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CRISPR/Cas9-mediated knockout of APOC3 stabilizes plasma lipids and inhibits atherosclerosis in rabbits
- 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.
- Subjects :
- Male
RC620-627
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Rabbit
Endocrinology
CRISPR-Associated Protein 9
Plasma lipids
Intestine, Small
CRISPR
Animals
Nutritional diseases. Deficiency diseases
CRISPR/Cas9
Triglycerides
Apolipoprotein C-III
Chemistry
Research
Biochemistry (medical)
Atherosclerosis
Lipids
Plaque, Atherosclerotic
Apolipoprotein
Cell biology
Liver
Gene Knockdown Techniques
Cytokines
lipids (amino acids, peptides, and proteins)
Female
Rabbits
CRISPR-Cas Systems
Subjects
Details
- Language :
- English
- Volume :
- 20
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Lipids in Health and Disease
- Accession number :
- edsair.doi.dedup.....4a17f14507da80f938afe9956aa1944a