Zebrafish Model for Screening Antiatherosclerosis Drugs

Area of Science:

• Cardiovascular Biology
• Pharmacology
• Zebrafish Models

Background:

• Atherosclerosis (AS) poses a significant global health burden.
• Developing effective and efficient models for AS research is crucial for drug discovery.
• Zebrafish offer a promising vertebrate model system due to their genetic tractability and rapid development.

Purpose of the Study:

• To establish a robust zebrafish model of atherosclerosis (AS).
• To validate the model's utility for high-throughput screening of anti-atherosclerotic drugs.
• To investigate the combined effects of high cholesterol diet (HCD) and lipopolysaccharide (LPS) in AS development.

Main Methods:

• Induction of AS in zebrafish using a combination of high cholesterol diet (HCD) and lipopolysaccharide (LPS).
• Monitoring of early AS symptoms including cholesterol accumulation, vascular inflammation, lipid metabolism disorder, and oxidative stress.
• Histopathological analysis of zebrafish vasculature to identify plaque formation after 45 days.
• Evaluation of anti-atherosclerotic drug efficacy (atorvastatin, aspirin, vitamin C).

Main Results:

• Both HCD and LPS induced early AS-like symptoms in zebrafish.
• Combined HCD and LPS treatment exacerbated AS symptoms and led to plaque formation resembling human AS plaques.
• Atorvastatin significantly ameliorated AS symptoms induced by both HCD and LPS.
• Aspirin and vitamin C showed significant efficacy against LPS-induced AS symptoms.

Conclusions:

• The developed zebrafish model accurately recapitulates key features of human atherosclerosis.
• This zebrafish model is suitable for high-throughput screening of novel anti-atherosclerotic compounds.
• The study validates the potential of zebrafish as a valuable tool in cardiovascular drug discovery.