Zebrafish Model for Screening Antiatherosclerosis Drugs

Abstract

This study is aimed at establishing a zebrafish model of AS, which can be applied for high-throughput screening anti-AS drugs. A zebrafish AS model was induced by high cholesterol diet (HCD) and lipopolysaccharide (LPS). In the early stage of modeling, HCD induced zebrafish to show some early symptoms similar to human AS, mainly cholesterol accumulation, vascular inflammation, lipid metabolism disorder, and oxidative stress. In addition to lipid metabolism disorders, LPS also induced the same symptoms. And when HCD and LPS exist at the same time, these AS symptoms in zebrafish become more severe. When the modeling time reached 45 days, HCD and LPS induce the formation of plaques in zebrafish blood vessels, and these plaques contain fibrous tissue and lipids, which are similar to human AS plaques. We also evaluated the efficacy of some anti-AS drugs (atorvastatin, aspirin, and vitamin C) through these zebrafish AS models. The results found that atorvastatin can significantly reduce the symptoms of AS induced by HCD and LPS, and aspirin and vitamins can significantly reduce the symptoms of AS induced by LPS. It is feasible to use zebrafish to establish an AS model, and the zebrafish AS model can be used for high-throughput screening of anti-AS drugs.