Lipoprotein size and susceptibility to atherosclerosis—insights from genetically modified mouse models.
Open accessAbstract
High plasma levels of the apo-B-containing lipoproteins are casually implicated in the pathogenesis of atherosclerosis. This finding, backed by decades of animal and human studies, has sparked interest in defining which classes of apo-B-containing lipoprotein particles are most atherogenic. Although small LDL particles and larger remnant lipoproteins both appear to be atherogenic, it has been difficult to discern which particles are the most atherogenic. Here, we summarize several mouse models that have provided insights into this issue. The influence of lipoprotein size on susceptibility to atherosclerosis was examined by studying the phenotypes of two strains of mice with virtually identical levels of plasma cholesterol--Ldlr(-/-)Apob(100/100) and Apoe(-/-) Apob(100/100) mice. The Ldlr(-/-) Apob(100/100) mice, where the cholesterol is in small LDL particles, had far more atherosclerosis than Apoe(-/-) Apob(100/100) mice, where virtually all of the cholesterol was in larger, VLDL-sized particles. Another intriguing animal model is the Gpihbp1-deficient mouse. GPIHBP1 is an endothelial cell platform for lipolysis, and mice lacking this protein have an accumulation of large, triglyceride-rich lipoproteins. Defining the extent of atherosclerosis in these mice should provide new insights into the atherogenicity of large, triglyceride-rich lipoproteins.
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A variety of animal models produced using dietary or genetic manipulations have confirmed that chylomicron remnants are atherogenic.
“A variety of animal models produced using dietary or genetic manipulations have confirmed that chylomicron remnants are atherogenic (139, 144).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [144]
In “Apo-B–Containing Lipoproteins and Atherosclerosis” (page unavailable), the paper says there is substantial evidence that chylomicron and VLDL remnants can be atherogenic. Its mouse-model discussion reports lesions in genetically modified mice with elevated remnants, but cautions that those mice also have LDL-sized particles, making the remnants’ contribution difficult to isolate. The cited passages do not establish the claim that a variety of dietary and genetic animal models have confirmed chylomicron remnants’ atherogenicity. (LLM, conf=0.83)
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Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline
Berglund, L., Brunzell, J. D., Goldberg, A. C., Goldberg, I. J., Sacks, F., Murad, M. H., & Stalenhoef, A. F. H. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-3213 · Cited by 887 · see citing works
“A variety of animal models produced using dietary or genetic manipulations have confirmed that chylomicron remnants are atherogenic (139, 144).”
Getz, G. S., & Reardon, C. A. (2016) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.116.306874 · Cited by 198 · see citing works
The burden of familial chylomicronemia syndrome: interim results from the IN-FOCUS study
Davidson, M., Stevenson, M., Hsieh, A., Ahmad, Z., Crowson, C., & Witztum, J. L. (2017) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2017.1311786 · Cited by 54 · see citing works
- Authors
- Young, S., Veniant, M., Beigneux, A., Bensadoun, A., & Fong, L.
- Affiliations
- Amgen (United States) (US)
- Venue
- Current Drug Targets
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2008-03-01
- Volume
- 9
- Issue
- 3
- Pages
- 174-189
- ISSN
- 1389-4501 (ISSN-L)
- PMC
- PMC3034977
- OpenAlex
- W2160255625
- Cited by
- 33
- References
- 55
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 1 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 2 · 2013: 1 · 2012: 3
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Drug Targets (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL090553, R01HL076839, R01HL087228)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- atherosclerosis, lipoprotein particle size, atherogenic lipoproteins, apolipoprotein B, small dense LDL, remnant lipoproteins, VLDL, Ldlr knockout mice, ApoE-deficient mice, triglyceride-rich lipoproteins, genetically engineered mouse models
- MeSH terms
- Animals, Disease Models, Animal, Humans, Lipoproteins, Genetic Predisposition to Disease, Animals, Genetically Modified, Atherosclerosis, Mice
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