Abstract 144: Zebrafish Larvae: A Model System for Early Stage Atherosclerosis?

Objectives: Published results show that overfeeding zebrafish larvae on a high-cholesterol diet (HCD) can result in hypercholesterolemia and sub-endothelial lipid deposition in macrophages and other cell types. However, results are so far based on small samples, and the atherogenic response has been heterogeneous. We aim to use zebrafish larvae for large-scale, CRISPR-Cas9-based genetic screens, using results from genome wide association studies for coronary heart disease as a starting point. Firstly however, we need to ensure the model system is appropriate and robust. Therefore, we examined the effect of a high-energy diet (HED) and HCD on vascular lipid deposition in a larger number of larvae (n=241). Methods: Starting at 5 days post fertilization (dpf), ~30 larvae/tank were fed 2x/day on: 1) 5 mg control diet (CD; n=33); 2) 15 mg control diet (HED; n=90); or 3) 15 mg control diet enriched with 4% cholesterol (HCD; n=94). At 14-17 dpf, larvae were soaked in monodansylpentane cadaverase - a lipid staini...