Isolation, Characterization, and Functional Assessment of Oxidatively Modified Subfractions of Circulating Low-Density Lipoproteins

Yang, Chao; Raya, Joe L.; Chen, Hsin Hung; Chen, Chu Huang; Abe, Yasunori; Pownall, Henry J.; Taylor, Addison A.; Smith, Charles V.

doi:10.1161/01.atv.0000071350.78872.c4

Cited by 101 publications

(108 citation statements)

References 40 publications

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“…Although some data show that the properties of the surface lipids of LDL À are different from those of normal LDL (17,37), these differences are likely to be transmitted from the core, which is more triglyceride-rich in LDL À . Of the compositional differences, the TG content might be expected to elicit the greatest differences both functionally and structurally.…”

Section: Properties Of Electronegative Ldlmentioning

confidence: 96%

“…LDL was separated according to charge using a LCC-500 programmer controlling two P-500 pumps on a UnoQ12 column, an anion-exchange column (Bio-Rad, Hercules, CA) preequilibrated with buffer A (0.02 M Tris-HCl, pH 8.0, and 0.5 mM EDTA) at 4jC (17). LDL-protein in buffer A was loaded onto the UnoQ12 column and eluted with a multistep gradient of buffer B (1 M NaCl in buffer A): 0%, 10 min; 0-15%, 10 min; 15-20%, 30 min; isocratic 20%, 10 min; 20-40%, 25 min; 40-100%, 10 min; 100%, 15 min; 100-0%, 5 min; and 0%, 25 min.…”

Section: Ldl Charged Fractionationmentioning

confidence: 99%

“…Thus, the sizes of charged LDL subfractions are similar and independent of charge. Calculation of the size of LDL from its composition (17) and weighted partial specific volumes of each component (26) gives diameters ranging from 18.6 to 19.0 nm ( Table 1). Fig.…”

Section: Size Comparison By Secmentioning

confidence: 99%

“…In type 1 diabetic patients, electronegative and electropositive LDLs are distinguished by higher contents in the former of triglyceride, nonesterified fatty acids, apoE, apoC-III, and platelet-activating factor acetylhydrolase, differences that are independent of oxidation and glycosylation (36). The composition of LDL À from FH patients is similarly altered (17). The calculated isoelectric points of 5.65 and 5.23 for apoE and apoC-III, respectively, could contribute to electronegativity, because the calculated isoelectric point for apoB-100 is 6.61.…”

Section: Properties Of Electronegative Ldlmentioning

confidence: 99%

“…LDL À isolated from the plasma of patients with familial hypercholesterolemia and diabetes induces in vitro EC apoptosis and inflammatory responses through the induction of monocyte chemotactic protein-1 and interleukin-8 production (15,16). Thus, the increased plasma LDL À concentrations in FH and diabetic patients (17,18) may increase CHD risk.…”

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confidence: 99%

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Electronegative LDLs from familial hypercholesterolemic patients are physicochemically heterogeneous but uniformly proapoptotic

Chen

Hosken

Huang

et al. 2007

Journal of Lipid Research

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A highly electronegative fraction of human plasma LDLs, designated L5, has distinctive biological activity that includes induction of apoptosis in bovine aortic endothelial cells (BAECs). This study was performed to identify a relationship between LDL density, electronegativity, and biological activity, namely, the induction of apoptosis in BAECs. Plasma LDLs from normolipidemic subjects and homozygotic familial hypercholesterolemia subjects were separated into five subfractions, with increasing electronegativity from L1 to L5, and into seven subfractions according to increasing density, D1 to D7. L1 to L5 were also separated according to density, and D1 to D7 were separated according to charge. The density profiles of L1 to L5 were similar (maximum density 5 1.030 6 0.002 g/ml). Induction of apoptosis by all seven density subfractions was confined to the highly electronegative fraction, L5, and within each density subfraction the magnitude of apoptosis correlated with the L5 content. Electronegative LDL is heterogeneous with respect to density and composition, and induction of apoptosis is more strongly associated with LDL electronegativity than with LDL size or density.-Chen, H-h., B.

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Section: Properties Of Electronegative Ldlmentioning

confidence: 96%

Section: Ldl Charged Fractionationmentioning

confidence: 99%

Section: Size Comparison By Secmentioning

confidence: 99%

Section: Properties Of Electronegative Ldlmentioning

confidence: 99%

mentioning

confidence: 99%

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Electronegative LDLs from familial hypercholesterolemic patients are physicochemically heterogeneous but uniformly proapoptotic

Chen

Hosken

Huang

et al. 2007

Journal of Lipid Research

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Role of Low‐Density Lipoprotein in Early Vascular Aging Associated With Systemic Lupus Erythematosus

Chan

Liang

Lee

et al. 2020

Arthritis & Rheumatology

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Objective. Patients with systemic lupus erythematosus (SLE) often have atherosclerotic complications at a young age but normal low-density lipoprotein (LDL) levels. This study was undertaken to investigate the role of LDL composition in promoting early vascular aging in SLE patients.Methods. Plasma LDL from 45 SLE patients (SLE-LDL) and from 37 normal healthy controls (N-LDL) was chromatographically divided into 5 subfractions (L1-L5), and the subfraction composition was analyzed. Correlations between subfraction levels and signs of early vascular aging were assessed. Mechanisms of lipid-mediated endothelial dysfunction were explored using in vitro assays and experiments in apoE −/− mice.Results. The L5 percentage was increased 3.4 times in the plasma of SLE patients compared with normal controls. This increased percentage of SLE-L5 was positively correlated with the mean blood pressure (r = 0.27, P = 0.04), carotid intima-media thickness (IMT) (right carotid IMT, r = 0.4, P = 0.004; left carotid IMT, r = 0.36, P = 0.01), pulse wave velocity (r = 0.29, P = 0.04), and blood levels of CD16+ monocytes (r = 0.35, P = 0.004) and CX3CL1 cytokines (r = 0.43, P < 0.001) in SLE patients. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis revealed that plasma levels of lysophosphatidylcholine (LPC) and platelet-activating factor (PAF) were increased in SLE-LDL and in the SLE-L5 plasma subfraction. Injecting SLE-LDL, SLE-L5, or LPC into young, male apoE −/− mice caused increases in plasma CX3CL1 levels, aortic fatty-streak areas, aortic vascular aging, and macrophage infiltration into the aortic wall, whereas injection of N-LDL or SLE-L1 had negligible effects (n = 3-8 mice per group). In vitro, SLE-L5 lipid extracts induced increases in CX3CR1 and CD16 expression in human monocytes; synthetic PAF and LPC had similar effects. Furthermore, lipid extracts of SLE-LDL and SLE-L5 induced the expression of CX3CL1 and enhanced monocyte-endothelial cell adhesion in assays with bovine aortic endothelial cells.Conclusion. An increase in plasma L5 levels, not total LDL concentration, may promote early vascular aging in SLE patients, leading to premature atherosclerosis.

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Charge density profiling of circulating human low‐density lipoprotein particles by capillary zone electrophoresis

2004

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Capillary zone electrophoresis (CZE) has been utilized to profile the low-density (LDL) particles in human blood serum in this study. A 5 mM sodium phosphate buffer, pH 7.40, was chosen as the most suitable CE buffer and an extensive ultrafiltration (UF) procedure was applied to purify the LDL sample. Two LDL particle species, LDL with lower mobility and LDL- with higher mobility were observed. The electropherograms were highly reproducible with good precision of effective mobilities, corrected peak areas (CPAs) and CPA ratio of LDL-/LDL. LDL particles shown on the electropherogram were also characterized by several procedures. The applications of Sigma HDL cholesterol reagent and CE on-line 2-propanol precipitation indicated that the two particle species shown in the electropherogram belong to LDL. The LDL particles were found to associate with the buoyant LDL fraction and the LDL- particles associate with the dense LDL fraction. This study utilizes CZE for the profiling of LDL isoforms and provides a new analytical method for the resolution of LDL subspecies. It demonstrates a high-mobility LDL particle which circulates in healthy subjects and diminishes in atherosclerotic patients. Diminution of the high-mobility LDL subspecies may be linked to minimal formation of arterial plaque in atherosclerotic patients.

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Isolation, Characterization, and Functional Assessment of Oxidatively Modified Subfractions of Circulating Low-Density Lipoproteins

Abstract: Relative to N-LDL, FH-LDL contains higher concentrations of a fraction, L5, that exhibits distinctive physicochemical properties and biological activities that may contribute to initiation and progression of atherogenesis in vivo.

Cited by 101 publications

References 40 publications

Electronegative LDLs from familial hypercholesterolemic patients are physicochemically heterogeneous but uniformly proapoptotic

Electronegative LDLs from familial hypercholesterolemic patients are physicochemically heterogeneous but uniformly proapoptotic

Role of Low‐Density Lipoprotein in Early Vascular Aging Associated With Systemic Lupus Erythematosus

Charge density profiling of circulating human low‐density lipoprotein particles by capillary zone electrophoresis

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