1. CRISPR/Cas9-mediated knockout of APOC3 stabilizes plasma lipids and inhibits atherosclerosis in rabbits.
- Author
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Zha Y, Lu Y, Zhang T, Yan K, Zhuang W, Liang J, Cheng Y, and Wang Y
- Subjects
- Animals, CRISPR-Associated Protein 9, CRISPR-Cas Systems, Cytokines blood, Female, Gene Knockdown Techniques, Intestine, Small metabolism, Liver metabolism, Male, Plaque, Atherosclerotic etiology, Rabbits, Apolipoprotein C-III metabolism, Atherosclerosis etiology, Lipids blood
- Abstract
Background: High levels of apolipoprotein C3 (APOC3) can lead to hypertriglyceridemia, which increases the risk of cardiovascular disease. We aim to create APOC3-knockout (KO) rabbits and explore the effects of APOC3 deletion on the occurrence and development of atherosclerosis., Methods: An sgRNA anchored to exon 2 of APOC3 was designed to edit embryo genomes using the CRISPR/Cas9 system. The founder rabbits were sequenced, and their lipid profile, inflammatory cytokines, and atherosclerotic plaques were analyzed., Results: When given a normal chow (NC) diet, all APOC3-KO rabbits had 50% lower triglyceride (TG) levels than those of the matched age control group. Additionally, their plasma lipoprotein lipase increased. When fed a high-fat diet, APOC3 deficiency was observed to be more conducive to the maintenance of plasma TG, total cholesterol, and low-density lipoprotein cholesterol levels, and the inhibition of the inflammatory response and the protection against atherosclerosis in rabbits., Conclusion: APOC3 deficiency can delay the formation of atherosclerosis-induced HFD in rabbits, indicating this is a novel therapeutic target to treat atherosclerosis., (© 2021. The Author(s).)
- Published
- 2021
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