Removal Of Low-density Lipoprotein Research Articles

Regenerated carboxymethyl cellulose beads for selective removal of low-density lipoprotein from whole blood

Low-density lipoprotein (LDL) plays a crucial role in the development of cardiovascular disease. Lowering the level of LDL is an effective therapeutic strategy for treating cardiovascular disease. Here, we developed a facile and robust method to prepare carboxymethyl cellulose beads (CMCBs) for selectively adsorbing LDL. CMCBs had plentiful carboxyl groups and large numbers of nanopores on their surface. The in vitro assay reveals that CMCBs had a high LDL adsorbing capability of 7.67 ± 0.16 mg/g, owing to the carboxyl group-induced electrostatic adsorption and the nanopore-mediated trapping effect. CMCBs also possessed the excellent mechanical strength to resist the impact of rushing blood. Moreover, CMCBs were highly blood-compatible and had anticoagulant activity. The in vivo experiment reveals that LDL were significantly reduced from 15.02 ± 1.62 to 9.35 ± 1.71 mmol/L after blood perfusion using CMCBs, while minimal side effects were detected for the blood routine parameters. The study provides an easy-to-fabricate adsorbent for selective and efficient clearance of LDL in hemoperfusion.

Simultaneous Rosiglitazone Release and Low-Density Lipoprotein Removal by Chondroitin Sodium Sulfate/Cyclodextrin/Poly(acrylic acid) Composite Adsorbents for Atherosclerosis Therapy.

Atherosclerosis (AS) is characterized by the accumulation of substantial low-density lipoprotein (LDL) and inflammatory response. Hemoperfusion is commonly employed for the selective removal of LDL from the body. However, conventional hemoperfusion merely focuses on LDL removal and does not address the symptom of plaque associated with AS. Based on the LDL binding properties of acrylated chondroitin sodium sulfate (CSA), acrylated beta-cyclodextrin (CD) and acrylic acid (AA), along with the anti-inflammatory property of rosiglitazone (R), the fabricated AA-CSA-CD-R microspheres could simultaneously release R and facilitate LDL removal for hemoperfusion. The AA and CSA offer electrostatic adsorption sites for LDL, while the CD provides hydrophobic adsorption sites for LDL and weak binding sites for R. According to the Sips model, the maximum static LDL adsorption capacity of AA-CSA-CD-R is determined to be 614.73 mg/g. In dynamic simulated perfusion experiments, AA-CSA-CD-R exhibits an initial cycle LDL adsorption capacity of 150.97 mg/g. The study suggests that the weakened inflammatory response favors plaque stabilization. The anti-inflammatory property of the microspheres is verified through an inflammation model, wherein the microsphere extracts are cocultured with mouse macrophages. Both qualitative analysis of iNOS\TNF-α and quantitative analysis of IL-6\TNF-α collectively demonstrate the remarkable anti-inflammatory effect of the microspheres. Therefore, the current study presents a novel blood purification treatment of eliminating pathogenic factors and introducing therapeutic factors to stabilize AS plaque.

Facile fabricate sandwich-structured molecularly imprinted dopamine polymer for simultaneously specific capture of Low-density lipoprotein and eliminate “bad cholesterol”

A simplified approach for preparation of sandwich type molecularly imprinted polymers (PPDA-MIPs) is proposed for simultaneously identify Low-density lipoprotein (LDL) and dispose “bad cholesterol”. Porous polydopamine nanosphere (PPDA) is applied as a matrix for immobilization of LDL, and the imprinted layer is formed by dopamine acting as a functional monomer. Since imprinted cavities exhibit shape memory effects in terms of recognizing selectivity, the PPDA-MIPs exhibit excellent selectivity toward LDL and a substantial binding capacity of 550.3 μg mg−1. Meanwhile, six adsorption/desorption cycles later, the adsorption efficiency of 83.09 % is still achieved, indicating the adequate stability and reusability of PPDA-MIPs. Additionally, over 80 % of cholesterol is recovered, indicating the completeness of “bad cholesterol” removal in LDL. Lastly, as demonstrated by gel electrophoresis, PPDA-MIPs performed satisfactory behavior for the removal of LDL from the goat serum sample.

Dextran sulfate bulk and surface-modified microfiltration membrane for simultaneous blood plasma harvesting and low-density lipoprotein removal during plasmapheresis

Plasmapheresis is currently used for the harvesting of blood plasma in medical labs and plasma donation centers. This is a fast, single-step membrane process for both collection of blood plasma and simultaneous blood cell isolation. This paper presents the development of a novel membrane that can be used to simultaneously harvest blood plasma and isolate low-density lipoprotein (LDL), known as bad cholesterol, from the blood. To achieve this goal, dual surface and bulk modification by dextran sulfate (DS) was performed on a polyethersulfone (PES) membrane containing single wall carbon nanotubes (SWCNT). DS is an anionic ligand that repels negatively charged substances like red blood cells (RBCs) and adsorbs positively charged substances like Apo B100; the apoprotein of LDL. Scanning Electron Microscope (SEM), Energy Dispersive X-Ray (EDX), and Fourier Transform Infrared (FTIR) spectroscopy analyses provided evidence of the grafting of DS on single wall carbon nanotubes (DS-SWCNT). Surface studies including water contact angle, zeta potential analysis, surface morphology, Attenuated Total Reflectance-FTIR (ATR-FTIR), and EDX, confirmed the presence of DS on the PES membrane surface. The SEM cross-section results showed the formation of a two-zone morphology with an open structure on the upside and a dense structure on the downside that provide optimal conditions for efficient separation of blood cells. The complete blood count (CBC) and biochemistry analyses revealed dual bulk and surface-modified membrane, and a specific sample (DM2) showed the best performance for blood cells and LDL separation. The maximum separation of blood cells was 87% RBC, 98% white blood cells (WBCs), and 83% platelets (PLTs). Moreover, DM2 exhibited a sieving ratio for LDL of 0.33. Blood compatibility analyses confirmed that DM2 and other related samples had low hemolysis and prolonged coagulation times.

One-step engineering dual-network reinforced hydrogel microspheres with excellent anti-coagulant and low-density lipoprotein removal

Low-density lipoprotein apheresis (LDL-a) is a potent therapeutic strategy for treating hyperlipidemia and preventing atherosclerotic cardiovascular disease. However, the use of water-soluble anticoagulant during LDL-a treatment increases the risk of severe bleeding. In this study, dual-network composite polyacrylonitrile (PAN) hydrogel microspheres (CAHMs) are prepared through a one-step synthesis method using PAN, acrylic acid (AA) and 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) as raw materials. Benefiting from the presence of PAN network, the CAHMs exhibit an average compressive stress of 7.16 MPa. Then, the hydrophilic network established by AA and AMPS leads to excellent LDL adsorption capacity and self-anticoagulant property, significantly inhibiting the activity of the blood coagulation factors VIII, IX, XI and XII, and prolonging the activated partial thromboplastin time (APTT) by fourfold. Moreover, according to the Sips model, the CAHMs exhibit a maximum static LDL adsorption capacity of 49.37 mg/g. In dynamic simulated perfusion experiments, the CAHMs achieve a total LDL adsorption capacity of 69.59 mg/g, 20 times higher than the adsorption capacity for HDL. The one-step synthesis method employed in this study guarantees rapid and large-scale production of the composite microspheres, which possess excellent mechanical strength, blood compatibility, self-anticoagulant property and LDL adsorption capacity. This one-step synthesis method has the advantage of abandoning organic solvent and stabilizer, thus provides a new idea for the industrial preparation of LDL absorbent used in whole blood.

Searching for new genes associated with the familial hypercholesterolemia phenotype using whole-genome sequencing and machine learning.

One of the most common congenital metabolic disorders is familial hypercholesterolemia. Familial hypercholesterolemia is a condition caused by a type of genetic defect leading to a decreased rate of removal of low-density lipoproteins from the bloodstream and a pronounced increase in the blood level of total cholesterol. This disease leads to the early development of cardiovascular diseases of atherosclerotic etiology. Familial hypercholesterolemia is a monogenic disease that is predominantly autosomal dominant. Rare pathogenic variants in the LDLR gene are present in 75-85 % of cases with an identified molecular genetic cause of the disease, and variants in other genes (APOB, PCSK9, LDLRAP1, ABCG5, ABCG8, and others) occur at a frequency of < 5 % in this group of patients. A negative result of genetic screening for pathogenic variants in genes of the low-density lipoprotein receptor and its ligands does not rule out a diagnosis of familial hypercholesterolemia. In 20-40 % of cases, molecular genetic testing fails to detect changes in the above genes. The aim of this work was to search for new genes associated with the familial hypercholesterolemia phenotype by modern high-tech methods of sequencing and machine learning. On the basis of a group of patients with familial hypercholesterolemia (enrolled according to the Dutch Lipid Clinic Network Criteria and including cases confirmed by molecular genetic analysis), decision trees were constructed, which made it possible to identify cases in the study population that require additional molecular genetic analysis. Five probands were identified as having the severest familial hypercholesterolemia without pathogenic variants in the studied genes and were analyzed by whole-genome sequencing on the HiSeq 1500 platform (Illumina). The whole-genome sequencing revealed rare variants in three out of five analyzed patients: a heterozygous variant (rs760657350) located in a splicing acceptor site in the PLD1 gene (c.2430-1G>A), a previously undescribed single-nucleotide deletion in the SIDT1 gene [c.2426del (p.Leu809CysfsTer2)], new missense variant c.10313C>G (p.Pro3438Arg) in the LRP1B gene, and single-nucleotide deletion variant rs753876598 [c.165del (p.Ser56AlafsTer11)] in the CETP gene. All these variants were found for the first time in patients with a clinical diagnosis of familial hypercholesterolemia. Variants were identified that may influence the formation of the familial hypercholesterolemia phenotype.

Fabrication and Study of Dextran/Sulfonated Polysulfone Blend Membranes for Low-Density Lipoprotein Adsorption.

The abnormal increase in low-density lipoprotein (LDL) in human blood is a main independent risk factor for the pathogenesis of atherosclerosis, whereas a reduced LDL level effectively lowers morbidity. It is important to develop LDL adsorption materials with high efficiency and selectivity, as well as to simplify their fabrication processes. In this paper, polysulfone (PSF), sulfonated polysulfone (SPSF), and sulfonated polysulfone/dextran (SPSF/GLU) membranes were successfully fabricated for LDL adsorption using a solution casting technique. Attenuated total reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy measurements confirmed the success of the preparation. The water contact angle decreased from 89.7 ± 3.4° (PSF) to 76.4 ± 3.2° (SPSF) and to 71.2 ± 1.9° (SPSF/GLU), respectively. BSA adsorption testing showed that the SPSF/GLU with surface enrichment of sulfonate groups and glycosyl groups possessed higher resistance to protein solution. The adsorption and desorption behaviors of the studied samples in single-protein or binary-protein solutions were systematically investigated by enzyme-linked immunosorbent assay (ELISA), The results showed that SPSF/GLU, which had excellent resistance to protein adsorption, possessed a similar adsorption capacity to that of PSF. SPSF membrane exhibited excellent selective affinity for LDL in single and binary protein solutions, suggesting potential applications in LDL removal.

Biomembrane-mimetic hemoperfusion adsorbent for efficient removal of low-density lipoprotein from hyperlipemia blood.

Lowering of low-density lipoprotein (LDL) levels in blood of patients with hyperlipidaemia can effectively prevent the progression of atherosclerosis and coronary heart disease. The present study demonstrated a facile synthesis strategy to prepare biomembrane-mimetic LDL adsorbent (PVA@COOH-PE) via directional immobilization of phospholipid onto macro-porous cross-linked poly(vinyl alcohol) spheres. The binding between the prepared adsorbent and LDL particles simulates the cytosolic lipid droplets to form a lipid-packing structure. The adsorbent possesses satisfactory removal efficiency for LDL and total cholesterol (TCH) in hyperlipemia serum, while remains high-density lipoprotein (HDL) concentration within the normal range. The adsorption capacities for LDL and TCH are about 1.13 and 1.74 mg/ml respectively, which are nearly three and four times higher than that of HDL (0.42 mg/ml). The adsorbent also possesses satisfactory anticoagulant properties, causes negligible effect on blood cells and produces low hemolysis ratios. The excellent blood compatibility plus LDL removal efficiency of PVA@COOH-PE indicates its good application prospect as hemoperfusion adsorbent in the treatment of hyperlipidaemia.

In-silico analysis of non-synonymous SNPs of human LDLR gene and their impact on familial hypercholesterolemia

Single nucleotide polymorphisms (SNPs) are the most regular type of genetic variation among human genome. The low-density lipoprotein receptors (LDLR) gene encoded receptor protein that specifically binds to low density lipoprotein (LDL), to act as prime cholesterol carriers in the blood. Unregulated removal of LDL from the circulation results from inherited mutations in the LDLR gene or, more rarely, in the apo B gene, the ligand for the LDLR causes familial hypercholesterolemia (FH). Several studies have shown that non-synonymous single nucleotide polymorphisms (nsSNPs) induce more than 50% genetic diseases. However, the growing number of SNPs in databases makes it difficult to evaluate the SNPs that come up with disease development. Therefore, we tried to identify the nsSNP within LDLR gene used mainly computational tools like: PROVEAN, Predict-SNP, SIFT, MAAP, SNAP, PhD-SNP, Polyphen v1, Polyphen v2, PANTHER and nsSNPAnalyzer. After analysing a total of 1114 missense SNPs, we found only 39 nsSNPs are most deleterious, whose conservation score ranges from grade ranges 7 to 9 that is assessed through ConSurf web server. Among 39 most significant nsSNPs, 11were predicted for involving in post translational modifications. Additionally, I-Mutant 2.0 and MUpro tool showed a decreased instability for these nsSNPs upon mutation. Protein structural analysis of these amino acid variants was performed by using I-Mutant 2.0. Stability analysis predicted 11 nsSNPs (C313W, F408K, A431P, A431S, A431T, D433H, D433Y, G546D, G546V, G546E and C697W), these are decreased protein stability. The in-silico analysis in current study may be a significant model for future research design studies.

Bio-inspired dual-functional phospholipid-poly(acrylic acid) brushes grafted porous poly(vinyl alcohol) beads for selective adsorption of low-density lipoprotein.

Elevated levels of low-density lipoproteins (LDL) are recognized as a crucial indicator of hyperlipidemia (HLP) and lowering of LDL levels represents an effective clinical treatment strategy. Inspired by the conjugation of phospholipid monolayers and the lipid content of the LDL particle, the current study describes the preparation of an innovative hemoperfusion adsorbent. The adsorbent was prepared by attachment of phosphatidyl ethanolamine to poly(acrylic acid) modified poly(vinyl alcohol-co-triallyl isocyanurate) beads (PVA@PAA-PE). The interaction between LDL and adsorbent mimics the lipoprotein microemulsion present in the blood and thus promotes efficient binding with high affinity. In vitro adsorption using serum from patients with HLP revealed that the LDL adsorption of PVA@PAA-PE was 4.44 times higher than that of controls and the removal rate of LDL using PVA@PAA-PE was about twice as high as that of the anti-atherogenic high-density lipoprotein (HDL). In vivo whole blood perfusion demonstrated the superior affinity of PVA@PAA-PE for LDL since LDL concentration was significantly reduced from 10.71 ± 2.36 mmol L-1 to 6.21 ± 1.45 mmol L-1, while the HDL level was not severely reduced (from 0.98 ± 0.12 mmol L-1 to 0.56 ± 0.15 mmol L-1). Additionally, PVA@PAA-PE exhibited excellent hemocompatibility and low cytotoxicity. Therefore, PVA@PAA-PE is a potential adsorbent for whole blood perfusion to treat hyperlipidemia.

Diet-induced hepatic steatosis abrogates cell-surface LDLR by inducing de novo PCSK9 expression in mice

The worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly. Although this condition is generally benign, accumulating evidence now suggests that patients with NAFLD are also at increased risk of cardiovascular disease (CVD); the leading cause of death in developed nations. Despite the well-established role of the liver as a central regulator of circulating low-density lipoprotein (LDL) cholesterol levels, a known driver of CVD, the mechanism(s) by which hepatic steatosis contributes to CVD remains elusive. Interestingly, a recent study has shown that circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels correlate positively with liver steatosis grade. Given that PCSK9 degrades the LDL receptor (LDLR) and prevents the removal of LDL from the blood into the liver, in the present study we examined the effect of hepatic steatosis on LDLR expression and circulating LDL cholesterol levels. We now report that in a manner consistent with findings in patients, diet-induced steatosis increases circulating PCSK9 levels as a result of de novo expression in mice. We also report the finding that steatosis abrogates hepatic LDLR expression and increases circulating LDL levels in a PCSK9-dependent manner. These findings provide important mechanistic insights as to how hepatic steatosis modulates lipid regulatory genes, including PCSK9 and the LDLR, and also highlights a novel mechanism by which liver disease may contribute to CVD.

A mussel-inspired approach towards heparin-immobilized cellulose gel beads for selective removal of low density lipoprotein from whole blood

In this study, we report a mussel-inspired approach to fabricate heparin-immobilized cellulose (HeTaCe) gel beads with self-anticoagulative and biocompatible properties which can selectively remove low density lipoprotein (LDL) from whole blood directly. First, a phase inversion technique was applied to prepare cellulose gel beads. Then the as-prepared gel beads were dipped into a mixed solution of heparin and tannic acid in phosphate buffered saline (PBS, pH 8.5) to obtain HeTaCe gel beads. Blood compatibility experiments indicated that the HeTaCe gel beads could suppress complement activation as well as contact activation and prolong the clotting times to the upper detect limits (activated partial thromboplastin time >600 s and thrombin time >180 s) of the automated blood coagulation analyzer. An ideal adsorption capacity of LDL in vitro was achieved by the HeTaCe gel beads with an amount of 79.1 mg/g. Besides, dynamic column adsorption test further demonstrated a selective adsorption of LDL without a significant reduction of high density lipoprotein (HDL) in a simulative hemoperfusion system. It is believed that the HeTaCe gel beads will be quite appealing to future clinical practice aiming at lowering LDL and improving the outcomes of patients with high cardiovascular risk.

Multilayer Cucurbit[6]uril-Based Magnetic Nanoparticles Prepared by Host-Guest Interaction: Remarkable Adsorbent for Low Density Lipoprotein Removal from Plasma.

Efficient removal of low density lipoprotein (LDL) is a key challenge due to its high level in plasma as a primary risk factor in the pathogenesis of atherosclerotic cardiovascular disease. In this work, a facile synthesis strategy based on host-guest interactions was developed to prepare multilayer cucurbit[6]uril-based magnetic nanoparticles, MNPs-(HA-DAH5 /HA-CB[6]5 ). The compound was employed as a blood purification material for the removal of LDL from plasma because it had good blood compatibility and could be easily separated with an external magnet. The efficient removal of LDL was attributed to the electrostatic interactions between the positive charged apoB-100 domain of LDL and the negative charged adsorbent. Moreover, the prepared material exhibited high recyclability and could release LDL in physiological saline for recyclable use. MNPs-(HA-DAH5 /HA-CB[6]5 ) offered promising perspectives and broad applications in extracorporeal treatment for the removal of LDL.

Familial hypercholesterolemia in primary care in Germany. Diabetes and cardiovascular risk evaluation: Targets and Essential Data for Commitment of Treatment (DETECT) study

Background and aimsFamilial hypercholesterolemia (FH) is an inherited disorder of lipoprotein metabolism characterised by impaired removal of low-density lipoproteins (LDL) from the circulation, which leads to an increased risk of cardiovascular disease (CVD). This risk can be significantly lowered by early diagnosis and treatment. In Germany, reliable estimates of the prevalence of FH are lacking. We therefore examined the prevalence rate of FH in Germany in a primary care based cohort. MethodWe utilized records of 4722 participants in the DETECT study, in whom complete data on blood lipids and medical history were available. Prevalence rates were assessed using the Dutch Lipid Clinics Network (DLCN) and the US-MEDPED criteria. We stratified for gender and age. Group differences were analyzed using Chi2 and ANOVA tests. ResultsUsing the DLCN (probable or definite FH) and the US.MEDPED criteria yielded prevalence rates of 1:278 and 1:295, respectively. The established diagnostic scores used in this analysis identify different patients. In women below 50 years of age, the LDL-C concentration is lower than in men, leading to the possibility of under-diagnosing FH in this group because women under the age of 50 are less likely to reach a higher DLCN-Score. ConclusionsFH has a higher than expected prevalence in Germany. Clinical diagnostic algorithms may not be concordant.

Facile preparation of heparinized polysulfone membrane assisted by polydopamine/polyethyleneimine co-deposition for simultaneous LDL selectivity and biocompatibility

Low-density lipoprotein (LDL) gains worldwide attention for decades as the key risk factor to atherosclerosis that progressively deteriorating into cardiovascular diseases. Until recent years, LDL-apheresis comes to be extensively used as a direct and efficient LDL removal method, with LDL adsorption materials particularly important. In this paper, a new strategy based on the co-deposition of polydopamine (PDA) with polyethylenimine (PEI) onto polysulfone (PSf) membranes, then subsequent heparinization by amino-carbonyl reactions, to achieve LDL selectivity and simultaneous biocompatibility, is proposed. Surface properties of modified PSf membranes are characterized by ATR-FTIR, XPS, FESEM, Zeta potential and WCA measurements. LDL adsorption ability is investigated by ELISA, while blood biocompatibility is evaluated by platelet adhesion experiments. Results suggest that heparin-modified PSf membranes show high selectivity for LDL removal and fine biocompatibility in contact with plasma, as excellent potential materials for LDL-apheresis.

PCSK9 Inhibitors: An Innovative Approach to Treating Hyperlipidemia.

Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are novel agents indicated for the treatment of hyperlipidemia. Inhibition of PCSK9 produces an increase in surface low-density lipoprotein (LDL) receptors and increases removal of LDL from the circulation. Alirocumab (Praluent; Sanofi/Regeneron, Bridgewater, NJ) and evolocumab (Repatha; Amgen, Thousand Oaks, CA) are currently available and approved for use in patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, and clinical atherosclerotic cardiovascular disease. Bococizumab (RN316; Pfizer, New York, NY) is currently being studied in similar indications, with an estimated approval date in late 2016. The pharmacodynamic effects of PCSK9 inhibitors have been extensively studied in various patient populations. They have been shown to produce significant reductions in LDL and are well tolerated in clinical studies, but they are very costly when compared with statins, the current mainstay of hyperlipidemia treatment. Clinical outcome studies are underway, but not yet available; however, meta-analyses have pointed to a reduction in cardiovascular death and cardiovascular events with the use of PCSK9 inhibitors. This review will discuss the novel mechanism of action of PCSK9 inhibitors, the results of clinical studies, and the clinical considerations of these agents in current therapy.

Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages.

High levels of circulating low-density lipoprotein (LDL) are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B-100 (ApoB100) that surrounds LDL. Punicalagin bound to ApoB100 at low concentrations (0.25–4 μM). Upon binding, it induced LDL influx to macrophages in a concentration-dependent manner, up to 2.5-fold. In contrast, another polyphenol which binds to ApoB100, glabridin, did not affect LDL influx. We further showed that LDL influx occurs specifically through the LDL receptor, with LDL then accumulating in the cell cytoplasm. Taken together with the findings of Aviram et al., 2000, that pomegranate juice and punicalagin induce plasma LDL removal and inhibit macrophage cholesterol synthesis and accumulation, our results suggest that, upon binding, punicalagin stimulates LDL influx to macrophages, thus reducing circulating cholesterol levels.

Serum proprotein convertase subtilisin/kexin type 9 concentration is not increased by plant stanol ester consumption in normo- to moderately hypercholesterolaemic non-obese subjects. The BLOOD FLOW intervention study

Proprotein convertase subtilisin/kexin type9 (PCSK9) regulates low-density lipoprotein (LDL) cholesterol (LDL-C) metabolism by targeting LDL receptors for degradation. Statins increase serum PCSK9 concentration limiting the potential of statins to reduce LDL-C, whereas ezetimibe, inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant stanols also reduce cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Therefore, we performed a controlled, randomized, double-blind study, in which 92 normo- to moderately hypercholesterolaemic subjects (35 males and 57 females) consumed vegetable-oil spread 20g/day enriched (plant stanol group, n=46) or not (control group, n=46) with plant stanols 3g/day as ester for 6 months. Fasting blood samples were drawn at baseline and at the end of the study. Serum PCSK9 concentration was analysed with Quantikine Elisa Immunoassay, serum and lipoprotein lipids enzymatically and serum non-cholesterol sterols with GLC. At baseline, PCSK9 concentration varied from 91 to 716ng/ml with a mean value of 278±11 (S.E.M.) ng/ml with no gender difference. It correlated with serum and LDL-C, serum triglycerides, age, body mass index (BMI) and plasma glucose concentration, but not with variables of cholesterol metabolism when adjusted to serum cholesterol. Plant stanols reduced LDL-C by 10% from controls (P<0.05), but PCSK9 levels were unchanged and did not differ between the groups. In conclusion, the present study demonstrated for the first time that inhibition of cholesterol absorption with plant stanol esters did not affect serum PCSK9 concentration. Thus, plant stanol esters provide an efficient dietary means to lower LDL-C without interfering with the PCSK9 metabolism and in this regard the LDL receptor-mediated cellular cholesterol uptake and removal.

Fe3O4@ZnO core-shell nanocomposites for efficient and repetitive removal of low density lipoprotein in plasma and on blood vessel

Low density lipoprotein (LDL)-apheresis therapy, which directly removes LDL from plasma by LDL-adsorbents in vitro is found to be clinically effective and safe to lower the LDL content in blood to prevent cardiovascular disease. Thus, developing excellent LDL adsorbents are becoming more and more attractive. Herein, functional Fe3O4@ZnO core–shell nanocomposites have been synthesized by a facile and eco-friendly two-step method. Not only do they possess high LDL adsorption (in PBS/plasma as well as on blood vessels) and favorable magnetic targeting ability but they can also be reused conveniently, which offer the Fe3O4@ZnO core–shell nanocomposites significant potential in the removal of LDL in vitro and in vivo.

Amphiphilic polyvinyl alcohol adsorbent for the removal of low-density lipoprotein

Spacer can effectively reduce the steric hindrance and synergistic effect of the hydrophilic and hydrophobic ligands immobilized in adsorbents can improve the specific adsorption for low-density lipoprotein (LDL). In this paper, in order to improve the adsorption capacity for the Low-density lipoprotein-cholesterol (LDL-C), specifically, amphiphilic adsorbent based on polyvinyl alcohol (PVA) containing cholesterol ligand and sulfonic dextran ligands was synthesized. All kinds of factors affecting the synthesis yield and adsorption properties were studied in detail. Results showed that the amphiphilic PVA adsorbent has higher adsorption capacity for total cholesterol (TC), (LDL-C), triglyceride (TG), and lower adsorption capacity, and percentage for high-density lipoprotein-cholesterol (HDL-C), while the ligand ratio of cholesterol to sulfonic ligands is 1.57:1, the adsorption percentage and adsorption capacity for TC, LDL-C, TG, and HDL-C were 54.4%, 67.6%, 42.5%, 10.4% and 4.02, 3.612, 2.154, 0.168 mg/g, respectively.