Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
FASEB J. 2019 Feb;33(2):2290-2300. doi: 10.1096/fj.201801267RR. Epub 2018 Sep 17.
C1q/tumor necrosis factor-related protein 13 (CTRP13) is a secreted adipokine that can ameliorate abnormal glucose and lipid metabolism. However, the functional role of CTRP13 in the development of atherosclerotic plaques has yet to be described. In this study, we collected blood samples from patients of coronary artery diseases and apolipoprotein E (ApoE) mice that were fed a Western diet for 12 wk to induce atherosclerosis and found that serum CTRP13 level was decreased. En face staining of aortas and aortic sinus in ApoE mice showed that ectopic CTRP13 infusion in vivo dramatically decreased lesion areas, as well as reduced inflammatory responses with less macrophage content. In primary peritoneal macrophages in vitro, CTRP13 supplement reduced oxidized LDL uptake, foam-cell formation, and trapping, together with the suppressed cluster of differentiation 36 (CD36) protein levels. Reduced CD36 protein level was attributed to the autophagy-lysosome-dependent degradation of CD36 at the post-transcriptional level. The blocking of autophagy-lysosome induction could increase CD36 protein level, foam-cell formation, and migration, thus abolishing the protective effects of CTRP13 on atherosclerosis. In summary, these findings define CTRP13 as a novel approach for preventing atherosclerotic plaque formation via modulation of lipid uptake and foam-cell migration.-Wang, C., Xu, W., Liang, M., Huang, D., Huang, K. CTRP13 inhibits atherosclerosis via autophagy-lysosome-dependent degradation of CD36.
C1q/肿瘤坏死因子相关蛋白 13（CTRP13）是一种分泌型脂肪因子，可改善异常的葡萄糖和脂质代谢。然而，CTRP13 在动脉粥样硬化斑块发展中的功能作用尚未被描述。在这项研究中，我们收集了冠心病患者和载脂蛋白 E（ApoE）小鼠的血液样本，这些小鼠喂食西方饮食 12 周以诱导动脉粥样硬化，结果发现血清 CTRP13 水平降低。ApoE 小鼠主动脉和主动脉窦的正面染色显示，体内异位 CTRP13 输注可显著减少病变面积，并减少炎症反应，巨噬细胞含量减少。在体外原代腹膜巨噬细胞中，CTRP13 补充减少了氧化型 LDL 的摄取、泡沫细胞形成和捕获，同时抑制了分化群 36（CD36）蛋白水平。CD36 蛋白水平的降低归因于 CD36 在转录后水平上的自噬溶酶体依赖性降解。阻断自噬溶酶体的诱导可以增加 CD36 蛋白水平、泡沫细胞形成和迁移，从而消除 CTRP13 对动脉粥样硬化的保护作用。总之，这些发现定义了 CTRP13 是一种通过调节脂质摄取和泡沫细胞迁移来预防动脉粥样硬化斑块形成的新方法。
