Dietary-Induced Elevations of Triglyceride-Rich Lipoproteins Promote Atherosclerosis in the Low-Density Lipoprotein Receptor Knockout Syrian Golden Hamster.
Dietary-Induced Elevations of Triglyceride-Rich Lipoproteins Promote Atherosclerosis in the Low-Density Lipoprotein Receptor Knockout Syrian Golden Hamster.
复制标题
饮食引起的富含甘油三酯的脂蛋白升高促进低密度脂蛋白受体敲除叙利亚金仓鼠的动脉粥样硬化
DOI：
10.3389/fcvm.2021.738060
复制
发表时间：
2021
影响因子：
3.6
通讯作者：
Liu G
中科院分区：
文献类型：
--
作者：
Lin X;Ma P;Yang C;Wang J;He K;Chen G;Huang W;Fan J;Xian X;Wang Y;Liu G
甘油三酯升高与心血管疾病（CVD）的风险增加有关。因此，在动物模型中了解富含磷脂脂蛋白（TRL）的代谢及其致动脉粥样硬化作用是非常重要的。使用低密度脂蛋白受体敲除（LDLR−/−）叙利亚金黄仓鼠，这项研究表明，与LDLR−/−小鼠不同，当LDLR−/−仓鼠被喂食高胆固醇高脂肪饮食（HFD）时，它们的甘油三酯和胆固醇血浆水平非常高。我们发现，LDLR−/−仓鼠在喂食HFD后表现出血清TRL和这些颗粒中的ApoB 100和48增加。依折麦布治疗2周可降低这些大颗粒，但不能降低LDL。此外，依折麦布可同时降低血浆和TRL中的ApoB 48和ApoE。LRP 1在肝脏中的表达没有变化。这些结果表明，显著减少的大颗粒主要是乳糜微粒残留物，并且这些残留物主要由仓鼠的LDL受体清除。在HFD治疗40天后，LDLR−/−仓鼠的主动脉粥样硬化加速，伴有重度脂肪肝，依折麦布治疗可降低高脂血症的后果。与LDLR−/−仓鼠血清相比，依折麦布处理的LDLR−/−仓鼠血清降低了血管内皮细胞中血管粘附因子的表达和巨噬细胞的脂质摄取。我们的研究结果表明，在LDLR−/−仓鼠模型中，动脉源性脂蛋白残余物具有高度致动脉粥样硬化性，并且来自巨噬细胞的内皮细胞和泡沫细胞的炎症反应引发了动脉粥样硬化。LDL受体可能是非常重要的乳糜微粒残留的清除在叙利亚金黄地鼠，这可能不会被补偿的另一种途径。我们认为LDLR−/−仓鼠是研究TRLs相关疾病的良好模型，因为它模拟更复杂的高脂血症。
Elevated triglycerides are associated with an increased risk of cardiovascular disease (CVD). Therefore, it is very important to understand the metabolism of triglyceride-rich lipoproteins (TRLs) and their atherogenic role in animal models. Using low-density lipoprotein receptor knockout (LDLR−/−) Syrian golden hamsters, this study showed that unlike LDLR−/− mice, when LDLR−/− hamsters were fed a high cholesterol high-fat diet (HFD), they had very high plasma levels of triglycerides and cholesterol. We found that LDLR−/− hamsters exhibited increased serum TRLs and the ApoB100 and 48 in these particles after being fed with HFD. Treatment with ezetimibe for 2 weeks decreased these large particles but not the LDL. In addition, ezetimibe simultaneously reduced ApoB48 and ApoE in plasma and TRLs. The expression of LRP1 did not change in the liver. These findings suggested that the significantly reduced large particles were mainly chylomicron remnants, and further, the remnants were mainly cleared by the LDL receptor in hamsters. After 40 days on an HFD, LDLR−/− hamsters had accelerated aortic atherosclerosis, accompanied by severe fatty liver, and ezetimibe treatment reduced the consequences of hyperlipidemia. Compared with the serum from LDLR−/− hamsters, that from ezetimibe-treated LDLR−/− hamsters decreased the expression of vascular adhesion factors in vascular endothelial cells and lipid uptake by macrophages. Our results suggested that in the LDLR−/− hamster model, intestinally-derived lipoprotein remnants are highly atherogenic and the inflammatory response of the endothelium and foam cells from macrophages triggered atherosclerosis. The LDL receptor might be very important for chylomicrons remnant clearance in the Syrian golden hamster, and this may not be compensated by another pathway. We suggest that the LDLR−/− hamster is a good model for the study of TRLs-related diseases as it mimics more complex hyperlipidemia.
登录
查看更多内容
DOI：
10.1016/0300-9629(91)90263-c
发表时间：
1991-01-01
期刊：
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-PHYSIOLOGY
影响因子：
--
作者：
LIU, GL;FAN, LM;REDINGER, RN
通讯作者：
REDINGER, RN
影响因子：
8.7
作者：
Davis, HR;Compton, DS;Tetzloff, G
通讯作者：
Tetzloff, G
影响因子：
3.5
作者：
Oklejewicz, M;Daan, S
通讯作者：
Daan, S
LDL 受体基因消除仓鼠：具有显性遗传和饮食诱导的冠状动脉粥样硬化的家族性高胆固醇血症的啮齿动物模型
影响因子：
11.1
作者：
Guo X;Gao M;Wang Y;Lin X;Yang L;Cong N;An X;Wang F;Qu K;Yu L;Wang Y;Wang J;Zhu H;Xian X;Liu G
通讯作者：
Liu G
影响因子：
1.9
作者：
Palmisano BT;Anozie U;Yu S;Neuman JC;Zhu L;Edington EM;Luu T;Stafford JM
通讯作者：
Stafford JM