Fenofibric acid, an active form of fenofibrate, increases apolipoprotein A-I-mediated high-density lipoprotein biogenesis by enhancing transcription of ATP-binding cassette transporter A1 gene in a liver X receptor-dependent manner
Fenofibric acid, an active form of fenofibrate, increases apolipoprotein A-I-mediated high-density lipoprotein biogenesis by enhancing transcription of ATP-binding cassette transporter A1 gene in a liver X receptor-dependent manner
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DOI：
10.1161/01.atv.0000163844.07815.c4
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发表时间：
2005-06-01
影响因子：
8.7
通讯作者：
Yokoyama, S
中科院分区：
文献类型：
--
作者：
Arakawa, R;Tamehiro, N;Yokoyama, S
目的-贝特类药物被广泛用于降低血浆甘油三酯和增加高密度脂蛋白。它们的活性形式，纤维酸，是过氧化物酶体增殖体激活受体- α激活剂，但没有直接证据证明它们激活atp结合盒转运蛋白A1 （ABCA1）与临床使用的纤维类药物有关。在这方面，我们研究了非纤维酸的反应。方法与结果：研究非诺纤维酸对ABCA1活性的影响。增强巨噬细胞细胞系细胞和成纤维细胞中ABCA1基因转录及其蛋白水平，增加载脂蛋白a - i介导的细胞脂质释放，均呈剂量依赖性。利用肝脏X受体反应元件（LXRE）及其失活突变体的报告基因检测系统检测基因转录的增强。结果表明，非诺纤维酸的作用依赖于活性LXRE。结论：非诺纤维酸以肝脏X受体依赖的方式增加ABCA1基因的转录。
Objective - Fibrates are widely used drugs to reduce plasma triglyceride and increase high-density lipoprotein. Their active forms, fibric acids, are peroxisome proliferator-activated receptor-alpha activators, but no direct evidence has been demonstrated for their activation of ATP-binding cassette transporter A1 (ABCA1) in relation to clinically used fibrates. We investigated the reaction of fenofibric acid in this regard.Methods and Results - Fenofibric acid was examined for the effect of increase of ABCA1 activity. It enhanced ABCA1 gene transcription and its protein level in macrophage cell line cells and fibroblasts and increased apolipoprotein A-I - mediated cellular lipid release, all in a dose-dependent manner. Enhancement of the gene transcription was examined by using a reporter assay system for liver X receptor responsive element (LXRE) and its inactive mutant. The results demonstrated that the effect of fenofibric acid is dependent on active LXRE.Conclusions - Fenofibric acid increased transcription of ABCA1 gene in a liver X receptor - dependent manner.