PPARs and the cardiovascular system.
PPARs and the cardiovascular system.
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DOI：
10.1089/ars.2008.2280
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发表时间：
2009-06
影响因子：
6.6
通讯作者：
Chen YE
中科院分区：
文献类型：
--
作者：
Hamblin M;Chang L;Fan Y;Zhang J;Chen YE
过氧化物酶体增殖物激活受体（PPARs）属于核激素受体超家族。PPARs最初于1990年克隆，被发现是诱导肝细胞过氧化物酶体增殖的药理学试剂的介体。PPARs也在心血管系统的细胞中表达。在动脉粥样硬化病变形成过程中，过氧化物酶体增殖物激活物受体γ似乎高度表达，这表明过氧化物酶体增殖物激活物受体γ表达增加可能是血管代偿反应。此外，配体激活的PPARγ降低心血管细胞，特别是内皮细胞的炎症反应。与PPARγ相似，PPARα在心血管系统中也具有多效性作用，包括抗炎和抗动脉粥样硬化特性。PPARα激活抑制血管平滑肌促炎反应，减缓动脉粥样硬化的发展。然而，PPARδ过表达可能导致巨噬细胞炎症和动脉粥样硬化的升高。另一方面，显示出PPARδ配体通过改善内皮细胞增殖和存活同时减少内皮细胞炎症和血管平滑肌细胞增殖来减弱动脉粥样硬化的发病机制。此外，就临床环境中显著减少心血管事件而言，以TZD和贝特类的形式施用PPAR配体令人失望。因此，更好地了解PPARs依赖和非依赖信号通路将为进一步研究PPARs在人类心血管生物学中的作用提供基础。
Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor superfamily. Originally cloned in 1990, PPARs were found to be a mediator of pharmacological agents that induce hepatocyte peroxisome proliferation. PPARs are also expressed in cells of the cardiovascular system. PPARγ appears to be highly expressed during atherosclerotic lesion formation, suggesting that increased PPARγ expression may be a vascular compensatory response. Also, ligand-activated PPARγ decreases the inflammatory response in cardiovascular cells, particularly in endothelial cells. PPARα, similar to PPARγ, also has pleiotropic effects in the cardiovascular system, including anti-inflammatory and anti-atherosclerotic properties. PPARα activation inhibits vascular smooth muscle pro-inflammatory responses, attenuating the development of atherosclerosis. However, PPARδ overexpression may lead to elevated macrophage inflammation and atherosclerosis. On the other hand, PPARδ ligands are shown to attenuate the pathogenesis of atherosclerosis by improving endothelial cell proliferation and survival while decreasing endothelial cell inflammation and vascular smooth muscle cell proliferation. Furthermore, the administration of PPAR ligands in the form of TZDs and fibrates has been disappointing in terms of markedly reducing cardiovascular events in the clinical setting. Therefore, a better understanding of PPAR-dependent and -independent signaling will provide the foundation for future research on the role of PPARs in human cardiovascular biology.
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影响因子：
4.8
作者：
Armoni, M;Harel, C;Karnieli, E
通讯作者：
Karnieli, E
影响因子：
4.8
作者：
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影响因子：
20.1
作者：
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DOI：
10.1073/pnas.012610299
发表时间：
2002-01-08
影响因子：
11.1
作者：
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通讯作者：
Evans, RM
影响因子：
4.8
作者：
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通讯作者：
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