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”.

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 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 The association between insulin and low-density lipoprotein receptors

2012 ◽  
Vol 9 (3) ◽  
pp. 196-204 ◽  
Author(s):  
Gopalakrishnan Ramakrishnan ◽  
Albina Arjuman ◽  
Shilpa Suneja ◽  
Chandana Das ◽  
Nimai C Chandra
Keyword(s):  
Low Density Lipoprotein ◽  
Surface Membrane ◽  
Density Lipoprotein ◽  
Low Density ◽  
Glucose And Lipid Metabolism ◽  
Ldl Particles ◽  
Increased Risk ◽  
Density Lipoprotein Receptor ◽  
Membrane Bound ◽  
Atherosclerotic Process

The insulin receptor (IR) and low-density lipoprotein receptor (LDLR) maintain glucose and lipid metabolism, respectively. Diabetes is associated with increased blood glucose, dyslipidaemia and increased risk of atherosclerosis. We hypothesise that interactions between IR and LDLR play a role in the atherosclerotic process in subjects with diabetes. Therefore, in this work we studied potential interactions between these two receptors. Our data show an intracellular and surface membrane-bound co-association of IR and LDLR. The co-association makes LDLR functionally poor in clearing extra-cellular LDL particles. A short 10 min exposure of cells to insulin disrupts the association between the two receptors and generates LDLR with higher LDL clearing activity without any change in protein expression. This co-association of LDLR with IR and their dissociation by insulin may be an important part of the regulatory mechanism of the normal physiological receptor function in a biological system. Modulation of receptor co-association is potentially a therapeutic target to reduce cardiovascular risk, and further studies are needed to investigate this possibility.

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.

Long-term stable reduction of low-density lipoprotein in nonhuman primates following in vivo genome editing of PCSK9

2021 ◽  
Author(s):  
Lili Wang ◽  
Camilo Breton ◽  
Claude C. Warzecha ◽  
Peter Bell ◽  
Hanying Yan ◽  
...  
Keyword(s):  
Genome Editing ◽  
Nonhuman Primates ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Stable Reduction

scholarly journals Aggregation Susceptibility of Low-Density Lipoproteins—A Novel Modifiable Biomarker of Cardiovascular Risk

2021 ◽  
Vol 10 (8) ◽  
pp. 1769
Author(s):  
Katariina Öörni ◽  
Petri T. Kovanen
Keyword(s):  
Ex Vivo ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Cholesterol Crystals ◽  
Ldl Particles ◽  
Arterial Intima ◽  
Matrix Bound ◽  
Atherosclerotic Cardiovascular Diseases

Circulating low-density lipoprotein (LDL) particles enter the arterial intima where they bind to the extracellular matrix and become modified by lipases, proteases, and oxidizing enzymes and agents. The modified LDL particles aggregate and fuse into larger matrix-bound lipid droplets and, upon generation of unesterified cholesterol, cholesterol crystals are also formed. Uptake of the aggregated/fused particles and cholesterol crystals by macrophages and smooth muscle cells induces their inflammatory activation and conversion into foam cells. In this review, we summarize the causes and consequences of LDL aggregation and describe the development and applications of an assay capable of determining the susceptibility of isolated LDL particles to aggregate when exposed to human recombinant sphingomyelinase enzyme ex vivo. Significant person-to-person differences in the aggregation susceptibility of LDL particles were observed, and such individual differences largely depended on particle lipid composition. The presence of aggregation-prone LDL in the circulation predicted future cardiovascular events in patients with atherosclerotic cardiovascular disease. We also discuss means capable of reducing LDL particles’ aggregation susceptibility that could potentially inhibit LDL aggregation in the arterial wall. Whether reductions in LDL aggregation susceptibility are associated with attenuated atherogenesis and a reduced risk of atherosclerotic cardiovascular diseases remains to be studied.

Treatment of familial hypercholesterolaemia in children and adolescents in the last three decades

2013 ◽  
Vol 24 (3) ◽  
pp. 437-441 ◽  
Author(s):  
Avishay Elis ◽  
Rong Zhou ◽  
Evan A. Stein
Keyword(s):  
Children And Adolescents ◽  
Familial Hypercholesterolaemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Cholesterol Levels ◽  
Heterozygous Familial Hypercholesterolaemia

AbstractBackground:This study evaluated the effectiveness of long-term intensive lipid-lowering therapy in children and adolescents with familial hypercholesterolaemia.Methods:The charts of 89 children and adolescents with heterozygous familial hypercholesterolaemia among ∼1000 patients treated from 1974 to 2008 were reviewed. Familial hypercholesterolaemia was defined as low-density lipoprotein cholesterol level >90th percentile in individuals with a history of familial hypercholesterolaemia.Results:Of the 89 patients, 51% were male; the mean age at diagnosis was 8 ± 4 years, and the mean follow-up was 13 ± 8 years. Baseline and most recent low-density lipoprotein cholesterol levels (mg/dl) under treatment were 250 ± 50 and 142 ± 49, respectively, reduced 43% from baseline (p < 0.0001). At the most recent visit, 39 patients received statin monotherapy, mainly atorvastatin or rosuvastatin, and 50 (56%) patients received combination therapy, mainly vytorin or rosuvastain/ezetimibe, 15 patients were >30 years of age, and none developed symptomatic cardiovascular disease or needed revascularisation.Conclusions:Long-term statin-based therapy can reduce low-density lipoprotein cholesterol levels in most children and adolescents with heterozygous familial hypercholesterolaemia and decrease cardiovascular risk significantly.

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
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