# Rodent Models for Atherosclerosis

## TL;DR

This review compares rodent models for atherosclerosis, highlighting their strengths and limitations in mimicking human disease and lipid metabolism.

## Contribution

The paper systematically evaluates rodent models for atherosclerosis, emphasizing species-specific lipid metabolism and model suitability for different study phases.

## Key findings

- C57BL/6 mice are preferred for late-stage plaque stability studies due to their hypercholesterolemia and survival on high-fat diets.
- Golden hamsters have human-like lipid metabolism but show poor reproducibility in lesion progression.
- Rats are better suited for early disease mechanism studies despite limited lesion progression.

## Abstract

Atherosclerosis, a leading cause of cardiovascular disease, is driven by a complex interplay of dyslipidemia, inflammation, and arterial plaque formation and progression. Animal models are indispensable to elucidate the pathogenesis and develop novel therapies. Rodent models are widely utilized due to their cost-effectiveness, reproducibility, and rapid disease progression. However, notable species differences exist in lipoprotein composition and lipid metabolism pathways. Mice and rats exhibit an HDL-dominant profile, whereas Syrian golden hamsters express cholesteryl ester transfer protein (CETP) and display a higher LDL fraction, but lower than that of humans, offering a model closer to human metabolically. Divergent CETP activity across species further complicates the translational relevance of the findings from these models for atherosclerosis and related metabolic disorders. This review systematically examines the key factors in rodent model selection and optimization, with consideration on the roles of sex and age. We focus on three commonly used and well-characterized rodent strains prone to atherosclerosis: C57BL/6J mice, Sprague-Dawley (SD) rats, Wistar rats, and golden hamsters. On Apoe−/− or Ldlr−/− backgrounds, male C57BL/6 mice, owing to their pronounced hypercholesterolemia and extended survival with high-fat diet, are preferentially used in late-stage plaque stability studies. In contrast, male SD or Wistar rats develop atherosclerosis slowly with limited lesion progression, while hamsters, despite their human-like lipid metabolism, exhibit substantial individual variability and lesions that typically arrest at early fatty streaks with poor reproducibility. Therefore, rats and hamsters are better suited for studies focusing on early disease mechanisms and human-mimetic lipid metabolism.