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Selective Retention of VLDL, IDL, and LDL in the Arterial Intima of Genetically Hyperlipidemic Rabbits In Vivo: Molecular Size as a Determinant of Fractional Loss From the Intima–Inner Media
Open accessAbstract
Abstract To explore possible mechanisms whereby the triglyceride-rich lipoproteins IDL and VLDL may promote atherosclerosis, fractional loss of these lipoproteins from the intima–inner media was measured in vivo in genetically hyperlipidemic rabbits of the St Thomas’s Hospital strain and compared with the fractional loss of LDL, HDL, and albumin. These rabbits exhibit elevated plasma levels of VLDL, IDL, and LDL. In each rabbit, two aliquots of the same macromolecule, one iodinated with 125 I and the other with 131 I, respectively, were injected intravenously on average 24 and 3 hours, respectively, before removal of the aortic intima–inner media. The fractional loss from the intima–inner media of newly entered macromolecules was then calculated. The average fractional losses for VLDL, IDL, LDL, HDL, and albumin in lesioned aortic arches were 0.1%/h (n=4), −0.2%/h (n=3), 1.8%/h (n=4), 11.4%/h (n=3), and 26.3%/h (n=1), respectively; in nonlesioned aortic arches fractional losses for IDL, LDL, HDL, and albumin were 1.7%/h (n=1), 0.6%/h (n=2), 14.6%/h (n=3), and 25.9%/h (n=3). In both lesioned and nonlesioned aortic arches, the logarithms of these fractional loss values were inversely and linearly dependent on the diameter of the macromolecules (R2=.57,P=.001 and R2=.84,P<.001), as determined from electron photomicrographs of negatively stained lipoproteins. These results suggest that after uptake into the arterial intima, VLDL and IDL as well as LDL are selectively retained in comparison with HDL and albumin.
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“Lipoproteins <70 nm in diameter (that is, all HDL, LDL and intermediate-density lipoprotein (IDL) particles, most VLDL remnants and the smallest chylo-micron remnants) can pass the endothelial barrier and enter the arterial intima from the circulation41,42.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [41]
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“triglycerides (TG) can enter the arterial wall with a mild to moderate increase concentration (2–10 mmol/L), and then accumulate at there, thus causing the possibility of atherosclerosis [4]”
From Effects of aerobic exercise on lipids and lipoproteins (2017) · cites this paper as [4]
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Nordestgaard, B. G., Benn, M., Schnohr, P., & Tybjærg-Hansen, A. (2007) · JAMA · doi:10.1001/jama.298.3.299 · Cited by 2,058
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Metadata
- Authors
- Nordestgaard, B. G., Wootton, R., & Lewis, B.
- Affiliations
- University of Copenhagen (DK)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 1995-04
- Volume
- 15
- Issue
- 4
- Pages
- 534-542
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2150460597
- Cited by
- 334
- References
- 49
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 15 · 2023: 21 · 2022: 18 · 2021: 22 · 2020: 23 · 2019: 14 · 2018: 14 · 2017: 16 · 2016: 8 · 2015: 13 · 2014: 10 · 2013: 6 · 2012: 3
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hjerteforeningen
- Sundhed og Sygdom, Det Frie Forskningsråd
- Medical Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- VLDL, IDL, low-density lipoprotein, HDL cholesterol, arterial intima, atherosclerosis, lipoprotein retention, aortic arch, lipoprotein particle size, serum lipoproteins
- MeSH terms
- Albumins, Animals, Arteries, Female, Hyperlipidemias, Lipoproteins, Lipoproteins, LDL, Lipoproteins, VLDL, Male, Microscopy, Electron, Particle Size, Rabbits, Tunica Intima, Tunica Media, Lipoproteins, IDL
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