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Influx in vivo of low density, intermediate density, and very low density lipoproteins into aortic intimas of genetically hyperlipidemic rabbits. Roles of plasma concentrations, extent of aortic lesion, and lipoprotein particle size as determinants.
Open accessAbstract
To compare the atherogenic potential of low density lipoprotein (LDL), intermediate density lipoprotein (IDL), and very low density lipoprotein (VLDL) under conditions where plasma levels of these lipoproteins are elevated, the influx of cholesterol in these lipoproteins into the aortic intima was measured in vivo in genetically hyperlipidemic rabbits from the St. Thomas's Hospital strain, an animal model that shares many of the features of the human disorder familial combined hyperlipidemia. Univariate linear regression showed that the arterial influx of LDL cholesterol (n = 25), IDL cholesterol (n = 14), and VLDL cholesterol (n = 10) was positively and linearly associated with plasma concentrations of LDL cholesterol in the range 0.2-6.4 mmol/l, of IDL cholesterol in the range 0.1-7.0 mmol/l, and of VLDL cholesterol in the range 0.7-8.5 mmol/l, respectively, and also with the extent of lesions in the arterial intima in the range 0-100% of the surface area. Multiple linear regression suggested that the arterial influx of LDL, IDL, and VLDL cholesterol was linearly dependent on plasma concentration, independent of lesion size. Furthermore, it appeared that the arterial influx of the three lipoproteins was linearly dependent on the extent of the lesions, independent of lipoprotein concentration. When influx was normalized for plasma concentration (intimal clearance) and for lesion size (compared within the same aorta), the intimal clearance of the larger IDL and VLDL particles was 15-35% less than that of the smaller LDL particles. These findings suggest that the quantitatively most important mechanism for transfer of plasma lipoproteins into the arterial intima involves nonspecific molecular sieving and that at elevated plasma levels, IDL and VLDL share with LDL the potential for causing atherosclerosis.
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“Very large triglyceride-rich lipoproteins, perhaps equivalent to unmetabolized chylomicrons, are not atherogenic if they are too large to penetrate into the arterial wall (60, 137).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [137]
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Metadata
- Authors
- Nordestgaard, B. G., Tybjaerg-Hansen, A., & Lewis, B.
- Affiliations
- St Thomas' Hospital (GB)
- Department of Chemical Pathology and Metabolic Disorders, United Medical School, St. Thomas's Hospital, London, UK.
- Venue
- Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
- Published
- 1992-01
- Volume
- 12
- Issue
- 1
- Pages
- 6-18
- ISSN
- 1049-8834 (ISSN-L)
- OpenAlex
- W2067328467
- Cited by
- 159
- References
- 37
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 7 · 2023: 14 · 2022: 8 · 2021: 5 · 2020: 9 · 2019: 5 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 6 · 2014: 4 · 2013: 4 · 2012: 3
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis and Thrombosis A Journal of Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hjerteforeningen
- Sundhed og Sygdom, Det Frie Forskningsråd
- Wellcome Trust
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- low-density lipoprotein, intermediate density lipoprotein, VLDL, aortic intima, atherosclerosis, familial combined hyperlipidemia, lipoprotein particle size, molecular sieving, cholesterol transfer, atherogenic potential
- MeSH terms
- Animals, Aorta, Cholesterol, Female, Hyperlipidemia, Familial Combined, Lipoproteins, Cholesterol, LDL, Male, Microscopy, Electron, Rabbits, Regression Analysis, Cholesterol, VLDL
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