Effect of fluid mechanical stresses and plasma constituents on aggregation of LDL

Talbot, Roy M.; Rio, Jessica D. del; Weinberg, Peter D.

doi:10.1194/jlr.m200477-jlr200

Cited by 7 publications

(9 citation statements)

References 33 publications

(25 reference statements)

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“…These aggregated LDLs were avidly ingested and degraded by macrophages, converting them into cholesterol ester-rich foam cells. Later studies using fluid stress model confirmed time-dependent LDL aggregation, which was monitored by light attenuation and sedimentation (96, 97). Notably, LDL aggregation was partially inhibited in total plasma, apparently due to the protective effects of other apolipoproteins that are also expected to inhibit LDL aggregation in circulation (described above).…”

Section: Physical Perturbationsmentioning

confidence: 93%

“…Khoo et al (41) showed that albumin reduced LDL aggregation upon vortexing. Talbot et al (96) showed that at physiological concentrations, albumin reduced flow-induced LDL aggregation. Notably, heat-denatured and fatty acid-stripped albumin was particularly effective in protecting LDLs from aggregation.…”

Section: Proteins Lipids Small Molecules and Polymers That Promotementioning

confidence: 99%

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Aggregation and fusion of low-density lipoproteins in vivo and in vitro

Gursky

2013

BioMolecular Concepts

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Low-density lipoproteins (LDLs, also known as ‘bad cholesterol’) are the major carriers of circulating cholesterol and the main causative risk factor of atherosclerosis. Plasma LDLs are 20- to 25-nm nanoparticles containing a core of cholesterol esters surrounded by a phospholipid monolayer and a single copy of apolipoprotein B (550 kDa). An early sign of atherosclerosis is the accumulation of LDL-derived lipid droplets in the arterial wall. According to the widely accepted ‘response-to-retention hypothesis’, LDL binding to the extracellular matrix proteoglycans in the arterial intima induces hydrolytic and oxidative modifications that promote LDL aggregation and fusion. This enhances LDL uptake by the arterial macrophages and triggers a cascade of pathogenic responses that culminate in the development of atherosclerotic lesions. Hence, LDL aggregation, fusion, and lipid droplet formation are important early steps in atherogenesis. In vitro, a variety of enzymatic and nonenzymatic modifications of LDL can induce these reactions and thereby provide useful models for their detailed analysis. Here, we summarize current knowledge of the in vivo and in vitro modifications of LDLs leading to their aggregation, fusion, and lipid droplet formation; outline the techniques used to study these reactions; and propose a molecular mechanism that underlies these pro-atherogenic processes. Such knowledge is essential in identifying endogenous and exogenous factors that can promote or prevent LDL aggregation and fusion in vivo and to help establish new potential therapeutic targets to decelerate or even block these pathogenic reactions.

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Section: Physical Perturbationsmentioning

confidence: 93%

Section: Proteins Lipids Small Molecules and Polymers That Promotementioning

confidence: 99%

Aggregation and fusion of low-density lipoproteins in vivo and in vitro

Gursky

2013

BioMolecular Concepts

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“…Larger lipid aggregates are then formed that flocculate and generate turbidity [8][9][10]. On one hand, LDL-aggregation is described to be prevented by both HDL [10] and albumin [8]. On the other hand, aggregated LDL is thought to be taken up by macrophages more easily [9].…”

Section: Discussionmentioning

confidence: 99%

“…Here, the vesicular structure of LDL-cholesterol particles is degraded by mechanical stress. Larger lipid aggregates are then formed that flocculate and generate turbidity [8][9][10]. On one hand, LDL-aggregation is described to be prevented by both HDL [10] and albumin [8].…”

Section: Discussionmentioning

confidence: 99%

Activation of T‐Lymphocytes by LDL‐Cholesterol

Arneth¹

2008

Lipids

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Native LDL-cholesterol can be mechanically stressed by strong vortexing. According to one hypothesis, mechanical shear stress within the vessel can lead to an aggregation of LDL-cholesterol and subsequently to activation of CD4 and CD8 T-lymphocytes. The goal of this study was to determine the proportion of activated CD4 and CD8 T-lymphocytes that is induced by adding unstressed and mechanically stressed LDL-cholesterol to whole blood samples. Whole blood was taken from 12 healthy subjects. All probands fasted for at least 12 h before blood withdrawal. In each case, 1 ml of whole blood from each subject was incubated for 16 h at 32 degrees C (89.3 degrees F) with concanavalin A (A), without additive (B), with mechanically stressed LDL-cholesterol (C) or with native LDL-cholesterol (D). Subsequently, the samples were measured by four-color flow cytometry. CD3, CD4, CD8, and CD69 were measured as activity markers. CD69 was plotted against CD4 and CD8, and the proportions of activated CD4 and CD8 T-lymphocytes were determined. Native and vortexed LDL-cholesterol elicited significantly different types of T-cell activation. While native LDL activated CD4 T-cells to only a small extent, mechanically stressed (vortexed) LDL potently activated CD8 T-cells. Purely mechanically-induced changes in LDL-cholesterol may be one mechanism that contributes to the activation of CD8 cells and, as a consequence, the emergence of arteriosclerosis.

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“…It was reported by some workers that LDL subjected to vortexing forms self-aggregates (Khoo et al, 1988(Khoo et al, , 1990Guyton et al, 1991;Pentikainen et al, 1996;Xu and Lin, 2001). LDL aggregation involves hydrophobic interactions (Talbot et al, 2003). LDL structure is profoundly disrupted by vortexing (Guyton et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Comparison of hydrophobic properties of thoracic duct lymph chylomicrons from rats given different fats or oils by gavage

Kaya

Isikgil

Güldür

2013

Animal Physiology Nutrition

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Lipoprotein aggregation is generated by hydrophobic nature of lipoproteins that is known to be one of the causes of atherosclerosis. Low density lipoproteins (LDL) has been extensively studied in this respect but not chylomicrons. There is strong evidence that post-prandial triacylglycerol-rich lipoproteins are atherogenic. Because biophysical properties of lipoproteins are largely determined by their lipid compositions, hydrophobic nature of thoracic lymph duct chylomicrons obtained from rats given different fats or oils by gavage was investigated by vortexing-induced aggregation and hydrophobic interaction chromatography. Contrary to LDL, vortexing did not cause aggregation in chylomicrons. Vortexing of fish oil and butter chylomicrons resulted in more prominent reduction in absorbances compared with chylomicrons from other sources that might indicate less micelle stability. Hydrophobic interaction chromatography of fish oil, palm oil and olive oil chylomicrons yielded three fractions, whereas that of sunflower, margarine and butter chylomicrons gave rise to two fractions. These results suggest that surface hydrophobicity of chylomicrons might be heterogenous. Our results also demonstrate that fish oil chylomicrons have less hydrophobicity and lower stability against vortexing compared with chylomicrons from other sources. Considering beneficial effects of fish oil in cardiovascular health, less hydrophobicity together with lower stability might provide an additional atherogeneicity index for lipoproteins.

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Effect of fluid mechanical stresses and plasma constituents on aggregation of LDL

Cited by 7 publications

References 33 publications

Aggregation and fusion of low-density lipoproteins in vivo and in vitro

Aggregation and fusion of low-density lipoproteins in vivo and in vitro

Activation of T‐Lymphocytes by LDL‐Cholesterol

Comparison of hydrophobic properties of thoracic duct lymph chylomicrons from rats given different fats or oils by gavage

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