosis
Role of the peroxisome proliferator-activated receptors (PPAR) in atherosclerosis
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DOI：
10.1016/s0006-2952(00)00430-5
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发表时间：
2000-10-15
影响因子：
5.8
通讯作者：
Staels, B
中科院分区：
文献类型：
--
作者：
Neve, BP;Fruchart, JC;Staels, B
过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptor，PPAR）是一类配体激活的转录因子，属于核受体基因家族的一个亚家族。过氧化物酶体增殖物激活物对代谢危险因素和动脉粥样硬化相关的血管炎症都有影响。过氧化物酶体增殖物激活受体对脂蛋白和脂肪酸的代谢有重要影响。过氧化物酶体增殖物激活受体α结合降血脂贝特类，而过氧化物酶体增殖物激活受体γ对抗糖尿病格列酮具有高亲和力。这两种过氧化物酶体增殖物激活的脂肪酸及其衍生物。激活的过氧化物酶体增殖物激活物受体α增加了几个水平的脂肪酸的catalysts。在肝脏中，它增加脂肪酸的摄取并激活其β-氧化。PPAR α对富含脂蛋白的脂蛋白的作用是由于其刺激脂蛋白脂酶和抑制载脂蛋白CIII的表达，而对高密度脂蛋白的作用取决于载脂蛋白AI和AII的调节。PPAR γ对脂肪组织的分化和功能具有深远的影响，在那里它被高度表达。在动脉粥样硬化病变中也有表达。PPAR存在于血管内皮细胞、平滑肌细胞、单核细胞和单核细胞衍生的巨噬细胞中。通过核因子-κ B和激活蛋白-1信号通路的负调节，PPAR α抑制炎症基因的表达，如白细胞介素-6、环氧合酶-2和内皮素-1。此外，PPAR α抑制单核细胞募集蛋白如血管细胞粘附分子（VCAM）-1的表达，并诱导单核细胞源性巨噬细胞的凋亡。巨噬细胞和泡沫细胞中的PPAR γ活化抑制活化基因如诱导型一氧化氮合酶、基质金属蛋白酶-9和清道夫受体A的表达。PPAR γ还可能影响动脉粥样硬化病变中单核细胞的募集，因为它参与血管内皮细胞中VCAM-1和细胞内粘附分子-1的表达。动脉粥样硬化是一种具有慢性炎症特征的疾病，而PPAR参与动脉粥样硬化，这表明它们也可能在其他炎症相关疾病中发挥作用。生物化学制药60; 8：1245 - 1250，2000年。(C)2000 Elsevier Science Inc.
Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors which form a subfamily of the nuclear receptor gene family. PPAR activators have effects on both metabolic risk factors and on vascular inflammation related to atherosclerosis. PPAR have profound effects on the metabolism of lipoproteins and fatty acids. PPAR alpha binds hypolipidemic fibrates, whereas PPAR gamma has a high affinity for antidiabetic glitazones. Both PPAR are activated by fatty acids and their derivatives. Activation of PPAR alpha increases the catabolism of fatty acids at several levels. In the liver, it increases uptake of fatty acids and activates their beta-oxidation. The effects that PPAR alpha exerts on triglyceride-rich lipoproteins is due to their stimulation of lipoprotein lipase and repression of apolipoprotein CIII expression, while the effects on high-density lipoproteins depend upon che regulation of apolipoproteins AI and AII. PPAR gamma has profound effects on the differentiation and function of adipose tissue, where it is highly expressed. PPAR are also expressed in atherosclerotic lesions. PPAR are present in vascular endothelial cells, smooth muscle cells, monocytes, and monocyte-derived macrophages. Via negative regulation of nuclear factor-kappa B and activator protein-1 signalling pathways, PPAR alpha inhibits expression of inflammatory genes, such as interleukin-6, cyclooxygenase-2, and endothelin-1. Furthermore, PPAR alpha inhibits expression of monocyte recruiting proteins such as vascular cell adhesion molecule (VCAM)-1 and induces apoptosis in monocyte-derived macrophages. PPAR gamma activation in macrophages and foam cells inhibits the expression of activated genes such as inducible nitric oxide synthase, matrix metalloproteinase-9 and scavenger receptor A. PPAR gamma may also affect the recruitment of monocytes in atherosclerotic lesions as it is involved in the expression of VCAM-1 and intracellular adhesion molecule-1 in vascular endothelial cells. The involvement of PPAR in atherosclerosis, a disease with a chronic inflammatory character, suggests that they may play a role in other inflammatory-related diseases as well. BIOCHEM PHARMACOL 60;8:1245-1250, 2000. (C) 2000 Elsevier Science Inc.