Lipoprotein lipase (LpL) affects low density lipoprotein (LDL) flux through vascular tissue: Evidence that LpL increases LDL accumulation in vascular tissue

John C Rutledge, I. J. Goldberg

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42 Citations (Scopus)

Abstract

A cardinal feature of the atherosclerotic lesion is increased low density lipoprotein (LDL) content of the arterial wall. Such increases in vascular wall LDL could result from either increased flux of circulating LDL across the arterial endothelial barrier or decreased efflux of LDL that has entered the vascular tissue. A number of studies have focused on factors that alter permeability of endothelial cell monolayers and intact blood vessels causing increased LDL influx. In contrast, the current studies were designed to test the hypothesis that lipoprotein lipase (LpL) increases LDL accumulation and decreases LDL efflux from vascular tissue. Frog mesenteric venular microvessels were cannulated and the rates of fluorescently labeled LDL accumulation (N/t) and efflux (T( 1/2 )) were measured by quantitative fluorescence microscopy. When the vessels were perfused with a solution containing bovine milk LpL (10-5 g/ml) and human LDL (protein = 0.68 mg/ml), N/t was >15 x greater than that of control vessels which were perfused with LDL alone. LpL addition did not change albumin permeability, suggesting that increased N/t was not related to changes in vessel permeability. Increased LDL accumulation within the vessel could have resulted from either an increase in LDL influx from the vessel lumen into the vascular tissue or a decrease in efflux of LDL. Therefore, LDL efflux from vascular tissue was determined by measuring the rate of decline in fluorescence intensity of control and LpL-treated vessels after washout of the vessel lumen with a clear, nonfluorescent solution. The half-life of fluorescence decay after LDL perfusions (T( 1/2 )) was 4.2 ± 1.6 (SD) sec and 53.3 ± 15.5 sec after LpL (10-5 g/ml) was added to LDL indicating reduced efflux of LDL in LpL-treated vessels. Heparin prevents interaction of LpL with proteoglycans on and within the vascular tissue and in low concentration does not interfere with the enzymatic actions of LpL. Addition of heparin to solutions containing LDL and LpL almost completely eliminated the LpL- mediated increase in vascular tissue LDL accumulation. These results suggest that the increase in LDL accumulation requires the interaction of LpL or LpL- LDL complexes with vascular tissue proteoglycans. We hypothesize that LpL serves as a molecular bridge between LDL and proteoglycans of in vivo perfused blood vessels.

Original languageEnglish (US)
Pages (from-to)1152-1160
Number of pages9
JournalJournal of Lipid Research
Volume35
Issue number7
StatePublished - 1994

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Lipoprotein Lipase
LDL Lipoproteins
Blood Vessels
Tissue
Fluxes
Proteoglycans
Permeability
Blood vessels
Heparin
Fluorescence

Keywords

  • blood vessels
  • efflux
  • fluorescence microscopy
  • permeability
  • retention

ASJC Scopus subject areas

  • Endocrinology

Cite this

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title = "Lipoprotein lipase (LpL) affects low density lipoprotein (LDL) flux through vascular tissue: Evidence that LpL increases LDL accumulation in vascular tissue",
abstract = "A cardinal feature of the atherosclerotic lesion is increased low density lipoprotein (LDL) content of the arterial wall. Such increases in vascular wall LDL could result from either increased flux of circulating LDL across the arterial endothelial barrier or decreased efflux of LDL that has entered the vascular tissue. A number of studies have focused on factors that alter permeability of endothelial cell monolayers and intact blood vessels causing increased LDL influx. In contrast, the current studies were designed to test the hypothesis that lipoprotein lipase (LpL) increases LDL accumulation and decreases LDL efflux from vascular tissue. Frog mesenteric venular microvessels were cannulated and the rates of fluorescently labeled LDL accumulation (N/t) and efflux (T( 1/2 )) were measured by quantitative fluorescence microscopy. When the vessels were perfused with a solution containing bovine milk LpL (10-5 g/ml) and human LDL (protein = 0.68 mg/ml), N/t was >15 x greater than that of control vessels which were perfused with LDL alone. LpL addition did not change albumin permeability, suggesting that increased N/t was not related to changes in vessel permeability. Increased LDL accumulation within the vessel could have resulted from either an increase in LDL influx from the vessel lumen into the vascular tissue or a decrease in efflux of LDL. Therefore, LDL efflux from vascular tissue was determined by measuring the rate of decline in fluorescence intensity of control and LpL-treated vessels after washout of the vessel lumen with a clear, nonfluorescent solution. The half-life of fluorescence decay after LDL perfusions (T( 1/2 )) was 4.2 ± 1.6 (SD) sec and 53.3 ± 15.5 sec after LpL (10-5 g/ml) was added to LDL indicating reduced efflux of LDL in LpL-treated vessels. Heparin prevents interaction of LpL with proteoglycans on and within the vascular tissue and in low concentration does not interfere with the enzymatic actions of LpL. Addition of heparin to solutions containing LDL and LpL almost completely eliminated the LpL- mediated increase in vascular tissue LDL accumulation. These results suggest that the increase in LDL accumulation requires the interaction of LpL or LpL- LDL complexes with vascular tissue proteoglycans. We hypothesize that LpL serves as a molecular bridge between LDL and proteoglycans of in vivo perfused blood vessels.",
keywords = "blood vessels, efflux, fluorescence microscopy, permeability, retention",
author = "Rutledge, {John C} and Goldberg, {I. J.}",
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T1 - Lipoprotein lipase (LpL) affects low density lipoprotein (LDL) flux through vascular tissue

T2 - Evidence that LpL increases LDL accumulation in vascular tissue

AU - Rutledge, John C

AU - Goldberg, I. J.

PY - 1994

Y1 - 1994

N2 - A cardinal feature of the atherosclerotic lesion is increased low density lipoprotein (LDL) content of the arterial wall. Such increases in vascular wall LDL could result from either increased flux of circulating LDL across the arterial endothelial barrier or decreased efflux of LDL that has entered the vascular tissue. A number of studies have focused on factors that alter permeability of endothelial cell monolayers and intact blood vessels causing increased LDL influx. In contrast, the current studies were designed to test the hypothesis that lipoprotein lipase (LpL) increases LDL accumulation and decreases LDL efflux from vascular tissue. Frog mesenteric venular microvessels were cannulated and the rates of fluorescently labeled LDL accumulation (N/t) and efflux (T( 1/2 )) were measured by quantitative fluorescence microscopy. When the vessels were perfused with a solution containing bovine milk LpL (10-5 g/ml) and human LDL (protein = 0.68 mg/ml), N/t was >15 x greater than that of control vessels which were perfused with LDL alone. LpL addition did not change albumin permeability, suggesting that increased N/t was not related to changes in vessel permeability. Increased LDL accumulation within the vessel could have resulted from either an increase in LDL influx from the vessel lumen into the vascular tissue or a decrease in efflux of LDL. Therefore, LDL efflux from vascular tissue was determined by measuring the rate of decline in fluorescence intensity of control and LpL-treated vessels after washout of the vessel lumen with a clear, nonfluorescent solution. The half-life of fluorescence decay after LDL perfusions (T( 1/2 )) was 4.2 ± 1.6 (SD) sec and 53.3 ± 15.5 sec after LpL (10-5 g/ml) was added to LDL indicating reduced efflux of LDL in LpL-treated vessels. Heparin prevents interaction of LpL with proteoglycans on and within the vascular tissue and in low concentration does not interfere with the enzymatic actions of LpL. Addition of heparin to solutions containing LDL and LpL almost completely eliminated the LpL- mediated increase in vascular tissue LDL accumulation. These results suggest that the increase in LDL accumulation requires the interaction of LpL or LpL- LDL complexes with vascular tissue proteoglycans. We hypothesize that LpL serves as a molecular bridge between LDL and proteoglycans of in vivo perfused blood vessels.

AB - A cardinal feature of the atherosclerotic lesion is increased low density lipoprotein (LDL) content of the arterial wall. Such increases in vascular wall LDL could result from either increased flux of circulating LDL across the arterial endothelial barrier or decreased efflux of LDL that has entered the vascular tissue. A number of studies have focused on factors that alter permeability of endothelial cell monolayers and intact blood vessels causing increased LDL influx. In contrast, the current studies were designed to test the hypothesis that lipoprotein lipase (LpL) increases LDL accumulation and decreases LDL efflux from vascular tissue. Frog mesenteric venular microvessels were cannulated and the rates of fluorescently labeled LDL accumulation (N/t) and efflux (T( 1/2 )) were measured by quantitative fluorescence microscopy. When the vessels were perfused with a solution containing bovine milk LpL (10-5 g/ml) and human LDL (protein = 0.68 mg/ml), N/t was >15 x greater than that of control vessels which were perfused with LDL alone. LpL addition did not change albumin permeability, suggesting that increased N/t was not related to changes in vessel permeability. Increased LDL accumulation within the vessel could have resulted from either an increase in LDL influx from the vessel lumen into the vascular tissue or a decrease in efflux of LDL. Therefore, LDL efflux from vascular tissue was determined by measuring the rate of decline in fluorescence intensity of control and LpL-treated vessels after washout of the vessel lumen with a clear, nonfluorescent solution. The half-life of fluorescence decay after LDL perfusions (T( 1/2 )) was 4.2 ± 1.6 (SD) sec and 53.3 ± 15.5 sec after LpL (10-5 g/ml) was added to LDL indicating reduced efflux of LDL in LpL-treated vessels. Heparin prevents interaction of LpL with proteoglycans on and within the vascular tissue and in low concentration does not interfere with the enzymatic actions of LpL. Addition of heparin to solutions containing LDL and LpL almost completely eliminated the LpL- mediated increase in vascular tissue LDL accumulation. These results suggest that the increase in LDL accumulation requires the interaction of LpL or LpL- LDL complexes with vascular tissue proteoglycans. We hypothesize that LpL serves as a molecular bridge between LDL and proteoglycans of in vivo perfused blood vessels.

KW - blood vessels

KW - efflux

KW - fluorescence microscopy

KW - permeability

KW - retention

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