OBJECTIVE Angiopoietin-1 (Ang-1), a secreted protein, mainly regulates angiogenesis. Ang-1 has been shown to promote the development of atherosclerosis, whereas little is known about its effects on lipid metabolism and inflammation in this process. METHOD Ang-1 was transfected into ApoE-/- mice via lentiviral vector or incubated with THP-1 derived macrophages. Oil red O and HE staining were performed to measure the size of atherosclerotic plaques in ApoE-/- mice. Immunofluorescence was employed to show the expression of target proteins in aorta. [3H] labeled cholesterol was performed to examine the efficiency of cholesterol efflux and reverse cholesterol transport (RCT) both in vivo and vitro. Western blot and qPCR were used to quantify target proteins both in vivo and vitro. ELISA detected the levels of pro-inflammatory cytokines in mouse peritoneal macrophage. RESULTS Our data showed that Ang-1 augmented atherosclerotic plaques formation and inhibited cholesterol efflux. The binding of Ang-1 to Tie2 resulted in downregulation of LXRα, ABCA1 and ABCG1 expression via inhibiting the translocation of TFE3 into nucleus. In addition, Ang-1 decreased serum HDL-C levels and reduced reverse cholesterol transport (RCT) in ApoE-/- mice. Furthermore, Ang-1 induced lipid accumulation followed by increasing TNF-α, IL-6, IL-1β，and MCP-1 produced by MPMs, as well as inducing M1 phenotype macrophage marker iNOS and CD86 expression in aorta of ApoE-/- mice. CONCLUSION Ang-1 has an adverse effect on cholesterol efflux by decreasing the expression of ABCA1 and ABCG1 via Tie2/TFE3/LXRα pathway, thereby promoting inflammation and accelerating atherosclerosis progression.

中文翻译：

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Angiopoietin-1通过抑制胆固醇外流并促进炎症反应而加剧动脉粥样硬化。

目的血管生成素-1（Ang-1）是一种分泌蛋白，主要调节血管生成。Ang-1已被证明能促进动脉粥样硬化的发展，而在这一过程中它对脂质代谢和炎症的影响知之甚少。方法通过慢病毒载体将Ang-1转染到ApoE-/-小鼠中，或与THP-1衍生的巨噬细胞一起孵育。进行油红O和HE染色以测量ApoE-/-小鼠中动脉粥样硬化斑块的大小。免疫荧光法用于显示靶蛋白在主动脉中的表达。进行[3H]标记的胆固醇以在体内和体外检查胆固醇外排和反向胆固醇转运（RCT）的效率。Western印迹和qPCR用于定量体内和体外靶蛋白。ELISA检测了小鼠腹膜巨噬细胞中促炎细胞因子的水平。结果我们的数据显示Ang-1可增加动脉粥样硬化斑块的形成并抑制胆固醇外流。Ang-1与Tie2的结合通过抑制TFE3向核内的移位而导致LXRα，ABCA1和ABCG1表达下调。此外，Ang-1降低了ApoE-/-小鼠的血清HDL-C水平并降低了胆固醇逆向转运（RCT）。此外，Ang-1诱导脂质蓄积，随后增加MPM产生的TNF-α，IL-6，IL-1β和MCP-1，并诱导ApoE-/-主动脉中M1表型巨噬细胞标志物iNOS和CD86表达。老鼠。结论Ang-1可通过Tie2 / TFE3 /LXRα途径降低ABCA1和ABCG1的表达，从而对胆固醇外流产生不利影响，