Zebrafish Atherosclerosis Models

Atherosclerosis (AS) is the pathological basis of many cardiovascular diseases and poses a serious threat to human health. Establishing an animal model of atherosclerosis is of great significance for studying its complex pathogenesis and screening and evaluating related drugs. Although researchers have established various models for atherosclerosis studies in rabbits, mice, and rats, the limitations of these models make it difficult to monitor the development of atherosclerosis, and these models are not suitable for large-scale screening of potential therapeutic targets.

In contrast, zebrafish can achieve these goals thanks to their in utero fecundity, rapid development, embryonic transparency and conserved lipid metabolism. The dramatic increase in oxidized lipoproteins was most pronounced in zebrafish fed a high cholesterol diet (HCD) compared to other AS animal models, making it an excellent model to study the mechanisms of lipoprotein oxidation. Therefore, zebrafish has become a popular surrogate animal model for atherosclerosis research.

Fig.1 Zebrafish model for atherosclerosis research.

Our Zebrafish Atherosclerosis Models

Creative Biogene provides HCD-induced zebrafish models, ldlr mutant zebrafish models, apoc2 mutant zebrafish models, and lxr mutant zebrafish models. Among them, the HCD-induced zebrafish model is frequently used to study the early development of AS. Specifically, we challenged with HCD for 10 days, and zebrafish larvae exhibited vascular lipid accumulation, myeloid cell aggregation, and early lipoprotein oxidation. Further, after we challenged with HCD for 8-12 weeks, adult zebrafish showed markedly elevated plasma total cholesterol levels and vascular lesions with intimal enlargement, lipid accumulation, and cell infiltration in dorsal aortic sections. Such lesions are classified as fatty streaks and are equivalent to human type II AS lesions, the early stages of type I-VI lesions.

We knocked out the low-density lipoprotein receptor (LDLR) in zebrafish by CRISPR/Cas9 technology to establish a model that after 5 days of HCD feeding, ldlr mutant larvae showed increased lipid accumulation in blood vessels and exacerbated hypercholesterolemia, thereby lead to type II AS lesions. apoc2^-/- zebrafish show lipid accumulation and lipid-containing macrophages in the vasculature, similar to what is observed in the development of human type II AS lesions, so we offer apoc2 mutant zebrafish to help you screen Potential drugs for hyperlipidemia. In addition, the lxr mutant zebrafish model we provide can display a marked increase in LDL when fed HCD or a high-fat diet, develop severe hypercholesterolemia and hepatic steatosis, with lipid deposits resembling fatty streaks in humans. This model can be used to screen gut-restricted LXR agonists that can be used to inhibit the development of dyslipidemia and atherosclerosis.

Advantages

• Dynamic monitoring of various cellular processes in vivo by real-time imaging of fluorescent reporter lines
• Easily monitor disease progression
• Macrophage tracking
• Transgenic models available
• High-throughput genetic and drug screening

References

1. Tang D, et al. Recent Application of Zebrafish Models in Atherosclerosis Research. Front Cell Dev Biol. 2021, 9:643697.
2. Schlegel A. Zebrafish Models for Dyslipidemia and Atherosclerosis Research. Front Endocrinol (Lausanne). 2016, 7:159.

For research use only. Not intended for any clinical use.