PPARγ is a very low-density lipoprotein sensor in macrophages
PPARγ is a very low-density lipoprotein sensor in macrophages
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DOI：
10.1073/pnas.0337331100
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发表时间：
2003-02-04
影响因子：
11.1
通讯作者：
Evans, RM
中科院分区：
文献类型：
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作者：
Chawla, A;Lee, CH;Evans, RM
尽管富含甘油三酯的颗粒，如极低密度脂蛋白(VLDL)，对人类动脉粥样硬化的形成有重要作用，但脂蛋白驱动致病的分子基础尚不清楚。我们证明，在巨噬细胞中，极低密度脂蛋白通过激活核受体过氧化体增殖物激活受体三角洲而发挥转录调节作用。天然极低密度脂蛋白的信号成分是其甘油三酯，其活性被脂蛋白脂肪酶增强。过氧化物酶体增殖物激活受体增量缺失巨噬细胞的产生证实了该转录因子在介导极低密度脂蛋白反应中的绝对需求。因此，我们的数据揭示了饮食甘油三酯和极低密度脂蛋白可以直接调节动脉粥样硬化病变中的基因表达的途径。
Although triglyceride-rich particles, such as very low-density lipoprotein (VLDL), contribute significantly to human atherogenesis, the molecular basis for lipoprotein-driven pathogenicity is poorly understood. We demonstrate that in macrophages, VLDL functions as a transcriptional regulator via the activation of the nuclear receptor peroxisome proliferator-activated receptor delta. The signaling components of native VLDL are its triglycerides, whose activity is enhanced by lipoprotein lipase. Generation of peroxisome proliferator-activated receptor delta null macrophages verifies the absolute requirement of this transcription factor in mediating the VLDL response. Thus, our data reveal a pathway through which dietary triglycerides and VLDL can directly regulate gene expression in atherosclerotic lesions.