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Updated: Dec 17, 2025

Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Small rodent models of atherosclerosis
Yihan Zhao1, Hua Qu2, Yuhui Wang3
1Department of Graduate School, Beijing University of Chinese Medicine, Beijing, China.
This review examines how different small rodents, including mice, rats, hamsters, and guinea pigs, are used to study heart disease. While mice are common, they differ from humans in how they process fats. Newer models like hamsters may better mimic human conditions, helping scientists test potential treatments more effectively.
Area of Science:
- Cardiovascular pathology and atherosclerosis research within metabolic medicine
- Comparative physiology and transgenic model development
Background:
No prior work had resolved which small rodent species best replicates human cardiovascular disease patterns. Researchers often rely on mice due to their rapid breeding cycles and low upkeep costs. That uncertainty drove the need to evaluate how well these animals mirror human lipid profiles. It was already known that mice possess distinct metabolic differences compared to human subjects. This gap motivated a comprehensive look at alternative species like hamsters and guinea pigs. Prior research has shown that mice fail to fully capture the complexity of human plaque development. Scientists continue to seek better platforms for testing pharmaceutical interventions for vascular health. This review addresses the limitations inherent in current standard laboratory animal practices.
Purpose Of The Study:
The aim of this review is to provide a comprehensive overview of both classic and innovative small rodent models used in cardiovascular research. Scientists face a persistent challenge because current animal systems often fail to perfectly mirror human disease progression. This uncertainty drove the need to evaluate the utility of mice, rats, hamsters, and guinea pigs. The authors seek to clarify how different species handle lipoprotein metabolism and develop vascular plaques. By comparing these models, the study intends to help researchers choose the best platform for their specific experimental needs. The review highlights the shift toward more realistic models enabled by recent technological advancements. It addresses the gap in knowledge regarding the limitations of standard mouse-based testing. Ultimately, the work serves as a guide for improving the translational value of preclinical atherosclerosis studies.
Main Methods:
The authors performed a systematic overview of current literature regarding various small animal species. They synthesized data focusing on lipoprotein metabolism and specific histopathological changes observed in these animals. The review approach involved comparing traditional transgenic mouse platforms against emerging alternatives like hamsters and rats. Investigators analyzed how different genetic modifications influence the development of vascular lesions. They examined the impact of dietary induction alongside modern gene-editing techniques. The synthesis prioritized studies that documented the strengths and weaknesses of each model. This methodology allowed for a critical assessment of how well these animals mimic human disease. The team structured their findings to guide researchers in selecting the most appropriate experimental systems.
Main Results:
Key findings from the literature indicate that mice, while convenient, do not accurately replicate the human lipoprotein profile. The authors report that classic transgenic mouse platforms, specifically apoE-/- and Ldlr-/-, remain the most utilized systems for studying disease mechanisms. Research shows that hamsters and guinea pigs possess lipid metabolism traits more similar to humans than mice do. The data reveal that rats, which are naturally resistant to plaque formation, can now be modified using CRISPR-Cas9 to exhibit atherosclerotic lesions. Recent studies demonstrate that Ldlr-/- hamsters develop severe hyperlipidemia and distinct lesion formation. The review notes that plaque progression and characteristics vary significantly between mice and humans. Evidence suggests that these differences limit the direct translation of mouse-based findings to clinical human applications. The synthesis confirms that each rodent model presents a unique set of advantages and limitations for cardiovascular investigators.
Conclusions:
The authors suggest that no single rodent model perfectly replicates all aspects of human vascular pathology. Mice remain the most frequent choice despite their clear metabolic divergence from human patients. Hamsters and guinea pigs appear to offer more accurate representations of human lipid metabolism. Recent advancements in gene editing allow researchers to induce disease states in previously resistant species like rats. The review highlights that selecting an appropriate animal system depends heavily on the specific research question. Investigators should carefully weigh the advantages and drawbacks of each species before starting experiments. These findings imply that diversifying model usage could improve the translation of preclinical results to clinical settings. Future studies might benefit from integrating these newer, more realistic rodent platforms into standard testing protocols.
Frequently Asked Questions
The researchers propose that hamsters and guinea pigs provide a more accurate representation of human lipoprotein metabolism compared to mice. While mice are the standard, they lack a humanized lipid profile, whereas hamsters exhibit similarities that better mimic human cardiovascular disease states.
The authors highlight CRISPR-Cas9 as a transformative tool that enables genetic manipulation in rats. This technology allows scientists to overcome the natural resistance rats typically exhibit toward developing atherosclerotic plaques, facilitating new avenues for cardiovascular investigation.
ApoE-/- and Ldlr-/- mice are necessary platforms for investigating molecular mechanisms and testing new drugs. These models are widely used because they consistently develop lesions, providing a baseline for understanding how plaque formation occurs in a controlled laboratory environment.
The authors state that Ldlr-/- hamsters are a significant development because they exhibit severe hyperlipidemia and clear atherosclerotic lesion formation. This makes them a viable alternative to traditional mouse models, offering a more realistic physiological context for studying human-like disease progression.
The researchers measure success by evaluating how well each animal's lipoprotein profile and histopathological changes align with human conditions. They emphasize that plaque progression and characteristics differ significantly between mice and humans, necessitating careful validation of each model used.
The authors suggest that the field must move beyond reliance on a single species to improve the translation of findings. By utilizing a broader range of rodents, scientists can better account for the complexities of human disease and improve the success rate of pharmaceutical development.

