scholarly journals Reduced β-strand content in apoprotein B-100 in smaller and denser low-density lipoprotein subclasses as probed by Fourier-transform infrared spectroscopy

1997 ◽  
Vol 322 (3) ◽  
pp. 765-769 ◽  
Author(s):  
Fabio TANFANI ◽  
Tiziana GALEAZZI ◽  
Giovanna CURATOLA ◽  
Enrico BERTOLI ◽  
Gianna FERRETTI
Keyword(s):  
Fourier Transform ◽  
Secondary Structure ◽  
Apolipoprotein B ◽  
Gradient Centrifugation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Subclasses ◽  
Ldl Particles ◽  
Ldl Subfractions

The secondary structure of apolipoprotein B-100 in low-density lipoprotein (LDL) subfractions was analysed by Fourier-transform IR spectroscopy. LDLs were isolated in three density ranges by gradient centrifugation of human plasma from healthy volunteers. The spectra revealed differences in the lipid content and composition of the three LDL fractions. The secondary structure of apolipoprotein B-100 was the same in the two fractions corresponding to the large less-dense LDL particles, whereas a lower content of β-strands was found in the third fraction corresponding to the smaller denser LDL particles. Analysis of the spectroscopic data suggests that, in the same set of LDL subfractions, the particle size is probably the cause of the observed differences in apolipoprotein B-100 secondary structure.

scholarly journals Long-term fasting improves lipoprotein-associated atherogenic risk in humans

2021 ◽  
Author(s):  
Franziska Grundler ◽  
Dietmar Plonné ◽  
Robin Mesnage ◽  
Diethard Müller ◽  
Cesare R. Sirtori ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Apolipoprotein A1 ◽  
Health Concern ◽  
Low Density ◽  
Lipoprotein Subclasses ◽  
Ldl Particles ◽  
Increased Risk

Abstract Purpose Dyslipidemia is a major health concern associated with an increased risk of cardiovascular mortality. Long-term fasting (LF) has been shown to improve plasma lipid profile. We performed an in-depth investigation of lipoprotein composition. Methods This observational study included 40 volunteers (50% men, aged 32–65 years), who underwent a medically supervised fast of 14 days (250 kcal/day). Changes in lipid and lipoprotein levels, as well as in lipoprotein subclasses and particles, were measured by ultracentrifugation and nuclear magnetic resonance (NMR) at baseline, and after 7 and 14 fasting days. Results The largest changes were found after 14 fasting days. There were significant reductions in triglycerides (TG, − 0.35 ± 0.1 mmol/L), very low-density lipoprotein (VLDL)-TG (− 0.46 ± 0.08 mmol/L), VLDL-cholesterol (VLDL-C, − 0.16 ± 0.03 mmol/L) and low-density lipoprotein (LDL)-C (− 0.72 ± 0.14 mmol/L). Analysis of LDL subclasses showed a significant decrease in LDL1-C (− 0.16 ± 0.05 mmol/L), LDL2-C (− 0.30 ± 0.06 mmol/L) and LDL3-C (− 0.27 ± 0.05 mmol/L). NMR spectroscopy showed a significant reduction in large VLDL particles (− 5.18 ± 1.26 nmol/L), as well as large (− 244.13 ± 39.45 nmol/L) and small LDL particles (− 38.45 ± 44.04 nmol/L). A significant decrease in high-density lipoprotein (HDL)-C (− 0.16 ± 0.04 mmol/L) was observed. By contrast, the concentration in large HDL particles was significantly raised. Apolipoprotein A1 decreased significantly whereas apolipoprotein B, lipoprotein(a), fibrinogen and high-sensitivity C-reactive protein were unchanged. Conclusion Our results suggest that LF improves lipoprotein levels and lipoprotein subclasses and ameliorates the lipoprotein-associated atherogenic risk profile, suggesting a reduction in the cardiovascular risk linked to dyslipidemia. Trial Registration Study registration number: DRKS-ID: DRKS00010111 Date of registration: 03/06/2016 “retrospectively registered”.

scholarly journals Modulation of apolipoprotein B antigenic determinants in human low density lipoprotein subclasses.

1985 ◽  
Vol 260 (8) ◽  
pp. 5067-5072 ◽  
Author(s):  
B Teng ◽  
A Sniderman ◽  
R M Krauss ◽  
P O Kwiterovich ◽  
R W Milne ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Antigenic Determinants ◽  
Low Density ◽  
Lipoprotein Subclasses

Circulating PCSK9 levels are positively correlated with NMR-assessed atherogenic dyslipidaemia in patients with high cardiovascular risk

2015 ◽  
Vol 128 (12) ◽  
pp. 877-882 ◽  
Author(s):  
Montse Guardiola ◽  
Núria Plana ◽  
Daiana Ibarretxe ◽  
Anna Cabré ◽  
Marta González ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Lipoprotein Profile ◽  
Lipoprotein Subclasses ◽  
Pcsk9 Gene ◽  
Glucose Levels ◽  
Ldl Particles

The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene regulates cholesterol homoeostasis by accelerating low-density lipoprotein receptor (LDLR) degradation resulting in the decreased catabolism of low-density lipoprotein (LDL) leading to hypercholesterolaemia. PCSK9 has also been related to other metabolic risk factors such as triglycerides (TGs) and glucose levels and body mass index (BMI). Therefore, our aim was to study the relationship between the PCSK9 and the lipid and lipoprotein profile. We studied 267 diabetic and metabolic syndrome patients who were not receiving any lipid-lowering therapy. We measured circulating lipids, cholesterol in remnant lipoproteins (RLPc) and PCSK9 levels. A detailed lipoprotein profile was determined based on NMR. Plasma PCSK9 levels were significantly and positively correlated with TG (r=0.136, P=0.033), total cholesterol (r=0.219, P<0.001) and apoB (apolipoprotein B; r=0.226, P=0.006) circulating levels and with an atherogenic profile of lipoprotein subclasses. In further detail, circulating PCSK9 levels were positively correlated with large very-low density lipoprotein (VLDL) particles, (r=0.210, P=0.001) and with their remnants, the intermediate-density lipoprotein (IDL) particles (r=0.206, P=0.001); positively correlated with smaller LDL particles (for small LDL: r=0.224, P<0.001; for medium small LDL: r=0.235, P<0.001; and for very small LDL: r=0.220, P<0.001); and with high-density lipoprotein (HDL) particles (r=0.146, P<0.001), which is mainly explained by the PCSK9 correlation with the smallest HDL particles (r=0.130, P=0.037). In addition, circulating PCSK9 levels were positively correlated with the pro-atherogenic circulating RLPc levels (r=0.171, P=0.006). All of the correlations were adjusted by age, gender and BMI. PCSK9 levels are significantly and positively correlated with atherogenic lipoproteins such as large VLDL, IDL, the smallest LDL, the smallest HDL particles and RLPc levels.

scholarly journals Regulation of plasma LDL: the apoB paradigm

2009 ◽  
Vol 118 (5) ◽  
pp. 333-339 ◽  
Author(s):  
Allan D. Sniderman ◽  
Jacqueline De Graaf ◽  
Patrick Couture ◽  
Ken Williams ◽  
Robert S. Kiss ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Critical Aspect ◽  
Lipoprotein Particles ◽  
Ldl Particles ◽  
Plasma Compartment

The objectives of this analysis are to re-examine the foundational studies of the in vivo metabolism of plasma LDL (low-density lipoprotein) particles in humans and, based on them, to reconstruct our understanding of the governance of the concentration of plasma LDL and the maintenance of cholesterol homoeostasis in the hepatocyte. We believe that regulation of cholesterol homoeostasis within the hepatocyte is demonstrably more complex than envisioned by the LDL receptor paradigm, the conventional model to explain the regulation of plasma LDL and the fluxes of cholesterol into the liver, a model which was generated in the fibroblast but has never been fully validated in the hepatocyte. We suggest that the LDL receptor paradigm should be reconfigured as the apoB (apolipoprotein B) paradigm, which states that the rate at which LDL particles are produced is at least an important determinant of their concentration in plasma as the rate at which they are cleared from plasma and that secretion of cholesterol within VLDL (very-low-density lipoprotein) particles is an important mechanism of maintaining cholesterol homoeostasis within the hepatocyte. These two paradigms are not mutually exclusive. The LDL receptor paradigm, however, includes only one critical aspect of the regulation of plasma LDL, namely the rate at which LDL particles are cleared through the LDL receptor pathway, but ignores another – the rate at which LDL particles are added to the plasma compartment. The apoB paradigm includes both and points to a different model of how the hepatocyte achieves cholesterol homoeostasis in a complex metabolic environment.

Discordantly Elevated Apolipoprotein B versus Low-Density Lipoprotein Cholesterol is Associated with Remnant Lipoproteins and Increased Cardiovascular Events

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S11-S11
Author(s):  
Paola Ramos ◽  
Leslie Donato ◽  
Linnea Baudhuin ◽  
Vlad Vasile ◽  
Allan Jaffe ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Superior Performance ◽  
Lipid Lowering ◽  
Low Density ◽  
Discovery Cohort ◽  
Ldl Particles ◽  
Remnant Lipoproteins

Abstract Atherosclerotic cardiovascular disease is a result of low-density lipoprotein (LDL) particles becoming trapped in arterial walls and forming plaques which ultimately restrict blood-flow. LDL cholesterol (LDL-C) and apolipoprotein B (apoB) are highly correlated measures of plaque-causing LDL particles. Both have been shown to predict major adverse cardiac events (MACE). ApoB is also carried on remnant lipoproteins (RLP). RLP-cholesterol (RLP-C) is increasingly appreciated as a MACE risk-factor. This study aimed to define discordances between apoB and LDL-C in a large data set from a clinical reference laboratory. We then applied this definition to evaluate which measure predicted the risk of MACE in a patient cohort referred for coronary angiography with &gt;10 years follow-up. LDL-C was measured by beta-quantification and RLP-C was defined as total cholesterol – LDL-C – HDL-C. Apo B discordance relative to LDL-C was determined by linear regression in a discovery cohort (n=17,203) using beta quantification. Discordance was defined by quartiles of the residual-apoB (expected–actual); discordant-low (&lt;25th percentile), concordant (25th to 75th percentile) and discordant-high (&gt;75th percentile). Associations with prevalence and incident of MACE were evaluated by odds-ratio and logistic regression. Risk of MACE was calculated based on the apoB-discordance and reported MACE events by several years follow up in a separate cohort (n=501). In the discovery cohort, age ranged from 18-95 years, 51% were female and mean (±SD) lipid values were: ApoB: 100.4 ± 30.0mg/dl, LDL-C: 121.7 ± 47.9mg/dl, and RLP-C: 17.2 ± 26.9mg/dl. Expected-apoB was described by the formula: (LDL-c X 0.6278 + 24.07, R=0.88). Residual-apoB (discordance) ranged from -1037 to 581.2 with a mean 0.01±18.6, and notably increased with triglyceride concentration (rho=0.65) and with RLP-C (rho=0.64), but was minimally influenced by apoB (rho=0.35) and LDL-C (rho=0.009) (p&lt;0.001 all cases). In the clinical follow-up cohort, age ranged from 26-77 years, 42% were female, 64% were current/former smokers, and 28% were on lipid-lowering therapy. Mean (±SD) lipids were: apoB: 97.8 ± 20.9mg/dl, LDL-C: 124.6 ± 36.6mg/dl, and RLP-C: 34.9 ± 25.6mg/dl. Serum triglycerides among subjects discordant-low apoB, concordant and discordant-high apoB were 148mg/dL, 157mg/dL and 238mg/dL, respectively; similarly for RLP-C. A total of 192 events occurred during a mean of 9 years follow-up. Subjects with discordantly elevated apoB had a significantly higher incidence of MACE compared to those with concordant values (47% vs. 36%, p=0.03). There was no difference in MACE for subjects with discordantly low apoB (35% vs. 36%). These data support previous reports of an association between apoB and LDL-C and the superior performance of apoB when discordantly elevated. Our data expand on previous studies by applying an externally defined threshold for discordant-apoB. Our data indicate that triglycerides, RLP-C are associated with discordances and MACE.

Platelet-activating factor acetylhydrolase and transacetylase activities in human plasma low-density lipoprotein

2001 ◽  
Vol 357 (2) ◽  
pp. 457-464 ◽  
Author(s):  
Demokritos C. TSOUKATOS ◽  
Theodoros A. LIAPIKOS ◽  
Alexandros D. TSELEPIS ◽  
M. John CHAPMAN ◽  
Ewa NINIO
Keyword(s):  
Human Plasma ◽  
Low Density Lipoprotein ◽  
Platelet Activating Factor ◽  
Density Lipoprotein ◽  
Biologically Active ◽  
Low Density ◽  
Ether Linkage ◽  
Small Dense Ldl ◽  
Ldl Particles ◽  
Ldl Subfractions

In this study, we demonstrate the presence of a transacetylase activity in human plasma low-density lipoprotein (LDL) that transfers short-chain fatty acids from platelet-activating factor (PAF) and its close ether- and ester-linked analogues to ether/ester-linked lysophospholipids (lyso-PL). We show evidence that both PAF acetylhydrolase (PAF-AH) and transacetylase activities are inhibited to the same extent by serine esterase inhibitors, are resistant to heat treatment, and exhibit identical distributions in lipoprotein classes and in LDL subfractions. Additionally, the competitive inhibition of PAF-AH by lyso-PL, and the evidence that the recombinant PAF-AH also showed a similar transacetylase activity, suggest that PAF-AH is responsible for both activities. Using PAF as a donor molecule and lyso-PAF (1-O-alkyl-sn-glycero-3-phosphocholine) as an acceptor, the transacetylase activity showed typical allosteric kinetics, due to the positive co-operativity of the substrates, with apparent Vmax = 19.6±3.4nmol/min per mg of protein, apparent h = 2.0±0.3 and apparent [S]0.5 = 9.4±2.3μM at saturation for the concentration of lyso-PAF. The substrate specificity of the donor molecules was decreased by increasing the chain length of the acyl moiety in the sn-2 position of the glycerol. The ether linkage in the sn-1 position of the substrate was 30% more effective than the ester bond; cholesteryl acetate was inactive as an acetyl donor. The two acceptors tested, lyso-PAF and the ester-linked lyso-PC (1-acyl-sn-glycero-3-phosphocholine), showed similar specificity. Addition of exogenous lyso-PAF induced the transient formation of PAF-like aggregating activity predominately in small dense LDL subfractions upon oxidation. We conclude that PAF-AH possesses both transacetylase and acetylhydrolase activities which remove PAF and its ether-linked analogues from LDL particles upon LDL oxidation. However, in atherogenic small dense LDL-5 particles, the transacetylase activity may acetylate extracellular lyso-PAF into biologically active PAF.

Intralysosomal Accumulation of Colloidal Gold-Low Density Lipoprotein Conjugates in Chloroquine-Treated Fibroblasts

1985 ◽  
Vol 43 ◽  
pp. 546-547 ◽  
Author(s):  
Dean A. Handley ◽  
Cynthia M. Arbeeny ◽  
Larry D. Witte
Keyword(s):  
Colloidal Gold ◽  
Cultured Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coated Vesicle ◽  
Low Density ◽  
Cholesterol Esters ◽  
Cultured Fibroblasts ◽  
Surface Receptors ◽  
Ldl Particles

Low density lipoproteins (LDL) are the major cholesterol carrying particles in the blood. Using cultured cells, it has been shown that LDL particles interact with specific surface receptors and are internalized via a coated pit-coated vesicle pathway for lysosomal catabolism. This (Pathway has been visualized using LDL labeled to ferritin or colloidal gold. It is now recognized that certain lysomotropic agents, such as chloroquine, inhibit lysosomal enzymes that degrade protein and cholesterol esters. By interrupting cholesterol ester hydrolysis, chloroquine treatment results in lysosomal accumulation of cholesterol esters from internalized LDL. Using LDL conjugated to colloidal gold, we have examined the ultrastructural effects of chloroquine on lipoprotein uptake by normal cultured fibroblasts.

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