scholarly journals Markedly Increased Small Dense Low-Density Lipoprotein During Acute Phase in Childhood and Adolescent Nephrotic Syndrome

2020 ◽  
Author(s):  
Keisuke Sugimoto ◽  
Kohei Miyazaki ◽  
Takuji Enya ◽  
Tomoki Miyazawa ◽  
Yuichi Morimoto ◽  
...  

Abstract Background: Hyperlipidemia is an important characteristic feature of idiopathic nephrotic syndrome (NS) in children. This study was conducted to examine the lipid profiles, including small dense low-density lipoprotein (sdLDL-C), in childhood-onset NS.Methods: This retrospective study enrolled patients diagnosed with initial-onset NS in childhood and adolescence. Study parameters included lipid profiles. The “alternative LDL window” comprises the number and sizes of LDL particles estimated according to non-HDL-C and TG levels.Results: A total of 39 patients were enrolled who exhibited markedly increased lipid abnormalities, including TC, TG, LDL-C, and non-HDL-C levels (TC, 409.7 TC, TG, and sizes of LDL particles estimated as non-HDL-C, 332.3). Of the 39 patients, 32 (82%) were categorized in the area of hyper-TG/-non-HDL levels, which is considered as sdLDL. A positive correlation was found between non-HDL-C and TC (r = 0.96, P < 0.001), TG (r = 0.38, P = 0.018), LDL-C (r = 0.84, P < 0.001), TC/HDL (r = 0.53, P < 0.001), and atherogenic index of plasma (r = 0.42, P = 0.008).Conclusions: Our study demonstrated markedly increased lipid profiles during the acute phase of NS. Evaluation of lipid profiles using the “alternative LDL window” may help understand the state of hyperlipidemia in NS.

Author(s):  
Dean A. Handley ◽  
Cynthia M. Arbeeny ◽  
Larry D. Witte

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.


2021 ◽  
Vol 10 (8) ◽  
pp. 1769
Author(s):  
Katariina Öörni ◽  
Petri T. Kovanen

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.


Author(s):  
Franziska Grundler ◽  
Dietmar Plonné ◽  
Robin Mesnage ◽  
Diethard Müller ◽  
Cesare R. Sirtori ◽  
...  

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”.


1984 ◽  
Vol 159 (2) ◽  
pp. 604-616 ◽  
Author(s):  
I F Rowe ◽  
A K Soutar ◽  
I M Trayner ◽  
M L Baltz ◽  
F C de Beer ◽  
...  

Immobilized rabbit and rat C-reactive protein (CRP) were found to selectively bind apolipoprotein B (apoB)-containing lipoproteins (low density lipoprotein, LDL and very low density lipoprotein, VLDL) from whole serum in a manner similar to that previously reported with human CRP. In acute phase human serum the CRP is in a free form, not complexed with lipoprotein or any other macromolecular ligand, and in acute phase serum from most rabbits fed on a normal diet the rabbit CRP was also free. However, in acute phase serum or heparinized plasma from hypercholesterolemic rabbits part or all of the CRP was found by gel filtration and immunoelectrophoretic techniques to be complexed with beta-VLDL, an abnormal apoB-containing plasma lipoprotein present in these animals. The presence of extent in different serum samples of CRP complexed with lipoprotein correlated closely with the serum apoB concentration. The formation of complexes between native, unaggregated rabbit CRP in solution and apoB-containing lipoproteins was readily demonstrable experimentally both with the isolated proteins and in whole serum. In all cases these interactions were calcium-dependent and inhibitable by free phosphoryl choline. The present findings extend earlier work in man and the rabbit and indicate that among the C-reactive proteins from different species, which are structurally highly conserved, the capacity for selective binding to apoB-containing plasma lipoproteins is also a constant feature. These interactions may therefore be related to the in vivo function of CRP in all species and this function may in turn be relevant to pathological conditions, such as atherosclerosis, in which lipoproteins are important.


Metabolism ◽  
1989 ◽  
Vol 38 (5) ◽  
pp. 491-495 ◽  
Author(s):  
J. Joven ◽  
L. Masana ◽  
C. Villabona ◽  
E. Vilella ◽  
T. Bargalló ◽  
...  

1982 ◽  
Vol 156 (1) ◽  
pp. 230-242 ◽  
Author(s):  
F C de Beer ◽  
A K Soutar ◽  
M L Baltz ◽  
I M Trayner ◽  
A Feinstein ◽  
...  

C-reactive protein (CRP), the classical acute-phase protein, can bind phospholipids by virtue of its specific, calcium-dependent reactivity with phosphorylcholine residues. However, analysis of acute-phase serum by gel filtration and by density gradient ultracentrifugation showed that the CRP was in a free, uncomplexed form, despite the coexistent presence of the various classes of serum lipoproteins, all of which contain phospholipids. In contrast, when isolated CRP was aggregated by immobilization at a sufficient density on a solid phase and then exposed to normal human serum, it selectively bound low density lipoprotein (LDL) and traces of very low density lipoprotein. The reaction was calcium dependent and reversible by free phosphorylcholine but not by heparin. LDL isolated from normal plasma was also bound by aggregated CRP. CRP reacts in vitro with a wide variety of different ligands both of extrinsic and of autogenous origin, e.g., microbial products and damaged cell membranes, respectively. If CRP aggregated in vivo by complexing with these ligands than acquires the capacity to selectively bind LDL, the phenomenon may have significant implications for the function of CRP and for the metabolism, clearance, and deposition of LDL.


2021 ◽  
Vol 23 (3) ◽  
pp. 411-416
Author(s):  
I. M. Bilai ◽  
M. I. Romanenko ◽  
D. H. Ivanchenko

Statin side effects are not a rare occurrence, in particular dyspeptic disorders, insomnia, headache, skin erythema, rash are often noted. All of this determines scientists to find new effective and low-toxic hypolipidemic agents. Various natural and synthetic xanthine derivatives have been recognized as therapeutically potential compounds and reported to control various diseases. Therefore, the study of new xanthine derivatives and their hypolipidemic effects, which would have a significant therapeutic effect with minimal side effects, is relevant. The aim of the study was to examine the effect of 7-β-hydroxy-γ-aryloxypropylxanthinyl-8-thioalkanic acid derivatives on lipidogram parameters in experimental laboratory rats. Materials and methods. The objects of the study were 7-β-hydroxy-γ-aryloxypropylxanthinyl-8-thioalkanic acid derivatives. The experiments were performed in white laboratory Wistar rats weighing 180–220 g. Experimental modeling of hyperlipidemia – tween model: intraperitoneal administration of tween-80 at a dose of 200 mg/100 g body weight. The test compounds were administered orally, simultaneously with tween, at a dose of 1/10 of LD50 (previously calculated by Prozorovsky express method) for 6 days. The following indicators of lipidogram were determined: total cholesterol (TC), high-density lipoprotein cholesterol (HDL cholesterol), low-density lipoprotein cholesterol (LDL cholesterol), triglycerides (TG) and atherogenic index of plasma: TC – HDL cholesterol / HDL cholesterol. The experiments were carried out with respect to Bioethical rules and norms. Results. The studies have shown data on the hypolipidemic activity of 7-β-hydroxy-γ-aryloxypropylxanthinyl-8-thioalkane acid derivatives. According to the conditional efficiency index Ʃ, which included the overall percentage of the following indicators – total cholesterol, low-density lipoprotein cholesterol and triglycerides, the leading compounds were 2439 (87.47 %), 6047 (82.30 %). The reference drug atorvastatin had a value of 82.98 %. Conclusions. The major compound was 2439 identified among all compared to the control group. The prospect of further research is a more detailed study on the ability of xanthine derivatives to exhibit hypolipidemic effects and to influence oxidative stress in various hyperlipidemic models.


2018 ◽  
Vol 6 ◽  
pp. 205031211875666 ◽  
Author(s):  
Alemu Gebrie ◽  
Natesan Gnanasekaran ◽  
Menakath Menon ◽  
Mekonnen Sisay ◽  
Abriham Zegeye

Introduction: Hypertension and dyslipidemia are the two coexisting and synergizing major risk factors for cardiovascular diseases. The cellular constituents of blood affect the volume and viscosity of blood, thus playing a key role in regulating blood pressure. Overweight and obesity are key determinants of adverse metabolic changes including an increase in blood pressure. The aim of this study was to evaluate lipid profiles and hematological parameters in hypertensive patients at Debre Markos Referral Hospital, Northwest Ethiopia. Methods: Laboratory-based cross-sectional study was conducted in 100 eligible hypertensive patients at the hospital. The required amount of blood was withdrawn from the patients by healthcare professionals for immediate automated laboratory analyses. Data were collected on socio-demographic factors, anthropometric measurements, blood pressure, lipid profiles, and hematological parameters. Result: The mean serum levels of triglyceride, total cholesterol, and low-density lipoprotein were significantly higher than their respective cut-off values in the hypertensive patients. Besides, 54%, 52%, 35%, and 11% of the hypertensive patients had abnormal low-density lipoprotein, total cholesterol, triglyceride, and high-density lipoprotein levels, respectively. Higher levels of low-density lipoprotein, hemoglobin, and red blood cell count were observed in the hypertensive patients whose blood pressure had been poorly controlled than the controlled ones ( p < 0.05). Waist circumference had a significant positive association with the serum levels of total cholesterol and white blood cell count ( p < 0.05). Conclusion: Hypertensive patients had a high prevalence of lipid profile abnormalities and poorly controlled blood pressure which synergize in accelerating other cardiovascular diseases. Some hematological parameters such as red blood cell count are also increased as do the severity of hypertension.


Author(s):  
Shahenda, M. Elaby ◽  
Asmaa A. Salem ◽  
Jehan, B. Ali ◽  
A. F. Abdel-Salam

Two lactobacilli strains; Lactobacillus acidophilus ATCC 20079 and Lactobacillus plantarum ATCC 20179 and two bifidobacteria strains; Bifidobacterium bifidum GSGG 5286 and Bifidobacterium longum ATCC 15707 were studied their abilities to reduce the cholesterol content in vitro. It was investigated that the in vivo cholesterol-lowering effect of L. plantarum ATCC 20179, B. bifidum GSGG 5286 and mixture of both probiotics (L. plantarum ATCC20179 and B. bifidum GSGG5286) on hyperlipidaemic rats for 8 weeks. All lactobacilli and bifidobacteria strains assimilate the cholesterol content in laboratory media. It was observed the highest assimilation of cholesterol was in L. plantarum ATCC 20179 and B. bifidum GSGG 5286 strains. In vivo, L. plantarum ATCC 20179  group was more effective in improving serum lipid profile levels [total cholesterol (TC), triglycerides (TG), low density lipoprotein – cholesterol (LDL-C), high density lipoprotein – cholesterol                   (HDL-C), very low density lipoprotein – cholesterol (VLDL-C) and Atherogenic Index (AI)],                      liver enzyme activities (ALT, AST and ALP),  malonaldehyde (MDA), hydrogen peroxide (H2O2) and total antioxidants capacity (TAC) levels than mixed-organisms and B. bifidum groups, respectively of hyperlipidaemic rats. It was concluded that L. plantarum ATCC 20179 showed more                     favourable results than B. bifidum GSGG 5286 in relation to cardiovascular risk factors in hyperlipidaemic rats.


2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Shayan Mohammadmoradi ◽  
Aida Javidan ◽  
Weihua Jiang ◽  
Jessica Moorleghen ◽  
Venkateswaran Subramanian

Background and Objective: Mimetic mediated activation of microRNA 146a (miR-146a) reduces atherosclerosis via suppression of nuclear factor-κB-driven inflammation in mice. The purpose of this study was to determine whether miR-146a influences plasma cholesterol in hypercholesterolemic mice. Methods and Results: To induce hypercholesterolemia, female C57BL/6 miR-146a WT (n=8) and miR-146a KO (n=8) mice were injected intraperitoneally with an adeno-associated viral vector (AAV) expressing the proprotein convertase subtilisin/kexin type 9 (PSCK9 D377Y) gain-of-function mutant at a dose of 3 x 10 10 genomic copies/mouse. After infection, mice were fed a Western diet (21% wt/wt milk fat; 0.15% wt/wt cholesterol) for sixteen weeks, and plasma PCSK9 and total cholesterol concentrations were monitored monthly using an enzymatic assay. Plasma PCSK9 concentrations were profoundly increased 4 weeks post injection (Baseline: WT - 179 ± 12 vs KO - 207 ± 12; Week 4: WT - 1700 ± 148 vs KO - 2689 ± 305 ng/ml) and remained significantly high during 16 weeks (WT - 882 ± 142 vs KO - 718 ± 109 ng/ml; p<0.05 vs baseline) of Western diet feeding. Consistent with increased plasma PCSK9 concentrations, plasma cholesterol concentrations were increased in both groups of mice. Interestingly, miR-146a KO group mice showed less significant increase in plasma cholesterol compared to WT group (Baseline: WT - 88 ± 3 vs KO - 83 ± 3; Week 4: WT - 328 ± 25 vs KO - 195 ± 18 mg/dl) irrespective of the comparable plasma PCSK9 concentrations. Also, lipoprotein distribution analysis with size exclusion gel chromatography revealed that miR-146a KO mice showed a strong reduction in high density lipoprotein (HDL) particles while very low density lipoprotein (VLDL) and low density lipoprotein (LDL) particles were not affected. Conclusion: Our findings suggests that miR146a plays a critical role in the regulation of HDL particles in PCSK9 gain-of-function mutant-induced hypercholesterolemia in mice. Future studies will identify gene targets influenced by miR-146a in regulating HDL-cholesterol in hypercholesterolemic mice.


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