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CRISPR/Cas9-mediated knockout of APOC3 stabilizes plasma lipids and inhibits atherosclerosis in rabbits

Authors :
Kunning Yan
Yingge Wang
Yiwen Zha
Wenwen Zhuang
Yong Cheng
Ting Zhang
Yaoyao Lu
Jingyan Liang
Source :
Lipids in Health and Disease, Vol 20, Iss 1, Pp 1-11 (2021), Lipids in Health and Disease
Publication Year :
2021
Publisher :
BMC, 2021.

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.

Details

Language :
English
Volume :
20
Issue :
1
Database :
OpenAIRE
Journal :
Lipids in Health and Disease
Accession number :
edsair.doi.dedup.....4a17f14507da80f938afe9956aa1944a