The fucoidan from the brown seaweed Ascophyllum nodosum ameliorates atherosclerosis in apolipoprotein E-deficient mice
The fucoidan from the brown seaweed Ascophyllum nodosum ameliorates atherosclerosis in apolipoprotein E-deficient mice
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来自棕色海藻泡叶藻的岩藻依聚糖可改善载脂蛋白 E 缺陷小鼠的动脉粥样硬化
DOI：
10.1039/c9fo00619b
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发表时间：
2019
期刊：
影响因子：
6.1
通讯作者：
Guo Shoudong
中科院分区：
文献类型：
--
作者：
Yin Jiayu;Wang Jin;Li Fahui;Yang Zixun;Yang Xiaoqian;Sun Wanli;Xia Bin;Li Ting;Song Weiguo;Guo Shoudong
高脂血症是动脉粥样硬化的主要原因。胆固醇反向转运（RCT）被认为可以减轻高脂血症和动脉粥样硬化的进展。尽管据报道岩藻依聚糖具有降血脂作用，但其潜在机制尚不清楚。此外，很少有报道揭示岩藻依聚糖的抗动脉粥样硬化作用及其潜在机制。本研究旨在探讨海藻 A. nodosum 中的岩藻依聚糖的抗动脉粥样硬化作用和机制。我们的结果表明，在喂食高脂肪饮食的载脂蛋白 E 缺陷 (apoE−/−) 小鼠中，岩藻依聚糖以剂量依赖性方式改善了动脉粥样硬化病变和血脂状况。在apoE−/−小鼠肝脏中，岩藻依聚糖治疗显着增加了清道夫受体B型1（SR-B1）、过氧化物酶体增殖物激活受体（PPAR）α和β、肝X受体（LXR）α、ATP结合盒转运蛋白（ABC）A1和ABCG8的表达；显着降低 PPARγ 和甾醇调节元件结合蛋白 (SREBP) 1c 的表达，但不降低低密度脂蛋白受体、前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型、胆固醇 7 α-羟化酶 A1、LXRβ 和 ABCG1。在 apoE−/− 小鼠的小肠中，岩藻依聚糖治疗显着降低了 Niemann-Pick C1-like 1 (NPC1L1) 的表达，并显着提高了 ABCG8 水平。这些结果首次证明，来自 A. nodosum 的岩藻依聚糖通过调节 apoE−/− 小鼠中 RCT 相关基因和蛋白质的表达来减轻动脉粥样硬化。总之，这种来自 A. nodosum 的岩藻依聚糖可被探索作为预防或治疗高脂血症引起的动脉粥样硬化的潜在化合物。
Hyperlipidemia is a major cause of atherosclerosis. Reverse cholesterol transport (RCT) is believed to attenuate hyperlipidemia and the progression of atherosclerosis. Although fucoidans are reported to have hypolipidemic effects, the underlying mechanisms are unclear. Furthermore, few reports have revealed the anti-atherosclerotic effects and the underlying mechanisms of fucoidans. This study was designed to investigate the anti-atherosclerotic effect and mechanisms of the fucoidan from seaweed A. nodosum. Our results demonstrated that the fucoidan administration ameliorated atherosclerotic lesion and lipid profiles in a dose-dependent manner in the apolipoprotein E-deficient (apoE−/−) mice fed a high-fat diet. In the apoE−/− mice liver, the fucoidan treatment significantly increased the expression of scavenger receptor B type 1 (SR-B1), peroxisome proliferator-activated receptor (PPAR) α and β, liver X receptor (LXR) α, ATP-binding cassette transporter (ABC) A1 and ABCG8; and markedly decreased the expression of PPARγ and sterol regulatory element-binding protein (SREBP) 1c, but not low-density lipoprotein receptor, proprotein convertase subtilisin/kexin type 9, cholesterol 7 alpha-hydroxylase A1, LXRβ and ABCG1. In the small intestine of the apoE−/− mice, the fucoidan treatment significantly reduced the expression of Niemann-Pick C1-like 1 (NPC1L1) and dramatically improved ABCG8 levels. These results demonstrated for the first time that the fucoidan from A. nodosum attenuated atherosclerosis by regulating RCT-related genes and proteins expression in apoE−/− mice. In summary, this fucoidan from A. nodosum may be explored as a potential compound for prevention or treatment of hyperlipidemia-induced atherosclerosis.