Arterial Permeability and Efflux of Apolipoprotein B–Containing Lipoproteins Assessed by In Situ Perfusion and Three-Dimensional Quantitative Confocal Microscopy
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Objectives— There is accumulating evidence that an increased risk of cardiovascular disease (CVD) is not simply caused by the degree of arterial exposure to plasma lipoproteins but, in addition, is determined by the affinity of the vasculature for different lipoprotein phenotypes. In this study we compare the delivery and efflux of 2 atherogenic lipoproteins to further understand the factors that regulate cholesterol accumulation in early atherogenesis. Methods and Results— Lipoproteins containing apolipoprotein (apo) B100 (a low-density lipoprotein [LDL]) and apoB48 (chylomicron remnants) were isolated and differentially conjugated with fluorophores and simultaneously perfused at equivalent concentrations in situ through rabbit carotid vessels. Perfusion systems were established to quantify and differentiate between lipoprotein arterial delivery and efflux. The total average rate of delivery for LDL particles (23 nm) compared with chylomicron remnants (50 nm) was 4427 particles/min −1 per μm 3 and 452 particles/min −1 per μm 3 , respectively. In contrast, the average rate of efflux was 3195 particles/min −1 per μm 3 and 163 particles/min −1 per μm 3 for LDL and chylomicron remnants, respectively. Conclusions— Results indicate that although LDL particles have a higher rate of delivery, they efflux more readily from arterial tissue compared with the larger chylomicron remnants. Collectively, our findings highlight that lipoproteins permeate through arterial tissue differently and may be dependent on the phenotype and potential interactions with extracellular matrix components.
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Possible mechanisms connecting small LDL particles to vascular events include greater oxidizability and increased passage through the endothelial barrier.
“Potential mechanisms that link small LDL particles to increased risk of vascular events include augmented oxidizability (36) and increased permeability through the endothelial barrier (37).”
From Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans (2013) · cites this paper as [37]
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Self-citation
- Authors
- Proctor, S. D., Vine, D. F., & Mamo, J. C. L.
- Affiliations
- Curtin University (AU)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2004-11
- Volume
- 24
- Issue
- 11
- Pages
- 2162-2167
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W1966788643
- Cited by
- 103
- References
- 30
- Citations by year
- 2025: 5 · 2024: 4 · 2023: 7 · 2022: 7 · 2021: 5 · 2020: 6 · 2019: 2 · 2018: 6 · 2017: 3 · 2015: 4 · 2014: 1 · 2013: 4 · 2012: 4
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart Foundation of Australia
- Medical Research Council
- National Health and Medical Research Council (229030)
- National Medical Research Council
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- arterial permeability, apolipoprotein B-100, apolipoprotein B-48, chylomicron remnants, low-density lipoprotein, atherogenesis, cholesterol accumulation, carotid artery, in situ perfusion, extracellular matrix, lipoprotein phenotype
- MeSH terms
- Animals, Apolipoproteins B, Capillary Permeability, Humans, Infusions, Intra-Arterial, Lipoproteins, LDL, Particle Size, Rabbits, Microscopy, Confocal, Imaging, Three-Dimensional
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