Yang-Xi Hu , Hong-Min You , Rong-Fang Zhu , Yu-Lai Liang , Fang-Fang Li , Yong-Wen Qin , Xian-Xian Zhao , Chun Liang , Qing Jing
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引用次数: 2
Abstract
Background and aims
ApoEb is a zebrafish homologous to mammalian ApoE, whose deficiency would lead to lipid metabolism disorders (LMDs) like atherosclerosis. We attempted to knock out the zebrafish ApoEb, then establish a zebrafish model with LMD.
Methods
ApoEb was knocked out using the CRISPR/Cas9 system, and the accumulation of lipids was confirmed by Oil Red O staining, confocal imaging, and lipid measurements. The lipid-lowering effects of simvastatin (SIM), ezetimibe (EZE) and Xuezhikang (XZK), an extract derived from red yeast rice, were evaluated through in vivo imaging in zebrafish larvae.
Results
In the ApoEb mutant, significant vascular lipid deposition occurred, and lipid measurement performed in the whole-body homogenate of larvae and adult plasma showed significantly increased lipid levels. SIM, EZE and XZK apparently relieved hyperlipidemia in ApoEb mutants, and XZK had a significant inhibitory effect on the recruitment of neutrophils and macrophages.
Conclusions
In this study, an LMD model has been established in ApoEb mutant zebrafish. We suggest that this versatile model could be applied in studying hypercholesterolemia and related vascular pathology in the context of early atherosclerosis, as well as the physiological function of ApoE.
背景与目的apoeb是斑马鱼中与哺乳动物ApoE同源的一种基因，缺乏ApoE会导致动脉粥样硬化等脂质代谢紊乱(LMDs)。我们尝试敲除斑马鱼的ApoEb，然后用LMD建立斑马鱼模型。方法利用CRISPR/Cas9系统敲除sapoeb，通过Oil Red O染色、共聚焦成像和脂质测量证实脂质积累。通过对斑马鱼幼鱼的体内显像，评价了辛伐他汀(SIM)、依泽替米(EZE)和血脂康(XZK)的降脂作用。结果ApoEb突变体发生了明显的血管脂质沉积，在幼虫和成虫的全身血浆匀浆中进行脂质测量，发现脂质水平显著升高。SIM、EZE和XZK明显缓解ApoEb突变体的高脂血症，XZK对中性粒细胞和巨噬细胞的募集有显著抑制作用。结论本研究建立了ApoEb突变斑马鱼LMD模型。我们认为这种多功能模型可以应用于研究早期动脉粥样硬化背景下的高胆固醇血症和相关血管病理，以及ApoE的生理功能。
期刊介绍：
Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review.
Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.
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