MafB promotes atherosclerosis by inhibiting foam-cell apoptosis

作者：Hamada Michito^*; Nakamura Megumi; Mai Thi Nhu Tran; Moriguchi Takashi; Hong Cynthia; Ohsumi Takayuki; Tra Thi Huong Dinh; Kusakabe Manabu; Hattori Motochika; Katsumata Tokio; Arai Satoko; Nakashima Katsuhiko; Kudo Takashi; Kuroda Etsushi; Wu Chien Hui; Kao Pei Han; Sakai Masaharu; Shimano Hitoshi; Miyazaki Toru; Tontonoz Peter; Takahashi Satoru

来源：Nature Communications, 2014, 5(1): 3147.

DOI：10.1038/ncomms4147

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.

• 出版日期2014-1