Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis
Abstract
Introduction Cardiovascular disease, the leading cause of death in much of the modern world, is the common symptomatic end stage of a number of distinct diseases and, therefore, is multifactorial and polygenetic in character. The two major underlying causes are disorders of lipid metabolism and metabolic syndrome. The ability to develop preventative and ameliorative treatments will depend on animal models that mimic human disease processes. The focus of this review is to identify suitable animal models and insights into cardiovascular disease achieved to date using such models.Criteria for animal models The ideal animal model of cardiovascular disease will mimic the human subject metabolically and pathophysiologically, will be large enough to permit physiological and metabolic studies, and will develop end-stage disease comparable to those in humans. Given the complex multifactorial nature of cardiovascular disease, no one species will be suitable for all studies.Available models Potential larger animal models are problematic due to cost, ethical considerations, or poor pathophysiological comparability to humans. Rabbits require high-cholesterol diets to develop cardiovascular disease, and there are no rabbit models of metabolic syndrome. Spontaneous mutations in rats provide several complementary models of obesity, hyperlipidemia, insulin resistance, and type 2 diabetes, one of which spontaneously develops cardiovascular disease and ischemic lesions. The mouse, like normal rats, is characteristically resistant to cardiovascular disease, although genetically altered strains respond to cholesterol feeding with atherosclerosis, but not with end-stage ischemic lesions.Conclusions The most useful and valid species/strains for the study of cardiovascular disease appear to be small rodents, rats, and mice. This fragmented field would benefit from a consensus on well-characterized appropriate models for the study of different aspects of cardiovascular disease and a renewed emphasis on the biology of underlying diseases.
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ZDF rats have an additional defect in beta-cells that accelerates beta-cell dysfunction leading to the early onset of severe type 2 diabetes.
“These animals have an additional defect in beta-cells that accelerates beta-cell dysfunction leading to the early onset of severe type 2 diabetes (305).”
From Cardiac remodeling in obesity (2008) · cites this paper as [305]
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Primary prevention of diabetes mellitus by prevention of obesity in monkeys
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Increased proliferation of explanted vascular smooth muscle cells: a marker presaging atherogenesis
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Effects of chronic ethanol consumption in atherosclerosis-prone JCR:LA-corpulent rat.
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Self-citationRenal injury: Similarities and differences in male and female rats with the metabolic syndrome
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The Yucatan minature pig as a laboratory animal.
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Glucose tolerance and insulin resistance in the JCR:LA-corpulent rat: Effect of miglitol (Bay m1099)
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Absher, P. M., Schneider, D. J., Baldor, L. C., et al. (1999) · Atherosclerosis · doi:10.1016/s0021-9150(98)00295-0 · Cited by 41 · see citing works
Attenuation of hypercholesterolemia and hyperglycemia in ob/ob mice by NPY Y2 receptor ablation
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Self-citationTHE ZUCKER DIABETIC FATTY (ZDF) RAT
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Vascular wall dysfunction in JCR:LA-cp rats: effects of age and insulin resistance
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Self-citationRespiratory infection in lipid-fed rabbits enhances sudanophilia and the expression of VCAM-1.
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Vascular dysfunction and myocardial contractility in the JCR:LA-corpulent rat
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Delayed insulin transport across endothelium in insulin-resistant JCR:LA-cp rats.
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Development of Atherosclerotic Lesions in Cholesterol-loaded Rabbits.
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Vasopeptidase Inhibition Improves Insulin Sensitivity and Endothelial Function in the JCR:LA-cp Rat
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Abel, E. D., Litwin, S. E., & Sweeney, G. (2008) · Physiological Reviews · doi:10.1152/physrev.00017.2007 · Cited by 736 · see citing works
Animal models in cardiovascular research: hypertension and atherosclerosis
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The Efficacy of Squalene in Cardiovascular Disease Risk-A Systematic Review
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Animal Models of Neointimal Hyperplasia and Restenosis
Ebert, M. L. A., Schmidt, V. F., Pfaff, L., von Thaden, A., Kimm, M. A., & Wildgruber, M. (2021) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2021.06.006 · Cited by 63 · see citing works
- Authors
- Russell, J. C., & Proctor, S. D.
- Affiliations
- University of Alberta (CA)
- Corresponding author
- Russell, James C.
- ORCID
- Proctor, Spencer D.
- Venue
- Cardiovascular Pathology
- Publisher
- Elsevier BV
- Published
- 2006-11
- Volume
- 15
- Issue
- 6
- Pages
- 318-330
- ISSN
- 1054-8807 (ISSN-L)
- OpenAlex
- W1971716779
- Cited by
- 317
- References
- 160
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 14 · 2020: 13 · 2019: 17 · 2018: 14 · 2017: 21 · 2016: 22 · 2015: 22 · 2014: 18 · 2013: 20 · 2012: 27
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cardiovascular Pathology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- cardiovascular disease, animal models, metabolic syndrome, dyslipidemia, atherosclerosis, lipid metabolism, spontaneously hypertensive rats, spontaneously diabetic rats, mouse model, rat model, high-cholesterol diet, insulin resistance, obesity, ischemic lesions
- MeSH terms
- Animals, Cardiovascular Diseases, Disease Models, Animal, Rabbits, Metabolic Syndrome, Dyslipidemias, Atherosclerosis, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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