Comparison of the effects of pioglitazone and rosiglitazone on macrophage foam cell formation
Comparison of the effects of pioglitazone and rosiglitazone on macrophage foam cell formation
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DOI：
10.1016/j.bbrc.2004.08.151
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发表时间：
2004-10-22
影响因子：
3.1
通讯作者：
Sugiyama, Y
中科院分区：
文献类型：
--
作者：
Hirakata, M;Tozawa, R;Sugiyama, Y
为了阐明吡格列酮（一种具有 PPARα 激动活性的过氧化物酶体增殖物激活受体 [PPAR]γ 激动剂）和罗格列酮（一种更具选择性的 PPARγ 激动剂）的抗动脉粥样硬化作用，我们检测了 THP-1 衍生巨噬细胞中的基因表达和胆固醇酯积累。吡格列酮可增强致动脉粥样硬化因子 CD36 和 adipophilin 的 mRNA 表达，但其效力比罗格列酮低约 10 倍。两种药物的效力似乎与其在这方面的 PPARgamma 激动活性相对应。然而，这两种药物在增强抗动脉粥样硬化因子肝 X 受体 α 和 ATP 结合盒转运蛋白 A1 的 mRNA 表达方面具有相似的功效。此外，这两种药物都能增强巨噬细胞中胆固醇酯水解酶 mRNA 的表达，并抑制酰基辅酶 A 胆固醇酰基转移酶 1 mRNA 的表达和胆固醇酯的积累。在这方面，它们的效力似乎与其 PPARα 激动活性相对应。这些结果表明，吡格列酮在抗动脉粥样硬化事件方面与罗格列酮具有同样的有益作用，尽管其效力比 PPARγ 激动剂低近 10 倍。 (C) 2004 Elsevier Inc. 保留所有权利。
In order to elucidate the antiatherogenic effects of pioglitazone (a peroxisome proliferator-activated receptor [PPAR]gamma agonist with PPARalpha agonistic activity) and rosiglitazone (a more selective PPARgamma agonist), we examined gene expression and cholesteryl ester accumulation in THP-1-derived macrophages. Pioglitazone enhanced the mRNA expression of the proatherogenic factors CD36 and adipophilin, but was approximately 10 times less potent than rosiglitazone. The potencies of the two agents appeared to correspond to their PPARgamma agonistic activities in this respect. However, both agents were similarly potent in enhancing the mRNA expression of the antiatherogenic factors liver X receptor alpha and ATP-binding cassette-transporter A1. Furthermore, both agents enhanced cholesteryl ester hydrolase mRNA expression and inhibited acyl-CoA cholesterol acyltransferase-1 mRNA expression and cholesteryl ester accumulation in macrophages. In this respect, their potencies appeared to correspond to their PPARalpha agonistic activities. These results suggest that pioglitazone has an equally beneficial effect on antiatherogenic events to rosiglitazone, despite being almost 10 times less potent than a PPARgamma agonist. (C) 2004 Elsevier Inc. All rights reserved.