PUBLICATION
Establishment of a lipid metabolism disorder model in ApoEb mutant zebrafish
- Authors
- Hu, Y.X., You, H.M., Zhu, R.F., Liang, Y.L., Li, F.F., Qin, Y.W., Zhao, X.X., Liang, C., Jing, Q.
- ID
- ZDB-PUB-221029-9
- Date
- 2022
- Source
- Atherosclerosis 361: 18-29 (Journal)
- Registered Authors
- Jing, Qing, Liang, Yulai, Li, Fangfang
- Keywords
- ApoEb, Apolipoprotein, Atherosclerosis, Hyperlipidemia, Xuezhikang, Zebrafish
- MeSH Terms
-
- Zebrafish/metabolism
- Simvastatin/pharmacology
- Apolipoproteins E/genetics
- Apolipoproteins E/metabolism
- Lipid Metabolism
- Ezetimibe
- Hypercholesterolemia*/metabolism
- Atherosclerosis*/pathology
- Mammals/metabolism
- Hyperlipidemias*
- Animals
- PubMed
- 36306655 Full text @ Atherosclerosis
Citation
Hu, Y.X., You, H.M., Zhu, R.F., Liang, Y.L., Li, F.F., Qin, Y.W., Zhao, X.X., Liang, C., Jing, Q. (2022) Establishment of a lipid metabolism disorder model in ApoEb mutant zebrafish. Atherosclerosis. 361:18-29.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping