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Published on: February 20, 2019
Non-rodent Models of Atherosclerosis: Repurposing of Existing Drugs and Search for Novel Treatment Strategies
Siarhei A Dabravolski1, Victoria A Khotina2,3, Mikhail A Popov3
1Department of Biotechnology Engineering, Braude Academic College of Engineering, Snunit 51, P.O. Box 78, Karmiel 2161002, Israel.
Abstract:
Atherosclerosis and associated cardiovascular diseases are the leading causes of illness and mortality worldwide. The development of atherosclerosis is a complex process involving oxidative stress, surplus lipid deposition and retention, endothelial dysfunction, and chronic inflammation. Developing novel anti-atherogenic and repurposing existing drugs requires the use of suitable animal models to characterise the fundamental mechanisms underlying atherosclerosis initiation and progression and to evaluate potential therapeutic effects. Commonly used rodent models, however, are not always appropriate, and other models may be required to translate these discoveries into valuable preventive and treatment agents for human applications. Recent advances in gene-editing tools for large animals have allowed the creation of animals that develop atherosclerosis faster and more similarly to humans in terms of lesion localisation and histopathology. In this review, we discuss the major advantages and drawbacks of the main non-rodent animal models of atherosclerosis, particularly rabbits, pigs, zebrafish, and non-human primates. Moreover, we review the application of recently invented novel therapeutic methods and agents, and repurposed existing drugs (such as antidiabetic and anticancer) for atherosclerosis treatment, the efficacy of which is verified on non-rodent animal models of atherosclerosis. In total, the proper selection of a suitable animal model of atherosclerosis facilitates reproducible and rigorous translational research in repurposing of existing drugs, discovering new therapeutic strategies, and validating novel anti-atherosclerotic drugs.
Insights
Selecting appropriate animal models is crucial for advancing atherosclerosis research. Non-rodent models, like pigs and rabbits, offer better human-like disease progression for developing new treatments and repurposing drugs.
Area of Science:
- Cardiovascular Research
- Translational Medicine
- Pharmacology
Background:
- Atherosclerosis is a leading cause of global mortality, driven by complex mechanisms including oxidative stress, lipid accumulation, and inflammation.
- Effective anti-atherosclerotic therapies require robust models to study disease initiation, progression, and treatment efficacy.
- Rodent models have limitations, necessitating exploration of alternative animal models for human-relevant translational research.
Purpose of the Study:
- To review the advantages and disadvantages of non-rodent animal models for atherosclerosis research.
- To discuss the application of novel and repurposed drugs for atherosclerosis treatment in these models.
- To highlight the importance of model selection for successful drug discovery and validation.
Main Methods:
- Review of current literature on non-rodent atherosclerosis models (rabbits, pigs, zebrafish, non-human primates).
- Analysis of gene-editing advancements in creating large animal models.
- Examination of therapeutic strategies, including novel agents and repurposed drugs (e.g., antidiabetics, anticancer agents).
Main Results:
- Non-rodent models, particularly large animals, exhibit atherosclerosis progression and lesion characteristics more similar to humans.
- Gene-editing has enabled the development of advanced animal models with faster disease development.
- Efficacy of various therapeutic agents has been validated in these non-rodent models.
Conclusions:
- The judicious selection of non-rodent animal models is essential for reproducible and rigorous translational research in atherosclerosis.
- These models facilitate the discovery of new therapeutic strategies and the validation of novel and repurposed drugs.
- Advancements in animal modeling accelerate the development of effective preventive and treatment agents for human cardiovascular diseases.
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