Division of Translational Medicine and Human Genetics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Division of Translational Medicine and Human Genetics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Atherosclerosis. 2014 Mar;233(1):234-41. doi: 10.1016/j.atherosclerosis.2013.12.043. Epub 2014 Jan 10.
Apolipoprotein F (ApoF) is a sialoglycoprotein that is a component of the HDL and LDL fractions of human serum. We sought to test the hypothesis that ApoF plays an important role in atherosclerosis in mice by modulating lipoprotein function. Atherosclerosis was assessed in male low density lipoprotein receptor knockout (Ldlr KO) and ApoF/Ldlr double knockout (DKO) mice fed a Western diet for 16 weeks. ApoF/Ldlr DKO mice showed a 39% reduction in lesional area by en face analysis of aortas (p < 0.05), despite no significant differences in plasma lipid parameters. ApoF KO mice had reduced expression of Interferon alpha (IFNα) responsive genes in liver and spleen, as well as impaired macrophage activation. Interferon alpha induced gene 27 like 2a (Ifi27l2a), Oligoadenylate synthetases 2 and 3 (Oas2 and Oas3) were significantly reduced in the ApoF KO mice relative to wild type controls. These effects were attributable to hypomorphic expression of Stat2 in the ApoF KO mice, a critical gene in the Type I IFN pathway that is situated just 425 base pairs downstream of ApoF. These studies implicate STAT2 as a potentially important player in atherosclerosis, and support the growing evidence that the Type I IFN pathway may contribute to this complex disease.
载脂蛋白 F（ApoF）是一种唾液酸糖蛋白，是人类血清中 HDL 和 LDL 部分的组成部分。我们试图通过调节脂蛋白功能来检验 ApoF 在小鼠动脉粥样硬化中起重要作用的假说。在喂食西方饮食 16 周的雄性低密度脂蛋白受体敲除（Ldlr KO）和 ApoF/Ldlr 双敲除（DKO）小鼠中评估动脉粥样硬化。尽管血浆脂质参数没有显着差异，但 ApoF/Ldlr DKO 小鼠的主动脉正面分析显示病变面积减少了 39％（p <0.05）。ApoF KO 小鼠的肝脏和脾脏中干扰素 alpha（IFNα）反应基因的表达减少，巨噬细胞激活受损。干扰素 alpha 诱导基因 27 样 2a（Ifi27l2a）、寡聚腺苷酸合成酶 2 和 3（Oas2 和 Oas3）在 ApoF KO 小鼠中相对野生型对照显着降低。这些效应归因于 ApoF KO 小鼠中 Stat2 的低功能表达，Stat2 是 I 型 IFN 途径中的关键基因，位于 ApoF 的下游仅 425 个碱基对。这些研究表明 STAT2 可能是动脉粥样硬化的一个潜在重要参与者，并支持 I 型 IFN 途径可能导致这种复杂疾病的证据越来越多。
