MafB promotes atherosclerosis by inhibiting foam-cell apoptosis
MafB promotes atherosclerosis by inhibiting foam-cell apoptosis
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DOI：
10.1038/ncomms4147
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发表时间：
2014-01-01
影响因子：
16.6
通讯作者：
Takahashi, Satoru
中科院分区：
文献类型：
--
作者：
Hamada, Michito;Nakamura, Megumi;Takahashi, Satoru
MafB是诱导骨髓单核细胞分化的转录因子。然而，MafB在巨噬细胞致病功能中的确切作用从未被阐明。在这里，我们证明MafB通过抑制泡沫细胞凋亡促进高脂血症性动脉粥样硬化。我们的数据显示MafB主要在动脉粥样硬化病变内发现的泡沫细胞中表达，其中MafB介导氧化LDL激活的LXR/RXR诱导的巨噬细胞凋亡抑制剂（AIM）的表达。在MafB不存在的情况下，活化的LXR/RXR不能诱导AIM的表达，AIM是一种通常负责保护巨噬细胞免于凋亡的蛋白质;因此，Mafb缺陷型巨噬细胞倾向于凋亡。在受体LDL受体缺陷型高脂血症小鼠中，Mafb缺陷型胎肝细胞的造血重建显示泡沫细胞凋亡加速，随后导致早期致动脉粥样硬化病变的衰减。这些发现代表了第一个证据表明，巨噬细胞相关的MafB转录因子参与动脉粥样硬化的加速。
MafB is a transcription factor that induces myelomonocytic differentiation. However, the precise role of MafB in the pathogenic function of macrophages has never been clarified. Here we demonstrate that MafB promotes hyperlipidemic atherosclerosis by suppressing foam-cell apoptosis. Our data show that MafB is predominantly expressed in foam cells found within atherosclerotic lesions, where MafB mediates the oxidized LDL-activated LXR/RXR-induced expression of apoptosis inhibitor of macrophages (AIM). In the absence of MafB, activated LXR/RXR fails to induce the expression of AIM, a protein that is normally responsible for protecting macrophages from apoptosis; thus, Mafb-deficient macrophages are prone to apoptosis. Haematopoietic reconstitution with Mafb-deficient fetal liver cells in recipient LDL receptor-deficient hyperlipidemic mice revealed accelerated foam-cell apoptosis, which subsequently led to the attenuation of the early atherogenic lesion. These findings represent the first evidence that the macrophage-affiliated MafB transcription factor participates in the acceleration of atherogenesis.