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Lipoprotein lipase increases lipoprotein binding to the artery wall and increases endothelial layer permeability by formation of lipolysis products.
Abstract
Mechanisms responsible for the accumulation of low-density lipoprotein (LDL) were investigated in a new model, the perfused hamster aorta. To do this, we developed a method to study LDL flux in real time in individually perfused arteries; each artery served as its own control. Using quantitative fluorescence microscopy, the rates of LDL accumulation and efflux were separately determined. Perfusion of arteries with buffer plus lipoprotein lipase (LpL) increased LDL accumulation 5-fold (0.1 +/- 0.03 mV/min [control] versus 0.5 +/- 0.05 mV/min [LpL]) by increasing LDL retention in the artery wall. This effect was blocked by heparin and monoclonal antibodies directed against the amino-terminal region of apolipoprotein B (apo B). This suggests that specific regions of apo B are involved in LDL accumulation within arteries. Also, the effect of hydrolysis of triglyceride-rich lipoproteins on endothelial barrier function was studied. We compared endothelial layer permeability using a water-soluble reference molecule, fluorescently labeled dextran. When LpL was added to hypertriglyceridemic plasma, dextran accumulation within the artery wall increased > 4-fold (0.024 +/- 0.01 mV/min [control] versus 0.098 +/- 0.05 mV/min [LpL]). Under the same conditions, LpL increased LDL accumulation approximately 3-fold (0.016 +/- 0.003 mV/min [control] versus 0.047 +/- 0.013 mV/min [LpL]). Rapid efflux of LDL from the artery wall indicated that increased endothelial layer permeability was the primary mechanism during periods of increased lipolysis. Our data demonstrate two LpL-mediated effects that may increase the amount of LDL in the artery wall. These findings may pertain to the observed relationship between increased postprandial lipemia and atherosclerosis.
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“In addition, ex vivo studies have shown that lipolysis leads to increased permeability of blood vessels (150), which may allow greater infiltration of LDL.”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [150]
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“Local conditions could make the endothelial barrier leaky, e.g. lipolysis leading to extremely high local concentrations of fatty acids and lysolipids might lead to defective barrier function 21) .”
BackgroundSelf-citationMeasurement of Endothelial Permeability
Marcus, B. C., & Gewertz, B. L. (1998) · Annals of Vascular Surgery · doi:10.1007/bf03035364 · Cited by 9
Liu, Y., Skudder‐Hill, L., Kimita, W., Shamaitijiang, X., Sequeira, I. R., & Petrov, M. S. (2025) · Diabetes Obesity and Metabolism · doi:10.1111/dom.16338 · Cited by 6
“62,63 Further, non-esterified fatty acids produced during VLDL hydrolysis by LPL increase the permeability of arteries, 64 enhance the production of inflammatory cytokines by macrophages 65 and pro-atherogenic proteoglycans by smooth muscle cells, 66 further exacerbating the atherogenesis process.”
MRI demonstration of orbital lipolysis in anorexia nervosa
Demaerel, P., Dekimpe, P., Muls, E., & Wilms, G. E. (2002) · European Radiology · doi:10.1007/s00330-002-1365-7 · Cited by 6
“increases the endothelial layer permeability of the vessel wall [3].”
BackgroundShepherd, G., Cam, M. C., Sambandam, N., Abrahani, M. A., & Rodrigues, B. B. (1998) · Hypertension · doi:10.1161/01.hyp.31.3.878 · Cited by 6
“Lipolytic products have also been shown to enhance endothelial permeability.(53,54) Interestingly, DIA demonstrate greater vascular permeability than nondiabetic SHR, or diabetic normotensive rats.”
BackgroundInflammatory Effects of Very low-density Lipoprotein and Fatty Acids
Ares, M. P. S., & Stollenwerk, M. M. (2006) · Future Cardiology · doi:10.2217/14796678.2.3.315 · Cited by 5
“They increase arterial permeability [33] and lipoprotein lipase (LPL) synthesis [34], stimulate phagocytosis [35], decrease nitric oxide production [36] and influence proteoglycan production [37].”
BackgroundRapid orbital lipolysis associated with critical illness and colectomy
Li, J., Rajput, A., Kosoy, D., Umekawa, S., Rajput, A., Chang, J. R., & Patel, V. N. (2021) · Radiology Case Reports · doi:10.1016/j.radcr.2021.06.001 · Cited by 3
Lipoprotein Lipase in the Arterial Wall: Regulation by Dietary Fatty Acids
Chang, C. L. (2011) · doi:10.7916/d81r6xh3 · Cited by 3
Myopathische Ver�nderungen durch transgene Expression von Lipoproteinlipase
Merkel, M., Radner, H., & Greten, H. (2003) · Medizinische Klinik - Intensivmedizin und Notfallmedizin · doi:10.1007/s00063-003-1313-6 · Cited by 2
Modulation of the adipogenic master regulator PPARγ
Taşdelen, I. (2014) · Utrecht University Repository (Utrecht University) · Cited by 1
Altered Substrate Utilization in the Diabetic Heart: Role of Lipoprotein Lipase
Pulinilkunnil, T., Sambandam, N., & Rodrigues, B. B. (2003) · Progress in experimental cardiology · doi:10.1007/978-1-4615-0455-9_10 · Cited by 1
GPIHBP1: a new chylomicronemia gene
Beigneux, A. P., Gin, P., Davies, B. S. J., Yin, L., Weinstein, M. M., Bensadoun, A., Fong, L. G., & Young, S. G. (2008) · Future Lipidology · doi:10.2217/17460875.3.2.203 · Cited by 1
Impacto del metabolismo lipídico en la aterogénesis femenina
García-Martínez, M. C., Cano, A., & Hermenegildo, C. (2001) · Progresos de Obstetricia y Ginecología · doi:10.1016/s0304-5013(01)75617-8
Association of Lipoprotein Lipase Gene Polymorphism and Coronary Artery Disease in Korean
Park, J., Chae, I., Kim, H.-S., Ju, J. R., Sohn, D., Oh, B., Lee, M., Park, Y.-B., Choi, Y.-S., & Lee, Y. (1999) · Korean Circulation Journal · doi:10.4070/kcj.1999.29.7.663
Regulation of cardiac lipoprotein lipase during hypertension and diabetes
Sambandam, N. (2009) · Library and Archives Canada (Government of Canada) · doi:10.14288/1.0089351
OBSOLETE: Lipid-mediated Mechanisms of Atherosclerosis
Fan, D. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.99555-2
Lipid-Mediated Mechanisms in Atherosclerosis
Liu, Q., Martinez, J., Hodge, J., & Fan, D. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809657-4.99555-3
Leveraging drug-target Mendelian randomization for tailored lipoprotein-lipid lowering
Gagnon, É., & Arsenault, B. J. (2025) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000977
An, B., Auger, S. A., Lutsey, P. L., Mielke, M. M., Yu, F., Hoogeveen, R. C., Gottesman, R. F., Zhang, L., Meyer, M. L., Sullivan, K., et al. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251401480
“Lipoprotein lipase can increase endothelial layer permeability through endothelial cell injury induced by lip-olysis products, 28 and higher permeability of the blood-brain barrier is associated with greater WMH volume.”
Pentikäinen, M. O. (1999) · Työväentutkimus Vuosikirja
Metadata
- Authors
- Rutledge, J. C., Woo, M. M., Rezai, A. A., Curtiss, L. K., & Goldberg, I. J.
- Affiliations
- Scripps Research Institute (US)
- ORCID
- Goldberg, Ira J.
- Venue
- Circulation Research
- Published
- 1997-06
- Volume
- 80
- Issue
- 6
- Pages
- 819-828
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2101670650
- Cited by
- 101
- References
- 48
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 3
- FWCI
- 5.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50hl021006-17)
- National Heart, Lung, and Blood Institute (HL55667, HL45095, HL 21006, R01HL055667)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- lipoprotein lipase, apolipoprotein B, lipolysis, endothelial permeability, triglyceride-rich lipoproteins, hypertriglyceridemia, postprandial lipemia, atherosclerosis, heparin, monoclonal antibodies
- MeSH terms
- Animals, Arteries, Capillary Permeability, Endothelium, Vascular, Cricetinae, Lipolysis, Lipoprotein Lipase, Lipoproteins, Lipoproteins, LDL, Mesocricetus, Microscopy, Fluorescence
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