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Relationship between total cholesterol\\/high-density lipoprotein cholesterol ratio, triglyceride\\/high-density lipoprotein cholesterol ratio, and high-density lipoprotein subclasses  

Microsoft Academic Search

Alterations in plasma lipid levels can influence the composition, content, and distribution of plasma lipoprotein subclasses that affect atherosclerosis risk. This study evaluated the relationship between plasma total cholesterol (TC)\\/high-density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)\\/HDL-C ratio, and HDL subclass distribution. The apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 442

Lianqun Jia; Shiyin Long; Mingde Fu; Bingyu Yan; Ying Tian; Yanhua Xu; Lantu Gou



Characteristics of High-density Lipoprotein Subclasses Distribution for Subjects with Desirable Total Cholesterol Levels  

Microsoft Academic Search

Background  To investigate alteration of high density lipoproteins (HDL) subclasses distribution in different total cholesterol (TC) levels,\\u000a mainly the characteristics of HDL subclasses distribution in desirable TC levels and analyze the related mechanisms.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  ApoA-I contents of plasma HDL subclasses were determined by 2-dimensional gel electrophoresis coupled with immunodetection.\\u000a 486 Chinese Adults subjects were assigned to different TC groups according to the

Li Tian; Shiyin Long; Mingde Fu; Yinghui Liu; Yanhua Xu; Lianqun Jia



Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men: genetic and pharmacological evidence  

Microsoft Academic Search

Several studies have reported an inverse relation- ship between hepatic lipase activity and plasma high density lipoprotein (HDL) cholesterol concentrations. The purpose of the present study was to determine whether genetic and pharmacological variation in hepatic lipase activity alters the distribution of HDL subclasses. Two independent ana- lytical methods (nuclear magnetic resonance and gradient gel electrophoresis) were used to compare

Scott M. Grundy; Gloria L. Vega; James D. Otvos; David L. Rainwater


Slowß-migrating lipoprotein: An atherogenic subclass of low density lipoproteins  

Microsoft Academic Search

Objective: To clarify the possibility that midband Lp in LDL fractions might act as an atherogenic lipoprotein in their interaction with macrophages.Design and Methods: Low density lipoproteins (LDL) isolated by zonal ultracentrifugation from midband lipoprotein-positive serum in type IIb hyperlipidemics were subjected to polyacrylamide gel disc electrophoresis.Results: A part of midband lipoprotein was observed between pre?- and ?-band, in addition

M. Kawano; M. Shinomiya; T. Kanzaki; N. Morisaki; K. Shirai; Y. Saito; S. Yoshida



The Interplay between Size, Morphology, Stability, and Functionality of High-Density Lipoprotein Subclasses  

Microsoft Academic Search

High-density lipoprotein (HDL) mediates reverse cholesterol transport (RCT), wherein excess cholesterol is conveyed from peripheral tissues to the liver and steroidogenic organs. During this process HDL continually transitions between subclass sizes, each with unique biological activities. For instance, RCT is initiated by the interaction of lipid-free\\/lipid-poor apolipoprotein A-I (apoA-I) with ABCA1, a membrane-associated lipid transporter, to form nascent HDL. Because

Giorgio Cavigiolio; Baohai Shao; Ethan G. Geier; Gang Ren; Jay W. Heinecke; Michael N. Oda



Longitudinal study on lipoprotein profile, high density lipoprotein subclass, and postheparin lipases during gestation in women  

Microsoft Academic Search

To understand the mechanism responsible for ma- ternal hyperlipidemia, 25 healthy pregnant women were stud- ied longitudinally during the three trimesters of gestation and at post-partum, and 11 were studied again at post-lactation. Triglyceride and cholesterol levels increased with gestation in all the lipoprotein fractions. However, the greatest change appeared in low density (LDL) and high density (HDL) lipo- proteins,

J. J. Alvarez; A. Montelongo; A. Iglesias; M. A. Lasuncion; E. Herreral


Low density lipoprotein subclasses and response to a low-fat diet in healthy men.  

National Technical Information Service (NTIS)

Lipid and lipoprotein response to reduced dietary fat intake was investigated in relation to differences in distribution of LDL subclasses among 105 healthy men consuming high-fat (46%) and low-fat (24%) diets in random order for six weeks each. On high-f...

R. M. Krauss D. M. Dreon



High-density lipoprotein subclass and particle size in coronary heart disease patients with or without diabetes  

PubMed Central

Background A higher prevalence of coronary heart disease (CHD) in people with diabetes. We investigated the high-density lipoprotein (HDL) subclass profiles and alterations of particle size in CHD patients with diabetes or without diabetes. Methods Plasma HDL subclasses were quantified in CHD by 1-dimensional gel electrophoresis coupled with immunodetection. Results Although the particle size of HDL tend to small, the mean levels of low density lipoprotein cholesterol(LDL-C) and total cholesterol (TC) have achieved normal or desirable for CHD patients with or without diabetes who administered statins therapy. Fasting plasma glucose (FPG), triglyceride (TG), TC, LDL-C concentrations, and HDL3 (HDL3b and 3a) contents along with Gensini Score were significantly higher; but those of HDL-C, HDL2b+pre?2, and HDL2a were significantly lower in CHD patients with diabetes versus CHD patients without diabetes; The pre?1-HDL contents did not differ significantly between these groups. Multivariate regression analysis revealed that Gensini Score was significantly and independently predicted by HDL2a, and HDL2b+pre?2. Conclusions The abnormality of HDL subpopulations distribution and particle size may contribute to CHD risk in diabetes patients. The HDL subclasses distribution may help in severity of coronary artery and risk stratification, especially in CHD patients with therapeutic LDL, TG and HDL levels.



Omacor in familial combined hyperlipidemia: effects on lipids and low density lipoprotein subclasses.  


Elevations of plasma cholesterol and/or triglycerides, and the prevalence of small, dense LDL particles remarkably increase coronary risk in patients with familial combined hyperlipidemia (FCHL). A total of 14 FCHL patients were studied, to investigate the ability of Omacor, a drug containing the n-3 fatty acids eicosapentaenoic and docosahexaenoic acid (EPA and DHA), to favorably correct plasma lipid/lipoprotein levels and LDL particle distribution. The patients received four capsules daily of Omacor (providing 3.4 g EPA+DHA per day) or placebo for 8 weeks in a randomized, double-blind, cross-over study. Omacor significantly lowered plasma triglycerides and VLDL-cholesterol levels, by 27 and 18%, respectively. Total cholesterol did not change but LDL-cholesterol and apolipoprotein B (apoB) concentrations increased by 21 and 6%. As expected, LDL particles were small (diameter=24.9+/-0.3 nm) and apoB-rich (LDL-cholesterol/apoB ratio=1.27+/-0.26) in the selected subjects. After Omacor treatment LDL became enriched in cholesterol (LDL-cholesterol/apoB ratio=1.40+/-0.17), mainly cholesteryl esters, indicating accumulation in plasma of more buoyant and core enriched LDL particles. Indeed, the separation of LDL subclasses by rate zonal ultracentrifugation showed an increase of the plasma concentration of IDL and of the more buoyant, fast floating LDL-1 and LDL-2 subclasses after Omacor, with a parallel decrease in the concentration of the denser, slow floating LDL-3 subclass. However, the average LDL size did not change after Omacor (25.0+/-0.3 nm). The resistance of the small LDL pattern to drug-induced modifications implies that a maximal lipid-lowering effect must be achieved to reduce coronary risk in FCHL patients. PMID:10657575

Calabresi, L; Donati, D; Pazzucconi, F; Sirtori, C R; Franceschini, G



Separation and Characterization of Subclasses of Human Serum High Density Lipoproteins and Their Determination in a California Population Sample.  

National Technical Information Service (NTIS)

Density gradient ultracentrifugation of human serum high density lipoproteins (HDL) from both normolipemic males and females resulted in a distribution of HDL concentration versus subfraction hydrated density which has three maxima. Gradient gel electroph...

D. W. Anderson



Small high-density lipoprotein (HDL) subclasses are increased with decreased activity of HDL-associated phospholipase A? in subjects with prediabetes.  


Alterations in high-density lipoprotein (HDL) subclass distribution, as well as in the activities of HDL-associated enzymes, have been associated with increased cardiovascular disease (CVD) risk. HDL subclass distribution and the activities of HDL-associated enzymes remain unknown in prediabetic patients, a condition also associated with increased CVD risk. The aim of the present study was to assess any differences in HDL subclass distribution (using polyacrylamide gel electrophoresis) and in activities of HDL-associated enzymes between prediabetic (impaired fasting glucose, IFG, n = 80) and non-prediabetic subjects (n = 105). Subjects with prediabetes had significantly increased waist circumference, blood pressure and triacylglycerol (TAG) levels compared with subjects with fasting glucose levels <100 mg/dL (all p < 0.05). The proportion of small HDL3 over HDL cholesterol (HDL-C) was significantly increased in prediabetic subjects compared with their controls (p < 0.05). The activity of the anti-atherogenic HDL-associated lipoprotein-associated phospholipase A? (HDL-LpPLA?) was significantly lower in subjects with prediabetes (p < 0.05), whereas the activity of paraoxonase 1 (using both paraoxon and phenyl acetate as substrates) did not significantly differ between subjects with or without prediabetes. In a stepwise linear regression analysis, the proportion of small HDL3 over HDL-C concentration was independently associated with the presence of prediabetes and with total cholesterol and TAG concentration (positively), as well as with HDL-C levels (negatively). We also observed a trend of increased small dense low-density lipoprotein cholesterol levels in prediabetic subjects compared with their controls. Subjects with IFG exhibit increased proportion of small HDL3 particles combined with decreased activity of the anti-atherogenic HDL-LpPLA?. PMID:23546765

Filippatos, Theodosios D; Rizos, Evangelos C; Tsimihodimos, Vasilios; Gazi, Irene F; Tselepis, Alexandros D; Elisaf, Moses S



Influence of low molecular weight heparin compared to conventional heparin for anticoagulation during haemodialysis on low density lipoprotein subclasses  

Microsoft Academic Search

Background. In haemodialysis (HD) patients, low density lipoprotein (LDL) particle distribution is characterized by a higher proportion of more athero- genic dense LDL. Though clinical studies showed favourable effects of low molecular weight (LMW) heparin compared to standard heparin on triglycerides (TG) and cholesterol (CH) in HD patients with hypertriglyceridaemia, it is not known if LMW heparin influences LDL subfraction

Jorg Wiemer; Karl Winkler; Manfred Baumstark; Winfried Mar; Jurgen E. Scherberich


Quantitative and compositional changes in high density lipoprotein subclasses in patients with various genotypes of cholesteryl ester transfer protein deficiency  

Microsoft Academic Search

High density lipoprotein (HDL) with and without apolipoprotein (apo) E was quantified and characterized in subjects with three genotypes of cholesteryl ester transfer pro- tein (CETP) deficiency: the nonsense mutation in intron 14 (10 homozygotes and 5 heterozygotes); the missense mutation in the exon 15 (3 homozygotes and 9 heterozygotes); and the Int14A\\/D442G in 6 compound heterozygotes. ApoE-poor and apoE-rich

Hitoshi Chiba; Harukuni Akita; Shu-Ping Hi; Yukihiro Takahashi; Hirotoshi Fuda; Haruki Suzuki; Hitoshi Shibuya; Masahiro Tsuji; Kunihiko Kobayashit


Conservation of Apolipoprotein A-I's Central Domain Structural Elements upon Lipid Association on Different High-Density Lipoprotein Subclasses.  


The antiatherogenic properties of apolipoprotein A-I (apoA-I) are derived, in part, from lipidation-state-dependent structural elements that manifest at different stages of apoA-I's progression from lipid-free protein to spherical high-density lipoprotein (HDL). Previously, we reported the structure of apoA-I's N-terminus on reconstituted HDLs (rHDLs) of different sizes. We have now investigated at the single-residue level the conformational adaptations of three regions in the central domain of apoA-I (residues 119-124, 139-144, and 164-170) upon apoA-I lipid binding and HDL formation. An important function associated with these residues of apoA-I is the activation of lecithin:cholesterol acyltransferase (LCAT), the enzyme responsible for catalyzing HDL maturation. Structural examination was performed by site-directed tryptophan fluorescence and spin-label electron paramagnetic resonance spectroscopies for both the lipid-free protein and rHDL particles 7.8, 8.4, and 9.6 nm in diameter. The two methods provide complementary information about residue side chain mobility and molecular accessibility, as well as the polarity of the local environment at the targeted positions. The modulation of these biophysical parameters yielded new insight into the importance of structural elements in the central domain of apoA-I. In particular, we determined that the loosely lipid-associated structure of residues 134-145 is conserved in all rHDL particles. Truncation of this region completely abolished LCAT activation but did not significantly affect rHDL size, reaffirming the important role of this structural element in HDL function. PMID:23984834

Oda, Michael N; Budamagunta, Madhu S; Geier, Ethan G; Chandradas, Sajiv H; Shao, Baohai; Heinecke, Jay W; Voss, John C; Cavigiolio, Giorgio



Effects of cardiovascular lifestyle change on lipoprotein subclass profiles defined by nuclear magnetic resonance spectroscopy  

PubMed Central

Background Low-density lipoprotein (LDL) cholesterol lowering is a primary goal in clinical management of patients with cardiovascular disease, but traditional cholesterol levels may not accurately reflect the true atherogenicity of plasma lipid profiles. The size and concentration of lipoprotein particles, which transport cholesterol and triglycerides, may provide additional information for accurately assessing cardiovascular risk. This study evaluated changes in plasma lipoprotein profiles determined by nuclear magnetic resonance (NMR) spectroscopy in patients participating in a prospective, nonrandomized lifestyle modification program designed to reverse or stabilize progression of coronary artery disease (CAD) to improve our understanding of lipoprotein management in cardiac patients. Results The lifestyle intervention was effective in producing significant changes in lipoprotein subclasses that contribute to CAD risk. There was a clear beneficial effect on the total number of LDL particles (-8.3%, p < 0.05 compared to matched controls), small dense LDL particles (-9.5%, p < 0.05), and LDL particle size (+0.8%; p < 0.05). Likewise, participants showed significant improvement in traditional CAD risk factors such as body mass index (-9.9%, p < 0.01 compared to controls), total cholesterol (-5.5%, p < 0.05), physical fitness (+37.2%, p < 0.01), and future risk for CAD (-7.9%, p < 0.01). Men and women responded differently to the program for all clinically-relevant variables, with men deriving greater benefit in terms of lipoprotein atherogenicity. Plasma lipid and lipoprotein responses to the lifestyle change program were not confounded by lipid-lowering medications. Conclusion In at risk patients motivated to participate, an intensive lifestyle change program can effectively alter traditional CAD risk factors and plasma lipoprotein subclasses and may reduce risk for cardiovascular events. Improvements in lipoprotein subclasses are more evident in men compared to women.

Decewicz, David J; Neatrour, David M; Burke, Amy; Haberkorn, Mary Jane; Patney, Heather L; Vernalis, Marina N; Ellsworth, Darrell L



Hypertriglyceridemia and unusual lipoprotein subclass distributions associated with late pregnancy  

SciTech Connect

In the human adult population elevated plasma triglyceride (TG) levels are associated with decreased high density lipoprotein-cholesterol (HDL-C) levels and decreased HDL and LDL particle sizes. Late pregnancy is a hypertriglyceridemic state where little is known about LDL and HDL subpopulation distribution. Plasma lipids, apolipoproteins (apo) and lipoprotein subpopulations were examined in 36 pregnant women at 36 wk pregnancy and 6 wk postpartum and correlated with HDL and LDL size. There was a significant decrease in LDL diameter at 36 wk pre, 25 {plus minus} 0.7 nm compared, with 6 wk post, 26.4 {plus minus} 0.8 nm. A total of 97% of the 36 wk pre subjects had small dense LDL which paralleled increases in apoB concentration. Unlike LDL HDL at 36 wks pre showed a significant increase in larger sized particles where HDL{sub 2b} predominated. There was a positive correlation between HDL{sub 2b} mass and apoAl and HDL-C concentrations. Late pregnancy is a metabolic state where the predominance of large, HDL{sub 2b} particles is discordant with the predominance of small LDL and elevated TG. This annual metabolic pattern may in part be due to hormonal changes occurring in late pregnancy.

Forte, T.M.; Kretchmer, N.; Silliman, K. (Lawrence Berkeley Lab., CA (United States))



Lipoprotein subclasses in genetic studies: The Berkeley Data Set.  

National Technical Information Service (NTIS)

Data from the Berkeley Data Set was used to investigate familial correlations of HDL-subclasses. Analysis of the sibling intraclass correlation coefficient by HDL particle diameter showed that sibling HDL levels were significantly correlated for HDL(sub 2...

R. M. Krauss P. T. Williams P. J. Blanche A. Cavanaugh L. G. Holl



Apolipoprotein B-Containing Lipoprotein Subclasses as Risk Factors for Cardiovascular Disease in Patients With Rheumatoid Arthritis  

PubMed Central

Objective The purpose of this study was to explore whether nontraditional risk factors, such as apolipoprotein C-III (Apo C-III) and its corresponding Apo B lipoprotein (Lp) subclasses, contribute to the risk of cardiovascular disease in rheumatoid arthritis (RA) patients. Methods Apolipoprotein and lipoproteins were measured in 152 RA patients by immunoturbidimetric procedures, electroimmunoassay, and immunoprecipitation. Patients had a coronary artery calcium (CAC) score assessed at baseline and at year 3. Differences in the CAC scores between baseline and year 3 were calculated and dichotomized at 0, where patients with a difference score >0 were denoted as progressors and the rest were denoted as nonprogressors. Differences between means were tested with a 2-sided independent Student’s t-test with Satterthwaite’s adjustment. Proportion differences were tested with a chi-square test. Multiple logistic regression was performed to assess the relationship between apolipoprotein and lipoprotein levels and the dichotomized CAC score. Results Progressors accounted for almost 60% of the cohort. Progressors had significantly higher levels of triglycerides, very low-density lipoprotein (VLDL) cholesterol, total cholesterol/high-density lipoprotein (HDL), triglycerides/HDL, Apo B, LpA-II:B:C:D:E, LpB:C, Apo B/Apo A-I, Apo C-III, and Apo C-III–heparin precipitate than the nonprogressors. After adjusting for age, sex, statin use (yes/no), and hypertension (yes/no), significant risk factors of progressors were total cholesterol, triglycerides, VLDL cholesterol, LDL cholesterol, Apo B, LpB:C, Apo C-III, and Apo B/Apo A-I. Conclusion Apo C-III–containing Apo B lipoprotein subclasses were found to be significantly elevated in progressors compared to nonprogressors. Many of these same lipoproteins were found to be associated with an increase in CAC scores among progressors. These lipoproteins may be considered new risk factors for progression of atherosclerosis in RA patients.




Biochemie der High Density Lipoproteine  

Microsoft Academic Search

Summary High density lipoproteins are a heterogeneous mixture of spherical macromolecules which differ in size (80–120 Å), chemical composition (apolipoprotein A–I: 30–35%; apolipoprotein A–II: 10–15%; apolipoprotein C: 3–5%; phospholipids 25–30%; cholesterol\\/cholesterol esters: 15–20%; triglycerides: 3–5%) and physico-chemical properties. They can be isolated through selective precipitation of apolipoprotein B-containing lipoproteins (very low density lipoproteins, low density lipoproteins, lipoprotein (a)) and, under

G. Assmann; H. Schriewer



Lipoprotein subclasses in genetic studies: The Berkeley Data Set  

SciTech Connect

Data from the Berkeley Data Set was used to investigate familial correlations of HDL-subclasses. Analysis of the sibling intraclass correlation coefficient by HDL particle diameter showed that sibling HDL levels were significantly correlated for HDL{sub 2b}, HDL{sub 3a} and HDL{sub 3b} subclasses. The percentage of the offsprings` variance explained by their two parents. Our finding that parents and offspring-have the highest correlation for HDL{sub 2b} is consistent with published reports that show higher heritability estimates for HDL{sub 2} compared with HDL{sub 3}{minus} cholesterol.

Krauss, R.M.; Williams, P.T.; Blanche, P.J.; Cavanaugh, A.; Holl, L.G. [Lawrence Berkeley Lab., CA (United States); Austin, M.A. [Washington Univ., Seattle, WA (United States). Dept. of Epidemiology



Acute effects of interleukin-6 infusion on apo-B-containing lipoprotein subclasses in humans.  


IL-6 is believed to mediate the elevation in plasma TG and VLDL lipids in patients with sepsis. Previous studies of lipoprotein density fractions do not reveal the extent to which cytokines change the immunochemically distinct TG-rich (LpB:C, LpB:C:E, LpAII:B:C:D:E) and cholesterol-rich (LpB, LpB:E) apoB-containing subclasses present in VLDL. Therefore, we have directly measured these subclasses following their isolation by sequential immunoprecipitation in seven healthy male subjects during a 3-h infusion with recombinant human (rh) IL-6. Though plasma TG and apoB-containing particle number were unchanged by IL-6, the distribution of TG-rich subclasses was significantly altered. Compared to baseline values, LpB:E + LpB:C:E increased significantly at 0.5 h (p < 0.02) and were higher than saline-infused controls at 0.5 and 1 h (p < 0.05). At 0.5 h LpAII:B:C:D:E reciprocally declined from baseline (p < 0.01). While the pattern of change for total apoB showed an overall decline (p < 0.05), these changes in LpB:E + LpB:C:E and LpAII:B:C:D:E in IL-6 subjects differed from controls (p < 0.05; p < 0.01, respectively). These findings indicate that physiologic concentrations of IL-6 rapidly and selectively regulate the transport of apoB particles that contain apoE. Since apoE has immunomodulatory and host defense functions, these changes may be a previously unrecognized early step in the innate immune response. PMID:21923231

Bagdade, John; Pedersen, Bente K; Schwenke, Dawn; Saremi, Aramesh; Alaupovic, Petar



A one-step separation of human serum high density lipoproteins 2 and 3 by rate-zonal density gradient ultracentrifugation in a swinging bucket rotor  

Microsoft Academic Search

A method was developed for the separation of the high density lipoprotein subclasses HDLn and HDLs from hu- man serum. Six serum samples are fractionated in a single- step ultracentrifugal procedure using the Beckman (SW-40) swinging bucket rotor. The method is based on a difference in flotation rate of the high density lipoprotein subclasses. Sep- aration of HDLp and HDLs

P. H. E. Groat; L. M. Scheek; L. Havekes; W. L. van Noort


High-density lipoproteins.  


Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary artery disease (CAD). HDL particles exert many effects in vitro and in vivo that may protect arteries from chemical or biological harm or facilitate repair of injuries. Nevertheless, HDL has not yet been successfully exploited for therapy. One potential reason for this shortfall is the structural and functional complexity of HDL particles, which carry more than 80 different proteins and more than 200 lipid species as well as several microRNAs and other potentially bioactive molecules. This physiological heterogeneity is further increased in several inflammatory conditions that increase cardiovascular risk, including CAD itself but also diabetes mellitus, chronic kidney disease, and rheumatic diseases. The quantitative and qualitative modifications of the proteome and lipidome, as well as the resulting loss of functions or gain of dysfunctions, are not recovered by the biomarker HDL-cholesterol. As yet the relative importance of the many physiological and pathological activities of normal and dysfunctional HDL, respectively, for the pathogenesis of atherosclerosis is unknown. The answer to this question, as well as detailed knowledge of structure-function-relationships of HDL-associated molecules, is a prerequisite to exploit HDL for the development of anti-atherogenic drugs as well as of diagnostic biomarkers for the identification, personalized treatment stratification, and monitoring of patients at increased cardiovascular risk.??(Circ J?2013; 77: 2432-2448). PMID:24067275

Annema, Wijtske; von Eckardstein, Arnold



Effects of 34 Risk Loci for Type 2 Diabetes or Hyperglycemia on Lipoprotein Subclasses and Their Composition in 6,580 Nondiabetic Finnish Men  

PubMed Central

OBJECTIVE We investigated the effects of 34 genetic risk variants for hyperglycemia/type 2 diabetes on lipoprotein subclasses and particle composition in a large population-based cohort. RESEARCH DESIGN AND METHODS The study included 6,580 nondiabetic Finnish men from the population-based Metabolic Syndrome in Men (METSIM) study (aged 57 ± 7 years; BMI 26.8 ± 3.7 kg/m2). Genotyping of 34 single nucleotide polymorphism (SNPs) for hyperglycemia/type 2 diabetes was performed. Proton nuclear magnetic resonance spectroscopy was used to measure particle concentrations of 14 lipoprotein subclasses and their composition in native serum samples. RESULTS The glucose-increasing allele of rs780094 in GCKR was significantly associated with low concentrations of VLDL particles (independently of their size) and small LDL and was nominally associated with low concentrations of intermediate-density lipoprotein, all LDL subclasses, and high concentrations of very large and large HDL particles. The glucose-increasing allele of rs174550 in FADS1 was significantly associated with high concentrations of very large and large HDL particles and nominally associated with low concentrations of all VLDL particles. SNPs rs10923931 in NOTCH2 and rs757210 in HNF1B genes showed nominal or significant associations with several lipoprotein traits. The genetic risk score of 34 SNPs was not associated with any of the lipoprotein subclasses. CONCLUSIONS Four of the 34 risk loci for type 2 diabetes or hyperglycemia (GCKR, FADS1, NOTCH2, and HNF1B) were significantly associated with lipoprotein traits. A GCKR variant predominantly affected the concentration of VLDL, and the FADS1 variant affected very large and large HDL particles. Only a limited number of risk loci for hyperglycemia/type 2 diabetes significantly affect lipoprotein metabolism.

Stancakova, Alena; Paananen, Jussi; Soininen, Pasi; Kangas, Antti J.; Bonnycastle, Lori L.; Morken, Mario A.; Collins, Francis S.; Jackson, Anne U.; Boehnke, Michael L.; Kuusisto, Johanna; Ala-Korpela, Mika; Laakso, Markku



Effects of cardiovascular lifestyle change on lipoprotein subclass profiles defined by nuclear magnetic resonance spectroscopy  

Microsoft Academic Search

BACKGROUND: Low-density lipoprotein (LDL) cholesterol lowering is a primary goal in clinical management of patients with cardiovascular disease, but traditional cholesterol levels may not accurately reflect the true atherogenicity of plasma lipid profiles. The size and concentration of lipoprotein particles, which transport cholesterol and triglycerides, may provide additional information for accurately assessing cardiovascular risk. This study evaluated changes in plasma

David J Decewicz; David M Neatrour; Amy Burke; Mary Jane Haberkorn; Heather L Patney; Marina N Vernalis; Darrell L Ellsworth



Subfractionation of human high density lipoproteins by heparin-Sepharose affinity chromatography  

Microsoft Academic Search

A reproducible and quantitative subfractiona- tion of human high density lipoproteins (HDL) by heparin- Sepharose affinity chromatography has been developed. Two elution methods (A and B) were used to subfractionate HDL, (d 1.063-1.125 g\\/ml) or total HDL (d 1.063-1.21 g\\/ml). Method A separated HDLz into three subclasses, each with distinct chemical properties and in vitro metabolic characteristics. The first subclass,

Karl H. Weisgraber; Robert W. Mahley


Acute changes in serum lipids and lipoprotein subclasses in triathletes as assessed by proton nuclear magnetic resonance spectroscopy.  


Exercise is associated with changes in lipids that may protect against coronary heart disease (CHD). In this study of 28 triathletes, we analyzed acute changes in serum lipid and lipoprotein concentrations after completion of the 1995 World Championship Hawaii Ironman Triathlon. With standard laboratory assays, we demonstrate significant decreases in total cholesterol, VLDL cholesterol, ApoB100, and Lp(a). Total HDL cholesterol increased significantly immediately after the race. With a novel proton NMR spectroscopy assay, we demonstrate that smaller diameter LDL particles, corresponding to small, dense LDL, declined by 62%. Moreover, larger HDL subclasses, whose levels are inversely associated with CHD, increased significantly by 11%. Smaller HDL subclasses, which have been directly associated with CHD in some studies, acutely decreased by 16%. Therefore, exercise not only acutely induces changes in lipoprotein concentrations among the standard species in a manner that favorably affects CHD risk, but also induces favorable changes in specific lipoprotein subclass size distribution that also may alter CHD risk independently of the total lipoprotein serum concentration. PMID:10446075

Yu, H H; Ginsburg, G S; O'Toole, M L; Otvos, J D; Douglas, P S; Rifai, N



Familial apolipoprotein Al and apolipoprotein CIII deficiency: subclass distribution, composition, and morphology of lipoproteins in a disorder associated with premature atherosclerosis  

SciTech Connect

Lipoprotein classes isolated from the plasma of two patients with apolipoprotein AI (apo AI) and apolipoprotein CIII (apo CIII) deficiency were characterized and compared with those of healthy, age- and sex-matched controls. The plasma triglyceride values for patients 1 and 2 were 31 and 51 mg/dl, respectively, and their cholesterol values were 130 and 122 mg/dl, respectively; the patients, however, had no measurable high density lipoprotein (HDL)-cholesterol. Analytic ultracentrifugation showed that patients' S/sub f//sup 0/ 0-20 lipoproteins posses a single peak with S/sub f//sup 0/ rates of 7.4 and 7.6 for patients 1 and 2, respectively, which is similar to that of the controls. The concentration of low density lipoprotein (LDL) (S/sub f//sup 0/ 0-12) particles, although within normal range (331 and 343 mg/dl for patients 1 and 2, respectively), was 35% greater than that of controls. Intermediate density lipoproteins (IDL) and very low density lipoproteins (VLDL) (S/sub f//sup 0/ 20-400) were extremely low in the patients. HDL in the patients had a calculated mass of 15.4 and 11.8 mg/dl for patients 1 and 2, respectively. No HDL could be detected by analytic ultracentrifugation, but polyacrylamide gradient gel electrophoresis (gge) revealed that patients possessed two major HDL subclasses: (HDL/sub sb/)/sub gge/ at 11.0 nm and (HDL/sub 3b/)/sub gge/ at 7.8 nm. The major peak in the controls (HDL/sub 3a/)/sub gge/, was lacking in the patients.

Forte, T.M.; Nichols, A.V.; Krauss, R.M.; Norum, R.A.



Linkage of low-density lipoprotein size to the lipoprotein lipase gene in heterozygous lipoprotein lipase deficiency.  

PubMed Central

Small low-density lipoprotein (LDL) particles are a genetically influenced coronary disease risk factor. Lipoprotein lipase (LpL) is a rate-limiting enzyme in the formation of LDL particles. The current study examined genetic linkage of LDL particle size to the LpL gene in five families with structural mutations in the LpL gene. LDL particle size was smaller among the heterozygous subjects, compared with controls. Among heterozygous subjects, 44% were classified as affected by LDL subclass phenotype B, compared with 8% of normal family members. Plasma triglyceride levels were significantly higher, and high-density lipoprotein cholesterol (HDL-C) levels were lower, in heterozygous subjects, compared with normal subjects, after age and sex adjustment. A highly significant LOD score of 6.24 at straight theta=0 was obtained for linkage of LDL particle size to the LpL gene, after adjustment of LDL particle size for within-genotype variance resulting from triglyceride and HDL-C. Failure to adjust for this variance led to only a modest positive LOD score of 1.54 at straight theta=0. Classifying small LDL particles as a qualitative trait (LDL subclass phenotype B) provided only suggestive evidence for linkage to the LpL gene (LOD=1. 65 at straight theta=0). Thus, use of the quantitative trait adjusted for within-genotype variance, resulting from physiologic covariates, was crucial for detection of significant evidence of linkage in this study. These results indicate that heterozygous LpL deficiency may be one cause of small LDL particles and may provide a potential mechanism for the increase in coronary disease seen in heterozygous LpL deficiency. This study also demonstrates a successful strategy of genotypic specific adjustment of complex traits in mapping a quantitative trait locus.

Hokanson, J E; Brunzell, J D; Jarvik, G P; Wijsman, E M; Austin, M A



Alterations of HDL subclasses in hyperlipidemia  

Microsoft Academic Search

Background: It is generally accepted that different high-density lipoprotein (HDL) subclasses have distinct but interrelated metabolic functions. HDL is known to directly influence the atherogenic process and changes in HDL subclasses distribution may be related to the incidence and prevalence of atherosclerosis. Method: The relative apolipoprotein (apo)A-I contents (% apoA-I) of plasma HDL subclasses were determined by two-dimensional gel electrophoresis

Yanhua Xu; Mingde Fu



Sulfated Polyvinylalcohol Based Low Density Lipoprotein Binders.  

National Technical Information Service (NTIS)

The thesis covers the synthesis and characterization of three Low Density Lipoprotein (LDL) binders based on sulfated polyvinylalcohol. These binders are to be used in extracorporeal bloodtreatment in order to reduce high plasma LDL levels, as encountered...

N. Maaskant



Low-Density Lipoprotein Apheresis  

PubMed Central

Executive Summary Objective To assess the effectiveness and safety of low-density lipoprotein (LDL) apheresis performed with the heparin-induced extracorporeal LDL precipitation (HELP) system for the treatment of patients with refractory homozygous (HMZ) and heterozygous (HTZ) familial hypercholesterolemia (FH). Background on Familial Hypercholesterolemia Familial hypercholesterolemia is a genetic autosomal dominant disorder that is caused by several mutations in the LDL-receptor gene. The reduced number or absence of functional LDL receptors results in impaired hepatic clearance of circulating low-density lipoprotein cholesterol (LDL-C) particles, which results in extremely high levels of LDL-C in the bloodstream. Familial hypercholesterolemia is characterized by excess LDL-C deposits in tendons and arterial walls, early onset of atherosclerotic disease, and premature cardiac death. Familial hypercholesterolemia occurs in both HTZ and HMZ forms. Heterozygous FH is one of the most common monogenic metabolic disorders in the general population, occurring in approximately 1 in 500 individuals1. Nevertheless, HTZ FH is largely undiagnosed and an accurate diagnosis occurs in only about 15% of affected patients in Canada. Thus, it is estimated that there are approximately 3,800 diagnosed and 21,680 undiagnosed cases of HTZ FH in Ontario. In HTZ FH patients, half of the LDL receptors do not work properly or are absent, resulting in plasma LDL-C levels 2- to 3-fold higher than normal (range 7-15mmol/L or 300-500mg/dL). Most HTZ FH patients are not diagnosed until middle age when either they or one of their siblings present with symptomatic coronary artery disease (CAD). Without lipid-lowering treatment, 50% of males die before the age of 50 and 25% of females die before the age of 60, from myocardial infarction or sudden death. In contrast to the HTZ form, HMZ FH is rare (occurring in 1 case per million persons) and more severe, with a 6- to 8-fold elevation in plasma LDL-C levels (range 15-25mmol/L or 500-1000mg/dL). Homozygous FH patients are typically diagnosed in infancy, usually due to the presence of cholesterol deposits in the skin and tendons. The main complication of HMZ FH is supravalvular aortic stenosis, which is caused by cholesterol deposits on the aortic valve and in the ascending aorta. The average life expectancy of affected individuals is 23 to 25 years. In Ontario, it is estimated that there are 13 to 15 cases of HMZ FH. An Ontario clinical expert confirmed that 9 HMZ FH patients have been identified to date. Diagnosis There are 2 accepted clinical diagnostic criterion for the diagnosis of FH: the Simon Broome FH Register criteria from the United Kingdom and the Dutch Lipid Network criteria from the Netherlands. The criterion supplement cholesterol levels with clinical history, physical signs and family history. DNA-based-mutation-screening methods permit a definitive diagnosis of HTZ FH to be made. However, given that there are over 1000 identified mutations in the LDL receptor gene and that the detection rates of current techniques are low, genetic testing becomes problematic in countries with high genetic heterogeneity, such as Canada. Treatment The primary aim of treatment in both HTZ and HMZ FH is to reduce plasma LDL-C levels in order to reduce the risk of developing atherosclerosis and CAD. The first line of treatment is dietary intervention, however it alone is rarely sufficient for the treatment of FH patients. Patients are frequently treated with lipid-lowering drugs such as resins, fibrates, niacin, statins and cholesterol absorption-inhibiting drugs (ezetimibe). Most HTZ FH patients require a combination of drugs to achieve or approach target cholesterol levels. A small number of HTZ FH patients are refractory to treatment or intolerant to lipid-lowering medication. According to clinical experts, the prevalence of refractory HTZ FH in Ontario is between 1 to 5%. Using the mean of 3%, it is estimated that there are approximately 765 refractory HTZ FH patients in Ontario, of which 115 are diagnosed



Membrane Permeabilization by Trypanosome Lytic Factor, a Cytolytic Human High Density Lipoprotein*S?  

PubMed Central

Trypanosome lytic factor (TLF) is a subclass of human high density lipoprotein (HDL) that mediates an innate immune killing of certain mammalian trypanosomes, most notably Trypanosoma brucei brucei, the causative agent of a wasting disease in cattle. Mechanistically, killing is initiated in the lysosome of the target trypanosome where the acidic pH facilitates a membrane-disrupting activity by TLF. Here we utilize a model liposome system to characterize the membrane binding and permeabilizing activity of TLF and its protein constituents, haptoglobin-related protein (Hpr), apolipoprotein L-1 (apoL-1), and apolipoprotein A-1 (apoA-1). We show that TLF efficiently binds and permeabilizes unilamellar liposomes at lysosomal pH, whereas non-lytic human HDL exhibits inefficient permeabilizing activity. Purified, delipidated Hpr and apoL-1 both efficiently permeabilize lipid bilayers at low pH. Trypanosome lytic factor, apoL-1, and apoA-1 exhibit specificity for anionic membranes, whereas Hpr permeabilizes both anionic and zwitterionic membranes. Analysis of the relative particle sizes of susceptible liposomes reveals distinctly different membrane-active behavior for native TLF and the delipidated protein components. We propose that lysosomal membrane damage in TLF-susceptible trypanosomes is initiated by the stable association of the TLF particle with the lysosomal membrane and that this is a property unique to this subclass of human HDL.

Harrington, John M.; Howell, Sawyer; Hajduk, Stephen L.



Modulation of High-Density Lipoprotein Cholesterol Metabolism and Reverse Cholesterol Transport  

Microsoft Academic Search

Low high-density lipoprotein (HDL)-cholesterol (C) is an important risk factor for coronary heart disease. In vitro, HDL exerts several potentially anti-atherogenic effects including reverse cholesterol transport (RCT) from peripheral cells to the liver. Hence, raising HDL-C has become an interesting target for anti-atherosclerotic drug therapy. Levels of HDL-C and the composition of HDL subclasses in plasma are regulated by apolipoproteins,

M. Hersberger; A. Eckardstein


Metabolic heterogeneity in the formation of low density lipoprotein from very low density lipoprotein in the rat: evidence for the independent production of a low density lipoprotein subfraction  

Microsoft Academic Search

The formation of low density lipoprotein (LDL) from very low density lipoprotein (VLDL) was studied after injecting 14C-radiomethylated or '251-radioiodinated VLDL into rats. VLDL and LDL B apoprotein specific radioactivity time curves were obtained after tetramethyl- urea extraction of the lipoproteins. In all experiments, the specific activity of LDL B apoprotein did not inter- cept the VLDL curve at maximal

Noel H. Fidge; Parissa Poulis


Klinik und Pathobiochemie der High Density Lipoproteine  

Microsoft Academic Search

Summary The determination of high density lipoprotein (HDL)-cholesterol in patients with mild hypercholesterolemia (240–300 mg\\/dl) allows one to distinguish between hyperbetalipoproteinemia (=high atherogenic risk) and hyperalphalipoproteinemia (=low atherogenic risk). In addition, analysis of HDL-cholesterol is of value in the prediction and early recognition of coronary heart disease, particularly in combination with known risk factors (hypertriglyceridemia, adipositas, smoking). This prognostic value

G. Assmann; H. Schriewer; W. Oberwittler



Nanobiotechnology applications of reconstituted high density lipoprotein  

Microsoft Academic Search

High-density lipoprotein (HDL) plays a fundamental role in the Reverse Cholesterol Transport pathway. Prior to maturation, nascent HDL exist as disk-shaped phospholipid bilayers whose perimeter is stabilized by amphipathic apolipoproteins. Methods have been developed to generate reconstituted (rHDL) in vitro and these particles have been used in a variety of novel ways. To differentiate between physiological HDL particles and non-natural

Robert O Ryan



Role of hepatic lipase in intermediate-density lipoprotein and small, dense low-density lipoprotein formation in hemodialysis patients  

Microsoft Academic Search

Role of hepatic lipase in intermediate-density lipoprotein and small, dense low-density lipoprotein formation in hemodialysis patients.BackgroundIt has been reported that remnant lipoproteins and small, dense low-density lipoproteins (LDLs) are risk factors for cardiovascular disease. To determine whether these risk factors are present in hemodialysis (HD) patients who are suffering from a high incidence of atherosclerotic vascular disease, we measured concentrations

Keiko Oi; Tsutomu Hirano; Soichi Sakai; Yoshindo Kawaguchi; Tatsuo Hosoya



Lipoprotein Subfraction Changes in Normal Pregnancy: Threshold Effect of Plasma Triglyceride on Appearance of Small, Dense Low Density Lipoprotein  

Microsoft Academic Search

A detailed longitudinal examination of plasma lipoprotein sub- fraction concentrations and compositions in pregnancy was per- formed with the objective of discovering the pattern of change in lipoprotein subfractions. Plasma triglyceride, cholesterol, very low density lipoprotein1 (VLDL1), very low density lipoprotein2 (VLDL2), intermediate density lipoprotein (IDL), low density lipoprotein (LDL) and its subfractions (LDL-I, LDL-II, LDL-III), and high density li-



Interrelationship between Apoproteins of Very Low Density Lipoprotein and Other Serum Lipoproteins in Lactating Goats  

Microsoft Academic Search

Lipoproteins of goat serum were labeled in vivo by intravenous injection of tritium labeled DL-lysine monohydro- chloride. The specific radioactivity of the very low density plus intermediate density fractions reached a maximum at 1.2 h, declined sharply until about 9 h, and then more slowly. The specific radioactivities of the low density and high density lipoproteins reached lower maxi- ma

D. Stead; M. Tamir; V. A. Welch



Alcohol alters low density lipoprotein composition and metabolism  

SciTech Connect

Two separate studies were conducted to examine the effect of ethanol (EtOH) dose on atherogenic low density lipoprotein (LDL) subfractions and LDL metabolism in vivo. In the first study, male, atherosclerosis-susceptible squirrel monkeys were divided in three treatments: controls fed liquid diet, and low and high alcohol groups given liquid diet with vodka substituted for carbohydrate at 12% and 24% of calories, respectively. After 6 months, LDL subclasses (LDL{sub 1a}, LDL{sub 1b} and LDL{sub 2}) were isolated by density gradient ultracentrifugation and polyacrylamide gradient gel electrophoresis, and their lipid and protein composition was determined. Low dose EtOH had no effect on LDL subfraction distribution while 24% EtOH resulted in an increase in the larger (LDL{sub 1a} and LDL{sub 1b}), buoyant subspecies without affecting the level of the more atherogenic, smaller, denser LDL{sub 2} particles. In the second study, {sup 125}I-LDL apolipoprotein B (apo B) was injected intravenously into Control and High EtOH monkeys and kinetic analyses were performed. Although the absolute catabolic rate (LDL production) was not altered, High EtOH primates showed a reduction in the fractional catabolic rate and a longer LDL apoB residence time.

Hoinacki, J.; Brown, J.; Dawson, M.; Deschenes, R.; Mulligan, J. (Univ. of Lowell, MA (United States))



Lipoproteins of the extravascular space: alterations in low density lipoproteins of interstitial inflammatory fluid  

Microsoft Academic Search

Although extrahepatic degradation of low density lipoproteins (LDL) by peripheral cells is considered to be a significant component of daily cholesterol homeostasis, the nature of lipoproteins in the extravascular space has not been well described. Using a sponge implantation model in the rab- bit, we examined lipoproteins prepared from interstitial in- flammatory fluid. Inflammatory fluid cholesterol is correlated with plasma

Thomas L. Raymond; Scott A. Reynolds


Double Superhelix Model of High Density Lipoprotein*  

PubMed Central

High density lipoprotein (HDL), the carrier of so-called “good” cholesterol, serves as the major athero-protective lipoprotein and has emerged as a key therapeutic target for cardiovascular disease. We applied small angle neutron scattering (SANS) with contrast variation and selective isotopic deuteration to the study of nascent HDL to obtain the low resolution structure in solution of the overall time-averaged conformation of apolipoprotein AI (apoA-I) versus the lipid (acyl chain) core of the particle. Remarkably, apoA-I is observed to possess an open helical shape that wraps around a central ellipsoidal lipid phase. Using the low resolution SANS shapes of the protein and lipid core as scaffolding, an all-atom computational model for the protein and lipid components of nascent HDL was developed by integrating complementary structural data from hydrogen/deuterium exchange mass spectrometry and previously published constraints from multiple biophysical techniques. Both SANS data and the new computational model, the double superhelix model, suggest an unexpected structural arrangement of protein and lipids of nascent HDL, an anti-parallel double superhelix wrapped around an ellipsoidal lipid phase. The protein and lipid organization in nascent HDL envisages a potential generalized mechanism for lipoprotein biogenesis and remodeling, biological processes critical to sterol and lipid transport, organismal energy metabolism, and innate immunity.

Wu, Zhiping; Gogonea, Valentin; Lee, Xavier; Wagner, Matthew A.; Li, Xin-Min; Huang, Ying; Undurti, Arundhati; May, Roland P.; Haertlein, Michael; Moulin, Martine; Gutsche, Irina; Zaccai, Giuseppe; DiDonato, Joseph A.; Hazen, Stanley L.



Why are low-density lipoproteins atherogenic?  

PubMed Central

Low-density lipoproteins (LDLs) carry most of the cholesterol in human plasma, and high levels of LDL cholesterol clearly cause heart disease. In recent years, many scientists have focused on elucidating the pathophysiologic steps that lie between elevated levels of LDL in the plasma and atherosclerotic plaques in the arterial wall. A large number of scientific studies indicate that oxidation of LDL within the arterial wall may be an important early step in atherogenesis. The uptake of oxidized LDL by macrophages is a likely explanation for the formation of macrophage foam cells in early atherosclerotic lesions. In addition, oxidized LDL has many other potentially proatherogenic properties. Images

Young, S G; Parthasarathy, S



Biosynthesis of high density lipoprotein by chicken liver: nature of nascent intracellular high density lipoprotein  

Microsoft Academic Search

ABSTRACI Young chickens were administered L-(SH)leucine and after 10 or 30 min the livers were removed and fractionated into rough (RER) and smooth (SER) endoplasmic reticulum fractions and into light, intermediate, and heavy Golgi cell fractions. The labeled high density lipoprotein (HDL), contained within these intracellular organelles was isolated either by immunoprecipitation using rabbit antiserum to rooster HDL, or by




The effects of statins on high-density lipoproteins  

Microsoft Academic Search

Statins inhibit cholesterol synthesis and are effective in lowering total cholesterol levels in plasma or serum due to reductions\\u000a in low-density lipoprotein and very low-density lipoproteins, as well as reducing progression of coronary atherosclerosis,\\u000a coronary heart disease, and stroke morbidity and mortality. These agents also modestly raise levels of high-density lipoprotein\\u000a (HDL) cholesterol and its major protein, apolipoprotein (apo) A-I.

Ernst J. Schaefer; Bela F. Asztalos



Abnormalities of High Density Lipoproteins in Abetalipoproteinemia*  

PubMed Central

Detailed studies of the high density lipoproteins from three patients with abetalipoproteinemia have revealed the following principal abnormalities: 1) High density lipoprotein 3 (HDL3) is reduced in both absolute and relative concentration, although HDL2 is present in normal amounts. 2) The phospholipid distribution of both HDL fractions is abnormal, with low concentrations of lecithin and an increased percentage (though normal absolute quantity) of sphingomyelin. 3) In both HDL fractions, lecithin contains less linoleate and more oleate than normal. The cholesteryl esters are also low in linoleic acid, and the sphingomyelin is high in nervonic acid. Dietary intake influences the linoleic acid concentration within 2 weeks, and perhaps sooner, but the elevated sphingomyelin nervonic acid is little affected by up to 6 months of corn oil supplementation. Qualitatively similar changes in fatty acid composition, but not phospholipid distribution, are also found in other malabsorption states. The available evidence suggests that the abnormally low levels of HDL3 and the deranged phospholipid distribution are more specific for abetalipoproteinemia than the fatty acid abnormalities. However, the absence of these abnormalities in obligate heterozygous subjects makes their relationship to the primary defect of abetalipoproteinemia difficult to assess. Images

Jones, John W.; Ways, Peter



Maturation of high-density lipoproteins  

PubMed Central

Human high-density lipoproteins (HDLs) are involved in the transport of cholesterol. The mechanism by which HDL assembles and functions is not well understood owing to a lack of structural information on circulating spherical HDL. Here, we report a series of molecular dynamics simulations that describe the maturation of discoidal HDL into spherical HDL upon incorporation of cholesterol ester as well as the resulting atomic level structure of a mature circulating spherical HDL particle. Sixty cholesterol ester molecules were added in a stepwise fashion to a discoidal HDL particle containing two apolipoproteins wrapped around a 160 dipalmitoylphosphatidylcholine lipid bilayer. The resulting matured particle, captured in a coarse-grained description, was then described in a consistent all-atom representation and analysed in chemical detail. The simulations show that maturation results from the formation of a highly dynamic hydrophobic core comprised of cholesterol ester surrounded by phospholipid and protein; the two apolipoprotein strands remain in a belt-like conformation as seen in the discoidal HDL particle, but with flexible N- and C-terminal helices and a central region stabilized by salt bridges. In the otherwise flexible lipoproteins, a less mobile central region provides an ideal location to bind lecithin cholesterol acyltransferase, the key enzyme that converts cholesterol to cholesterol ester during HDL maturation.

Shih, Amy Y.; Sligar, Stephen G.; Schulten, Klaus



Inhibition of human low density lipoprotein and high density lipoprotein oxidation by oligostilbenes from rhubarb.  


The objective of the present study was to elucidate the beneficial properties of ampelopsine B (1) and epsilon-Viniferin (2), two oligostilbenes isolated from rhubarb, toward cardiovascular disease by protecting human lipoproteins against lipid peroxidation. In low density lipoprotein (LDL) oxidation, both 1 and 2 exert an inhibitory activity against Cu(2+)-, 2,2'-azobis-(2-amidinopropane) hydrochloride (AAPH)-induced, as exhibited by prolongation of lag time from 52 to 118 and 136 min, respectively, and also increasing the lag time 38 to 105 and 128 min in high density lipoprotein (HDL) oxidation for 1 and 2, respectively, at the concentration of 3.0 microM. In generation of thiobarbituric acid reactive substances (TBARS), compounds 1 and 2 inhibited LDL oxidation mediated by either catalytic Cu(2+) or thermo-labile radical initiator (AAPH) in a dose-dependent manner with IC(50) values of 3.6 and 6.0 microM for 1, and 1.7 and 3.2 microM for 2, respectively. In addition, compounds 1-2 also showed strong ability to protect HDL oxidation induced by both Cu(2+) and AAPH with low IC(50) values. The results suggest that oligostilbenes 1-2 may have a role in preventing lipoprotein oxidation. PMID:18758083

Ngoc, Tran Minh; Hung, Tran Manh; Thuong, Phuong Thien; Na, MinKyun; Kim, HongJin; Ha, Do Thi; Min, Byung-Sun; Minh, Pham Thi Hong; Bae, KihWan



Native and oxidized low density lipoproteins modulate mesangial cell apoptosis  

Microsoft Academic Search

Native and oxidized low density lipoproteins modulate mesangial cell apoptosis. Hyperlipidemia has been demonstrated to contribute to hypercellularity of the mesangium in experimental animal models of glomerulosclerosis. We studied whether it also has the potential to convert a hypercellular mesangium into a hypocellular one by inducing mesangial cell (MC) apoptosis. Low density lipoprotein (LDL) enhanced (P < 0.001) mouse mesangial

Pratima Sharma; Krishna Reddy; Nicholas Franki; Vibha Sanwal; Ramkumar Sankaran; Tejinder S Ahuja; Nora Gibbons; Joseph Mattana; Pravin C Singhal



Statins but not fibrates improve the atherogenic to anti-atherogenic lipoprotein particle ratio: a randomized crossover study  

Microsoft Academic Search

BACKGROUND: Prior studies suggested low density lipoprotein particle (LDLP) size is a predictor of atherosclerosis. Knowledge of effects of lipid lowering drugs on lipoprotein subclasses is useful. We treated subjects with hyperlipidemia sequentially with statins and fibrates, the 2 main classes of lipid lowering therapy and studied changes in NMR lipoprotein subclasses. METHODS: 35 subjects (21 males; 60 ± 12

Sammy Y Chan; GB John Mancini; Andrew Ignaszewski; Jiri Frohlich



21 CFR 866.5600 - Low-density lipoprotein immunological test system.  

Code of Federal Regulations, 2010 CFR

...2009-04-01 false Low-density lipoprotein immunological test...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...Systems § 866.5600 Low-density lipoprotein immunological test...Identification. A low-density lipoprotein...



21 CFR 866.5600 - Low-density lipoprotein immunological test system.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 false Low-density lipoprotein immunological test...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...Systems § 866.5600 Low-density lipoprotein immunological test...Identification. A low-density lipoprotein...



Changes in the distribution and composition of plasma high density lipoproteins after ingestion of fat.  


Following ingestion of a fatty meal there is an increase in concentration of phospholipids and proteins in the plasma high density lipoproteins (HDL). To evaluate the resulting changes in HDL subclasses, the plasma HDL of six subjects were analyzed 4 to 8 h after ingestion of 100 ml of corn oil or 80 ml of corn oil with four eggs. Isopycnic density gradient ultracentrifugation of fasting plasma showed two broad components of HDL: a major peak of density (d) 1.11 to 1.17 g/ml (HDL3) and a smaller peak of d 1.07 to 1.11 g/ml (HDL2). Following ingestion of either type of fatty meal, there was an increase in lipoprotein mass in both peaks of HDL and their centers of mass were shifted to lower density (1.140 leads to 1.120 to 1.130 g/ml; 1.095 leads to 1.090 g/ml). Calculation of changes in HDL concentration (lipemic minus fasting) showed that the alterations in density gradient profile were due to a major increase in lipoproteins of d 1.102 to 1.137 g/ml, a smaller increase in a separate lipoprotein peak of 1.080 to 1.102 g/ml, and a small decrease in lipoproteins of d 1.137 to 1.165 g/ml. Redistribution of HDL mass into larger, less dense lipoproteins was also demonstrated by agarose gel chromatography or by minimal spin density gradient ultracentrifugation in a vertical rotor. The increase in mass of 1.080 to 1.102 lipoproteins was largely due to increased concentrations of phospholipid, cholesterol ester, and apoA-I, while the increase in 1.102 to 1.137 lipoproteins was due to increased concentrations of apoA-I, apoA-II, phospholipids, cholesterol, and cholesterol esters. Analytical ultracentrifugation of representative samples within these density intervals showed lipoprotein species with molecular weights and sedimentation coefficients, respectively, of 378,000, 5.8 (d 1.080 to 1.095); 248,000, 3.5 (d 1.110 to 1.120); and 173,000, 1.6 (d 1.135 to 1.150). Polyacrylamide gradient gel electrophoresis showed that the 1.080 to 1.102 lipoproteins contained a single lipoprotein band of diameter approximately 10.7 nm; the 1.102 to 1.137 lipoproteins contained a single band which varied in size fro 10.0 to 9.2 nm: and the 1.137 to 1.165 lipoproteins contained three species of diameters approximately 9.2, 8.8, and 8.2 nm. Within density intervals, the molecular weights, sedimentation coefficients, and diameters of the different lipoproteins were similar in fasting and lipemic plasma. Calculation of average molecular compositions shows that the major incremental HDL of d approximately 1.12 g/ml could be derived by addition of lipids to the largest species of fasting HDL3. Within density intervals, the particle contents of apoA-I and apoA-II were unchanged during lipemia, suggesting that apoprotein transfer causes interconversion of existing HDL species or formation of new particles with the same content of apoA-I and apoA-II as existing species. PMID:6796585

Tall, A R; Blum, C B; Forester, G P; Nelson, C A



High-density lipoprotein cholesterol: How High.  


The high-density lipoprotein cholesterol (HDL-C) is considered anti-atherogenic good cholesterol. It is involved in reverse transport of lipids. Epidemiological studies have found inverse relationship of HDL-C and coronary heart disease (CHD) risk. When grouped according to HDL-C, subjects having HDL-C more than 60 mg/dL had lesser risk of CHD than those having HDL-C of 40-60 mg/dL, who in turn had lesser risk than those who had HDL-C less than 40 mg/dL. No upper limit for beneficial effect of HDL-C on CHD risk has been identified. The goals of treating patients with low HDL-C have not been firmly established. Though many drugs are known to improve HDL-C concentration, statins are proven to improve CHD risk and mortality. Cholesteryl ester transfer protein (CETP) is involved in metabolism of HDL-C and its inhibitors are actively being screened for clinical utility. However, final answer is still awaited on CETP-inhibitors. PMID:23565387

Rajagopal, G; Suresh, V; Sachan, Alok



Low-density lipoproteins oxidation and endometriosis.  


The etiopathogenesis of endometriosis still remains unknown. Recent data provide new valuable information concerning the role of oxidative stress in the pathophysiology of the disease. It has been proved that levels of different lipid peroxidation end products are increased in both peritoneal fluid (PF) and serum of endometriotic patients. We assessed the concentration of oxidized low-density lipoproteins (oxLDL) in PF of 110 women with different stages of endometriosis and 119 women with serous (n = 78) or dermoid (n = 41) ovarian cysts, as the reference groups. PF oxLDL levels were evaluated by ELISA. We found that concentrations of oxLDL in PF of endometriotic women were significantly higher compared to women with serous but not dermoid ovarian cysts. Interestingly, by analyzing concentrations of oxLDL in women with different stages of the disease, it was noted that they are significantly higher only in the subgroup of patients with stage IV endometriosis as compared to women with ovarian serous cysts. In case of minimal, mild, and moderate disease, PF oxLDL levels were similar to those noted in reference groups. Our results indicate that disrupted oxidative status in the peritoneal cavity of women with endometriosis may play a role in the pathogenesis of advanced stages of the disease. PMID:23861560

Polak, Grzegorz; Barczy?ski, Bart?omiej; Kwa?niewski, Wojciech; Bednarek, Wies?awa; Wertel, Iwona; Derewianka-Polak, Magdalena; Kotarski, Jan



Nanobiotechnology applications of reconstituted high density lipoprotein.  


High-density lipoprotein (HDL) plays a fundamental role in the Reverse Cholesterol Transport pathway. Prior to maturation, nascent HDL exist as disk-shaped phospholipid bilayers whose perimeter is stabilized by amphipathic apolipoproteins. Methods have been developed to generate reconstituted (rHDL) in vitro and these particles have been used in a variety of novel ways. To differentiate between physiological HDL particles and non-natural rHDL that have been engineered to possess additional components/functions, the term nanodisk (ND) is used. In this review, various applications of ND technology are described, such as their use as miniature membranes for solubilization and characterization of integral membrane proteins in a native like conformation. In other work, ND harboring hydrophobic biomolecules/drugs have been generated and used as transport/delivery vehicles. In vitro and in vivo studies show that drug loaded ND are stable and possess potent biological activity. A third application of ND is their use as a platform for incorporation of amphiphilic chelators of contrast agents, such as gadolinium, used in magnetic resonance imaging. Thus, it is demonstrated that the basic building block of plasma HDL can be repurposed for alternate functions. PMID:21122135

Ryan, Robert O



Nanobiotechnology applications of reconstituted high density lipoprotein  

PubMed Central

High-density lipoprotein (HDL) plays a fundamental role in the Reverse Cholesterol Transport pathway. Prior to maturation, nascent HDL exist as disk-shaped phospholipid bilayers whose perimeter is stabilized by amphipathic apolipoproteins. Methods have been developed to generate reconstituted (rHDL) in vitro and these particles have been used in a variety of novel ways. To differentiate between physiological HDL particles and non-natural rHDL that have been engineered to possess additional components/functions, the term nanodisk (ND) is used. In this review, various applications of ND technology are described, such as their use as miniature membranes for solubilization and characterization of integral membrane proteins in a native like conformation. In other work, ND harboring hydrophobic biomolecules/drugs have been generated and used as transport/delivery vehicles. In vitro and in vivo studies show that drug loaded ND are stable and possess potent biological activity. A third application of ND is their use as a platform for incorporation of amphiphilic chelators of contrast agents, such as gadolinium, used in magnetic resonance imaging. Thus, it is demonstrated that the basic building block of plasma HDL can be repurposed for alternate functions.



Association of Cholesteryl Ester Transfer Protein-TaqIB Polymorphism With Variations in Lipoprotein Subclasses and Coronary Heart Disease Risk The Framingham Study  

Microsoft Academic Search

Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides and cholesteryl esters between lipoprotein particles, a key step in reverse cholesterol transport in humans. Variations at the CETP locus have been shown to be determinants of the levels and activity of CETP and high density lipoprotein (HDL) plasma concentration. The associations of the common CETP polymorphism, TaqIB in intron

Jose M. Ordovas; L. Adrienne Cupples; Dolores Corella; James D. Otvos; Doreen Osgood; Antonia Martinez; Carlos Lahoz; Oscar Coltell; Peter W. F. Wilson; Ernst J. Schaefer


Reducing cardiovascular risk by targeting high-density lipoprotein cholesterol  

Microsoft Academic Search

Although lowering low-density lipoprotein (LDL) cholesterol with statins can substantially reduce cardiovascular morbidity\\u000a and mortality, many treated patients retain a residual risk for cardiovascular events. Low levels of high-density lipoprotein\\u000a (HDL) cholesterol may underpin this residual risk and may represent an additional target for intervention. Several new therapies\\u000a for substantially increasing HDL cholesterol levels are under investigation, including cholesteryl ester

Peter P. Toth



Structures of Discoidal High Density Lipoproteins  

PubMed Central

Conversion of discoidal phospholipid (PL)-rich high density lipoprotein (HDL) to spheroidal cholesteryl ester-rich HDL is a central step in reverse cholesterol transport. A detailed understanding of this process and the atheroprotective role of apolipoprotein A-I (apoA-I) requires knowledge of the structure and dynamics of these various particles. This study, combining computation with experimentation, illuminates structural features of apoA-I allowing it to incorporate varying amounts of PL. Molecular dynamics simulated annealing of PL-rich HDL models containing unesterified cholesterol results in double belt structures with the same general saddle-shaped conformation of both our previous molecular dynamics simulations at 310 K and the x-ray structure of lipid-free apoA-I. Conversion from a discoidal to a saddle-shaped particle involves loss of helicity and formation of loops in opposing antiparallel parts of the double belt. During surface expansion caused by the temperature-jump step, the curved palmitoyloleoylphosphatidylcholine bilayer surfaces approach planarity. Relaxation back into saddle-shaped structures after cool down and equilibration further supports the saddle-shaped particle model. Our kinetic analyses of reconstituted particles demonstrate that PL-rich particles exist in discrete sizes corresponding to local energetic minima. Agreement of experimental and computational determinations of particle size/shape and apoA-I helicity provide additional support for the saddle-shaped particle model. Truncation experiments combined with simulations suggest that the N-terminal proline-rich domain of apoA-I influences the stability of PL-rich HDL particles. We propose that apoA-I incorporates increasing PL in the form of minimal surface bilayers through the incremental unwinding of an initially twisted saddle-shaped apoA-I double belt structure.

Gu, Feifei; Jones, Martin K.; Chen, Jianguo; Patterson, James C.; Catte, Andrea; Jerome, W. Gray; Li, Ling; Segrest, Jere P.



High-density lipoprotein and low-density lipoprotein-mediated signal transduction in cultured human skin fibroblasts  

Microsoft Academic Search

The signalling mechanisms whereby high-density lipoproteins (HDL) and low-density lipoproteins (LDL) affect a number of cellular functions in fibroblasts are unclear. This study has analyzed the influence of HDL3 and LDL on the phosphatidylinositol specific phospholipase C pathway in human skin fibroblasts. Exposure of myo-[2-3H]-inositol prelabelled fibroblasts to HDL3 or LDL elicited major increases in IP1 and minor increases in

Christoph Möllers; Wolfgang Drobnik; Thérèse Resink; Gerd Schmitz



Marked removal of bezafibrate-induced high-density lipoprotein-cholesterol by low-density lipoprotein apheresis  

Microsoft Academic Search

Background: A case of marked reduction of the bezafibrate-induced increase of high-density lipoprotein (HDL)-cholesterol by low-density lipoprotein apheresis (LDL-apheresis) has not been previously reported. Methods: A 68-year-old Japanese man with arteriosclerosis obliterans (ASO), diabetes mellitus, and hyperlipidemia underwent LDL-apheresis, followed by the concomitant bezafibrate administration. Plasma lipids of pre- and post-LDL-apheresis were measured and apolipoprotein E (apoE) localization of the

Mikihiko Kawano; Yutaka Kuroda; Motohiko Terao; Toshio Yaginuma; Masanobu Kawakami; Yasunori Kanazawa



Reverse cholesterol transport: High-density lipoprotein’s magnificent mile  

Microsoft Academic Search

High-density lipoproteins (HDLs) are among the most structurally complex and functionally versatile forms of circulating serum\\u000a lipoproteins. HDLs undergo extensive enzymatic remodeling during their maturation in serum, interact with highly specific\\u000a receptors in peripheral tissues and the liver, and are able to exert a variety of antiatherogenic effects (eg, inhibit inflammation, oxidation, and apoptosis). Considerable epidemiologic, clinical, and basic scientific

Peter P. Toth



Interfacial Tension and Surface Pressure of High Density Lipoprotein, Low Density Lipoprotein, and Related Lipid Droplets  

PubMed Central

Lipid droplets play a central role in energy storage and metabolism on a cellular scale. Their core is comprised of hydrophobic lipids covered by a surface region consisting of amphiphilic lipids and proteins. For example, high and low density lipoproteins (HDL and LDL, respectively) are essentially lipid droplets surrounded by specific proteins, their main function being to transport cholesterol. Interfacial tension and surface pressure of these particles are of great interest because they are related to the shape and the stability of the droplets and to protein adsorption at the interface. Here we use coarse-grained molecular-dynamics simulations to consider a number of related issues by calculating the interfacial tension in protein-free lipid droplets, and in HDL and LDL particles mimicking physiological conditions. First, our results suggest that the curvature dependence of interfacial tension becomes significant for particles with a radius of ?5 nm, when the area per molecule in the surface region is <1.4 nm2. Further, interfacial tensions in the used HDL and LDL models are essentially unaffected by single apo-proteins at the surface. Finally, interfacial tensions of lipoproteins are higher than in thermodynamically stable droplets, suggesting that HDL and LDL are kinetically trapped into a metastable state.

Ollila, O. H. Samuli; Lamberg, Antti; Lehtivaara, Maria; Koivuniemi, Artturi; Vattulainen, Ilpo



Total cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol and coronary heart disease in Scotland.  

PubMed Central

OBJECTIVE--To investigate long term changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations and in measures of other risk factors for coronary heart disease and to assess their importance for the development of coronary heart disease in Scottish men. DESIGN--Longitudinal study entailing follow up in 1988-9 of men investigated during a study in 1976. SETTING--Edinburgh, Scotland. SUBJECTS--107 men from Edinburgh who had taken part in a comparative study of risk factors for heart disease with Swedish men in 1976 when aged 40. INTERVENTION--The men were invited to attend a follow up clinic in 1988-9 for measurement of cholesterol concentrations and other risk factor measurements. Eighty three attended and 24 refused to or could not attend. MAIN OUTCOME MEASURES--Changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations, body weight, weight to height index, prevalence of smoking, and alcohol intake; number of coronary artery disease events. RESULTS--Mean serum total cholesterol concentration increased over the 12 years mainly due to an increase in the low density lipoprotein cholesterol fraction (from 3.53 (SD 0.09) to 4.56 (0.11) mmol/l) despite a reduction in high density lipoprotein cholesterol concentration. Body weight and weight to height index increased. Fewer men smoked more than 15 cigarettes/day in 1988-9 than in 1976. Blood pressure remained stable and fasting triglyceride concentrations did not change. The frequency of corneal arcus doubled. Alcohol consumption decreased significantly. Eleven men developed clinical coronary heart disease. High low density lipoprotein and low high density lipoprotein cholesterol concentrations in 1976, but not total cholesterol concentration, significantly predicted coronary heart disease (p = 0.05). Almost all of the men who developed coronary heart disease were smokers (91% v 53%, p less than 0.05). CONCLUSION--Over 12 years the lipid profile deteriorated significantly in this healthy cohort of young men. Smoking, a low high density lipoprotein concentration and a raised low density lipoprotein concentration were all associated with coronary heart disease in middle aged Scottish men, whereas there was no association for total cholesterol concentration. The findings have implications for screening programmes.

Hargreaves, A D; Logan, R L; Thomson, M; Elton, R A; Oliver, M F; Riemersma, R A



Role of Low-Density and High-Density Lipoproteins in Atherogenesis  

Microsoft Academic Search

Among the cholesterol-carrying lipoproteins, low-density lipoproteins (LDL) have been associated with coronary heart disease as a risk factor while high-density lipoproteins (HDL) appear to protect against coronary heart disease. According to studies with cells in tissue culture, control mechanisms of receptor-mediated LDL uptake are important in maintaining the cholesterol balance within the arterial cells. HDL may be a vehicle for

G. Assmann; H. Schriewer



Serum high density lipoprotein in diabetic patients  

Microsoft Academic Search

Summary  The purpose of the present investigation was the study of HDL lipoprotein changes in patients with diabetes mellitus. The comparison was made between 40 normal and 109 diabetic subjects and the following data was obtained: relative HDL concentration (polyacrylamide gel electrophoresis), HDL-cholesterol and apolipoprotein A concentrations. We found significant decreases in HDL (18–28%) and HDL-cholesterol (31–40 mg\\/ 100 ml) in

M. F. L. Lopes-Virella; P. G. Stone; J. A. Colwell



Uraemic dyslipidaemia revisited: role of high-density lipoprotein.  


Chronic kidney disease (CKD) is accompanied by strong cardiovascular risk. In a rather rigid picture of lipoprotein biology, low-density lipoprotein (LDL) is referred to as 'bad cholesterol', while high-density lipoprotein (HDL) is referred to as 'good cholesterol'. However, recent experimental evidence suggests that HDL may be rendered dysfunctional regarding its effects on the vasculature under various clinical conditions such as CKD. Indeed, HDL from the blood of CKD patients has been shown to transform into a particle which promotes endothelial dysfunction, endothelial proinflammatory activation and, thereby, sets the conditions for the development of atherosclerotic disease. Notably, pharmaceutical interventions to raise serum HDL-cholesterol levels have not been proven beneficial so far. Collectively, these findings indicate that HDL cholesterol levels do not represent a valuable marker for indicating the vascular properties of HDL. PMID:23645475

Speer, Thimoteus; Zewinger, Stephen; Fliser, Danilo



Lipolytic degradation of human very low density lipoproteins by human milk lipoprotein lipase: the identification of lipoprotein B as the main lipoprotein degradation product.  


Although the direct conversion of very low density lipoproteins (VLDL) into low density (LDL) and high density (HDL) lipoproteins only requires lipoprotein lipase (LPL) as a catalyst and albumin as the fatty acid acceptor, the in vitro-formed LDL and HDL differ chemically from their native counterparts. To investigate the reason(s) for these differences, VLDL were treated with human milk LPL in the presence of albumin, and the LPL-generated LDL1-, LDL2-, and HDL-like particles were characterized by lipid and apolipoprotein composition. Results showed that the removal of apolipoproteins B, C, and E from VLDL was proportional to the degree of triglyceride hydrolysis with LDL2 particles as the major and LDL1 and HDL + VHDL particles as the minor products of a complete in vitro lipolysis of VLDL. In comparison with native counterparts, the in vitro-formed LDL2 and HDL + VHDL were characterized by lower levels of triglyceride and cholesterol ester and higher levels of free cholesterol and lipid phosphorus. The characterization of lipoprotein particles present in the in vitro-produced LDL2 showed that, as in plasma LDL2, lipoprotein B (LP-B) was the major apolipoprotein B-containing lipoprotein accounting for over 90% of the total apolipoprotein B. Other, minor species of apolipoprotein B-containing lipoproteins included LP-B:C-I:E and LP-B:C-I:C-II:C-III. The lipid composition of in vitro-formed LP-B closely resembled that of plasma LP-B. The major parts of apolipoproteins C and E present in VLDL were released to HDL + VHDL as simple, cholesterol/phospholipid-rich lipoproteins including LP-C-I, LP-C-II, LP-C-III, and LP-E. However, some of these same simple lipoprotein particles were present after ultracentrifugation in the LDL2 density segment because of their hydrated density and/or because they formed, in the absence of naturally occurring acceptors (LP-A-I:A-II), weak associations with LP-B. Thus, the presence of varying amounts of these cholesterol/phospholipid-rich lipoproteins in the in vitro-formed LDL2 appears to be the main reason for their compositional difference from native LDL2. These results demonstrate that the formation of LP-B as the major apolipoprotein B-containing product of VLDL lipolysis only requires LPL as a catalyst and albumin as the fatty acid acceptor. However, under physiological circumstances, other modulating agents are necessary to prevent the accumulation and interaction of phospholipid/cholesterol-rich apolipoprotein C- and E-containing particles. PMID:3080947

Alaupovic, P; Wang, C S; McConathy, W J; Weiser, D; Downs, D



Biosynthesis of high density lipoprotein by chicken liver: nature of nascent intracellular high density lipoprotein  

PubMed Central

Young chickens were administered L-[(3)H]leucine and after 10 or 30 min the livers were removed and fractioned into rough (RER) and smooth (SER) endoplasmic reticulum fractions and into light, intermediate, and heavy golgo cell fractions. The labeled high density lipoprotein (HDL), contained within these intracellular organelles was isolated either by immunoprecipitation using rabbit antiserum to rooster HDL, or by ultracentrifugal glotation between densities 1.063 and 1.21 g/ml. The radioactive apoproteins of nascent HDL were analyzed by SDS PAGE and detected by fluorography. Analyses of radioactive apoproteins obtained by immunoprecipitation from the contents of the RER, the SER, and the three golgi complex fractions revealed only one apoprotein, A1. The C peptide present in serum HDL was not detected intracellularly. The radioactive apoprotein A1 which is present within the cisternae of the RER and the SER fractions failed to float, whereas apoprotein A1, present within the golgi apparatus, readily floated between densities 1.063 and 1.21 g/ml. The HDL particles, isolated by flotation from the golgi apparatus content, were further characterized by lipid and protein analyses and by electron microscopy. Golgi HDL particles have the same density as serum HDL. On a percentage basis, golgi HDL contains less protein and more phospholipids than does serum HDL. Morphologically, golgi HDL is different in appearance from serum HDL. It is more heterogeneous in size, with most of the particles ranging 8.3-25 nm in diameter. The spherical particles contain small membrane tails. Occasionally, a few disk-shaped bilayer structures are also found within the golgi apparatus. These studies show that the newly synthesized apoprotein A1, present within the RER and the SER cell fractions, is not fully complexed with lipid and that apoprotein A1 does not acquire sufficient lipid to float at the proper HDL density until it enters the golgi apparatus. The difference in chemical composition and the heterogeneous size of golgi HDL may be attributed to the different stages of HDL maturation.

Banerjee, D; Redman, CM



Characterization of chick serum lipoproteins isolated by density gradient ultracentrifugation.  


Serum lipoproteins from 12h fasted male chicks (15-day-old) were separated into 20 fractions by isopycnic density gradient ultracentrifugation. A new procedure was described by collecting the different fractions from the bottom of tube instead of by aspiration from the meniscus of each tube. Analyses of chemical composition of serum lipoproteins have permitted to reevaluate the density limits of major classes: VHDL, d greater than 1.132 g/ml; HDL, d 1.132-1.084 g/ml; LDL, d 1.084-1.038; IDL, d 1.038-1.022; and VLDL d less than 1.022. HDL fractions clearly predominated (approx. 77% of total lipoproteins) while IDL and VLDL were present at low percentage. LDL was the fraction richest in cholesterol; triacylglycerol content clearly increased from HDL to VLDL, while protein content decreased. All the chemical components of chick serum lipoproteins were accumulated in HDL, although triacylglycerol was relatively distributed in all the lipoprotein classes. PMID:1380327

Rodriguez-Vico, F; Lopez, J M; Castillo, M; Zafra, M F; Garcia-Peregrin, E


Nonoxidative modification of low density lipoprotein by ruptured myocytes  

Microsoft Academic Search

In this study, the interaction of ruptured cardiac myocytes with low density lipoprotein (LDL) has been investigated and the consequent extent of uptake by macrophages. The results show that lysate released from ruptured myocytes is capable of inducing LDL oxidation and that the resulting modified form is recognised and degraded by macrophages. Peroxyl radical scavengers inhibit the LDL oxidation but

Louise C Bourne; David J Lamb; Cliff S Collis; Michael O'Brien; David S Leake; Catherine Rice-Evans



Human Granulosa Cells Use High Density Lipoprotein Cholesterol for Steroidogenesis  

Microsoft Academic Search

This study examines the ability of human high density lipoproteins (HDL3) to deliver cholesteryl esters to human granulosa cells and describes the selective cholesterol pathway by which this occurs. Luteinized cells obtained from subjects undergoing in vitro fertiliza- tion-embryo transfer procedures were incubated with native HDL3 (or radiolabeled or fluorescently labeled HDL cholesteryl esters) to de- termine whether cells from




Recycling of vitamin E in human low density lipoproteins  

Microsoft Academic Search

Oxidative modification of low density lipoproteins (LDL) and their unrestricted scavenger receptordependent uptake is believed to account for cholesterol deposition in macrophagederived foam cells. It has been suggested that vitamin E that is transported by LDL plays a critical role in protecting against LDL oxidation. We hypothesize that the maintenance of sufficiently high vitamin E concentrations in LDL can be

Elena A. Serbinova; Trudy Forte; Giorgio Scita; Lester Packer


Effect of Obesity on High-density Lipoprotein Metabolism  

Microsoft Academic Search

Reduced levels of high-density lipoproteins (HDL) in non-obese and obese states are associated with increased risk for the development of coronary artery disease. Therefore, it is imperative to determine the mechanisms responsible for reduced HDL in obese states and, conversely, to examine therapies aimed at increasing HDL levels in these individuals. This paper examines the multiple causes for reduced HDL

Shirya Rashid; Jacques Genest



High density lipoprotein-induced cardiac prostacyclin synthesis in vitro: relationship to cardiac arachidonate mobilization  

Microsoft Academic Search

The objectives of this study were to characterize the effects of plasma lipoproteins on prostacyclin (PGIp) production by the Langendorff-perfused rabbit heart, and to determine the mechanism of lipoprotein-induced cardiac PG12 production. PGIp production by perfused rabbit hearts was stimulated by in- jections of rabbit very low density lipoproteins (VLDL), low den- sity lipoproteins (LDL), and high density lipoproteins (HDL).

William A. Van Sickle; Henry G. Wilcox


VAP II analysis of lipoprotein subclasses in mixed hyperlipidemic patients on treatment with ezetimibe\\/simvastatin and fenofibrate  

Microsoft Academic Search

This analysis evaluates the effects on lipoprotein subfractions and LDL particle size of ezetimibe\\/simvastatin with or without coadministration of fenofibrate in patients with mixed hyperlipidemia. This multicenter, double-blind, placebo-controlled, parallel-group study included 611 pa- tients aged 18-79 years randomized in 1:3:3:3 ratios to one of four 12 week treatment groups: placebo; ezetimibe\\/simva- statin 10\\/20 mg\\/day; fenofibrate 160 mg\\/day; or ezetimibe\\/

Michel Farnier; Inna Perevozskaya; William V. Taggart; Debra Kush; Yale B. Mitchel



Acute Changes in Serum Lipids and Lipoprotein Subclasses in Triathletes as Assessed by Proton Nuclear Magnetic Resonance Spectroscopy  

Microsoft Academic Search

Exercise is associated with changes in lipids that may protect against coronary heart disease (CHD). In this study of 28 triathletes, we analyzed acute changes in serum lipid and lipoprotein concentrations after completion of the 1995 World Championship Hawaii Ironman Triathlon. With standard laboratory assays, we demonstrate significant decreases in total cholesterol, VLDL cholesterol, ApoB100, and Lp(a). Total HDL cholesterol

Harry H. Yu; Geoffrey S. Ginsburg; Mary L. O'Toole; James D. Otvos; Pamela S. Douglas; Nader Rifai


Low density lipoprotein causes general cellular activation with increased phosphatidylinositol turnover and lipoprotein catabolism.  

PubMed Central

Low density lipoprotein (LDL), at concentrations high enough for receptor binding but not high enough to saturate the receptor, induces activation of phosphatidylinositol (PtdIns) turnover in a variety of cell types with various biological functions. Using both biochemical and electron microscopic studies, we have shown that blood platelets take up and degrade LDL in a manner reminiscent of phagocytic cell types. The activation of both PtdIns turnover and LDL metabolism is inhibited by high density lipoprotein. Thus, LDL at hormonal concentrations causes general cellular activation. Since all cell types studied responded to LDL with increased PtdIns turnover and uptake of LDL cholesterol, the PtdIns cycle may also be involved in the cellular regulation of LDL cholesterol metabolism. Images

Block, L H; Knorr, M; Vogt, E; Locher, R; Vetter, W; Groscurth, P; Qiao, B Y; Pometta, D; James, R; Regenass, M



The genetic architecture of lipoprotein subclasses in Gullah-speaking African American families enriched for type 2 diabetes: The Sea Islands Genetic African American Registry (Project SuGAR)  

PubMed Central

We sought to partition the genetic and environmental influences on lipoprotein subclasses and identify genomic regions that may harbor genetic variants that influence serum lipoprotein levels in a sample of Gullah-speaking African-Americans. We genotyped 5,974 SNPs in 979 subjects from 418 pedigrees and used the variance component approach to compute heritability estimates, genetic and environmental correlations, and linkage analyses for selected lipoprotein subclasses. The highest heritability estimate was observed for large VLDL particle concentration (0.56 ± 0.14). Mean LDL particle size and small LDL particle concentration (?0.94) had the strongest genetic correlation estimate. The highest logarithm of odds (LOD) score detected (3.0) was on chromosome 6p24 for small LDL particle concentration. The strongest signal, obtained with the reduced sample of diabetic individuals only, was observed on chromosome 20p13 for small LDL particle concentration. The highest bivariate linkage signal (LOD 2.4) was observed on chromosome 6p24 for mean LDL particle size and small LDL particle concentration.jlr Our results suggest a significant genetic contribution to multiple lipoprotein subclasses studied in this sample and that novel loci on chromosomes 6, 10, 16, and 20 may harbor genes contributing to small, atherogenic LDL particle concentration and large, triglyceride-rich VLDL particle concentration.

Divers, Jasmin; Sale, Michele M.; Lu, Lingyi; Chen, Wei-Min; Lok, Kerry H.; Spruill, Ida J.; Fernandes, Jyotika K.; Langefeld, Carl D.; Garvey, W. Timothy



Triglyceride, small, dense low-density lipoprotein, and the atherogenic lipoprotein phenotype  

Microsoft Academic Search

This review provides an overview of the recent data evaluating triglyceride and low-density lipoprotein (LDL) size, two highly\\u000a interrelated, genetically influenced, risk factors for cardiovascular disease (CVD). An examination of new epidemiologic studies\\u000a continues to demonstrate that plasma triglyceride levels predict CVD. The first prospective study of the familial forms of\\u000a hypertriglyceridemia has shown that relatives in familial-combined hyperlipidemia families

Melissa A. Austin




PubMed Central

Very low-density lipoproteins (VLDL) are metabolic precursors of low-density lipoproteins (LDL) and a risk factor for atherosclerosis. Human VLDL are heterogeneous complexes containing triacylglyceride-rich apolar lipid core and polar surface comprised of phospholipids, a non-exchangeable apolipoprotein B, and exchangeable apolipoproteins E and Cs. We report the first stability study of VLDL. Circular dichroism and turbidity data reveal an irreversible heat-induced VLDL transition that involves formation of larger particles and repacking of apolar lipids but no global protein unfolding. Heating rate effect on the melting temperature indicates a kinetically controlled reaction with high activation energy, Ea. Arrhenius analysis of the turbidity data reveals two kinetic phases with Ea=53±7 kcal/mol that correspond to distinct morphological transitions observed by electron microscopy. One transition involves VLDL fusion, partial rupture and dissociation of small spherical particles (d=7–15 nm), and another involves complete lipoprotein disintegration and lipid coalescence into droplets accompanied by dissociation of apolipoprotein B. The small particles, which are unique to VLDL denaturation, are comparable in size and density to high-density lipoproteins (HDL); they have apolar lipid core and polar surface comprised of exchangeable apolipoproteins (E and possibly Cs) and phospholipids. We conclude that, similar to HDL and LDL, VLDL are stabilized by kinetic barriers that prevent particle fusion and rupture and decelerate spontaneous inter-conversion among lipoprotein classes and subclasses. In addition to fusion, VLDL disruption involves transient formation of HDL-like particles that may mimic protein exchange among VLDL and HDL pools in plasma.

Guha, Madhumita; England, Cheryl; Herscovitz, Haya; Gursky, Olga



Purification of very high density lipoproteins by differential density gradient ultracentrifugation.  


Differential density gradient ultracentrifugation procedures, utilizing a vertical rotor, were developed for the preparative purification of very high density lipoproteins (VHDL, density greater than 1.21 g/ml). The VHDLs of several insect species were purified as follows. An initial density gradient ultracentrifugation step removed lipoproteins of lower density from the VHDL-fraction, which partially separated from the nonlipoproteins present in the infranatant. A complete separation was achieved by a second centrifugation step employing a modified gradient system. The use of a vertical rotor and specially designed discontinuous gradients allows a relatively fast, efficient, and economical isolation of the class of very high density lipoproteins. Similar gradient systems should be useful for the detection and purification of VHDLs from other sources. PMID:3578796

Haunerland, N H; Ryan, R O; Law, J H; Bowers, W S



High density lipoproteins-based therapies for cardiovascular disease  

PubMed Central

Atherosclerosis is the leading cause of death in developed countries. High density lipoproteins (HDL) cholesterol level correlates inversely with the risk of cardiovascular diseases. Thus, HDL has obtained lots of interest for drug development. In this review, we summarized the mechanisms for the antiatherogenic function of HDL, current HDL-based drugs in clinical use and the future direction for HDL-based therapy development.

Gao, Xuan; Yuan, Shujun



Nutritional and Lifestyle Factors and High-Density Lipoprotein Metabolism  

Microsoft Academic Search

\\u000a The purpose of this chapter is to review our knowledge of the effects of nutritional and lifestyle factors on high-density\\u000a lipoprotein (HDL) metabolism. Alcohol intake increases HDL apolipoprotein (apo) A-I by increasing its production, and is the\\u000a topic of a chapter by Dr. Brinton. Dietary cholesterol increases HDL apolipoprotein (apo) A-I by increasing its secretion,\\u000a probably due to a greater

Ernst J. Schaefer


Characterization of Monoclonal Antibodies Against Human Low Density Lipoprotein  

Microsoft Academic Search

Seven monoclonal antibodies against human low density lipoprotein (LDL) have been characterized as to their specificity and ability to interfere with the LDL pathway in cultured human flbroblasts. The Immunoreactivity with LDL of two of the antibodies (2D8 and 4G3) was particularly sensitive to modification of lysine and arginlne resi- dues In LDL. Cotitration experiments indicated that the antibodies 3A8

Ross W. Milne; Richard Theolis; Roy B. Verdery; Yves L Marcel



Structure of Apolipoprotein B100 of Human Low Density Lipoproteins  

Microsoft Academic Search

We have analyzed low density lipoproteins (LDL) apolipoprotein (apo) B structure by direct sequence analysis of LDL apo B-100 tryptlc peptides. Native LDL were digested with trypsin, and the products were fractionated on a Sephadex G-50 column. The partially digested apo B-100 still associated with liplds was recovered In the void volume (designated trypsln-nonreleasable, TN, peptides). The released peptides (designated

Chao-yuh Yang; Zi-Wei Gu; Shi-ai Weng; Tae W. Kim; San-Hwan Chen; Henry J. Pownall; Paul M. Sharp; Shyan-Woei Liu; Wen-Hsiung Li; Antonio M. Gotto; Lawrence Chan



Low-Density Lipoprotein Cholesterol and Coronary Artery Disease  

Microsoft Academic Search

Except for age, dyslipidemia is the most important predictive factor for coronary artery disease (CAD) (1). The strong, independent, continuous, and graded relationship between total cholesterol (TC) levels, or low-density lipoprotein\\u000a (LDL)-cholesterol (C) level and the risk of CAD events has been clearly demonstrated world wide in men and women and in all\\u000a age groups (2–6). High cholesterol levels are

JoAnne Micale Foody


Differentiation of oxidized low density lipoproteins by nanosensors  

Microsoft Academic Search

Oxidized low density lipoprotein (oxLDL) is considered a biomarker for acute heart attack in patients with coronary artery disease (CAD). LDL cholesterol in the circulatory system can undergo oxidative modification to oxidized LDL (oxLDL), leading to the development of CAD. We tested whether indium oxide (In2O3) nanowires network- and carbon nanotube network-based field effect transistors (FETs) were able to differentiate

Mahsa Rouhanizadeh; Tao Tang; Chao Li; Juliana Hwang; Chongwu Zhou; Tzung K. Hsiai



Imaging of Hepatic Low Density Lipoprotein Receptors by Radionuclide Scintiscanning in vivo  

Microsoft Academic Search

The low density lipoprotein (LDL) receptor mediates the cellular uptake of plasma lipoproteins that are derived from very low density lipoproteins (VLDL). Most of the functional LDL receptors in the body are located in the liver. Here, we describe a radionuclide scintiscanning technique that permits the measurement of LDL receptors in the livers of intact rabbits. 123I-labeled VLDL were administered

Manfred Huettinger; James R. Corbett; Wolfgang J. Schneider; James T. Willerson; Michael S. Brown; Joseph L. Goldstein



Low levels of high density lipoproteins in Turks, a population with elevated hepatic lipase: high density lipoprotein characterization and gender-specific effects of apolipoprotein E genotype  

Microsoft Academic Search

? g Abstract Turks have strikingly low levels of high density lipoprotein cholesterol (HDL-C) (10-15 mg\\/dL lower than those of Americans or Western Europeans) associated with elevated hepatic lipase mass and activity. Here we report that Turks have low levels of high density lipoprotein sub- class 2 (HDL 2 ), apoA-I-containing lipoproteins (LpA-I), and pre- b -1 HDL and increased

Robert W. Mahley; Judy Pépin; Erhan Palao; Mary J. Malloy; John P. Kane; Thomas P. Bersot


Metabolism of high density lipoprotein subfractions and constituents in Tangier disease following the infusion of high density lipoproteins1  

Microsoft Academic Search

The metabolism of apolipoproteins A-I and A-11, as well as other high density lipoprotein (HDL) constitu- ents, was studied in patients with homozygous familial HDL deficiency (Tangier disease) prior to and after plasma ex- change or HDL infusion. Mean plasma apoA-I, apoA-11, and HDL cholesterol values in homozygotes (n = 2) were 2.0 mg\\/dl, 2.7 mg\\/dl, and 1.5 mg\\/dl, respectively,

Ernst J. Schaefer; David W. Anderson; Loren A. Zech; Frank T. Lindgren; Thomas B. Bronzert; Elizabeth A. Rubalcaba; H. Bryan Brewer


Esterification of Low Density Lipoprotein Cholesterol in Human Fibroblasts and Its Absence in Homozygous Familial Hypercholesterolemia  

PubMed Central

A new mechanism is described for the cellular esterification of cholesterol derived from extra-cellular lipoproteins. Incubation of monolayers of cultured fibroblasts from normal human subjects with low density lipoproteins led to a 30- to 40-fold increase in the rate of incorporation of either [14C]acetate or [14C]oleate into the fatty acid fraction of cholesteryl [14C]esters. This stimulation of cholesteryl ester formation by low density lipoproteins occurred despite the fact that endogenous synthesis of free cholesterol was completely suppressed by the lipoprotein. Thus, exogenous cholesterol contained in low density lipoproteins, rather than endogenously synthesized sterol, appeared to provide the cholesterol substrate for this cellular esterfication process. High density lipoproteins and the lipoprotein-deficient fraction of serum neither stimulated cholesteryl ester formation nor inhibited cholesterol synthesis. Both the low density lipoprotein-dependent increase in cholesterol esterification and decrease in free cholesterol synthesis required the interaction of the lipoprotein with its recently described cell surface receptor. Cells from homozygotes with familial hypercholesterolemia, which lack specific low density lipoprotein receptors, showed neither lipoprotein-dependent cholesterol esterification nor suppression of cholesterol synthesis. The reciprocal changes in free cholesterol synthesis and cholesteryl ester formation produced by low density lipoprotein-receptor interactions may play an important role in the regulation of the cholesterol content of mammalian cells.

Goldstein, Joseph L.; Dana, Suzanna E.; Brown, Michael S.



Oxidized low-density lipoprotein stimulates monocyte adhesion to glomerular endothelial cells  

Microsoft Academic Search

Oxidized low-density lipoprotein stimulates monocyte adhesion to glomerular endothelial cells.BackgroundAbnormalities in lipid and lipoprotein metabolism have been implicated in the pathogenesis of glomerulosclerosis. Atherogenic lipoproteins [for example, low-density lipoprotein (LDL) and oxidized LDL (ox-LDL)] have been shown to stimulate glomerular monocyte chemoattractants involved in monocyte infiltration. However, the role of LDL and ox-LDL in the early monocyte adhesion to glomerular

Vaijinath S. Kamanna; Rama Pai; Hunjoo Ha; Michael A. Kirschenbaum; Daeyoung D. Roh



Comparative Studies of Vertebrate Lipoprotein Lipase: A Key Enzyme of Very Low Density Lipoprotein Metabolism  

PubMed Central

Lipoprotein lipase (LIPL or LPL; E.C. serves a dual function as a triglyceride lipase of circulating chylomicrons and very-low-density lipoproteins (VLDL) and facilitates receptor-mediated lipoprotein uptake into heart, muscle and adipose tissue. Comparative LPL amino acid sequences and protein structures and LPL gene locations were examined using data from several vertebrate genome projects. Mammalian LPL genes usually contained 9 coding exons on the positive strand. Vertebrate LPL sequences shared 58–99% identity as compared with 33–49% sequence identities with other vascular triglyceride lipases, hepatic lipase (HL) and endothelial lipase (EL). Two human LPL N-glycosylation sites were conserved among seven predicted sites for the vertebrate LPL sequences examined. Sequence alignments, key amino acid residues and conserved predicted secondary and tertiary structures were also studied. A CpG island was identified within the 5'-untranslated region of the human LPL gene which may contribute to the higher than average (x4.5 times) level of expression reported. Phylogenetic analyses examined the relationships and potential evolutionary origins of vertebrate lipase genes, LPL, LIPG (encoding EL) and LIPC (encoding HL) which suggested that these have been derived from gene duplication events of an ancestral neutral lipase gene, prior to the appearance of fish during vertebrate evolution. Comparative divergence rates for these vertebrate sequences indicated that LPL is evolving more slowly (2–3 times) than for LIPC and LIPG genes and proteins.

Holmes, Roger S; Vandeberg, John L; Cox, Laura A



Imaging and manipulation of high-density lipoproteins.  

PubMed Central

The atomic force microscope (AFM) has been used to image a variety of biological systems, but has rarely been applied to soluble protein-lipid complexes. One of the primary physiological protein-lipid complexes is the high-density lipoproteins (HDL), responsible for the transport of cholesterol from the peripheral tissues and other lipoproteins to the liver. We have used the AFM to directly image discoidal reconstituted HDL (rHDL) particles for the first time. The height of these particles is consistent with a phospholipid bilayer structure, but careful high resolution measurements of particle diameters has indicated that they fuse when adsorbed to mica. Furthermore, it has been demonstrated that the AFM can be used to initiate this bilayer fusion in a controlled manner, allowing the fabrication of stabilized, nanometer scale, phospholipid bilayer "domains." Images FIGURE 1

Carlson, J W; Jonas, A; Sligar, S G



Measurement of small high density lipoprotein subclass by an improved immunoblotting technique  

Microsoft Academic Search

An improved method of immunoblotting of plasma onto agarose gel matrix containing antiapolipoprotein A-I is described. Fresh plasma samples were subjected to gradient polyacrylamide gel electrophoresis (4-25%) followed by elec- trotransfer onto agarose gel layer containing antiapolipopro- tein A-I. This method was compared with immunoblotting onto nitrocellulose where the transfer onto agarose gel matrix has been shown to be more

Ragheb F. Atmeh; Horst Robenekt


Identifying the predominant peak diameter of high- density and low-density lipoproteins by electrophoresis  

Microsoft Academic Search

Particle size distributions of high-density (HDL) and low-density (LDL) lipoproteins, obtained by polyacrylamide gradient gel electrophoresis, exhibit apparent predominant and minor peaks within characteristic subpopulation migration in- tervals. In the present report, we show that identification of such peaks as predominant or minor depends on whether the particle size distribution is analyzed according to migration distance or particle size. The

Paul T. Williams; Ronald M. Krauss; Alex V. Nichols; Karen M. Vranizan; Peter D. S. Wood


High-Density Lipoprotein Therapy: Is There Hope?  

Microsoft Academic Search

Opinion statement  The treatment of lipid abnormalities generally has focused on low-density lipoprotein cholesterol (LDL-C) reduction based\\u000a on extensive clinical trials and the National Cholesterol Education Program Adult Treatment Panel III guidelines. Unfortunately,\\u000a it has become increasingly clear that a significant percentage of patients continue to have cardiovascular events despite\\u000a being on LDL-C–lowering medications and having LDL-C levels below 100 mg\\/dL. Numerous

Kunal N. Bhatt; Bryan J. Wells; Laurence S. Sperling; Jefferson T. Baer



Biomimetic high density lipoprotein nanoparticles for nucleic acid delivery.  


We report a gold nanoparticle-templated high density lipoprotein (HDL AuNP) platform for gene therapy that combines lipid-based nucleic acid transfection strategies with HDL biomimicry. For proof-of-concept, HDL AuNPs are shown to adsorb antisense cholesterylated DNA. The conjugates are internalized by human cells, can be tracked within cells using transmission electron microscopy, and regulate target gene expression. Overall, the ability to directly image the AuNP core within cells, the chemical tailorability of the HDL AuNP platform, and the potential for cell-specific targeting afforded by HDL biomimicry make this platform appealing for nucleic acid delivery. PMID:21319839

McMahon, Kaylin M; Mutharasan, R Kannan; Tripathy, Sushant; Veliceasa, Dorina; Bobeica, Mariana; Shumaker, Dale K; Luthi, Andrea J; Helfand, Brian T; Ardehali, Hossein; Mirkin, Chad A; Volpert, Olga; Thaxton, C Shad



Low density lipoprotein cytotoxicity induced by free radical peroxidation of lipid  

Microsoft Academic Search

Low density lipoprotein (LDL) has been reported to be injurious or toxic to cells in vitro. This injurious effect is, in some instances, due to oxidation of the lipid moiety of the lipoprotein. The objectives of this study were to determine if the oxidation rendering the lipoprotein toxic to human skin fibroblasts occurred by free radical mechanisms, and if so,

Diane W. Morel; James R. Hessler; Guy M. Chisolm


Relative atherogenicity and predictive value of non-high-density lipoprotein cholesterol for coronary heart disease  

Technology Transfer Automated Retrieval System (TEKTRAN)

Although low-density lipoprotein cholesterol (LDL-C) is a well-established atherogenic factor for coronary heart disease, it does not completely represent the risk associated with atherogenic lipoproteins in the presence of high triglyceride (TG) levels. Constituent lipoproteins constituting non–hig...


Herpes simplex virus binds to human serum lipoprotein.  


Binding of herpes simplex virus (HSV) type 1 to the various subclasses of human serum lipoproteins was investigated. Studies were performed with human serum lipoproteins purified by differential ultracentrifugation and artificial proteoliposomes containing only one type of apolipoprotein (A1, E) by using an enzyme-linked immunosorbent assay technique, column chromatography, and electron microscopy. All tested lipoprotein subclasses (very low, low-, high-density lipoproteins; VLDL, LDL, HDL, HDL1) showed significant binding of purified HSV type 1. Furthermore, HSV bound to all different synthetic proteoliposomes. Adsorption of envelope proteins isolated from purified HSV to Sepharose-bound lipoproteins revealed binding of HSV glycoprotein B. Based on these results we reached the conclusion that in HSV-lipoprotein complex formation the lipid component in the lipoproteins and the glycoprotein B in HSV are the preferential reaction partners. PMID:2842273

Huemer, H P; Menzel, H J; Potratz, D; Brake, B; Falke, D; Utermann, G; Dierich, M P



Role of low-density and high-density lipoproteins in atherogenesis.  


Among the cholesterol-carrying lipoproteins, low-density lipoproteins (LDL) have been associated with coronary heart disease as a risk factor while high-density lipoproteins (HDL) appear to protect against coronary heart disease. According to studies with cells in tissue culture, control mechanisms of receptor-mediated LDL uptake are important in maintaining the cholesterol balance within the arterial cells. HDL may be a vehicle for transporting cholesterol from peripheral cells to the liver. Recent results, derived from studies of patients affected with Tangier disease (absence of HDL in plasma), favor the hypothesis that HDL precursors (e.g. surface remnants of chylomicrons) may be more potent in cholesterol uptake than mature HDL. PMID:6256692

Assmann, G; Schriewer, H



An evaluation of serum high density lipoproteins-phospholipids.  


Phospholipids in high density lipoproteins (HDL) is being used as a negative risk indicator of atherosclerosis. Phospholipids in HDL may not demonstrate the actual level of HDL-phospholipids when determined by the precipitation or ultracentrifugal methods, because HDL fractions contain very high density lipoproteins (VHDL) and albumin. In the present study, the true level of phospholipids in HDL was estimated using high performance liquid chromatography (HPLC), and it was compared with the level of phospholipids in HDL determined by the precipitation method. Sera from 18 healthy subjects were used as materials. In the HPLC method, the HDL fraction was extracted making sure that it contained no free albumin, which is albumin not bound to phospholipids. The HDL fraction was separated into subfractions. It was found that phospholipids in the VHDL fraction make a 20.2 +/- 7.3% (mean +/- S.D.) part of the total HDL-phospholipids. A large part of the VHDL fraction was constituted of albumin-bound phospholipids. A significant correlation was observed between HDL-phospholipids determined by the precipitation method, which contain albumin, and the actual HDL fraction phospholipids determined by HPLC, which do not contain VHDL (r = 0.903, p less than 0.01). These results suggest that HDL-phospholipids values determined by the precipitation method give useful clinical data. PMID:3176021

Ide, H; Tsuji, M; Shimada, M; Kondo, T; Fujiya, S; Asanuma, Y; Agishi, Y



Protein carbamylation renders high-density lipoprotein dysfunctional  

PubMed Central

Aim Carbamylation of proteins through reactive cyanate has been demonstrated to predict an increased cardiovascular risk. Cyanate is formed in vivo by break-down of urea and at sites of inflammation by the phagocyte protein myeloperoxidase. Since myeloperoxidase (MPO) associates with high-density lipoprotein (HDL) in human atherosclerotic intima, we examined in the present study whether cyanate specifically targets HDL. Results Mass spectrometry analysis revealed that protein carbamylation is a major post-translational modification of HDL. The carbamyllysine content of lesion derived HDL was more than 20-fold higher in comparison to 3-chlorotyrosine levels, a specific oxidation product of MPO. Notable, the carbamyllysine content of lesion-derived HDL was 5 to 8-fold higher when compared to lesion derived low-density lipoprotein (LDL) or total lesion protein and increased with lesion severity. Importantly, the carbamyllysine content of HDL, but not of LDL, correlated with levels of 3-chlorotyrosine, suggesting MPO mediated carbamylation in the vessel wall. Remarkably, one carbamyllysine residue per HDL associated apolipoprotein A-I was sufficient to induce cholesterol accumulation and lipid droplet formation in macrophages through a pathway requiring the HDL receptor scavenger receptor class B, type I. Conclusion The present results raise the possibility that HDL carbamylation contributes to foam cell formation in atherosclerotic lesions.



Evaluation of phospholipid transfer protein and cholesteryl ester transfer protein as contributors to the generation of pre beta-high-density lipoproteins  

Microsoft Academic Search

High-density lipoproteins (HDLs) are considered anti-atherogenic because\\u000a they mediate peripheral cell cholesterol transport to the liver for\\u000a excretion and degradation. An important step in this reverse\\u000a cholesterol-transport pathway is the uptake of cellular cholesterol by a\\u000a specific subclass of small, lipid-poor apolipoprotein A-I particles\\u000a designated pre beta-HDL. The two lipid-transfer proteins present in human\\u000a plasma, cholesteryl ester transfer protein (CETP)

J. Lie; M. Jauhiainen; Gent van T; Haperen van R; L. Scheek; H. Jansen; C. Ehnholm; Tol van A; Crom de M. P. G




Technology Transfer Automated Retrieval System (TEKTRAN)

Defects in lipoprotein metabolism alter the lipoprotein distribution of oxidized PUFAs, and we speculate that lipoprotein lipase (LpL) is a determinant in the release of VLDL-associated oxylipins. Here, using 12 wk old normolipidemic (lean) and hyperlipidemic (obese) Zucker-rats, we measured PUFA al...


Atherogenic lipoprotein phenotype in end-stage renal failure: Origin and extent of small dense low-density lipoprotein formation  

Microsoft Academic Search

End-stage renal failure (ESRF) is associated with dyslipidemia and accelerated atherosclerosis. Triglyceride-rich lipoproteins accumulate and qualitative changes take place in low-density lipoprotein (LDL), with a predominance of the small dense LDL phenotype. Increased small dense LDL (LDLIII) is a known risk factor for cardiovascular disease. To assess the extent of LDLIII formation in ESRF and identify factors contributing to LDLIII

Christopher J. Deighan; Muriel J. Caslake; Michael McConnell; J. Michael Boulton-Jones; Christopher J. Packard



Direct Measurement of Low-Density-Lipoprotein Cholesterol Is More Effective Than Total Cholesterol for the Purpose of Lipoprotein Screening  

Microsoft Academic Search

Background. We have developed a new method for chemically measuring blood low-density-lipoprotein (LDL) cholesterol. In the present study, we simulated guidelines of the National Cholesterol Education Program (NCEP) using our LDL cholesterol measurements.Methods. Blood samples were collected from 1,069 individuals (519 males, 550 females) who were referred to our laboratory at Niigata University Hospital for lipoprotein analysis. LDL cholesterol levels

Masahiko Okada; Riichiro Ishida



Autoantibodies against malondialdehyde-modified LDL are elevated in subjects with an LDL subclass pattern B  

Microsoft Academic Search

Small low density lipoproteins (LDL) are more susceptible to in vitro oxidation than larger LDL. To study whether this leads to more oxidation of small LDL in vivo, we determined the level of autoantibodies against malondialdehyde-modified LDL (MDA-LDL) in subjects with small or large LDL (LDL subclass pattern B or A) by ELISA. The study group consisted of 92 subjects

Hans Jansen; Hosam Ghanem; Jac H. S. A. M. Kuypers; Jan C. Birkenhäger



Changes in the physical behavior of low density lipoprotein in the presence of glycosaminoglycans and high density lipoprotein.  


Temperature dependent techniques - differential scanning calorimetry (DSC), polarizing microscopy - were used to study the properties of human serum low density lipoprotein (LDL) and its glycosaminoglycan (GAG) complexes, and to investigate the influence of the addition of high density lipoprotein (HDL) to the complex system. In the LDL molecule a reversible endothermic transition took place with its peak at 33 degrees C. Cholesteryl esters within the LDL core existed as an isotropic solution above this temperature (i.e. around body temperature), and in the form of smectic liquid crystals below it. When LDL was converted in vitro into GAG-LDL complexes by the addition of chondroitin-6-sulfate, dermatan sulfate, heparin or heparan sulfate, the DSC curves showed an evaluation of the transition temperature: the peak values in these samples were found at 40 degrees C and under the polarizing microscope a birefringence developed, typical of smectic liquid crystals. In chondroitin-4-sulfate-LDL complexes no alteration of the physical structure of the LDL molecule could be demonstrated. HDL decreased the transition temperature of GAG-LDL complexes and the disappearance of birefringence indicated that in the presence of HDL the lipids within the GAG-LDL complexes existed in a liquid phase at a temperature in the vicinity of body temperature. PMID:6788046

Bihari-Varga, M; Sztatisz, J; Gál, S



Low Density Lipoprotein-Cholesterol/High Density Lipoprotein-Cholesterol Ratio Predicts Plaque Vulnerability in Patients With Stable Angina  

PubMed Central

Background and Objectives The relationship between lipid profile and coronary plaque tissue characteristics in patients with stable angina pectoris (SAP) is unclear. The aim of this study was to evaluate the relationship between tissue characteristics and lipid profile and predictors of unstable plaques (UPs) in patients with SAP by virtual histology intravascular ultrasonography (VH-IVUS). Subjects and Methods VH-IVUS was performed for target lesions in patients with SAP (61.7±9.2 years, 174 males, n=266) at the time of coronary angiography. UPs are characterized by thin-cap fibroatheroma, ruptured plaque, or remaining thrombus with VH-IVUS. Results The present study showed that 34 SAP patients had UPs (61.6±9.2 years, 24 males, 12.8%). The percentage of plaque area in the minimum luminal area in high low density lipoprotein-cholesterol (LDL-C)/high density lipoprotein-cholesterol (HDL-C) ratio patients was significantly higher than in low LDL-C/HDL-C ratio patients (72.7±9.5% vs. 69.9±9.3%, p=0.035). An LDL-C/HDL-C ratio >2.0 was an independent predictor for UPs in SAP patients (odds ratio 5.252, 95% confidence interval 1.132-24.372, p=0.034). Conclusion An elevated LDL-C/HDL-C ratio is a positive predictor for coronary plaque vulnerability in patients with SAP.

Kim, Jeong Hun; Hong, Young Joon; Lee, Ki Hong; Kim, In Soo; Choi, Yun Ha; Lee, Min Goo; Park, Keun-Ho; Sim, Doo Sun; Kim, Ju Han; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Kang, Jung Chaee



Effects of high-density lipoproteins on storage at 4 degrees C of fowl spermatozoa.  


Qualitative and quantitative characterization of lipoproteins found in seminal plasma from domestic cocks was performed after isolation by density gradient ultracentrifugation. Trigyceride-rich lipoproteins (very low, intermediate- and low density lipoproteins) were not detectable in seminal plasma. High-density lipoproteins (HDL), identified on the basis of size, chemical composition and protein moiety, were present at a concentration of 66 micrograms/ml. A fraction possibly corresponding to VHDL (very high density lipoproteins, 77% protein, 23% lipid) was also detected but appeared contaminated by a protein-rich opalescent material. Since HDL contains mostly phospholipid and cholesterol, the physiological role of these lipoproteins on the storage of fowl spermatozoa was studied. Replacing seminal plasma with a solution containing chicken HDL at physiological concentration (66 micrograms/ml) had no effect on fertilizing ability of spermatozoa stored at 4 degrees C for 24 h. However, higher concentrations of HDL (560 micrograms/ml) had deleterious effects on spermatozoa stored in vitro. PMID:2250247

Blesbois, E; Hermier, D



Cryoelectron microscopy of low density lipoprotein in vitreous ice.  

PubMed Central

In this report, images of low density lipoprotein (LDL) in vitreous ice at approximately 30 A resolution are presented. These images show that LDL is a quasi-spherical particle, approximately 220-240 A in diameter, with a region of low density (lipid) surrounded by a ring (in projection) of high density believed to represent apolipoprotein B-100. This ring is seen to be composed of four or five (depending on view) large regions of high density material that may represent protein superdomains. Analysis of LDL images obtained at slightly higher magnification reveals that areas of somewhat lower density connect these regions, in some cases crossing the projectional interiors of the LDL particles. Preliminary image analysis of LDL covalently labeled at Cys3734 and Cys4190 with 1.4-nm Nanogold clusters demonstrates that this methodology will provide an important site-specific marker in studies designed to map the organization of apoB at the surface of LDL. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 6

Spin, J M; Atkinson, D



Distinct Hepatic Receptors for Low Density Lipoprotein and Apolipoprotein E in Humans  

NASA Astrophysics Data System (ADS)

Since the liver is a central organ for lipid and lipoprotein synthesis and catabolism, hepatic receptors for specific apolipoproteins on plasma lipoproteins would be expected to modulate lipid and lipoprotein metabolism. The role of hepatic receptors for low density lipoproteins and apolipoprotein E-containing lipoproteins was evaluated in patients with complementary disorders in lipoprotein metabolism: abetalipoproteinemia and homozygous familial hypercholesterolemia. In addition, hepatic membranes from a patient with familial hypercholesterolemia were studied and compared before and after portacaval shunt surgery. The results establish that the human liver has receptors for apolipoproteins B and E. Furthermore, in the human, hepatic receptors for low density lipoproteins and apolipoprotein E are genetically distinct and can undergo independent control.

Hoeg, Jeffrey M.; Demosky, Stephen J.; Gregg, Richard E.; Schaefer, Ernst J.; Brewer, H. Bryan



Human granulosa cells use high density lipoprotein cholesterol for steroidogenesis.  


This study examines the ability of human high density lipoproteins (HDL3) to deliver cholesteryl esters to human granulosa cells and describes the selective cholesterol pathway by which this occurs. Luteinized cells obtained from subjects undergoing in vitro fertilization-embryo transfer procedures were incubated with native HDL3 (or radiolabeled or fluorescently labeled HDL cholesteryl esters) to determine whether cells from humans (in which HDL is not the primary circulating lipoprotein species) can nevertheless interiorize and appropriately process cholesteryl esters for steroidogenesis. The results indicate that hormone-stimulated granulosa cells actively and efficiently use human HDL-derived cholesterol for progesterone production. More than 95% of the mass of HDL cholesteryl esters entering cells does so through the nonlysosomal (selective) pathway, i.e. cholesteryl esters released from HDL are taken up directly by the cells without internalization of apoproteins. Once internalized, the cholesteryl esters are either hydrolyzed and directly used for steroidogenesis or stored in the cells as cholesteryl esters until needed. The utilization of the internalized cholesteryl esters is a hormone-regulated event; i.e. luteinized human granulosa cells internalize and store large quantities of HDL-donated cholesteryl esters when available, but further processing of the cholesteryl esters (hydrolysis, re-esterification, or use in steroidogenesis) does not occur unless the cells are further stimulated to increase progesterone secretion. PMID:9506760

Azhar, S; Tsai, L; Medicherla, S; Chandrasekher, Y; Giudice, L; Reaven, E



Kinetic studies of the transfer of esterified cholesterol between human plasma low and high density lipoproteins  

Microsoft Academic Search

In vitro incubations (6 hr at 37°C) of human low density lipoproteins (LDL), high density lipoproteins (HDL), and lipoprotein-free plasma revealed no significant net mass transfers of esterified cholesterol from either lipo- protein fraction to the other. Transfers of esterified (3H)cholesterol from LDL to HDL must therefore have represented a process of molecular exchange between the two fractions. In molar

Philip J. Barter; Michael E. Jones


A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk  

Microsoft Academic Search

BACKGROUND: Whether apolipoprotein B (apoB) or non-high-density lipoprotein cholesterol (HDL-C) adds to the predictive power of low-density lipoprotein cholesterol (LDL-C) for cardiovascular risk remains controversial. METHODS AND RESULTS: This meta-analysis is based on all the published epidemiological studies that contained estimates of the relative risks of non-HDL-C and apoB of fatal or nonfatal ischemic cardiovascular events. Twelve independent reports, including

A. D. Sniderman; K. Williams; J. H. Contois; H. M. Monroe; M. J. McQueen; J. de Graaf; C. D. Furberg



Correlation of non-high-density lipoprotein cholesterol with apolipoprotein B: effect of 5 hydroxymethylglutaryl coenzyme A reductase inhibitors on non-high-density lipoprotein cholesterol levels  

Microsoft Academic Search

Apolipoprotein B has been shown to be a better predictor of coronary heart disease than low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol may also be a better parameter for coronary heart disease risk assessment and as a target for therapy. Data from the Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS) were used to assess the correlation between

Christie M Ballantyne; Thomas C Andrews; Judith A Hsia; Jeffrey H Kramer; Charles Shear



Oxidized low density lipoprotein, stem cells, and atherosclerosis  

PubMed Central

Oxidized low density lipoprotein (ox-LDL), a risk factor of atherosclerosis, facilitates the formation and vulnerability of atherosclerotic plaque, thus contributing to several clinical complications. Stem cells participate in vascular repair after damage and atherosclerosis is a process of inflammation accompanied with vascular injury. Researchers have proposed that stem cells participate in the formation of atherosclerotic plaque. Also, because ox-LDL is capable of inducing toxic effects on stem cells, it is reasonable to postulate that ox-LDL promotes the progress of atherosclerosis via acting on stem cells. In the present article, we review the relationship between ox-LDL, stem cells, and atherosclerosis and a portion of the associated mechanisms.



High density lipoprotein biogenesis, cholesterol efflux, and immune cell function.  


This review provides a summary of recent research on the role of high-density lipoprotein (HDL)/apolipoprotein A-I cholesterol efflux and immune cell function. Plasma concentrations of HDL have been known to inversely correlate with risk for coronary vascular disease. Bulk transport of HDL cholesterol from the peripheral tissues to the liver is a major pathway, termed reverse cholesterol transport, responsible for maintaining whole body cholesterol homeostasis. In addition to participating in this pathway, HDL and apolipoprotein A-I exert anti-inflammatory effects through different pathways. One pathway that seems to be important in atherosclerosis and autoimmunity is its role in modulation of T cell activation. HDL/apolipoprotein A-I helps regulate cell signaling by accepting membrane cholesterol from ATP binding cassette transporter A1 on immune cells and, thereby, fine tuning the amount of cholesterol present in plasma membrane lipid rafts. PMID:23077142

Sorci-Thomas, Mary G; Thomas, Michael J



Changes of Compressibility of Low Density Lipoproteins Following Copper Mediated Oxidation  

Microsoft Academic Search

The methods of measuring the ultrasound velocity and density were used for study the adiabatic compressibility of low density lipoproteins (LDL) dur- ing their oxidation. We showed, that copper-mediated oxidation of LDL resulted in a decrease of apparent specic compressibility, 'k=0, of lipoproteins. The changes of ultrasound velocity and 'k=0 value started much earlier than the beginning of propagation phase

T. Hianik; P. RybÆr; A. Hermetter



Dense low density lipoprotein subspecies with diminished oxidative resistance predominate in combined hyperlipidemia  

Microsoft Academic Search

Patients presenting combined hyperlipidemia (CHL) display an elevated risk of coronary heart disease. The athero- genic lipoprotein particles implicated in this disorder remain ill defined. We determined the qualitative and quantitative charac- teristics of the density distribution of low density lipoprotein (LDL) particle subspecies in nine subjects defined phenotypi- cally as presenting CHL, and under strict dietary control. Seven CHL

Sylvie Dejager; M. John Chapman



Microsoft Academic Search

Wick, JM, Grotthus, JL, Gressick, BA, Thao J. Effects of passive smoke on high density lipoprotein cholesterol in college aged individuals. Journal of Undergraduate Kinesiology Research 2008; 3 (2):26-33. Purpose: The purpose of this study was to compare high density lipoprotein cholesterol levels in college aged students who are exposed to passive smoke in the workplace and who work in

Julie Wick; Jenna Grotthus; Brett Gressick; Jerry Thao


Inhibition of Low Density Lipoprotein Synthesis by Dietary Omega3 Fatty Acids in Humans  

Microsoft Academic Search

Diets rich in omega-3 fatty acids derived from fish oils lower the plasma concentra- tions of low density lipoproteins (LDL) and very low density lipoproteins in humans. The present study was designed to examine the mechanism(s) by which diets en- riched in omega-3 fatty acids reduce plasma LDL cholesterol levels in normal sub- jects. Seven healthy volunteers with normal plasma

D. Roger Illingworth; William S. Harris; William E. Connor



Identification of Scavenger Receptor SR-BI as a High Density Lipoprotein Receptor  

Microsoft Academic Search

High density lipoprotein (HDL) and low density lipoprotein (LDL) are cholesterol transport particles whose plasma concentrations are directly (LDL) and inversely (HDL) correlated with risk for atherosclerosis. LDL catabolism involves cellular uptake and degradation of the entire particle by a well-characterized receptor. HDL, in contrast, selectively delivers its cholesterol, but not protein, to cells by unknown receptors. Here it is

Susan Acton; Attilio Rigotti; Katherine T. Landschulz; Shangzhe Xu; Helen H. Hobbs; Monty Krieger



Effects of high density lipoprotein subfractions on cholesterol homeostasis in human fibroblasts and arterial smooth muscle cells.  


Ultracentrifugally isolated high density lipoprotein (HDL) particles of d greater than 1.125 g/ml promote net transport of cholesterol from cultured cells. Consequently, when cultured human fibroblasts and arterial smooth muscle cells were incubated with HDL3 (d = 1.125-1.21 g/ml) and "very high" density lipoprotein (VHDL, d = 1.21-1.25 g/ml), low density lipoprotein (LDL) receptor activity was induced and the rate of LDL degradation by the cells was increased. Enhancement of LDL degradation by HDL3 and VHDL was sustained over incubation periods of 5 days at medium LDL concentrations greater than needed to saturate the LDL receptors. Even during these long-term incubations with LDL, HDL3 and VHDL caused marked reductions in cellular cholesterol content. Thus, an increase in the rate of cholesterol transport from cells may lead to a steady-state decrease in cellular cholesterol content and a sustained increase in the rate of clearance of LDL from the extracellular fluid. In contrast to the effects of HDL3 and VHDL, the major subclasses of HDL2 (HDL2b, d = 1.063-1.100 g/ml; HDL2a, d = 1.100-1.125 g/ml) did not promote net cholesterol transport from cells. Moreover, by apparent direct blockage of the effects that HDL3 and VHDL had on cholesterol transport, HDL2 reversed the increased rate of LDL degradation induced by HDL3 and VHDL. These results suggest that the relative proportion of HDL subfractions in the extracellular fluid may be an important determinant of both the rate of cholesterol transport from cells and the rate of receptor-mediated catabolism of LDL. PMID:6312947

Oram, J F


Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol.  


Nowadays, bisphosphonates are considered the drugs of choice for the treatment of several bone disorders. Their exact mechanism of action is not clear but recently it has been reported that the aminobisphosphonates inhibit cholesterol biosynthesis and that this might be relevant for their actions on bone osteoclasts. The study includes 87 postmenopausal women with moderate to severe osteoporosis. The patients were randomly assigned to intravenous (iv) infusion of 50 mg of the aminobisphosphonate Neridronate dissolved in 100 ml of saline solution every 2 months for a year (44 patients). The remaining 43 served as controls. At the time of each infusion blood samples were obtained for the evaluation of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), and total and bone alkaline phosphatase (AP). Free deoxypyridinoline (f-DPD) was measured in fasting urine specimens. In the control group no significant changes were observed throughout the study period for any of the biochemical variables. In the Neridronate-treated patients both bone AP and f-DPD excretion fell significantly by 15-20%. In these patients serum total cholesterol and serum triglycerides showed marginal decreases, which were occasionally significant. LDL-C and Apo B fell by 5-6% and these changes were statistically significant at most time points. Apo A-I and HDL-C rose progressively with time. At the 12th month, HDL-C rose 17-18% (p < 0.0001) above the baseline values. Similar findings were obtained in four postmenopausal women given high iv doses of Pamidronate or Alendronate. In conclusion aminobisphophonates, at least when given iv, induce remarkable and unexpected effects on lipid metabolism with a final profile that might be clinically relevant. PMID:10750576

Adami, S; Braga, V; Guidi, G; Gatti, D; Gerardi, D; Fracassi, E



A 90 minute soccer match decreases triglyceride and low density lipoprotein but not high-density lipoprotein and cholesterol levels  

PubMed Central

BACKGROUND: The association between the lipid profiles level and the incidence and severity of coronary heart disease (CHD) is very pronounced in epidemiological studies, and an inverse relation between physical fitness and the incidence of coronary heart disease has been observed in many studies. The aim of this study was to investigate the impact of a soccer match on lipid parameters of professional soccer players. METHODS: Twenty two professional soccer players participated in the study. Blood (10ml) for determination of lipid profiles was obtained at rest and immediately after a 90 minute soccer match. Lipid parameters were measured using Boehringer Mannheim kits and Clinilab and BioMerieux analyser. RESULTS: The results of this study showed that the triglyceride was significantly higher before the match than afterwards (159.09 ± 58.2 vs. 88.63 ± 34.1 mg/dl, p < 0.001), whereas the low-density lipoprotein (LDL) was lower before the match than after it (98.04 ± 28.9 vs. 112.31 ± 30.5 mg/dl). Moreover, there were no significant differences in cholesterol concentration (171.4 ± 30.28 mg/dl vs. 173.18 ± 32.75 mg/dl) and high-density lipoprotein (HDL) concentration (34.04 ± 5.58 mg/dl vs. 34.4 ± 4.6 mg/dl) between before and after the match. CONCLUSIONS: Although the soccer competitive match has no favourable acute effect on lipid profiles, the lower rate of LDL, cholesterol and triglyceride as well as the higher level of HDL in players suggest a beneficial effect of regular soccer training on arthrosclerosis and perhaps on CHD risk as well.

Rahnama, Nader; Younesian, Ali; Mohammadion, Morteza; Bambaeichi, Effat



Degradation of high density lipoprotein in cultured rat luteal cells  

SciTech Connect

In rat ovary luteal cells, degradation of high density lipoprotein (HDL) to tricholoracetic acid (TCA)-soluble products accounts for only a fraction of the HDL-derived cholesterol used for steroidogenesis. In this study the authors have investigated the fate of /sup 125/I)HDL bound to cultured luteal cells using pulse-chase technique. Luteal cell cultures were pulse labeled with (/sup 125/I)HDL/sub 3/ and reincubated in the absence of HDL. By 24 h about 50% of the initallay bound radioactivity was released into the medium, of which 60-65% could be precipitated with 10% TCA. Gel filtration of the chase incubation medium on 10% agarose showed that the amount of TCA-soluble radioactivity was nearly completely accounted for by a sharp peak in the low molecular weight region which was identified as 96% monoiodotyrosine by paper chromatography. The TCA-precipitable radioactivity was nearly completely accounted for by a sharp peak in the low molecular weight region which was identified as 96% monoiodotyrosine by paper chromatography. The TCA-precipitable radioactivity eluted over a wide range of molecular weights (15,000-80,000), and there was very little intact HDL present. Electrophoresis of the chase medium showed that component of the TCA-precipitable portion had mobility similar to apo AI. Lysosomal inhibitors of receptor-mediated endocytosis had no effect on the composition or quantity of radioactivity released during chase incubation. The results show that HDL/sub 3/ binding to luteal cells is followed by complete degradation of the lipoprotein, although the TCA-soluble part does not reflect the extent of degradation.

Rajan, V.P.; Menon, K.M.J.



Decreased high-density lipoprotein cholesterol levels in polyarticular juvenile idiopathic arthritis  

PubMed Central

OBJECTIVES: To investigate the prevalence of dyslipoproteinemia in a homogeneous cohort of polyarticular juvenile idiopathic arthritis patients. METHODS: Based on the National Cholesterol Education Program, fasting lipoprotein levels and risk levels for coronary artery disease were determined in 28 patients with polyarticular juvenile idiopathic arthritis. The exclusion criteria included diabetes, thyroid dysfunction, smoking, proteinuria, lipid-lowering drugs, and hormone/diuretic therapy. Disease activity, disease duration, and therapy with corticosteroids and/or chloroquine were defined at the time of lipid measurements. RESULTS: Dyslipoproteinemia was identified in 20 of the 28 (71%) patients with polyarticular juvenile idiopathic arthritis. The primary lipoprotein risk factor was decreased high-density lipoprotein cholesterol (57%), followed by elevated levels of low-density lipoprotein cholesterol (18%), triglycerides (14%), and total cholesterol (7%). The male patients had decreased high-density lipoprotein cholesterol levels than the female patients (p<0.05). The incidence of decreased high-density lipoprotein cholesterol levels did not seem to be affected by disease activity or therapy because the incidence was similar in patients with active or inactive disease, with or without corticosteroid use and with or without chloroquine use. In addition, the frequency of decreased high-density lipoprotein cholesterol levels was similar in patients with short (?5 years) vs. long (>5 years) disease duration. CONCLUSIONS: Dyslipoproteinemia is highly prevalent in patients with polyarticular juvenile idiopathic arthritis and is primarily related to decreased high-density lipoprotein cholesterol levels; therefore, early intervention is essential.

Marangoni, Roberta Goncalves; Hayata, Andre L.; Borba, Eduardo F.; Azevedo, Pedro M.; Bonfa, Eloisa; Goldenstein-Schainberg, Claudia



Myeloperoxidase and inflammatory proteins: Pathways for generating dysfunctional high-density lipoprotein in humans  

Microsoft Academic Search

High-density lipoprotein (HDL) inhibits atherosclerosis by removing cholesterol from artery wall macrophages. Additionally,\\u000a HDL is anti-inflammatory in animal studies, suggesting that this property might also be important for its cardioprotective\\u000a effects. Recent studies in subjects with established cardiovascular disease (CVD) demonstrate that myeloperoxidase targets\\u000a HDL for oxidation and blocks the lipoprotein’s ability to remove excess cholesterol from cells, raising the

Tomáš Vaisar; Baohai Shao; Pattie S. Green; Michael N. Oda; John F. Oram; Jay W. Heinecke



PPAR is a very low-density lipoprotein sensor in macrophages  

Microsoft Academic Search

Although triglyceride-rich particles, such as very low-density lipoprotein (VLDL), contribute significantly to human atherogenesis, the molecular basis for lipoprotein-driven pathogenicity is poorly understood. We demonstrate that in macrophages, VLDL functions as a transcriptional regulator via the activation of the nuclear receptor peroxisome proliferator-activated receptor . The signaling components of native VLDL are its triglycerides, whose activity is enhanced by lipoprotein

Ajay Chawla; Chih-Hao Lee; Yaacov Barak; Weimin He; John Rosenfeld; Debbie Liao; Jungyeob Han; Heonjoong Kang; Ronald M. Evans



HIV Entry Inhibitor TAK-779 Attenuates Atherogenesis in Low-Density Lipoprotein Receptor-Deficient Mice  

Microsoft Academic Search

Objective—HIV combination therapy using protease inhibitors is associated with elevated plasma levels of atherogenic lipoproteins and increased risk for atherosclerosis. We investigated whether the HIV entry inhibitor TAK-779 affects lipoprotein levels and atherogenesis in low-density lipoprotein receptor-deficient mice. TAK-779 is an antagonist for the chemokine receptors CCR5 and CXCR3, which are expressed on leukocytes, especially T-helper 1 cells, and these

Eva J. A. van Wanrooij; Arnaud D. Hauer; Takeshi Imanishi; Hiromi Fujiwara; Theo J. C. van Berkel; Johan Kuiper




Technology Transfer Automated Retrieval System (TEKTRAN)

Hormonal replacement therapy (HRT) in postmenopausal women has been shown to increase both triglyceride (TG) and high-density lipoprotein (HDL) cholesterol levels. To better understand the effects of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA), the 2 most commonly prescrib...


The action of human high density lipoprotein on cholesterol crystals. Part 1. Light-microscopic observations.  


High density lipoprotein (HDL) was found in vitro to form myelin buds (liposomes) from washed crystals of free cholesterol (commercial or atheroma sources). This activity led to the progressive destruction and solubilization of the crystals. Low density and very low density lipoproteins did not have any effect. Liposome formation and solubilization were accelerated by calcium ions, phospholipase A and polyunsaturated lecithin (Lipostabil). Cholesterol crystals were nearly completely destroyed after 18 h incubation with HDL-Lipostabil. PMID:215176

Adams, C W; Abdulla, Y H



Oleic Acid Rich Diet Protects Against the Oxidative Modification of High Density Lipoprotein  

Microsoft Academic Search

Oxidative modifications of lipoproteins could contribute to the development of atherosclerosis, but the influence of dietary fats on high density lipoprotein (HDL) oxidative modification is unknown. This study was designed to determine whether a diet rich in oleic acid could modulate the oxidative modification of HDL3. Twenty two healthy men were randomly placed on a 32-wk crossover study of an

Rosa Solà; Agnes E La Ville; Jean Louis Richard; Claude Motta; M. Teresa Bargalló; Josefa Girona; Lluis Masana; Bernard Jacotot



Lipid peroxidation of circulating low density lipoproteins with age, smoking and in peripheral vascular disease  

Microsoft Academic Search

In this study, lipid peroxides in plasma and the low density lipoprotein (LDL) fraction and plasma concentrations of vitamin E, lipids and lipoproteins were measured in 22 smokers (mean age 35 years), 26 non-smoking patients with peripheral vascular disease (PVD, mean age 66 years), and 23 younger (ages ?55 years) and 26 older (ages > 55 years) healthy subjects. Plasma

Kevin J. Sanderson; André M. van Rij; Christopher R. Wade; Wayne H. F. Sutherland



The low-density lipoprotein receptor gene family: a cellular Swiss army knife?  

Microsoft Academic Search

The low-density lipoprotein receptor gene family is an evolutionarily conserved group of cell-surface receptors produced by mammals and other organisms. Initially thought to be endocytic receptors that mediate the uptake of lipoproteins, recent findings have shown that these receptors have other roles in a range of cellular processes. Among other activities, members of this family act as signal transducers in

Anders Nykjaer; Thomas E. Willnow



Mathematical model for low density lipoprotein (LDL) endocytosis by hepatocytes.  


Individuals with elevated levels of plasma low density lipoprotein (LDL) cholesterol (LDL-C) are considered to be at risk of developing coronary heart disease. LDL particles are removed from the blood by a process known as receptor-mediated endocytosis, which occurs mainly in the liver. A series of classical experiments delineated the major steps in the endocytotic process; apolipoprotein B-100 present on LDL particles binds to a specific receptor (LDL receptor, LDL-R) in specialized areas of the cell surface called clathrin-coated pits. The pit comprising the LDL-LDL-R complex is internalized forming a cytoplasmic endosome. Fusion of the endosome with a lysosome leads to degradation of the LDL into its constituent parts (that is, cholesterol, fatty acids, and amino acids), which are released for reuse by the cell, or are excreted. In this paper, we formulate a mathematical model of LDL endocytosis, consisting of a system of ordinary differential equations. We validate our model against existing in vitro experimental data, and we use it to explore differences in system behavior when a single bolus of extracellular LDL is supplied to cells, compared to when a continuous supply of LDL particles is available. Whereas the former situation is common to in vitro experimental systems, the latter better reflects the in vivo situation. We use asymptotic analysis and numerical simulations to study the longtime behavior of model solutions. The implications of model-derived insights for experimental design are discussed. PMID:18716843

Wattis, J A D; O'Malley, B; Blackburn, H; Pickersgill, L; Panovska, J; Byrne, H M; Jackson, K G



Ethanol enhances de novo synthesis of high density lipoprotein cholesterol  

SciTech Connect

Male squirrel monkeys fed ethanol at variable doses were used to assess whether alcohol enhances de novo synthesis of high density lipoprotein (HDL) cholesterol in vivo. Monkeys were divided into three groups: 1) controls fed isocaloric liquid diet; 2) low ethanol monkeys fed liquid diet with vodka substituted isocalorically for carbohydrate at 12% of calories; and 3) High Ethanol animals fed diet plus vodka at 24% of calories. High Ethanol primates had significantly higher levels of HDL nonesterified cholesterol than Control and Low Ethanol animals while serum glutamate oxaloacetate transaminase was similar for the three treatments. There were no significant differences between the groups in HDL cholesteryl ester mass or specific activity following intravenous injection of labeled mevalonolactone. By contrast, High Ethanol monkeys had significantly greater HDL nonesterified cholesterol specific activity with approximately 60% of the radioactivity distributed in the HDL/sub 3/ subfraction. This report provides the first experimental evidence that ethanol at 24% of calories induces elevations in HDL cholesterol in primates through enhanced de novo synthesis without adverse effects on liver function.

Cluette, J.E.; Mulligan, J.J.; Noring, R.; Doyle, K.; Hojnacki, J.



Immunomodulating effect of low density lipoprotein on human monocytes.  

PubMed Central

Low density lipoprotein (LDL) isolated from sera of healthy volunteers in 50 micrograms protein/ml concentration induced an early adenylate cyclase activation in human monocytes followed by elevation of cGMP level. In addition, a rapid 45Ca2+ influx was also detected on addition of 25-100 micrograms protein/ml concentrations. The monocyte activating effect of LDL under in vitro circumstances was characterized by an enhanced O2 consumption, H2O2 generation and by the increased release of lysosomal enzymes such as beta-glucuronidase and elastase like protease (ELP). On the other hand, LDL diminished markedly the Fc gamma receptor (Fc gamma R) mediated rosette formation, phagocytosis and the antibody dependent cellular cytotoxicity (ADCC) of monocytes without a significant decrease in the IgG binding capability of cells. High levels of serum LDL may play a significant role in the arterial wall injury by elastase like protease as well as biologically active oxygen species released from monocytes of patients suffering from arteriosclerosis.

Paragh, G; Nagy, J T; Szondy, E; Foris, G; Leovey, A



In vivo protection against endotoxin by plasma high density lipoprotein.  

PubMed Central

Overwhelming bacterial infection is accompanied by fever, hypotension, disseminated intravascular coagulation, and multiple organ failure leading to death in 30-80% of cases. These classical symptoms of septic shock are caused by potent cytokines that are produced in response to endotoxin released from Gram-negative bacteria. Treatments with antibodies and receptor antagonists to block endotoxin or cytokine mediators have given mixed results in clinical trials. High density lipoprotein (HDL) is a natural component of plasma that is known to neutralize endotoxin in vitro. We report here that raising the plasma HDL concentration protects mice against endotoxin in vivo. Transgenic mice with 2-fold-elevated plasma HDL levels had more endotoxin bound to HDL, lower plasma cytokine levels, and improved survival rates compared with low-HDL mice. Intravenous infusion of HDL also protected mice, but only when given as reconstituted HDL prepared from phospholipid and either HDL apoprotein or an 18-amino acid peptide synthesized to mimic the structure of apolipoprotein A-I of HDL. Intact plasma HDL was mildly toxic, and HDL apoprotein was ineffective. The effectiveness of the reconstituted peptide renders very unlikely any significant contribution to protection by trace proteins in apo-HDL. These data suggest a simple leaflet insertion model for binding and neutralization of lipopolysaccharide by phospholipid on the surface of HDL. Plasma HDL may normally act to protect against endotoxin; this protection may be augmented by administration of reconstituted HDL or reconstituted peptides. Images Fig. 1 Fig. 2 Fig. 3

Levine, D M; Parker, T S; Donnelly, T M; Walsh, A; Rubin, A L



Aging affects high-density lipoprotein composition and function.  


Most coronary deaths occur in patients older than 65years. Age associated alterations in the composition and function of high-density lipoproteins (HDL) may contribute to cardiovascular mortality. The effect of advanced age on the composition and function of HDL is not well understood. HDL was isolated from healthy young and elderly subjects. HDL composition, cellular cholesterol efflux/uptake, anti-oxidant properties and paraoxonase activity were assessed. We observed a 3-fold increase of the acute phase protein serum amyloid A, an increased content of complement C3 and proteins involved in endopeptidase/protease inhibition in HDL of elderly subjects, whereas levels of apolipoprotein E were significantly decreased. HDL from elderly subjects contained less cholesterol but increased sphingomyelin. Most importantly, HDL from elderly subjects showed defective antioxidant properties, lower paraoxonase 1 activity and was more rapidly taken up by macrophages, whereas cholesterol efflux capability was not altered. These findings suggest that aging alters HDL composition, resulting in functional impairment that may contribute to the onset/progression of cardiovascular disease. PMID:23792422

Holzer, Michael; Trieb, Markus; Konya, Viktoria; Wadsack, Christian; Heinemann, Akos; Marsche, Gunther



Pluronic block copolymers inhibit low density lipoprotein self-association.  


Little is known about exogenous inhibitors of low-density lipoprotein (LDL) aggregation. The search for nontoxic and bioavailable inhibitors of LDL aggregation is of interest, especially considering that the suppression of the aggregation of LDL might represent a therapeutic approach. We hypothesized that amphiphilic copolymers of propylene oxide and ethylene oxide, the so-called Pluronic block copolymers, can be used to influence the aggregation of LDL. In this work we used Pluronic® P85, L61 and F68. A comparative study of the effects of Pluronic block copolymers with various hydrophilic-lipophilic properties on the aggregation process of LDL showed that Pluronic copolymers with strong hydrophobic properties (P85 and L61) at concentrations close to or greater than the respective critical concentration of micelle formation inhibited the aggregation process of LDL; however, the "hydrophilic" Pluronic F68 had no effect on the aggregation of LDL at any concentration. Thus, the study demonstrated for the first time that Pluronic® block copolymers inhibit LDL self-association. The possibility of modulating the aggregation of LDL by various Pluronic copolymers can be regarded as a prerequisite in the creation of new types of anti-atherosclerotic drugs. PMID:22797973

Melnichenko, Alexandra A; Aksenov, Denis V; Myasoedova, Veronika A; Panasenko, Oleg M; Yaroslavov, Alexander A; Sobenin, Igor A; Bobryshev, Yuri V; Orekhov, Alexander N



High density lipoprotein/sphingosine-1-phosphate-induced cardioprotection  

PubMed Central

High density lipoprotein (HDL) cholesterol has beneficial effects beyond its atheroprotective function in reverse cholesterol transport, including cardioprotection against ischemia reperfusion (IR) injuries. Two major constituents of HDL, namely the structural protein apolipoprotein AI (apoAI) and the sphingolipid sphingosine-1-phosphate (S1P) appear to contribute to this cardioprotective effect via the activation of intrinsic prosurvival signaling pathways that still remain to be clarified.   Recently, a powerful prosurvival signaling pathway, termed the survivor activating factor enhancement (SAFE) pathway, which involves the activation of signal transducer and activator of transcription 3 (STAT3) and tumor necrosis factor ? (TNF), has been shown to protect against ischemia-reperfusion injuries. The present review summarizes the evidence for the roles of HDL and S1P in cardioprotection and discusses the signaling pathways that have been implicated. It thus provides support for our contention that S1P should be considered in potential formulations of reconstituted HDL (reHDL) that may be tested for cardioprotection against coronary artery disease via the activation of the SAFE pathway.

Frias, Miguel A.; Lecour, Sandrine; James, Richard W.; Pedretti, Sarah



Aging affects high-density lipoprotein composition and function?  

PubMed Central

Most coronary deaths occur in patients older than 65 years. Age associated alterations in the composition and function of high-density lipoproteins (HDL) may contribute to cardiovascular mortality. The effect of advanced age on the composition and function of HDL is not well understood. HDL was isolated from healthy young and elderly subjects. HDL composition, cellular cholesterol efflux/uptake, anti-oxidant properties and paraoxonase activity were assessed. We observed a 3-fold increase of the acute phase protein serum amyloid A, an increased content of complement C3 and proteins involved in endopeptidase/protease inhibition in HDL of elderly subjects, whereas levels of apolipoprotein E were significantly decreased. HDL from elderly subjects contained less cholesterol but increased sphingomyelin. Most importantly, HDL from elderly subjects showed defective antioxidant properties, lower paraoxonase 1 activity and was more rapidly taken up by macrophages, whereas cholesterol efflux capability was not altered. These findings suggest that aging alters HDL composition, resulting in functional impairment that may contribute to the onset/progression of cardiovascular disease.

Holzer, Michael; Trieb, Markus; Konya, Viktoria; Wadsack, Christian; Heinemann, Akos; Marsche, Gunther



Quantification of high-density-lipoprotein cholesterol by precipitation with phosphotungstic acid/MgCl2.  


We evaluated the use of a modified phosphotungstic acid/MgCl2 precipitation procedure for the precipitation of apolipoprotein B-containing lipoproteins. Precipitation of these lipoproteins [very-low- and low-density lipoproteins, and lipoprotein (a)] is complete, with negligible coprecipitation of high-density lipoprotein subfractions (HDL1, HDL2, HDL3), even in hypertriglyceridemic sera. In comparison with ultracentrifugation, the precipitation method yields, on the average, values that are 0.17 mmol/L lower for cholesterol values but almost identical for apolipoprotein A-I and phosphatidylcholine. Looking for delta 3,5-cholestadiene formed from cholesterol in the precipitation residue, we used "high-performance" liquid chromatography and "high-performance" thin-layer chromatography and found none. PMID:6640896

Assmann, G; Schriewer, H; Schmitz, G; Hägele, E O



Identification of a Domain That Mediates Association of Platelet-activating Factor Acetylhydrolase with High Density Lipoprotein*S?  

PubMed Central

The plasma form of platelet-activating factor (PAF) acetylhydrolase (PAF-AH), also known as lipoprotein-associated phospholipase A2 (Lp-PLA2) inactivates potent lipid messengers such as PAF and modified phospholipids generated in settings of oxidant stress. In humans, PAF-AH circulates in blood in fully active form and associates with high and low density lipoproteins (HDL and LDL). Several studies suggest that the location of PAF-AH affects both the catalytic efficiency and the function of the enzyme in vivo. The distribution of PAF-AH among lipoproteins varies widely among mammals. Here, we report that mouse and human PAF-AHs associate with human HDL particles of different density. We made use of this observation in the development of a binding assay to identify domains required for association of human PAF-AH with human HDL. Sequence comparisons among species combined with domain-swapping and site-directed mutagenesis studies led us to the identification of C-terminal residues necessary for the association of human PAF-AH with human HDL. Interestingly, the region identified is not conserved among PAF-AHs, suggesting that PAF-AH interacts with HDL particles in a manner that is unique to each species. These findings contribute to our understanding of the mechanisms responsible for association of human PAF-AH with HDL and may facilitate future studies aimed at precisely determining the function of PAF-AH in each lipoprotein particle.

Gardner, Alison A.; Reichert, Ethan C.; Topham, Matthew K.; Stafforini, Diana M.



Oxidized low-density lipoprotein as a biomarker of in vivo oxidative stress: from atherosclerosis to periodontitis  

PubMed Central

Oxidized low-density lipoprotein is known as an important factor in the development of atherosclerosis. The introduction of a sensitive procedure for the determination of oxidized low-density lipoprotein in human circulating plasma using a monoclonal antibody recognizing oxidized phosphatidylcholines has opened new fields of research based on in vivo oxidized low-density lipoprotein. The plasma oxidized low-density lipoprotein levels are significantly elevated in patients with acute myocardial infarction, cerebral infarction or chronic renal failure accompanied by hemodialysis. It was found that the plasma oxidized low-density lipoprotein level increased prior to aortic atherosclerotic lesion enlargement in apolipoprotein E-knockout mice. Recent studies have pointed out that oxidized low-density lipoprotein is transferrable between vessel wall tissue and the circulation, so it is a reasonable hypothesis that plasma oxidized low-density lipoprotein levels reflect the oxidative status at local sites of atherogenesis. Oxidized low-density lipoprotein measurement has been applied to human gingival crevicular fluids, which can be collected easily and safely, and relatively high levels of oxidized low-density lipoprotein were shown to be present. These findings, together with recent clinical follow-up studies, suggest that oxidized low-density lipoprotein is a predictive biomarker of a variety of diseases related to oxidative stress. This review summarizes the current understanding of in vivo oxidized low-density lipoprotein and its potential significance as a biomarker of disease.

Itabe, Hiroyuki



Influence of Feeding Cottonseed Oil to Laying Hens on the Low Density Lipoproteins of Their Eggs 'â  

Microsoft Academic Search

Low density lipoproteins, isolated from yolks of eggs produced by hens fed a normal diet and from those of hens fed 2.5% cottonseed oil in the diet, were studied to determine the effect of crude cottonseed oil on properties of the yolk lipoproteins. Low density lipoproteins isolated from eggs produced by hens fed crude cottonseed oil contained more saturated fatty



21 CFR 866.5600 - Low-density lipoprotein immunological test system.  

Code of Federal Regulations, 2013 CFR




Racial differences in the distribution of a low density lipoprotein receptor-related protein (LRP) polymorphism and its association with serum lipoprotein, lipid and apolipoprotein levels  

Microsoft Academic Search

The low density lipoprotein (LDL) receptor-related protein (LRP) is a cell receptor that has close structural homology to the LDL and very low density lipoprotein receptors and thus is believed to play an important role in lipid metabolism. This study was carried out to evaluate the distribution of a known tetranucleotide repeat polymorphism in the LRP gene and its association

Meagan R Harris; Clareann H Bunker; Richard F Hamman; Dharambir K Sanghera; Christopher E Aston; M. Ilyas Kamboh



Synthetic farnesoid X receptor agonists induce high-density lipoprotein-mediated transhepatic cholesterol efflux in mice and monkeys and prevent atherosclerosis in cholesteryl ester transfer protein transgenic low-density lipoprotein receptor (-/-) mice.  


Farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor, plays an important role in the regulation of cholesterol and more specifically high-density lipoprotein (HDL) homeostasis. Activation of FXR is reported to lead to both pro- and anti-atherosclerotic effects. In the present study we analyzed the impact of different FXR agonists on cholesterol homeostasis, plasma lipoprotein profiles, and transhepatic cholesterol efflux in C57BL/6J mice and cynomolgus monkeys and atherosclerosis development in cholesteryl ester transfer protein transgenic (CETPtg) low-density lipoprotein receptor (LDLR) (-/-) mice. In C57BL/6J mice on a high-fat diet the synthetic FXR agonists isopropyl 3-(3,4-difluorobenzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate (FXR-450) and 4-[2-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methoxy]phenyl]cyclopropyl]benzoic acid (PX20606) demonstrated potent plasma cholesterol-lowering activity that affected all lipoprotein species, whereas 3-[2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]benzoic acid (GW4064) and 6-ethyl chenodeoxycholic acid (6-ECDCA) showed only limited effects. In FXR wild-type mice, but not FXR(-/-) mice, the more efficacious FXR agonists increased fecal cholesterol excretion and reduced intestinal cholesterol (re)uptake. In CETPtg-LDLR(-/-) mice PX20606 potently lowered total cholesterol and, despite the observed HDL cholesterol (HDLc) reduction, caused a highly significant decrease in atherosclerotic plaque size. In normolipidemic cynomolgus monkeys PX20606 and 6-ECDCA both reduced total cholesterol, and PX20606 specifically lowered HDL(2c) but not HDL(3c) or apolipoprotein A1. That pharmacological FXR activation specifically affects this cholesterol-rich HDL(2) subclass is a new and highly interesting finding and sheds new light on FXR-dependent HDLc lowering, which has been perceived as a major limitation for the clinical development of FXR agonists. PMID:22918042

Hambruch, Eva; Miyazaki-Anzai, Shinobu; Hahn, Ulrike; Matysik, Silke; Boettcher, Alfred; Perovi?-Ottstadt, Sanja; Schlüter, Thomas; Kinzel, Olaf; Krol, Helen Desiree; Deuschle, Ulrich; Burnet, Michael; Levi, Moshe; Schmitz, Gerd; Miyazaki, Makoto; Kremoser, Claus



Selective uptake of high-density lipoprotein-associated cholesteryl esters by human hepatocytes in primary culture.  


High-density lipoprotein cholesteryl esters are taken up by many cells without simultaneous uptake of high-density lipoprotein apolipoproteins. This selective uptake was investigated in human hepatocytes in primary culture. Human high-density lipoprotein-3 (density, 1.125 to 1.21 gm/ml) was radiolabeled in both its apolipoprotein and in its cholesteryl ester moiety; uptake of these high-density lipoprotein3 tracers by hepatocytes was investigated. Apparent high-density lipoprotein3 particle uptake as measured with the cholesteryl ester tracer was in excess of that from the apolipoprotein tracer, indicating selective uptake of high-density lipoprotein3 cholesteryl esters by hepatocytes. This selective uptake is a regulated pathway in hepatocytes, as demonstrated by an inverse relationship between cell cholesterol and the rate of selective uptake. Studies on the mechanism of selective uptake have used inhibitors such as monensin, chloroquine, heparin, and a monoclonal antibody directed against low-density lipoprotein receptors. These experiments provide no evidence for a role of cell-secreted apolipoprotein E, endocytosis or retroendocytosis in selective uptake. The intracellular fate of high-density lipoprotein3-associated cholesteryl esters was investigated with [3H]cholesteryl oleate-labeled high-density lipoprotein3. Hepatocytes hydrolyzed [3H]cholesteryl oleate internalized from labeled high-density lipoprotein3; this catabolism was not inhibited by the presence of chloroquine. In parallel hepatocytes were incubated with [3H]cholesteryl oleate-labeled low-density lipoprotein. Cells hydrolyzed [3H]cholesteryl oleate taken up with low-density lipoprotein; however, this hydrolysis was inhibited by chloroquine, indicating lysosomal low-density lipoprotein cholesteryl ester catabolism. These experiments show that high-density lipoprotein3 cholesteryl esters selectively taken up by hepatocytes are hydrolyzed independently from the classical lysosomal catabolic pathway. The question was addressed if selective uptake mediates a net mass uptake of cholesterol rather than an isotope exchange phenomenon. Incubation of hepatocytes with high-density lipoprotein-3 suppressed endogenous sterol synthesis from sodium [14C]acetate. Hepatocytes were incubated in the presence of high-density lipoprotein3; medium cholesteryl esters decreased as a result of incubation with hepatocytes. These results show a net mass delivery of high-density lipoprotein cholesteryl esters to hepatocytes. In conclusion, the pathway for selective uptake of high-density lipoprotein cholesteryl esters could be demonstrated in human hepatocytes in primary culture. A role for selective uptake in high-density lipoprotein-mediated cholesterol delivery to the liver in human beings in vivo is proposed. PMID:8175132

Rinninger, F; Brundert, M; Jäckle, S; Galle, P R; Busch, C; Izbicki, J R; Rogiers, X; Henne-Bruns, D; Kremer, B; Broelsch, C E



Role of lipoprotein lipase in the regulation of high density lipoprotein apolipoprotein metabolism. Studies in normal and lipoprotein lipase-inhibited monkeys.  

PubMed Central

Mechanisms that might be responsible for the low levels of high density lipoprotein (HDL) associated with hypertriglyceridemia were studied in an animal model. Specific monoclonal antibodies were infused into female cynomolgus monkeys to inhibit lipoprotein lipase (LPL), the rate-limiting enzyme for triglyceride catabolism. LPL inhibition produced marked and sustained hypertriglyceridemia, with plasma triglyceride levels of 633-1240 mg/dl. HDL protein and cholesterol and plasma apolipoprotein (apo) AI levels decreased; HDL triglyceride (TG) levels increased. The fractional catabolic rate of homologous monkey HDL apolipoproteins injected into LPL-inhibited animals (n = 7) was more than double that of normal animals (0.094 +/- 0.010 vs. 0.037 +/- 0.001 pools of HDL protein removed per hour, average +/- SEM). The fractional catabolic rate of low density lipoprotein apolipoprotein did not differ between the two groups of animals. Using HDL apolipoproteins labeled with tyramine-cellobiose, the tissues responsible for this increased HDL apolipoprotein catabolism were explored. A greater proportion of HDL apolipoprotein degradation occurred in the kidneys of hypertriglyceridemic than normal animals; the proportions in liver were the same in normal and LPL-inhibited monkeys. Hypertriglyceridemia due to LPL deficiency is associated with low levels of circulating HDL cholesterol and apo AI. This is due, in part, to increased fractional catabolism of apo AI. Our studies suggest that variations in the rate of LPL-mediated lipolysis of TG-rich lipoproteins may lead to differences in HDL apolipoprotein fractional catabolic rate. Images

Goldberg, I J; Blaner, W S; Vanni, T M; Moukides, M; Ramakrishnan, R



A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol  

Microsoft Academic Search

The accurate quantitation of high density lipo- proteins has recently assumed greater importance in view of studies suggesting their negative correlation with coronary heart disease. High density lipoproteins may be estimated by measuring cholesterol in the plasma frac- tion of d > 1.063 g\\/ml. A more practical approach is the specific precipitation of apolipoprotein B (apoB)-contain- ing lipoproteins by sulfated

G. Russell Warnick; John J. Albers


Atorvastatin effect on high-density lipoprotein-associated paraoxonase activity and oxidative DNA damage  

Microsoft Academic Search

Objective High-density lipoprotein (HDL)-associated antioxidant paraoxonase (PON) may reduce low-density lipoprotein (LDL) oxidation and prevent atherosclerosis. The aim of this present study was to investigate the effect of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin on hydrogen-peroxide-induced DNA damage by comet assay and the correlation between oxidative DNA damage and antioxidant PON activity. Methods Thirteen type-II\\/a hyperlipidemic patients were

Mariann Harangi; Ildikó Seres; Zsuzsa Varga; Gabriella Emri; Zoltán Szilvássy; György Paragh; Éva Remenyik



High-density lipoprotein particles are large in patients with variant angina  

Microsoft Academic Search

Objective: Dyslipidemia in patients with coronary vasospasm may be characterized by low level of high-density lipoprotein . . HDL -cholesterol as well as apolipoprotein apo A-I but not high level of low-density lipoprotein-cholesterol. This study sought to examine the HDL particle size in patients with variant angina. Methods: The HDL particle size was examined by analyzing serum lipid levels in

Kunihisa Miwa; Naohiro Yoshida; Keiko Nakagawa; Hiroshi Inoue


Enhanced Macrophage Degradation of Low Density Lipoprotein Previously Incubated with Cultured Endothelial Cells: Recognition by Receptors for Acetylated Low Density Lipoproteins  

Microsoft Academic Search

Human low density lipoprotein (LDL) was incubated with an established line of rabbit aortic endothelial cells. Density gradient fractionation showed a time-, concentration-, and temperature-dependent increase in the average density of the LDL (from about 1.036 to as high as 1.070 g\\/ml). Incubation without cells or with other types of cultured cells (fibroblasts, hepatocytes, 3T3-L1 cells) caused no significant change

Tore Henriksen; Eileen M. Mahoney; Daniel Steinberg



Recycling of vitamin E in human low density lipoproteins.  


Oxidative modification of low density lipoproteins (LDL) and their unrestricted scavenger receptor-dependent uptake is believed to account for cholesterol deposition in macrophage-derived foam cells. It has been suggested that vitamin E that is transported by LDL plays a critical role in protecting against LDL oxidation. We hypothesize that the maintenance of sufficiently high vitamin E concentrations in LDL can be achieved by reducing its chromanoxyl radicals, i.e., by vitamin E recycling. In this study we demonstrate that: i) chromanoxyl radicals of endogenous vitamin E and of exogenously added alpha-tocotrienol, alpha-tocopherol or its synthetic homologue with a 6-carbon side-chain, chromanol-alpha-C6, can be directly generated in human LDL by ultraviolet (UV) light, or by interaction with peroxyl radicals produced either by an enzymic oxidation system (lipoxygenase + linolenic acid) or by an azo-initiator, 2,2'-azo-bis(2,4-dimethylvaleronitrile) (AMVN; ii) ascorbate can recycle endogenous vitamin E and exogenously added chromanols by direct reduction of chromanoxyl radicals in LDL; iii) dihydrolipoic acid is not efficient in direct reduction of chromanoxyl radicals but recycles vitamin E by synergistically interacting with ascorbate (reduces dehydroascorbate thus maintaining the steady-state concentration of ascorbate); and iv) beta-carotene is not active in vitamin E recycling but may itself be protected against oxidative destruction by the reductants of chromanoxyl radicals. We suggest that the recycling of vitamin E and other phenolic antioxidants by plasma reductants may be an important mechanism for the enhanced antioxidant protection of LDL. PMID:1314881

Kagan, V E; Serbinova, E A; Forte, T; Scita, G; Packer, L



Speciated Human High Density Lipoprotein Protein Proximity Profiles†  

PubMed Central

It is expected that the attendant structural heterogeneity of human high density lipoprotein (HDL) complexes is a determinant of its varied metabolic functions. To determine structural heterogeneity of HDL, major apolipoprotein stoichiometry profiles in human HDL were determined. First, HDL was separated into two main populations, with and without apolipoprotein (apo) A-II, LpA-I and LpA-I/A-II respectively. Each main population was further separated into six individual subfractions using size exclusion chromatography (SEC). Protein proximity profiles (PPP) of major apolipoproteins in each individual subfraction was determined by optimally cross-linking apolipoproteins within individual particles with bis(sulfosuccinimidyl)suberate (BS3), a bifunctional cross linker, followed by molecular weight determination by MALDI-MS. The PPPs of LpA-I subfractions indicated that the number of apoA-I molecules increased from two to three to four upon increase in the LpA-I particle size. On the other hand, the entire population of LpA-I/A-II demonstrated the presence of only two proximal apoA-I molecules per particle, while the number of apoA-II molecules varied from one dimeric apoA-II to two and then to three. For most of the above PPP profiles, an additional population that contained a single molecule of apoC-III in addition to apoA-I and/or apoA-II was detected. Upon composition analyses of individual subpopulations, LpA-I/A-II displayed comparable proportions for total protein (~58%), phospholipids (~21%) total cholesterol (~16%), triglycerides (~5%) and free cholesterol (~4%) across subfractions. LpA-I components, on the other hand, showed significant variability. This novel information on HDL subfractions will form a basis for better understanding particle specific functions of HDL.

Gauthamadasa, Kekulawalage; Rosales, Corina; Pownall, Henry J.; Macha, Stephen; Jerome, W. Gray; Huang, Rong; Silva, R. A.Gangani. D.



[15] Two-dimensional nondenaturing electrophoresis of lipoproteins: Applications to high-density lipoprotein speciation  

Microsoft Academic Search

No single technique is able to separate each of the many HDL species present in native plasma. Some are present in only trace proportions. Some HDL have no obvious independent metabolic role, beyond perhaps serving as reservoirs of apoproteins active in metabolic events in other lipoproteins. The choice of HDL analytical technique depends mainly on the problem under study. Two-dimensional

Christopher J. Fielding; Phoebe E. Fielding



Increased Very Low Density Lipoprotein Secretion, Hepatic Steatosis, and Insulin Resistance  

PubMed Central

Insulin resistance (IR) not only affects regulation of carbohydrate metabolism, but all aspects of lipid and lipoprotein metabolism. IR is associated with increased secretion of very low density lipoproteins (VLDL) and increased plasma triglycerides, as well as hepatic steatosis, despite the increased VLDL secretion. Here, we link IR with increased VLDL secretion and hepatic steatosis at both the physiologic and molecular levels. Increased VLDL secretion, together with the downstream effects on high density lipoprotein cholesterol and low density lipoprotein size is pro-atherogenic. Hepatic steatosis is a risk for steatohepatitis and cirrhosis. Understanding the complex inter-relationship between IR and these abnormalities of liver lipid homeostasis may provide insights relevant to new therapies for these increasing clinical problems.

Choi, Sung Hee; Ginsberg, Henry N



Influence of etofibrate on low density lipoprotein metabolism.  


This study examined the effect of single dose etofibrate (1.0 g/day) on plasma lipids and lipoproteins in a group of eleven hypercholesterolemic individuals. The drug lowered plasma triglyceride and cholesterol by 32% and 14%, respectively (P less than 0.005). The cholesterol reduction came from a decrement in both VLDL and LDL. The cholesterol content of HDL did not change although its mass as determined by analytical ultracentrifugation rose by 29%. LDL metabolism was followed before and during drug therapy. Treatment increased catabolism of this lipoprotein by 14%, without affecting synthesis. The increased clearance resulted from activation (64%) of the LDL receptor pathway. There was a reciprocal decrease in the amount of lipoprotein channelled into the receptor-independent route. PMID:3348843

Series, J J; Caslake, M J; Kilday, C; Cruickshank, A; Demant, T; Packard, C J; Shepherd, J



Macrophage receptors responsible for distinct recognition of low density lipoprotein containing pyrrole or pyridinium adducts: models of oxidized low density lipoprotein  

Microsoft Academic Search

Oxidation of low density lipoproteins (LDL) in- duced by incubation with Cu 2 1 ions results in the formation of a heterogeneous group of aldehydic adducts on lysyl resi- dues (Lys) of apolipoprotein B (apoB) that are thought to be responsible for the uptake of oxidized LDL (oxLDL) by macrophages. To define the structural and chemical criteria governing such cell

Eugene A. Podrez; George Hoppe; June O'Neil; Lawrence M. Sayre; Nader Sheibani; Henry F. Hoff


Troglitazone inhibits long-term glycation and oxidation of low-density lipoprotein.  


Troglitazone (T) is a member of a new class of antidiabetic drugs termed thiazolidinediones (TZDs), which has previously been used as an anti-diabetic agent. In this study we investigated the influence of T, a ligand for PPAR-gamma receptor, on copper-catalyzed or cell-mediated oxidation of native, glycated, and glycoxidated low-density lipoprotein (LDL). A dose-dependent inhibition of copper-mediated low-density lipoprotein-oxidation, as monitored by the formation of oxidation-specific fluorescence, was observed for both native and glycated low-density lipoprotein. At the concentration of 20 microg/mL the inhibition amounted from 14.7% to 64.7% by all low-density lipoprotein forms. For glycated low-density lipoprotein we obtained the highest oxidation rate, but the most pronounced inhibition by T was found for glycoxidated low-density lipoprotein (goLDL). Inhibitory effects of T were also investigated by measurement of relative electrophoretic mobility (REM) in the concentration range of 0 to 20 microg/mL. The inhibition of 4h oxidation of native low-density lipoprotein was found in the entire concentration range, but significance was seen at 10 microg/mL. The long-term glycation and glycoxidation of low-density lipoprotein as measured by 5-hydroxymethyl-2-furaldehyde (5-HMF) formation and binding of fructosamine was found to be inhibited by T. In endothelial cell-mediated oxidation of low-density lipoprotein cytotoxicity of T in the concentration range of 0 to 160 microg/mL during 2 to 24 h oxidation was investigated. In the non-cytotoxic concentration range of 5 to 20 microg/mL, a significantly reduced liberation of isoprostane 8-epi-PGF2alpha during 24 h cell-mediated oxidation of low-density lipoprotein and its modifications was found. This inhibitory action of T was most significant in the case of goLDL and amounted to approximately 20% to 60% inhibition at 5 to 20 microg/mL T, respectively. In the concentration range of 40 to 160 microg/mL, however, T showed an increasing cytotoxic action, as evidenced by loss of cell adhesion, loss of cellular protein, morphological changes, and cell disintegration as well as by strongly enhanced troglitazone-mediated isoprostane 8-IP liberation (fivefold to sixfold). T may be used as a model to explore the thiazolidinediones' mechanism on oxidation in a more general aspect for treatment for T2DM, because T is not clinically available. PMID:16220075

Sobal, Grazyna; Menzel, E J; Sinzinger, H



Comparison of gemfibrozil versus simvastatin in familial combined hyperlipidemia and effects on apolipoprotein-B-containing lipoproteins, low-density lipoprotein subfraction profile, and low-density lipoprotein oxidizability  

Microsoft Academic Search

We evaluated in a double-blind, placebo-controlled, randomized trial of 45 well-defined patients with familial combined hyperlipidemia, the effect of gemfibrozil (1, 200 mg\\/day) or simvastatin (20 mg\\/day) on apolipoprotein-B (apo-B)-containing lipoproteins, low-density lipoprotein (LDL) subfraction profile, and LDL oxidizability. Although both drugs reduced plasma cholesterol and triglyceride concentrations, gemfibrozil reduced plasma triglycerides more effectively and simvastatin reduced plasma cholesterol more

Sebastian J. H. Bredie; Tjerk W. A. de Bruin; Pierre N. M. Demacker; John J. P. Kastelein; Anton F. H. Stalenhoef



Computational Lipidology: Predicting Lipoprotein Density Profiles in Human Blood Plasma  

Microsoft Academic Search

Monitoring cholesterol levels is strongly recommended to identify patients at risk for myocardial infarction. However, clinical markers beyond “bad” and “good” cholesterol are needed to precisely predict individual lipid disorders. Our work contributes to this aim by bringing together experiment and theory. We developed a novel computer-based model of the human plasma lipoprotein metabolism in order to simulate the blood

Katrin Hübner; Thomas Schwager; Karl Winkler; Jens-Georg Reich; Hermann-Georg Holzhütter



Computational Lipidology: Predicting Lipoprotein Density Profiles in Human Blood Plasma  

Microsoft Academic Search

Monitoring cholesterol levels is strongly recommended to identify patients at risk for myocardial infarction. However, clinical markers beyond ''bad'' and ''good'' cholesterol are needed to precisely predict individual lipid disorders. Our work contributes to this aim by bringing together experiment and theory. We developed a novel computer-based model of the human plasma lipoprotein metabolism in order to simulate the blood

Katrin Hübner; Thomas Schwager; Karl Winkler; Jens-Georg Reich; Hermann-Georg Holzhütter



High-density lipoprotein cholesterol subfractions and lecithin: cholesterol acyltransferase activity in collegiate soccer players.  


Many of the published data on the lipid profile of athletes is based on studies of endurance athletes. The data on soccer players are rare. The purpose of this study was to examine serum high-density lipoprotein cholesterol subfractions and lecithin:cholesterol acyltransferase activity in collegiate soccer players. 31 well-trained male collegiate soccer players were divided into 2 groups: 16 defenders and 15 offenders. They were compared with 16 sedentary controls. Dietary information was obtained with a food frequency questionnaire. The subjects were all non-smokers and were not taking any drug known to affect the lipid and lipoprotein metabolism. The offenders had significantly higher high-density lipoprotein cholesterol, high-density lipoprotein2 cholesterol, and apolipoprotein A-I than the defenders and controls, whereas the defenders had the significantly higher high-density lipoprotein2 cholesterol than the controls. Both groups of athletes had significantly higher lecithin:cholesterol acyltransferase activity than the controls. The results indicate that favorable lipid and lipoprotein profile could be obtained by vigorous soccer training. PMID:23152129

Imamura, H; Nagata, A; Oshikata, R; Yoshimura, Y; Miyamoto, N; Miyahara, K; Oda, K; Iide, K



Effect of proteolysis of low-density serum lipoproteins on their interaction with macrophages  

SciTech Connect

The authors previously postulated, on the basis of changes observed in the structural stability of low-density lipoproteins during treatment with pepsin or aortic cathepsin, that enzymatic modifications may lead to potentiation of the atherogenic properties of the lipoproteins. They also reported that treatment of lipoproteins with trypsin causes an increase in their binding with aortic glycosaminoglycans and to increased degradation by fibroblasts of patients with hereditary hypercholesterolemia. Limited proteolysis of lipoproteins with pepsin facilitated their binding with fibronectin. In this paper the authors investigate the uptake and degradation of low-density lipoproteins by macrophages after their limited hydrolysis by pepsin, an analog of tissue cathepsin D. The lipoproteins were isolated from the serum of healthy blood donors by ultracentrifugation. Iodination of the proteins with I 125 was carried out by the iodine monochloride method. Uptake and retention of the labelled lipoprotein were measured with a gamma counter. The increased uptake of the proteins, partially hydrolized by pepsin, was accompanied by their more intense degradation by macrophages.

Karmanskii, I.M.; Kovaleva, G.G.; Viktorova, L.N.; Shpikiter, V.O.



Effects of 1,2-cyclohexanedione modification on the metabolism of very low density lipoprotein apolipoprotein B: potential role of receptors in intermediate density lipoprotein catabolism  

SciTech Connect

The conversion of very low density (VLDL) to low density lipoproteins (LDL) is a two-step process. The first step is mediated by lipoprotein lipase, but the mechanism responsible for the second is obscure. In this study we examined the possible involvement of receptors at this stage. Apolipoprotein B (apoB)-containing lipoproteins were separated into three fractions, VLDL (Sf 100-400), an intermediate fraction IDL (Sf 12-100), and LDL (Sf 0-12). Autologous 125I-labeled VLDL and 131I-labeled 1,2-cyclohexanedione-modified VLDL were injected into the plasma of four normal subjects and the rate of transfer of apoB radioactivity was followed through IDL to LDL. Modification did not affect VLDL to IDL conversion. Thereafter, however, the catabolism of modified apoB in IDL was retarded and its appearance in LDL was delayed. Hence, functional arginine residues (and by implication, receptors) are required in this process. Confirmation of this was obtained by injecting 125I-labeled IDL and 131I-labeled cyclohexanedione-treated IDL into two additional subjects. Again, IDL metabolism was delayed by approximately 50% as a result of the modification. These data are consistent with the view that receptors are involved in the metabolism of intermediate density lipoprotein.

Packard, C.J.; Boag, D.E.; Clegg, R.; Bedford, D.; Shepherd, J.



PPAR? is a very low-density lipoprotein sensor in macrophages  

PubMed Central

Although triglyceride-rich particles, such as very low-density lipoprotein (VLDL), contribute significantly to human atherogenesis, the molecular basis for lipoprotein-driven pathogenicity is poorly understood. We demonstrate that in macrophages, VLDL functions as a transcriptional regulator via the activation of the nuclear receptor peroxisome proliferator-activated receptor ?. The signaling components of native VLDL are its triglycerides, whose activity is enhanced by lipoprotein lipase. Generation of peroxisome proliferator-activated receptor ? null macrophages verifies the absolute requirement of this transcription factor in mediating the VLDL response. Thus, our data reveal a pathway through which dietary triglycerides and VLDL can directly regulate gene expression in atherosclerotic lesions.

Chawla, Ajay; Lee, Chih-Hao; Barak, Yaacov; He, Weimin; Rosenfeld, John; Liao, Debbie; Han, Jungyeob; Kang, Heonjoong; Evans, Ronald M.



Low-density lipoprotein receptors in liver: Old acquaintances and a newcomer.  


The lipoprotein receptors low-density lipoprotein receptor (LDLR), the low-density lipoprotein receptor-related protein 1 (LRP1) and megalin/LRP2 share characteristic structural elements. In addition to their well-known roles in endocytosis of lipoproteins and systemic lipid homeostasis, it has been established that LRP1 mediates the endocytotic clearance of a multitude of extracellular ligands and regulates diverse signaling processes such as growth factor signaling, inflammatory signaling pathways, apoptosis, and phagocytosis in liver. Here, possible functions of LRP1 expression in hepatocytes and non-parenchymal cells in healthy and injured liver are discussed. Recent studies indicate the expression of megalin (LRP2) by hepatic stellate cells, myofibroblasts and Kupffer cells and hypothesize that LRP2 might represent another potential regulator of hepatic inflammatory processes. These observations provide the experimental framework for the systematic and dynamic analysis of the LDLR family during chronic liver injury and fibrogenesis. PMID:23545565

Pieper-Fürst, Ursula; Lammert, Frank



Low-density lipoprotein receptors in liver: old acquaintances and a newcomer.  


The lipoprotein receptors low-density lipoprotein receptor (LDLR), the low-density lipoprotein receptor-related protein 1 (LRP1) and megalin/LRP2 share characteristic structural elements. In addition to their well-known roles in endocytosis of lipoproteins and systemic lipid homeostasis, it has been established that LRP1 mediates the endocytotic clearance of a multitude of extracellular ligands and regulates diverse signaling processes such as growth factor signaling, inflammatory signaling pathways, apoptosis, and phagocytosis in liver. Here, possible functions of LRP1 expression in hepatocytes and non-parenchymal cells in healthy and injured liver are discussed. Recent studies indicate the expression of megalin (LRP2) by hepatic stellate cells, myofibroblasts and Kupffer cells and hypothesize that LRP2 might represent another potential regulator of hepatic inflammatory processes. These observations provide the experimental framework for the systematic and dynamic analysis of the LDLR family during chronic liver injury and fibrogenesis. PMID:24046859

Pieper-Fürst, Ursula; Lammert, Frank



Effects of fish oil fatty acids on low density lipoprotein size, oxidizability, and uptake by macrophages  

Microsoft Academic Search

The effect of fish oil and corn oil supplementation on plasma lipids and lipoproteins and on low density lipoprotein (LDL) oxidation was examined in 20 treated hypertensive sub- jects. The randomized double-blind crossover study consisted of two 6-week interventions with 4 g\\/day of a highly purified fish oil or corn oil. Fish oil significantly (- 24%, P < 0.01) reduced

Michio Suzukawa; Mavis Abbey; Peter R. C. Howe; Paul J. Nestel


Combined Statin and Niacin Therapy Remodels the High-Density Lipoprotein Proteome  

Microsoft Academic Search

Background—Boosting low high-density lipoprotein (HDL) levels is a current strategy for preventing clinical events that result from cardiovascular disease. We previously showed that HDL3 of subjects with coronary artery disease is enriched in apolipoprotein E and that the lipoprotein carries a distinct protein cargo. This observation suggests that altered protein composition might affect the antiatherogenic and antiinflammatory properties of HDL.

Pattie S. Green; Tomas Vaisar; Subramaniam Pennathur; J. Jacob Kulstad; Andrew B. Moore; Santica Marcovina; John Brunzell; Robert H. Knopp; Xue-Qiao Zhao; Jay W. Heinecke



Receptor-mediated uptake of low density lipoprotein stimulates bile acid synthesis by cultured rat hepatocytes  

Microsoft Academic Search

The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms\\/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, respectively. As a result of the uptake of LDL, the synthesis of (14C)cholesterol from

Louis H. Junker; Roger A. Davis



The significance of autoantibodies against oxidatively modified low-density lipoprotein (LDL) in patients with psoriasis  

Microsoft Academic Search

Psoriasis is associated with changes in plasma lipid and lipoproteins, which may play a role in the development of occlusive vascular disease. The oxidation of low-density lipoprotein (LDL) is considered a key event in the development and progression of atherosclerosis. Autoantibodies against oxidized LDL (auAb-oxLDL) may contribute to understanding the relationship between oxidative processes and development of atherosclerosis. Thirty-three patients

Asim Örem; Gülseren Çim?it; Orhan De?er; Cihan Örem; Birgül Vanizor



Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants  

Microsoft Academic Search

Human serum paraoxonase (PON1) can protect low density lipoprotein (LDL) from oxidation induced by either copper ion or by the free radical generator azo bis amidinopropane hydrochloride (AAPH). During LDL oxidation in both of these systems, a time-dependent inactivation of PON arylesterase activity was observed. Oxidized LDL (Ox-LDL) produced by lipoprotein incubation with either copper ion or with AAPH, indeed

Michael Aviram; Mira Rosenblat; Scott Billecke; John Erogul; Robert Sorenson; Charles L Bisgaier; Roger S Newton; Bert La Du



Evaluation of oxidized low-density lipoprotein and large molecular size low-density lipoproteins in atherosclerosis.  


To study the roles of modified low-density lipoprotein (LDL) and the molecular size of LDL in atherogenesis, the following studies were carried out. Eight white male rabbits fed a standard oriental diet with 1% cholesterol were used to isolate LDL and to observe changes in the molecular size of LDL due to cholesterol feeding. The tissue LDLs in the aorta were analyzed to confirm the existence of modified LDL (namely, LDL with peroxidized cholesteryl ester) by thin-layer chromatography. In addition, plasma LDLs were isolated from 18 patients with myocardial infarction and 11 patients with angina pectoris to confirm the existence of LDL with peroxidized cholesteryl ester. Each LDL separated consisted of 3 fractions; namely, IDL (1.006-1.018), LDL1 (1.019-1.052) and LDL2 (1.053-1.063) by sequential ultracentrifugation. The molecular sizes of LDL were measured by a planimeter from electron microscopic photographs, with negative staining. The estimation of peroxidized cholesteryl linoleate in LDL was performed using our method. The modified LDLs with peroxidized cholesteryl ester were poorly estimated in the LDL separated from the plasma of cholesterol-fed rabbits and from the aorta extraction after 16 weeks of feeding. The peroxidized cholesteryl ester was clearly identified in the plasma LDLs of the patients with myocardial infarction and angina pectoris, and in whole extracts from human aortic atheroma, although it was not clearly identified in the tissue LDL fraction. The molecular sizes of LDL1 enlarged week by week with cholesterol feeding, but two fractions of IDL and LDL2 did not change in size. The infusion of cholesterol-rich LDL of large molecular size or LDL with peroxidized cholesteryl ester into the vessels led to fixation, on the surface of the arteries of many platelets, red cells, and white cells, and to marked irregularities in the endothelial folds. The evidence suggests that atheromas, formed in a short period in rabbits with cholesterol feeding, are caused mainly by the increase in LDL1 of large molecular size, and that foam cells, formed in human atheromas, are caused mainly by the production of modified LDL with peroxidized cholesteryl ester. PMID:8216842

Kanazawa, T; Osanai, T; Uemura, T; Onodera, K; Oike, Y



Effects of oxidized low-density lipoprotein on leukocyte-endothelial interactions in the rat mesenteric microcirculation during pregnancy  

Microsoft Academic Search

ObjectiveThe accumulation of evidence implicates oxidized lipoproteins in atherosclerosis. Treatment of endothelial cells with these lipoproteins stimulates monocyte binding and the production of chemotactic factors that contribute to inflammation and endothelial injury and dysfunction. In preeclampsia, circulating low-density lipoprotein particles, which are susceptible to oxidation, are increased. We studied leukocyte-endothelial interactions that were related to oxidized lipoproteins in pregnant rats.

Tomihiro Katayama; Akari Tanaka-Shiraishi; Masaki Kiyomura; Takashi Matsumoto; Yasuki Kusanagi; Masaharu Ito



ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins.  


The mechanisms responsible for the inverse relationship between plasma high-density lipoprotein (HDL) levels and atherosclerotic cardiovascular disease are poorly understood. The ATP-binding cassette transporter A1 (ABCA1) mediates efflux of cellular cholesterol to lipid-poor apolipoproteins but not to HDL particles that constitute the bulk of plasma HDL. We show that two ABC transporters of unknown function, ABCG1 and ABCG4, mediate isotopic and net mass efflux of cellular cholesterol to HDL. In transfected 293 cells, ABCG1 and ABCG4 stimulate cholesterol efflux to both smaller (HDL-3) and larger (HDL-2) subclasses but not to lipid-poor apoA-I. Treatment of macrophages with an liver X receptor activator results in up-regulation of ABCG1 and increases cholesterol efflux to HDL. RNA interference reduced the expression of ABCG1 in liver X receptor-activated macrophages and caused a parallel decrease in cholesterol efflux to HDL. These studies indicate that ABCG1 and ABCG4 promote cholesterol efflux from cells to HDL. ABCG1 is highly expressed in macrophages and probably mediates cholesterol efflux from macrophage foam cells to the major HDL fractions, providing a mechanism to explain the relationship between HDL levels and atherosclerosis risk. PMID:15210959

Wang, Nan; Lan, Debin; Chen, Wengen; Matsuura, Fumihiko; Tall, Alan R



Impact of oxidized low density lipoprotein on vascular cells  

Microsoft Academic Search

Oxidized LDL (OxLDL) is a proatherogenic lipoprotein, accumulating in the vascular wall and contributing to the pathogenesis of vascular dysfunction early in the development of atherosclerosis. Enhanced serum levels of OxLDL, as well as antibodies against its epitopes, are predictive for endothelial dysfunction and coronary heart disease. While enhanced oxidative stress is one factor triggering formation of OxLDL, OxLDL itself

Jan Galle; Thomas Hansen-Hagge; Christoph Wanner; Stefan Seibold



Simvastatin and preparation of polyunsaturated phospholipids produce similar changes in the phospholipid composition of high-density lipoproteins during hypercholesterolemia.  


We studied the phospholipid composition of high-density lipoproteins in patients with coronary heart disease and hypercholesterolemia treated with simvastatin (Zocor, inhibitor of the key enzyme of cholesterol synthesis) and preparation of polyunsaturated phospholipids (lipostabil forte). Simvastatin produced a hypolipidemic effect and modulates the phospholipid composition of high-density lipoproteins (similarly to lipostabil forte). These changes contribute to functional activity of high-density lipoproteins in the reverse cholesterol transport. PMID:16027809

Ozerova, I N; Akhmedzhanov, N M; Perova, N V; Paramonova, I V



Acetaldehyde binding increases the catabolism of rat serum low-density lipoproteins  

SciTech Connect

Acetaldehyde was found to form adducts with rat serum lipoproteins. The binding of (/sup 14/C)acetaldehyde to lipoproteins was studied at low concentrations which are known to exist during ethanol oxidation. The amount of lipoprotein adducts was a linear function of acetaldehyde concentration up to 250 Incubation of rat plasma low-density lipoproteins (LDL) with 200 acetaldehyde increased the disappearance rate of the /sup 3/H-label from the cholesterol ester moiety of LDL injected into normal rats. The data show that even low concentrations of acetaldehyde are capable of affecting LDL metabolism. These findings may provide an explanation for the low concentrations of serum LDL in alcoholics. The alcohol-induced hyperlipidemia includes either a lack of increase or a decrease in the low-density lipoprotein (LDL) concentration, but the underlying mechanism is not known. It has been shown previously, that the acetylation of lysine residues of LDL apoprotein (apoB) by acetanhydride leads to rapid uptake of LDL particles by macrophages through a non-LDL receptor pathway. Since acetaldehyde, the first toxic metabolite of ethanol, is a chemically reactive compound capable of binding to proteins, they tested whether acetaldehyde forms adducts with serum lipoproteins and subsequently alters the catabolism of LDL. 19 references, 2 figures, 1 table.

Savolainen, M.J.; Baraona, E.; Lieber, C.S.



Catalytically inactive lipoprotein lipase expression in muscle of transgenic mice increases very low density lipoprotein uptake: Direct evidence that lipoprotein lipase bridging occurs in vivo  

PubMed Central

Lipoprotein lipase (LPL) is the central enzyme in plasma triglyceride hydrolysis. In vitro studies have shown that LPL also can enhance lipoprotein uptake into cells via pathways that are independent of catalytic activity but require LPL as a molecular bridge between lipoproteins and proteoglycans or receptors. To investigate whether this bridging function occurs in vivo, two transgenic mouse lines were established expressing a muscle creatine kinase promoter-driven human LPL (hLPL) minigene mutated in the catalytic triad (Asp156 to Asn). Mutated hLPL was expressed only in muscle and led to 3,100 and 3,500 ng/ml homodimeric hLPL protein in post-heparin plasma but no hLPL catalytic activity. Less than 5 ng/ml hLPL was found in preheparin plasma, indicating that proteoglycan binding of mutated LPL was not impaired. Expression of inactive LPL did not rescue LPL knock-out mice from neonatal death. On the wild-type (LPL2) background, inactive LPL decreased very low density lipoprotein (VLDL)-triglycerides. On the heterozygote LPL knock-out background (LPL1) background, plasma triglyceride levels were lowered 22 and 33% in the two transgenic lines. After injection of radiolabeled VLDL, increased muscle uptake was observed for triglyceride-derived fatty acids (LPL2, 1.7×; LPL1, 1.8×), core cholesteryl ether (LPL2, 2.3×; LPL1, 2.7×), and apolipoprotein (LPL1, 1.8×; significantly less than cholesteryl ether). Skeletal muscle from transgenic lines had a mitochondriopathy with glycogen accumulation similar to mice expressing active hLPL in muscle. In conclusion, it appears that inactive LPL can act in vivo to mediate VLDL removal from plasma and uptake into tissues in which it is expressed.

Merkel, Martin; Kako, Yuko; Radner, Herbert; Cho, Irene S.; Ramasamy, Ravi; Brunzell, John D.; Goldberg, Ira J.; Breslow, Jan L.



Overexpression of hepatic lipase in transgenic rabbits leads to a marked reduction of plasma high density lipoproteins and intermediate density lipoproteins.  

PubMed Central

To elucidate the precise metabolic roles of hepatic lipase (HL), a human HL cDNA in a liver-specific expression vector was used to generate transgenic lines in the rabbit, an animal that normally expresses low levels of this enzyme. HL was detected in the plasma of all rabbits only after the administration of heparin; HL activity in transgenic rabbits was found at levels up to 80-fold greater than that in nontransgenic littermates. This increase in enzyme activity was associated with as much as a 5-fold decrease in total plasma cholesterol levels. Expression of the transgene resulted in a dramatic reduction in the level of large high density lipoproteins (HDL1 and HDL2) as well as dense HDL3. A reduction in the quantity of intermediate density lipoproteins (IDL) was also observed. These results demonstrate that HL functions in the metabolism of HDL and IDL, thereby playing a key role in plasma cholesterol homeostasis. Images

Fan, J; Wang, J; Bensadoun, A; Lauer, S J; Dang, Q; Mahley, R W; Taylor, J M



Endothelial vasodilator function is related to low-density lipoprotein particle size and low-density lipoprotein vitamin E content in type 1 diabetes  

Microsoft Academic Search

OBJECTIVESWe sought to determine whether endothelial vasodilator function (EVF) in patients with type 1 diabetes was related to low-density lipoprotein (LDL) particle size (LDLPS), LDL vitamin E content (LDLVE) or the susceptibility of LDL to oxidation (OxLDL).BACKGROUNDImpaired EVF is an early feature of diabetic vascular disease and may be related to oxidant stress. Although small, dense LDL and oxidized LDL

R. Andrew P Skyrme-Jones; Richard C O’Brien; Ming Luo; Ian T Meredith



Detection of autoantibodies against oxidized low-density lipoproteins and of IgG-bound low density lipoproteins in patients with coronary artery disease  

Microsoft Academic Search

The role of oxidized low-density lipoprotein (ox-LDL) in the pathogenesis of atherosclerosis has been the object of intense investigation. It has been proposed that, due to the antigenic properties of ox-LDL, the anti-ox-LDL antibody titre could represent a useful index of in vivo LDL oxidation. On the other hand, LDL immune complexes (LDL-IC) have been demonstrated in patients with coronary

Agnés Boullier; Martial Hamon; Evelyne Walters-Laporte; Françoise Martin-Nizart; Régine Mackereel; Jean-Charles Fruchart; Michel Bertrand; Patrick Duriez



Acute changes in lipid, lipoprotein, apolipoprotein, and low-density lipoprotein particle size after an endurance triathlon.  


The effect of an endurance triathlon (2.4-mile swim, 112-mile bicycle ride, 26.2-mile run, in succession) on plasma total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein (apo) A-I and B levels, and LDL particle size was determined in 34 male and six female participants 6 to 12 hours before and immediately after the completion of the triathlon. Plasma TG decreased significantly (70% decrease) in both men and women. In men the change in plasma TG was inversely associated with baseline TG values (P less than .0001). Plasma TC and LDL cholesterol did not change significantly in male athletes but decreased significantly in women. A significant increase in HDL cholesterol was observed in both men (18% increase, P less than .0001) and women (5% increase, P less than .01). In men the increase in HDL cholesterol was inversely correlated with the decrease in triglycerides (P less than .0002). Plasma apo A-I levels increased significantly only in the male group (P less than .005), whereas plasma apo B levels decreased significantly in both men and women (P less than .0005). LDL particle size increased in seven males, whereas in the remaining males and all females no change in LDL size was observed. The increase in LDL particle size in these seven subjects was associated with a greater decline in plasma TG compared with the remaining men (P less than .005) and women (P less than .03). These results indicate that prolonged strenuous physical exercise can induce acute modifications of plasma lipoproteins, which may in part be related to enhanced lipolysis. PMID:2505019

Lamon-Fava, S; McNamara, J R; Farber, H W; Hill, N S; Schaefer, E J



Two subpopulations of intermediate density lipoprotein and their relationship to plasma triglyceride and cholesterol levels  

Microsoft Academic Search

We observed the appearance of two intermediate density lipoprotein (IDL) subfractions on gradient gel electrophoresis of lipoproteins in the density range 1.006–1.030 g\\/ml and estimated their approximate concentrations in plasma in subjects with a wide range of lipid levels, from 0.55 to 28.0 mmol\\/l plasma triglyceride and 3.75–10.0 mmol\\/l cholesterol. The larger species, IDL-I (31.7±0.7 nm, mean±SD), showed little variation

Barbara J. Meyer; Muriel J. Caslake; Michael M. McConnell; Chris J. Packard



Hepatitis C virus and other Flaviviridae viruses enter cells via low density lipoprotein receptor  

PubMed Central

Endocytosis of the Flaviviridae viruses, hepatitis C virus, GB virus C/hepatitis G virus, and bovine viral diarrheal virus (BVDV) was shown to be mediated by low density lipoprotein (LDL) receptors on cultured cells by several lines of evidence: by the demonstration that endocytosis of these virus correlated with LDL receptor activity, by complete inhibition of detectable endocytosis by anti-LDL receptor antibody, by inhibition with anti-apolipoprotein E and -apolipoprotein B antibodies, by chemical methods abrogating lipoprotein/LDL receptor interactions, and by inhibition with the endocytosis inhibitor phenylarsine oxide. Confirmatory evidence was provided by the lack of detectable LDL receptor on cells known to be resistant to BVDV infection. Endocytosis via the LDL receptor was shown to be mediated by complexing of the virus to very low density lipoprotein or LDL but not high density lipoprotein. Studies using LDL receptor-deficient cells or a cytolytic BVDV system indicated that the LDL receptor may be the main but not exclusive means of cell entry of these viruses. Studies on other types of viruses indicated that this mechanism may not be exclusive to Flaviviridae but may be used by viruses that associate with lipoprotein in the blood. These findings provide evidence that the family of LDL receptors may serve as viral receptors.

Agnello, Vincent; Abel, Gyorgy; Elfahal, Mutasim; Knight, Glenn B.; Zhang, Qing-Xiu



Modification of Low Density Lipoprotein by Advanced Glycation End Products Contributes to the Dyslipidemia of Diabetes and Renal Insufficiency  

Microsoft Academic Search

Atherosclerosis develops rapidly in patients with diabetes or renal insufficiency. Plasma lipoprotein profiles are frequently abnormal in these conditions and reflect an elevation in the level of the apoprotein B (ApoB)-containing components very low density lipoprotein (VLDL) and low density lipoprotein (LDL). High levels of circulating advanced glycation end products (AGEs) also occur in diabetes and end-stage renal disease (ESRD).

Richard Bucala; Zenji Makita; Gloria Vega; Scott Grundy; Theodor Koschinsky; Anthony Cerami; Helen Vlassara



Orange juice decreases low-density lipoprotein cholesterol in hypercholesterolemic subjects and improves lipid transfer to high-density lipoprotein in normal and hypercholesterolemic subjects.  


Orange juice (OJ) is regularly consumed worldwide, but its effects on plasma lipids have rarely been explored. This study hypothesized that consumption of OJ concentrate would improve lipid levels and lipid metabolism, which are important in high-density lipoprotein (HDL) function in normolipidemic (NC) and hypercholesterolemic (HCH) subjects. Fourteen HCH and 31 NC adults consumed 750 mL/day OJ concentrate (1:6 OJ/water) for 60 days. Eight control subjects did not consume OJ for 60 days. Plasma was collected before and on the last day for biochemical analysis and an in vitro assay of transfers of radioactively labeled free-cholesterol, cholesteryl esters, phospholipids, and triglycerides from lipoprotein-like nanoemulsions to HDL. Orange juice consumption decreased low-density lipoprotein cholesterol (160 ± 17 to 141 ± 26 mg/dL, P < .01) in the HCH group but not in the NC group. HDL-cholesterol and triglycerides remained unchanged in both groups. Free-cholesterol transfer to HDL increased (HCH: 4.4 ± 2 to 5.6 ± 1%, NC: 3.2 ± 2 to 6.2 ± 1%, P< .05) whereas triglyceride (HCH 4.9 ± 1 to 3.1 ± 1%, NC 4.4 ± 1 to 3.4 ± 1%, P< .05) and phospholipid (HCH 21.6 ± 2 to 18.6 ± 3%, NC 20.2 ± 2 to 18.4 ± 2%, P < .05) transfers decreased in both groups. Cholesteryl-ester transfer decreased only in HCH (3.6 ± 1 to 3.1 ± 1%, P < .05), but not in NC. In control subjects, plasma lipids and transfers were unaltered for 60 days. Thus, by decreasing atherogenic low-density lipoprotein cholesterol in HCH and increasing HDL ability to take up free cholesterol in HCH and NC, OJ may be beneficial to both groups as free-cholesterol transfer to HDL is crucial for cholesterol esterification and reverse cholesterol transport. PMID:21056284

Cesar, Thais B; Aptekmann, Nancy P; Araujo, Milena P; Vinagre, Carmen C; Maranhão, Raul C



Pharmacogenomics of high-density lipoprotein-cholesterol-raising therapies.  


High levels of HDL cholesterol (HDL-C) have traditionally been linked to lower incidence of cardiovascular disease, prompting the search for effective and safe HDL-C raising pharmaceutical agents. Although drugs such as niacin and fibrates represent established therapeutic approaches, HDL-C response to such therapies is variable and heritable, suggesting a role for pharmacogenomic determinants. Multiple genetic polymorphisms, located primarily in genes encoding lipoproteins, cholesteryl ester transfer protein, transporters and CYP450 proteins have been shown to associate with HDL-C drug response in vitro and in epidemiologic studies. However, few of the pharmacogenomic findings have been independently validated, precluding the development of clinical tools that can be used to predict HDL-C response and leaving the goal of personalized medicine to future efforts. PMID:23469915

Aslibekyan, Stella; Straka, Robert J; Irvin, Marguerite R; Claas, Steven A; Arnett, Donna K



Expression of Scavenger Receptor-BI and Low-Density Lipoprotein Receptor and Differential Use of Lipoproteins to Support Early Steroidogenesis in Luteinizing Macaque Granulosa Cells  

PubMed Central

An ovulatory hCG stimulus to rhesus macaques undergoing controlled ovarian stimulation protocols results in a rapid and sustained increase in progesterone synthesis. The use of lipoproteins as a substrate for progesterone synthesis remains unclear, and the expression of lipoprotein receptors [very-low-density lipoprotein receptor (VLDLR), low-density lipoprotein receptor (LDLR), and scavenger receptor-BI (SR-BI)] soon after human chorionic gonadotropin (hCG) (<12 h) has not been characterized. This study investigated lipoprotein receptor expression and lipoprotein (VLDL, LDL, and HDL) support of steroidogenesis during luteinization of macaque granulosa cells. Granulosa cells were aspirated from rhesus monkeys undergoing controlled ovarian stimulation before or up to 24 h after an ovulatory hCG stimulus. The expression of VLDLR decreased within 3 h of hCG, whereas LDLR and SR-BI increased at 3 and 12 h, respectively. Granulosa cells isolated before hCG were cultured for 24 h in the presence of FSH or FSH plus hCG with or without VLDL, LDL, or HDL. Progesterone levels increased in the presence of hCG regardless of lipoprotein addition, although LDL, but not HDL, further augmented hCG-induced progesterone. Other cells were cultured with FSH or FSH plus hCG without an exogenous source of lipoprotein for 24 h, followed by an additional 24 h culture with or without lipoproteins. Cells treated with hCG in the absence of any lipoprotein were unable to maintain progesterone levels through 48 h, whereas LDL (but not HDL) sustained progesterone synthesis. These data suggest that an ovulatory stimulus rapidly mobilizes stored cholesterol esters for use as a progesterone substrate and that as these are depleted, new cholesterol esters are obtained through an LDLR- and/or SR-BI-mediated mechanism.

Cherian-Shaw, Mary; Puttabyatappa, Muraly; Greason, Erin; Rodriguez, Annabelle; VandeVoort, Catherine A.; Chaffin, Charles L.




Technology Transfer Automated Retrieval System (TEKTRAN)

The purpose of this review is to summarize the current understanding of the potentially anti-atherogenic properties of high-density lipoprotein related to its different components. Recent findings on the role of the different high-density lipoprotein subspecies in reverse cholesterol transport, infl...


Effects of Cancer upon High-Density and Other Lipoproteins1  

Microsoft Academic Search

SUMMARY Serum lipoprotein levels were measured in normal subjects and in patients with cancer. All normal adult subjects were classified according to the amounts of high-density lipopro- tein-2 in their sera. It was observed that subjects with low values also had a pronounced positive history of cancer in close blood relatives. The only significant difference between the groups of normal

Marion Barclay; Vladimir P. Skipski; Olga Terebus-Kekish; Edward M. Greene; Richard J. Kaufman; C. Chester Stock



Original Contribution Alcohol consumption is directly associated with circulating oxidized low-density lipoprotein  

Microsoft Academic Search

Findings on the association of alcohol consumption and oxidation of low-density lipoprotein (LDL), which is thought to play a crucial role in the generation of atherosclerotic lesion, are inconsistent. The aim of the present study was to investigate the association of total alcohol consumption and type of alcoholic beverage with circulating plasma LDL oxidation. This cross-sectional study included data of

Helmut Schroder; Montserrat Fíto; Tanja Weinbrenner; Maria-Isabel Covas


Hepatitis C Virus and other Flaviviridae Viruses Enter Cells via Low Density Lipoprotein Receptor  

Microsoft Academic Search

Endocytosis of the Flaviviridae viruses, hepatitis C virus, GB virus C\\/hepatitis G virus, and bovine viral diarrheal virus (BVDV) was shown to be mediated by low density lipoprotein (LDL) receptors on cultured cells by several lines of evidence: by the demonstration that endocytosis of these virus correlated with LDL receptor activity, by complete inhibition of detectable endocytosis by anti-LDL receptor

Vincent Agnello; Gyorgy Abel; Mutasim Elfahal; Glenn B. Knight; Qing-Xiu Zhang



Influence of Honey on the Suppression of Human Low Density Lipoprotein (LDL) Peroxidation (In Vitro)  

Microsoft Academic Search

The antioxidant activity of four honey samples from different floral sources (Acacia, Coriander, Sider and Palm) were evaluated with three different assays; DPPH free radical scavenging assay, superoxide anion generated in xanthine-xanthine oxidase (XOD) system and low density lipoprotein (LDL) peroxidation assay. The dark Palm and Sider honeys had the highest antioxidant activity in the DPPH assay. But all the

Ahmed G. Hegazi; Faten K. Abd El-Hady



Glycemic Index and Serum High-Density Lipoprotein Cholesterol Concentration Among US Adults  

Microsoft Academic Search

Background: Dietary glycemic index, an indicator of the ability of the carbohydrate to raise blood glucose lev- els, and glycemic load, the product of glycemic index and carbohydrate intake, have been positively related to risk of coronary heart disease. However, the relationships be- tween glycemic index and glycemic load and high- density lipoprotein cholesterol (HDL-C) concentration in the US population

Earl S. Ford; Simin Liu



Calcium-channel blockers inhibit human low-density lipoprotein oxidation by oxygen radicals  

Microsoft Academic Search

Previous studies have shown that calcium channel blockers may reduce the development of experimental athero-sclerosis, and that nifedipine may slow the progression of coronary atherosclerosis in humans. The mechanisms responsible for this antiatherogenic effect are still unclear. It has been recently proposed that oxygen free radicals can induce the oxidation of human low-density lipoproteins (LDL) and that oxidized LDL may

Claudio Napoli; Massimo Chiariello; Giuseppe Palumbo; Giuseppe Ambrosio



Localization of Low Density Lipoproteins In vivo: Final Technical Report, September 28, 1987-September 27, 1988.  

National Technical Information Service (NTIS)

We have found that low density lipoprotein derivatized with I-123- tyramine cellobiose (I-123-TyC-LDL) behaves like native LDL when used for biodistribution studies in animals and in humans, and that I-123-TyC-LDL appears more promising than Tc-99m-labele...

P. V. Harper



Low density lipoprotein receptor related protein 1 variant interacts with saturated fatty acids in Puerto Ricans  

Technology Transfer Automated Retrieval System (TEKTRAN)

Low density lipoprotein related receptor protein 1 (LRP1) is a multi-functional endocytic receptor that is highly expressed in adipocytes and the hypothalamus. Animal models and in vitro studies support a role for LRP1 in adipocyte metabolism and leptin signaling, but genetic polymorphisms have not ...


High density lipoprotein cholesterol concentration as a predictor of coronary heart disease in West Indian men.  

PubMed Central

STUDY OBJECTIVE--The aim of the study was to determine whether the inverse association between high density lipoprotein cholesterol concentration and risk of coronary heart disease described in people of European stock was also present in other racial groups. DESIGN--The study was a prospective population survey. Cardiovascular risk factors were examined, including fasting serum lipid estimation (obtained at recruitment). SETTING--This was a community based study within a defined survey area in Trinidad. PARTICIPANTS--All men aged between 35 and 69 years within the survey area were identified and followed between 1977 and 1986. Analysis was confined to those of African, Asian Indian, and mixed descent who were free of coronary heart disease at entry (n = 960, 69% of age eligible men in the survey population). MEASUREMENTS AND MAIN RESULTS--64 men developed coronary heart disease during the study period. A strong inverse curvilinear relation was found between high density lipoprotein cholesterol and coronary heart disease incidence (p less than 0.005), independent of age or other relevant characteristics including low density lipoprotein cholesterol. CONCLUSIONS--A low serum concentration of high density lipoprotein cholesterol is a risk factor for coronary heart disease in non-whites as well as in whites.

Miller, G J; Beckles, G L; Maude, G H; Carson, D C; Price, S G



Additive or synergetic effects of phenolic compounds on human low density lipoprotein oxidation  

Microsoft Academic Search

The in vitro assessment of the antioxidant capacity of four phenolic compounds; catechin, hesperidin, ferulic acid, and quercetin was evaluated by the examination of their ability to inhibit copper (Cu2+)-mediated human low density lipoprotein (LDL) oxidation by using the thiobarbituric acid-reactive substances (TBARS) assay. Individually, the enrichment of LDLs with various concentrations of catechin, hesperidin, ferulic acid, and quercetin produced

Tatiana. L. Cirico



Mechanisms by which cysteine can inhibit or promote the oxidation of low density lipoprotein by copper  

Microsoft Academic Search

Oxidised low density lipoprotein (LDL) may play a role in atherogenesis. We have investigated some of the mechanisms by which the thiol cysteine and the disulphide cystine can influence the oxidation of LDL by copper ions. Cysteine or cystine (100 ?M) inhibited the oxidation of native LDL by copper in a simple phosphate buffer. One of the mechanisms by which

Rebecca A. Patterson; David J. Lamb; David S. Leake



Antioxidant and prooxidant activity of a-tocopherol in human plasma and low density lipoprotein  

Microsoft Academic Search

a-Tocopherol is a classical lipophilic antioxidant well known as a scavenger of free radicals in a hydrophobic milieu. However, it can develop both anti- and prooxidant activity in isolated low density lipoprotein (LDL). It is un- known how these activities are balanced in vivo in human plasma. We studied oxidation of plasma and LDL isolated from healthy donors or from

Anatol Kontush; Barbara Finckh; Barbara Karten; Alfried Kohlschutter; Ulrike Beisiegel


High-Density Lipoprotein Particle Size and Concentration and Coronary Risk  

Microsoft Academic Search

Background: High-density lipoprotein (HDL) cholesterol levels are inversely related to risk for coronary artery disease (CAD). Because HDL particles are heterogeneous in size and composition, they may be differentially associated with other cardiovascular risk factors and with cardiovascular risk. Objective: To study the independent relationships of HDL size and particle concentration to risk for future CAD. Design: Nested case-control study

Harchaoui El K; B. J. Arsenault; R. Franssen; J. P. Després; G. K. Hovingh; E. S. G. Stroes; J. D. Otvos; N. J. Wareham; J. J. P. Kastelein; K. T. Khaw; S. M. Boekholdt



Comparative Effects of Copper, Iron, Vanadium and Titanium on Low Density Lipoprotein Oxidation in vitro  

Microsoft Academic Search

Introduction: Oxidation of low density lipoprotein (LDL) has been strongly implicated in the phathogenesis of atherosclerosis. The use of oxidants in dietary food stuff may lead to the production of oxidized LDL and may increase both the development and the progression of atherosclerosis. The present work investigated the effects of some elements including: copper (Cu), iron (Fe), vanadium (V) and

Mohsen Ani; Ali Asghar Moshtaghie; Hassan Ahmadvand



Identification and genetic control of two rabbit low-density lipoprotein allotypes  

Microsoft Academic Search

Rabbits were immunized with a low-density lipoprotein (LDL) preparation isolated from rabbit serum by ultracentrifugation. This elicited precipitin isoantibodies which distinguished two antigenically different genetic variants, i.e., allotypes of serum LDL. Both allotypes were identified as LDL by the following criteria: (1) the precipitin lines stained intensely with the lipid stain Sudan black B; (2) the antigens were found in

John J. Albers; Sheldon Dray



Low-density lipoprotein cholesterol can be chemically measured: A new superior method  

Microsoft Academic Search

The association between elevated levels of low-density lipoprotein (LDL) cholesterol and an increased risk of premature coronary heart disease (CHD) is well documented. Most clinical laboratories estimate LDL cholesterol concentrations according to the Friedewald formula. It provides a relatively reliable estimate of LDL cholesterol concentration, provided the triglyceride concentration is

Masahiko Okada; Hiroshi Matsui; Yasuki Ito; Akira Fujiwara; Koichi Inano



Direct Low Density Lipoprotein Cholesterol and Glycated Albumin Levels in Type 2 Diabetes Mellitus  

Technology Transfer Automated Retrieval System (TEKTRAN)

Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) have been associated with a decreased risk of these complications. The aim in this st...


Oxidized plasma high-density lipoprotein is decreased in Alzheimer's disease  

Microsoft Academic Search

Oxidative stress is implicated in the pathogenesis of Alzheimer's disease (AD), and the enzyme myeloperoxidase (MPO) has been identified as one source of reactive oxidants. MPO-mediated oxidation of high-density lipoprotein (HDL) plays an important role in the pathogenesis of atherosclerosis and although several links between cardiovascular disease and AD have been reported, surprisingly little is known about the role of

Constanze Bergt; Takanari Nakano; Jochen Ditterich; Charles DeCarli; Jason P. Eiserich



Association of low-density lipoprotein receptor polymorphisms and outcome of hepatitis C infection  

Microsoft Academic Search

The low-density lipoprotein receptor (LDLR) has been proposed to promote hepatitis C virus endocytosis and the cell membrane protein CD81 may also promote HCV host cell entry. The CD81 gene was sequenced to screen for novel polymorphisms, but no SNPs were identified. Polymorphisms within the LDLR gene are associated with the pathogenesis of familial hypercholesterolemia, atherosclerosis and obesity. We therefore

B J W Hennig; S Hellier; A J Frodsham; L Zhang; P Klenerman; S Knapp; M Wright; H C Thomas; M Thursz; A V S Hill



Identification of deletions in the human low density lipoprotein receptor gene  

Microsoft Academic Search

DNA samples from 70 unrelated UK patients with heterozygous familial hypercholesterolaemia were screened by Southern blot hybridisation with a 5' fragment of the human low density lipoprotein (LDL) receptor cDNA. In the majority of cases, the restriction fragment pattern of the LDL receptor gene was indistinguishable from that observed in normal subjects. However, three patients were found to have a

B Horsthemke; A Dunning; S Humphries



Native and Oxidized Low–Density Lipoproteins Enhance Superoxide Production from Diabetic Rat Glomeruli  

Microsoft Academic Search

Oxygen free radicals have been implicated in mediating diabetic complications, and patients with diabetic nephropathy frequently show increased levels of circulating and oxidized low–density lipoproteins (LDL). In the present study, we measured the superoxide production of glomeruli isolated from poorly controlled diabetic (streptozotocin) rats sacrificed 1 week and 1, and 3 months after the induction of diabetes. The animals were



Native and minimally oxidized low density lipoprotein depress smooth muscle matrix metalloproteinase levels  

Microsoft Academic Search

Vascular lesion development is associated with an accumulation of extracellular matrix proteins within the vessel wall. Matrix metalloproteinases (MMPs) degrade these proteins. Conversely, oxidized low density lipoprotein (LDL) is implicated in atherogenesis through, amongst other cellular effects, a stimulation of the deposition of collagen within the vascular lesion. The present study investigated the potential for an interaction between oxidized LDL

David Wilson; Hamid Massaeli; Grant N. Pierce; Peter Zahradka



Metabolic Heterogeneity Underlying Postprandial Lipemia among Men with Low Fasting High Density Lipoprotein Cholesterol Concentrations  

Microsoft Academic Search

The high triglyceride (TG) and low high density lipoprotein (HDL) cholesterol dyslipidemia has been associated with increased post- prandial lipemia. Although fasting TG is a powerful predictor of postprandial hyperlipidemia, the role of hypoalphalipoproteinemia in postprandial TG metabolism is uncertain. We have studied postpran- dial lipemia among 63 men with low fasting plasma HDL cholesterol concentrations (,0.9 mmol\\/L), but with




Impact of postprandial variation in triglyceridemia on low-density lipoprotein particle size  

Microsoft Academic Search

The fasting atherogenic dyslipidemia of visceral obesity, which includes the presence of small, dense low-density lipoprotein (LDL) particles, is predictive of an increased risk of coronary heart disease (CHD). It has also been suggested that progression of atherosclerosis may be accelerated in the presence of postprandial hyperlipidemia independently from the fasting dyslipidemic state. Studies have shown that the best predictor

Patricia Blackburn; Mélanie Côté; Charles Couillard; Agnès Pascot; Angelo Tremblay; Jean Bergeron; Isabelle Lemieux; Jean-Pierre Després



Intake of trans fatty acids and low-density lipoprotein size in a Costa Rican population  

Microsoft Academic Search

Intervention studies show that dietary composition altered low-density lipoprotein (LDL) particle size, but population studies are scarce, and the potential effects of trans fatty acids (FA) on LDL size are unknown. Trans FA intake has been associated with a more atherogenic lipid profile and increased coronary heart disease (CHD). We examined the association between dietary intake, including trans FA and

Mi Kyung Kim; Hannia Campos



Comparison of apolipoprotein B to cholesterol in low density lipoproteins of patients with coronary heart disease  

Microsoft Academic Search

This study was carried out to determine whether patients with coronary heart disease (CHD) have an unusually high level of apolipoprotein B (apoB) relative to cholesterol (C) in low density lipoproteins (LDL). Seven groups of men were studied. Seventy-two with normolipidemia (NLP) had CHD doc- umented on clinical grounds; another 34 NLP patients had proven coronary artery disease (CAD) by

Gloria Lena Vega; Scott M. Grundy


Serum High-Density Lipoprotein Cholesterol Levels and Mortality in Frail, Community-Living Elderly  

Microsoft Academic Search

Background: High-density lipoprotein (HDL) cholesterol has been hypothesized to be a reliable marker of frailty and poor prognosis among the oldest elderly. Objective: In the present study, we evaluate the impact of HDL cholesterol on the risk of all-cause mortality in a large population of frail octogenarians and nonagenarians living in a community. Methods: We analyzed data from the Aging

Francesco Landi; Andrea Russo; Marco Pahor; Ettore Capoluongo; Rosa Liperoti; Matteo Cesari; Roberto Bernabei; Graziano Onder



Familial defective apolipoprotein B100: low density lipoproteins with abnormal receptor binding  

Microsoft Academic Search

Previous in vivo turnover studies suggested that retarded clearance of low density lipoproteins (LDL) from the plasma of some hypercholesterolemic patients is due to LDL with defective receptor binding. The present study examined this postulate directly by receptor binding experiments. The LDL from a hypercholesterolemic patient (G.R.) displayed a reduced ability to bind to the LDL receptors on normal human

T. L. Innerarity; K. H. Weisgraber; K. S. Arnold; R. W. Mahley; R. M. Krauss; G. L. Vega; S. M. Grundy



Low density lipoprotein oxidation is inhibited in vitro by olive oil constituents  

Microsoft Academic Search

Oxidation of low density lipoproteins maybe a factor in the development of atherosclerosis. The Mediterranean diet rich in vegetables, grains, legumes, fruits, and oils, mainly olive oil, has been suggested to reduce the incidence of coronary heart disease, because of its low saturated and high monounsaturated fatty acids content. It is also possible that the natural antioxidants in the oil

Francesco Visioli; Giorgio Bellomo; GianFranco Montedoro; Claudio Galli



Heparinized polyvinyl alcohol to specifically adsorb low-density lipoprotein from plasma  

Microsoft Academic Search

IntroductionA medical adsorbent for blood purification was developed to specifically adsorb low-density lipoprotein (LDL) from hypercholesterolemia patient’s plasma by covalently immobilizing heparin onto the surface of polyvinyl alcohol (PVA) with the couplant toluence-2,4-diisocyanate (TDI).

Kai-wang Ma; Xiao-zhen Dai; Shu-ying Feng; Ai-hua Jing; Jian-ying Yang



Effect of ingestion of virgin olive oil on human low-density lipoprotein composition  

Microsoft Academic Search

Objective: To measure the incorporation of oleic acid and antioxidants (phenols and vitamin E) to low density lipoprotein (LDL) after acute and short-term ingestion of virgin olive oil. To study whether this incorporation contributes to an increase in LDL resistance to oxidation.Setting: Department of Food and Nutrition, University of Barcelona, Spain and Department of Lipids and Cardiovascular Epidemiology, IMIM, Barcelona,

E Gimeno; M Fitó; RM Lamuela-Raventós; AI Castellote; M Covas; M Farré; MC de la Torre-Boronat; MC López-Sabater



Oxidized low density lipoprotein inhibits the migration of aortic endothelial cells in vitro  

Microsoft Academic Search

Endothelial cell (EC) migration is a critical and initiating event in the formation of new blood ves- sels and in the repair of injured vessels. Compelling evidence suggests that oxidized low density lipoprotein (LDL) is present in atherosclerotic lesions, but its role in lesion formation has not been defined. We have ex- amined the role of oxidized LDL in regulating

Gurunathan Murugesan; Guy M. Chisolm; Paul L. Fox



Surface properties of native human plasma lipoproteins and lipoprotein models.  

PubMed Central

Plasma lipoprotein surface properties are important but poorly understood determinants of lipoprotein catabolism. To elucidate the relation between surface properties and surface reactivity, the physical properties of surface monolayers of native lipoproteins and lipoprotein models were investigated by fluorescent probes of surface lipid fluidity, surface lateral diffusion, and interfacial polarity, and by their reactivity to Naja melanoleuca phospholipase A2 (PLA2). Native lipoproteins were human very low, low-, and subclass 3 high-density lipoproteins (VLDL, LDL, and HDL3); models were 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or its ether analog in single-bilayer vesicles, large and small microemulsions of POPC and triolein, and reassembled HDL (apolipoprotein A-I plus phospholipid). Among lipoproteins, surface lipid fluidity increased in the order HDL3 < LDL < VLDL, varying inversely with their (protein + cholesterol)/phospholipid ratios. Models resembled VLDL in fluidity. Both lateral mobility in the surface monolayer and polarity of the interfacial region were lower in native lipoproteins than in models. Among native lipoproteins and models, increased fluidity in the surface monolayer was associated with increased reactivity to PLA2. Addition of cholesterol (up to 20 mol%) to models had little effect on PLA2 activity, whereas the addition of apolipoprotein C-III stimulated it. Single-bilayer vesicles, phospholipid-triolein microemulsions, and VLDL have surface monolayers that are quantitatively similar, and distinct from those of LDL and HDL3. Surface property and enzymatic reactivity differences between lipoproteins and models were associated with differences in surface monolayer protein and cholesterol contents. Thus differences in the surface properties that regulate lipolytic reactivity are a predictable function of surface composition.

Massey, J B; Pownall, H J



Niacin extended-release/simvastatin combination therapy produces larger favorable changes in high-density lipoprotein particles than atorvastatin monotherapy  

PubMed Central

Background The purpose of this research was to compare the effects of niacin extended-release in combination with simvastatin (NER/S) versus atorvastatin monotherapy on high-density lipoprotein (HDL) particle number and size in patients with hyperlipidemia or dyslipidemia from the SUPREME study. Methods This was a post hoc analysis of patients (n = 137) who completed the SUPREME study and who had lipid particle number and size measurements at both baseline and at week 12 by nuclear magnetic resonance spectroscopy. Following ?4 weeks without lipid-modifying therapy (washout period), the patients received NER/S 1000/40 mg/day for 4 weeks followed by NER/S 2000/40 mg/day for 8 weeks, or atorvastatin 40 mg/day for 12 weeks. Median percent changes in HDL particle number and size from baseline to week 12 were compared between the NER/S and atorvastatin treatment groups using the Wilcoxon rank-sum test. Distribution of HDL particle subclasses at week 12 was compared between the treatment groups using the Cochran–Mantel–Haenszel test. Results Treatment with NER/S resulted in a significantly greater percent reduction in small HDL particle number at week 12 compared with atorvastatin monotherapy (?1.8% versus 4.2%, P = 0.014), and a numerically greater percent increase in large HDL particle number (102.4% versus 39.2%, P = 0.078) compared with atorvastatin monotherapy. A significantly greater percent increase in HDL particle size from baseline at week 12 was observed with NER/S compared with atorvastatin (6.0% versus 1.3%, P < 0.001). NER/S treatment also resulted in a significant shift in HDL particle size from small and medium at baseline to large at week 12 (P < 0.0001). Conclusion Treatment with NER/S resulted in larger favorable changes in number and size of HDL particle subclasses compared with atorvastatin monotherapy, including a numerically greater increase in number of large HDL particles, and a significantly greater decrease in number of small HDL particles compared with atorvastatin monotherapy. In addition, NER/S treatment resulted in a significant change in HDL particle size distribution from small and medium to large.

Toth, Peter P; Thakker, Kamlesh M; Jiang, Ping; Padley, Robert J



A very-high-density lipoprotein with clotting ability from hemolymph of sand crayfish, Ibacus ciliatus.  


A very-high-density lipoprotein (VHDL) with a density of 1.27-1.29 g/ml was the most abundant lipoprotein in the hemolymph of the sand crayfish Ibacus ciliatus. The VHDL isolated by a density gradient ultracentrifugation consisted of 94% protein and 6% lipid reflecting its high density, and phospholipid was a predominant lipid component. The VHDL had an apolipoprotein of molecular mass 195 kDa and its N-terminal amino acid sequence was identified as follows: LQPGLEYQYRYNGRVAA. This sequence was similar to those of clotting proteins from the spiny lobster Panulirus interruptus and the freshwater crayfish Pacifastacus leniusculus. Transglutaminase and Ca2+ also induced the VHDL to clot. Considering large amounts of VHDL in the hemolymph of sand crayfish, the VHDL not only functions as lipid carrier but plays an important role in the defense process of crustacea. PMID:9571775

Komatsu, M; Ando, S



Lipoprotein lipase mediates an increase in the selective uptake of high density lipoprotein-associated cholesteryl esters by hepatic cells in culture  

Microsoft Academic Search

In this study the effect of lipoprotein lipase (LPL) on the selective uptake of high density lipoprotein (HDL) cholesteryl esters (CE) by hepatic cells was investi- gated. Human HDL 3 (d 1.125-1.21 g\\/ml) was radiolabeled with 125 I in the protein moiety and with 3 H in the CE moiety. LPL was prepared from bovine milk. Human hepatocytes in primary

Franz Rinninger; Tatjana Kaiser; W. Alexander Mann; Nicolette Meyer; Heiner Greten; Ulrike Beisiegel


Intensive insulin therapy reduces small dense low-density lipoprotein particles in patients with type 2 diabetes mellitus: relationship to triglyceride-rich lipoprotein subspecies  

Microsoft Academic Search

It remains unclear whether insulin improves dyslipidemia in patients with type 2 diabetes mellitus. Small dense low-density lipoprotein (sd-LDL) particles are recognized as a powerful risk factor for coronary heart disease and are often elevated in type 2 diabetes mellitus. We examined the effect of intensive insulin therapy on sd-LDL particles and triglyceride (TG)–rich lipoprotein subspecies. Intensive insulin therapy (insulin

Toshiyuki Hayashi; Tsutomu Hirano; Takeshi Yamamoto; Yasuki Ito; Mitsuru Adachi



Serum high density lipoprotein cholesterol, alcohol, and coronary mortality in male smokers.  

PubMed Central

OBJECTIVE--To determine whether the increase in mortality from coronary heart disease with high concentration (> 1.75 mmol/l) of high density lipoprotein cholesterol could be due to alcohol intake. DESIGN--Cohort study. SETTING--Placebo group of the alpha tocopherol, beta carotene cancer prevention (ATBC) study of south western population in Finland. PARTICIPANTS--7052 male smokers aged 50-69 years enrolled to the ATBC study in the 1980s. MAIN OUTCOME MEASURES--The relative and absolute rates adjusted for risk factors for clinically or pathologically verified deaths from coronary heart disease for different concentrations of high density lipoprotein cholesterol with and without stratification for alcohol intake. Similar rates were also calculated for different alcohol consumption groups. RESULTS--During the average follow up period of 6.7 years 258 men died from verified coronary heart disease. Coronary death rate steadily decreased with increasing concentration of high density lipoprotein cholesterol until a high concentration. An increase in the rate was observed above 1.75 mmol/l. This increase occurred among those who reported alcohol intake. Mortality was associated with alcohol intake in a J shaped dose response, and those who reported consuming more than five drinks a day (heavy drinkers) had the highest death rate. Mortality was higher in heavy drinkers than in non-drinkers or light or moderate drinkers in all high density lipoprotein categories from 0.91 mmol/l upward. CONCLUSIONS--Mortality from coronary heart disease increases at concentrations of high density lipoprotein cholesterol over 1.75 mmol/l. The mortality was highest among heavy drinkers, but an increase was found among light drinkers also.

Paunio, M.; Virtamo, J.; Gref, C. G.; Heinonen, O. P.



Reconstituted high density lipoprotein enriched with the polyene antibiotic amphotericin B  

Microsoft Academic Search

The polyene antibiotic amphotericin B (AMB) is an effective antifungal agent whose therapeutic potential is limited by poor aqueous solubility and toxicity toward host tissues. Addition of apolipoprotein A-I to a multilamellar phospholipid vesicle dispersion containing 20% (w\\/w) AMB induces the formation of reconstituted high density lipoprotein (rHDL), with solubilization of the antibiotic. Density gradient ultracentrifugation resulted in flotation of

Michael N. Oda; Peter L. Hargreaves; Jennifer A. Beckstead; Katherine A. Redmond; Rik van Antwerpen; Robert O. Ryan



Cholesteryl ester transfer activity in plasma measured by using solid-phase-bound high-density lipoprotein  

SciTech Connect

We studied the ability of lipid-transfer factors in plasma to promote transfer, to endogenous lipoproteins, of (/sup 3/H)cholesteryl ester from high-density lipoprotein (HDL) covalently bound to Sepharose 4B beads. After incubation for 2 h at 37 degrees C, 12 to 14% of the (/sup 3/H)cholesteryl ester had been transferred to the lipoproteins of the plasma, in the proportions 57% to HDL and 43% to low- and very-low-density lipoproteins. This process was a function of the amount of plasma present and was stimulated by addition of partly purified lipid-transfer protein. Transfer also depended on the concentration of donor HDL but was independent of the amount of acceptor lipoprotein. This simple evaluation of cholesteryl ester transfer does not require removal of lipoproteins from the plasma before incubation.

Sparks, D.L.; Frohlich, J.; Cullis, P.; Pritchard, P.H.



Catalytically Inactive Lipoprotein Lipase Expression in Muscle of Transgenic Mice Increases Very Low Density Lipoprotein Uptake: Direct Evidence that Lipoprotein Lipase Bridging Occurs in vivo  

Microsoft Academic Search

Lipoprotein lipase (LPL) is the central enzyme in plasma triglyceride hydrolysis. In vitro studies have shown that LPL also can enhance lipoprotein uptake into cells via pathways that are independent of catalytic activity but require LPL as a molecular bridge between lipoproteins and proteoglycans or receptors. To investigate whether this bridging function occurs in vivo, two transgenic mouse lines were

Martin Merkel; Yuko Kako; Herbert Radner; Irene S. Cho; Ravi Ramasamy; John D. Brunzell; Ira J. Goldberg; Jan L. Breslow



Low density lipoprotein fraction assay for cardiac disease risk  


A variable rate density gradient electrophoric gel is described which separates LDL subfractions with the precision of ultracentrifugation techniques. Also, an innovative bottom inlet mixing chamber particularly useful for producing these gels is described. 8 figs.

Krauss, R.M.; Blanche, P.J.; Orr, J.



Low and high density lipoprotein--cholesterol and coronary atherothrombosis.  


After reviewing the general characteristics of lipids (LDL-C, VLDL-C, HDL-C) and atherothrombosis, including the I-VIII degrees of its histopathological arterial lesions (with contributions of J. E. Edwards and R. Virmani), the authors described the P. Libby's data on lipoprotein-associated phospholipaseA2 (Lp-PLA2) and its two inflammatory mediators: lysophosphatidylcholine and oxidized nonesterified fatty acids. They are involved in plaque progression and vulnerability. Lp-PLA2 is an emerging proinflammatory marker. The new drug darapladib inhibits Lp-PLA2 and acts against inflammation. LDL-C is present in the atherosclerotic plaque from the circulating blood in arterial lumen (through the dysfunctional endothelium) and vasa vasorum as well as after the decomposition of foam cells (monocytes-phagocytes, smooth muscle and dendritic cells) and outpoured erythrocytes (its membranes) after hemorrhage. The blood from the arterial lumen can also enter the atherosclerotic plaque through the lesions in its fibrous cap (erosion, fissure, rupture). Atherosclerosis as a disease or as an inevitable accompaniment of aging ("the senescence hypothesis"). The familial hypercholesterolemia is usually due to mutation of just one gene--a defective LDL-C receptor gene on chromosome 19. The accelerated and severe atherosclerosis very resistant to therapy occurs. The patients with homozygous familial hypercholesterolemia can die of myocardial infarction in early childhood. Therapeutic decrease of LDL-C and increase of HDL-C slows down the evolution of atherosclerosis, stabilizes the atherosclerotic plaques, and even brings about their partial regression. Statins, niacin, ezetimibe, LDL-C apheresis, and surgery: shunt between the portal and inferior caval veins, liver transplantation, and partial ileal bypass. The elevated LDL-C is the most established risk factor for atherosclerosis with impact on coronary heart disease mortality of 26%, and it should be the primary target of preventive and therapeutic efforts. PMID:19702110

Kanjuh, Vladimir; Ostoji?, Miodrag; Lali?, Nebojsa; Stoki?, Edita; Adi?-Cemerli?, Nada; Gojkovi?-Bukarica, Ljiljana



Regulation of low density lipoprotein receptor activity in freshly isolated human lymphocytes.  


Circulating human lymphocytes freshly isolated from venous blood of 15 normal subjects exhibited a low capacity to bind, take up, and degrade 125I-labeled low density lipoprotein (LDL). However, when these cells were incubated for 72 h in the absence of lipoproteins, they gradually acquired in increased number of high affinity cell surface receptors for LDL. The increase in the number of LDL receptors was associated with a 16-fold increase in the rate at which the cells were able to take up and degrade the lipoprotein. The LDL binding and degradation processes that developed in normal lymphocytes exhibited the following characteristics; (a) high affinity (saturation was achieved at LDL concentrations below 50 mug protein/ml); (b) specificity (unlabeled LDL was much more effective than human high density lipoprotein or other plasma proteins in competing with 125I-LDL for binding to the LDL receptor); and(c) feedback regulation (the increase in the number of LDL receptors that appeared after incubation of freshly isolated lymphocytes in lipoprotein-deficient medium was prevented by exposure of the cells to either LDL or a mixture of 25-hydroxycholesterol plus cholesterol but not to HDL). Freshly isolated lymphocytes obtaine from three subjects with the homozygous form of familial hypercholesterolemia failed to develop normal amounts of LDL receptor activity when incubated in medium devoid of lipoproteins. The current data indicate: (a) that the LDL receptors that appear on the surface of cholesterol-deprived, normal human lymphocytes are genetically identical to the previously characterized LDL receptors of cultured human fibroblasts and long-term lymphoid cells and (b) that at least one cell type in the human body, the circulating human lymphocyte, has the capacity to produce a high affinity LDL receptor that mediates the cellular uptake and degradation of plasma LDL. PMID:186492

Ho, Y K; Brown, S; Bilheimer, D W; Goldstein, J L



Regulation of low density lipoprotein receptor activity in freshly isolated human lymphocytes.  

PubMed Central

Circulating human lymphocytes freshly isolated from venous blood of 15 normal subjects exhibited a low capacity to bind, take up, and degrade 125I-labeled low density lipoprotein (LDL). However, when these cells were incubated for 72 h in the absence of lipoproteins, they gradually acquired in increased number of high affinity cell surface receptors for LDL. The increase in the number of LDL receptors was associated with a 16-fold increase in the rate at which the cells were able to take up and degrade the lipoprotein. The LDL binding and degradation processes that developed in normal lymphocytes exhibited the following characteristics; (a) high affinity (saturation was achieved at LDL concentrations below 50 mug protein/ml); (b) specificity (unlabeled LDL was much more effective than human high density lipoprotein or other plasma proteins in competing with 125I-LDL for binding to the LDL receptor); and(c) feedback regulation (the increase in the number of LDL receptors that appeared after incubation of freshly isolated lymphocytes in lipoprotein-deficient medium was prevented by exposure of the cells to either LDL or a mixture of 25-hydroxycholesterol plus cholesterol but not to HDL). Freshly isolated lymphocytes obtaine from three subjects with the homozygous form of familial hypercholesterolemia failed to develop normal amounts of LDL receptor activity when incubated in medium devoid of lipoproteins. The current data indicate: (a) that the LDL receptors that appear on the surface of cholesterol-deprived, normal human lymphocytes are genetically identical to the previously characterized LDL receptors of cultured human fibroblasts and long-term lymphoid cells and (b) that at least one cell type in the human body, the circulating human lymphocyte, has the capacity to produce a high affinity LDL receptor that mediates the cellular uptake and degradation of plasma LDL.

Ho, Y K; Brown, S; Bilheimer, D W; Goldstein, J L



Anti-oxidized low-density lipoprotein antibodies in patients with coronary heart disease and normal healthy volunteers  

Microsoft Academic Search

Summary  We have developed a solid-phase enzyme immunoassay for anti-oxidized low-density lipoprotein antibodies. Most sera showed\\u000a some degree of non-specific binding to plates coated with oxidized low-density lipoprotein and the autoantibodies to oxidized\\u000a low-density lipoprotein often appeared to have a relatively low affinity. To differentiate between specific and non-specific\\u000a binding each sample was tested untreated and after absorption with oxidized low-density

Gabriel Virella; Isabel Virella; Robert B. Leman; Michael B. Pryor; Maria F. Lopes-Virella



Low density lipoprotein uptake by an endothelial-smooth muscle cell bilayer  

SciTech Connect

To study the interaction of endothelial and smooth muscle cells, and the means by which such interaction may affect lipid permeability of the arterial wall, cell bilayers were established by use of a transwell culture system. After confluent growth of both cell types had been achieved, iodine 125 bound to low-density lipoprotein (10 ng protein/ml) was added to the media of the upper well. After a 3-hour incubation period, the iodine 125-bound low-density lipoprotein content of the upper and lower media demonstrated an impedance to lipoprotein movement across the endothelial cell monolayer as compared to the bare porous polycarbonate filter of the transwell (p less than 10(-6)). The presence of smooth muscle cells in the bottom well significantly enhanced the permeability of the endothelial cell layer (p less than 10(-60)). This effect remained unchanged over a 9-day time course. Membrane binding and cellular uptake of low-density lipoprotein by endothelial cells was not altered by smooth muscle cells, indicating that this change in permeability could not be easily attributed to changes in receptor-mediated transport or transcytosis. Membrane binding (p less than 0.02) and cellular uptake (p less than 10(-6)) of low-density lipoprotein by smooth muscle cells in the bilayer, when adjusted for counts available in the smooth muscle cell media, were both reduced in the early incubation period as compared to isolated smooth muscle cells. The disproportionate reduction in uptake as compared to binding would suggest that this was not entirely a receptor-dependent process.

Alexander, J.J.; Miguel, R.; Graham, D. (Case Western Reserve Univ., Cleveland, OH (USA))



Hypertriglyceridemic Very Low Density Lipoproteins Induce Triglyceride Synthesis and Accumulation in Mouse Peritoneal Macrophages  

PubMed Central

Triglyceride-rich lipoproteins may be responsible for the lipid accumulation in macrophages that can occur in hypertriglyceridemia. Chylomicrons and very low density lipoproteins (VLDL, total and with flotation constant [Sf] 100-400) from fasting hypertriglyceridemic subjects induced a massive accumulation of oil red O-positive inclusions in unstimulated peritoneal macrophages. Cell viability was not affected. The predominant lipid that accumulated in cells exposed to hypertriglyceridemic VLDL was triglyceride. Hypertriglyceridemic VLDL stimulated the incorporation of [14C]oleate into cellular triglyceride up to ninefold in 16 h, but not into cholesteryl esters. Mass increase in cellular triglyceride was 38-fold. The stimulation of cellular triglyceride formation was dependent on time, temperature, and concentration of hypertriglyceridemic VLDL. By contrast, VLDL, low density, and high density lipoproteins from fasting normolipemic subjects had no significant effect on oleate incorporation into neutral lipids or on visible lipid accumulation. 125I-Hypertriglyceridemic VLDL (Sf 100-400) were degraded by macrophages in a dose-dependent manner, with 50 and 100% saturation observed at 3 and 24 ?g protein/ml (2.5 and 20 nM), respectively. Hypertriglyceridemic VLDL inhibited the internalization and degradation of 125I-hypertriglyceridemic VLDL (4 nM) by 50% at 3 nM. Cholesteryl ester-rich VLDL from cholesterol-fed rabbits gave 50% inhibition at 5 nM. Low density lipoproteins (LDL) inhibited by 10% at 5 nM and 40% at 47 nM. Acetyl LDL at 130 nM had no effect. We conclude that the massive triglyceride accumulation produced in macrophages by hypertriglyceridemic VLDL is a direct consequence of uptake via specific receptors that also recognize cholesteryl ester-rich VLDL and LDL but are distinct from the acetyl LDL receptor. Uptake of these triglyceride-rich lipoproteins by monocyte-macrophages in vivo may play a significant role in the pathophysiology of atherosclerosis. Images

Gianturco, Sandra H.; Bradley, William A.; Gotto, Antonio M.; Morrisett, Joel D.; Peavy, Duane L.



Low Density Lipoprotein Receptor-Related Protein-i Expression in the Testis: Regulated Expression in Sertoli Cells  

Microsoft Academic Search

The low density lipoprotein receptor-related protein (LRP-1) is a multiligand receptor capable of mediating endocytosis of a wide array of ligands that relate to both lipoprotein metabolism and proteinase regulation. Many of its ligands are proteinases, pro- teinase-inhibitor complexes, and lipoproteins known to be contained within the luminal fluid of the seminiferous tubules or in the interstitial spaces of the



Effects of fenofibrate and ezetimibe, both as monotherapy and in coadministration, on cholesterol mass within lipoprotein subfractions and low-density lipoprotein peak particle size in patients with mixed hyperlipidemia  

Microsoft Academic Search

Coadministration of fenofibrate and ezetimibe (FENO + EZE) produced complementary and favorable effects on the major lipids and lipoproteins, low-density lipoprotein cholesterol (LDL-C), triglycerides, high-density lipoprotein cholesterol (HDL-C), and non–HDL-C levels, and was well tolerated in patients with mixed hyperlipidemia. The current analysis evaluates the effects of FENO and EZE, as monotherapies and in coadministration, on lipoprotein subfractions and LDL

Diane L. Tribble; Michel Farnier; Geraldine Macdonell; Inna Perevozskaya; Michael J. Davies; Barry Gumbiner; Thomas A. Musliner



Reconstituted high density lipoprotein reduces the capacity of oxidatively modified low density lipoprotein to accumulate cholesteryl esters in mouse peritoneal macrophages  

Microsoft Academic Search

Oxidized low density lipoprotein (ox-LDL) was incubated with discoidal complexes of apolipoprotein A-I (apo A-I) and dimyristoylphosphatidylcholine (DMPC) (DMPC\\/apo A-I) in a cell-free system and re-isolated on Sephacryl S-400 gel filtration chromatography. Analyses of re-isolated ox-LDL showed that apo A-I was transferred from DMPC\\/apo A-I to ox-LDL, which accounted for 10% of the total protein of ox-LDL. Re-isolated ox-LDL also

Masakazu Sakai; Akira Miyazaki; Hideki Hakamata; Yoshiko Suginohara; Yu-Ichiro Sakamoto; Wataru Morikawa; Shozo Kobori; Motoaki Shichiri; Seikoh Horiuchi



Detection of haptoglobin in the high-density lipoprotein and the very high-density lipoprotein fractions from sera of calves with experimental pneumonia and cows with naturally occurring fatty liver.  


In addition to the lipoprotein-deficient d > 1.25 fraction, haptoglobin was detected in the high-density lipoprotein (HDL) and the very high-density lipoprotein (VHDL) fractions from sera of calves with experimental pneumonia and cows with naturally occurring fatty liver. It was not found in the chylomicrons, very low-density lipoprotein and low-density lipoprotein fractions. Washing of the HDL fraction did not decrease the haptoglobin concentration. Transferrin and immunoglobulin G were immunoblotted to examine the possibility of contamination of the lipoprotein fractions by the d > 1.25 fraction. The two serum proteins were detected only in the d > 1.25 fraction, not in any lipoprotein fractions. The distribution pattern of haptoglobin in the lipoprotein fractions was distinct from that of serum albumin. Concentrations of haptoglobin in the HDL fractions from pneumonic sera were largely proportional to those in whole sera. Cholesteryl ester concentrations were decreased in sera from calves with pneumonia, as in cows with fatty liver. A protein immunologically related to hemoglobin was also detected in particular in the VHDL fractions from sera of both groups. These results suggest that haptoglobin or a complex with the hemoglobin-like protein may have a role or roles related to the lipid metabolism. PMID:10081748

Katoh, N; Nakagawa, H



a Cyclodextrin extracts diacylglycerol from insect high density lipoproteins  

Microsoft Academic Search

a -Cyclodextrins are water-soluble cyclic hexa- mers of glucose units with hydrophobic cavities capable of solubilizing lipophiles. Incubating a -cyclodextrin with high density lipophorin from Manduca sexta or Bombyx mori re- sulted in a cloudy, turbid solution. Centrifugation separated a pale yellowish precipitate. Thin-layer chromatography anal- ysis of the lipid extract of the precipitate showed that the major lipid was

Zeina E. Jouni; Jorge Zamora; Marcus Snyder; William R. Montfort; Andrzej Weichsel; Michael A. Wells


Changes in the Serum Level of High Density Lipoprotein-cholesterol after Smoking Cessation among Adult Men  

PubMed Central

Background Smoking and obesity are known risk factors for cardiovascular diseases, while low serum levels of high density lipoprotein-cholesterol is an independent risk factor for mortality from ischemic heart diseases. This study examines changes in the serum level of high density lipoprotein-cholesterol depending on changes in the state of smoking and body mass index. Methods A survey and blood check-up were conducted on medical examination, along with acts of smoking among male adults of 25 years or older who visited the health promotion center of Daegu Medical Center from 2007 to 2010, and the results were analyzed. The subjects were divided into two different groups, current smokers and abstainers, and body mass index, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, and triglycerides for three years were compared in both groups. Changes between the first and second visits in body mass index and lipid profiles of the two groups were compared to analyze changes after abstaining. Results The subject group which showed a significant increase in high density lipoprotein-cholesterol level was only abstainers whose body mass index had decreased by more than 0.5 kg/m2. Conclusion Smoking cessation increases serum levels of high density lipoprotein-cholesterol. If reduction of body mass index and smoking cessation are combined, the risk of cardiovascular disease will be lower in proportion to the increase in serum high density lipoprotein.

Noh, Jung-Mun; Kim, Hyun-Woo; Yang, Hong-Seok



Apolipoprotein E on Hepatitis C Virion Facilitates Infection through Interaction with Low Density Lipoprotein Receptor  

PubMed Central

Hepatitis C virus (HCV) infection is a major cause of liver disease. HCV associates with host apolipoproteins and enters hepatocytes through complex processes involving some combination of CD81, claudin-I, occludin, and scavenger receptor BI. Here we show that infectious HCV resembles very low density lipoprotein (VLDL) and that entry involves co-receptor function of the low density lipoprotein receptor (LDL-R). Blocking experiments demonstrate that ?-VLDL itself or anti-apolipoprotein E (apoE) antibody can block HCV entry. Knockdown of the LDL-R by treatment with 25-hydroxycholesterol or siRNA ablated ligand uptake and reduced HCV infection of cells, whereas infection was rescued upon cell ectopic LDL-R expression. Analyses of gradient-fractionated HCV demonstrate that apoE is associated with HCV virions exhibiting peak infectivity and dependence upon the LDL-R for cell entry. Our results define the LDL-R as a cooperative HCV co-receptor that supports viral entry and infectivity through interaction with apoE ligand present in an infectious HCV/lipoprotein complex comprising the virion. Disruption of HCV/LDL-R interactions by altering lipoprotein metabolism may therefore represent a focus for future therapy.

Owen, David M.; Huang, Hua; Ye, Jin; Gale, Michael



[Beta amyloid in blood and cerebrospinal fluid is associated with high density lipoproteins].  


Cerebrovascular and parenchymal amyloid deposits found in brains of Alzheimer's disease, Down's syndrome and normal aging are mainly composed of aggregated amyloid beta protein (A beta), a unique peptide 39 to 44 amino acids long. A similar but soluble A beta (s A beta) has been identified in plasma, cerebrospinal fluid (CSF) and cell supernatants, indicating that it is a normal protein. We report here that s A beta in normal human plasma and CSF is complexed to high density lipoprotein (HDL) 3 and very high density lipoprotein (VHDL). Biotinylated synthetic peptide A beta 1-40 was traced in normal human plasma in in vitro experiments. Both tracer biotin-labeled A beta 1-40 and native s A beta were specifically recovered in HDL3 and VHDL as it was assessed in immunoprecipitation experiments of purified plasma lipoproteins and lipoprotein depleted plasma. This fact prompted us to ascertain whether the interaction of s A beta with HDL does occur in normal human CSF in vivo. For this purpose normals human CSF was fractionated by means of sequential flotation ultracentrifugation. The presence of s A beta in the resulting lipoprotein fractions as well as in the lipoprotein depleted CSF was analysed by immunoblot analysis, electron and immune-electron microscopy and native size exclusion chromatography. Immunoblot analysis with 6E10 monoclonal anti-A beta antibodies revealed s A beta association with all HDL subspecies of CSF, primarily HDL3 and VHDL and immunoelectron microscopy confirmed an association of s A beta with CSF-HDL particles of 16.8 + 3.2 nm. Native size exclusion chromatography followed by immunoblot analysis with antibodies against A beta and different apoliproproteins indicated an association of s A beta with HDL complexes of approximately 200 kDa molecular weight. Soluble A beta association with HDL3 and VHDL may be involved in maintaining the solubility of A beta in biological fluids and points to a possible role of lipoproteins and lipoprotein lipid in the biology of aminoloidogenic peptides. PMID:9139461

Kudinova, N V; Kudinov, A R; Berezov, T T


Combined roles of human IgG subclass, alternative complement pathway activation, and epitope density in the bactericidal activity of antibodies to meningococcal factor h binding protein.  


Meningococcal vaccines containing factor H binding protein (fHbp) are in clinical development. fHbp binds human fH, which enables the meningococcus to resist complement-mediated bacteriolysis. Previously, we found that chimeric human IgG1 mouse anti-fHbp monoclonal antibodies (MAbs) had human complement-mediated bactericidal activity only if the MAb inhibited fH binding. Since IgG subclasses differ in their ability to activate complement, we investigated the role of human IgG subclasses on antibody functional activity. We constructed chimeric MAbs in which three different murine fHbp-specific binding domains were each paired with human IgG1, IgG2, or IgG3. Against a wild-type group B isolate, all three IgG3 MAbs, irrespective of their ability to inhibit fH binding, had bactericidal activity that was >5-fold higher than the respective IgG1 MAbs, while the IgG2 MAbs had the least activity. Against a mutant with increased fHbp expression, the anti-fHbp MAbs elicited greater C4b deposition (classical pathway) and greater bactericidal activity than against the wild-type strain, and the IgG1 MAbs had similar or greater activity than the respective IgG3 MAbs. The bactericidal activity against both wild-type and mutant strains also was dependent, in part, on activation of the alternative complement pathway. Thus, at lower epitope density in the wild-type strain, the IgG3 anti-fHbp MAbs had the greatest bactericidal activity. At a higher epitope density in the mutant, the IgG1 MAbs had similar or greater bactericidal activity than the IgG3 MAbs, and the activity was less dependent on the inhibition of fH binding than at a lower epitope density. PMID:22064712

Giuntini, Serena; Reason, Donald C; Granoff, Dan M



Combined Roles of Human IgG Subclass, Alternative Complement Pathway Activation, and Epitope Density in the Bactericidal Activity of Antibodies to Meningococcal Factor H Binding Protein  

PubMed Central

Meningococcal vaccines containing factor H binding protein (fHbp) are in clinical development. fHbp binds human fH, which enables the meningococcus to resist complement-mediated bacteriolysis. Previously, we found that chimeric human IgG1 mouse anti-fHbp monoclonal antibodies (MAbs) had human complement-mediated bactericidal activity only if the MAb inhibited fH binding. Since IgG subclasses differ in their ability to activate complement, we investigated the role of human IgG subclasses on antibody functional activity. We constructed chimeric MAbs in which three different murine fHbp-specific binding domains were each paired with human IgG1, IgG2, or IgG3. Against a wild-type group B isolate, all three IgG3 MAbs, irrespective of their ability to inhibit fH binding, had bactericidal activity that was >5-fold higher than the respective IgG1 MAbs, while the IgG2 MAbs had the least activity. Against a mutant with increased fHbp expression, the anti-fHbp MAbs elicited greater C4b deposition (classical pathway) and greater bactericidal activity than against the wild-type strain, and the IgG1 MAbs had similar or greater activity than the respective IgG3 MAbs. The bactericidal activity against both wild-type and mutant strains also was dependent, in part, on activation of the alternative complement pathway. Thus, at lower epitope density in the wild-type strain, the IgG3 anti-fHbp MAbs had the greatest bactericidal activity. At a higher epitope density in the mutant, the IgG1 MAbs had similar or greater bactericidal activity than the IgG3 MAbs, and the activity was less dependent on the inhibition of fH binding than at a lower epitope density.

Giuntini, Serena; Reason, Donald C.



DNA polymorphisms at the lipoprotein lipase gene and their association with quantitative variation in plasma high-density lipoproteins and triacylglycerides.  


Lipoprotein lipase (LPL) plays a critical role in the metabolism of lipoproteins because this enzyme hydrolyzes the triacylglycerides in chylomicrons and very low density lipoproteins. This process influences the production of high-density lipoprotein (HDL), which takes up tissue cholesterol for transport to the liver for excretion. Accordingly, LPL qualifies as a candidate gene for understanding lipid metabolic disorders and atherosclerosis. Studies on the relationship between genetic variation at the LPL locus and lipid phenotypes have produced equivocal results to date. To help clarify this issue, we investigated 144 outwardly healthy male Mediterranean migrants (from Italy and Greece), age between 40 and 70 years and resident in Australia, for associations between two common LPL restriction site polymorphisms and the following lipid and lipoprotein phenotypes: total plasma cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triacylglycerides. A series of analysis of variance tests, controlling for age, body mass index, and ethnicity, showed that the HindIII polymorphism at the LPL locus is significantly associated with both triacylglyceride and HDL cholesterol concentrations in this sample. The PvUII polymorphism, however, showed no association with any lipid. Kruskal-Wallis tests confirmed the significance of the associations between the HindIII RFLP and both HDL (p = 0.008) and triacylglycerides (p = 0.03). When the sample was subdivided into subjects who exhibited primary hypertriacylglyceridemia and normolipidemics, a significant difference was observed in the frequency of HindIII (p < 0.05) but not PvuII genotypes. HindIII heterozygotes (H1,H2) were least and H2,H2 individuals were most at risk for triacylglyceridemia. Examination of the normolipidemic sample revealed some evidence for an independent effect of the PvuII polymorphism on both LDL cholesterol and total cholesterol levels. PMID:8026810

Mitchell, R J; Earl, L; Bray, P; Fripp, Y J; Williams, J



Isolation and characterization of a low-density lipoprotein fraction from plasma of the aquatic snail Ampullaria canaliculata  

Microsoft Academic Search

A novel gastropod lipoprotein was detected in Ampullaria canaliculata plasma after labeling the hemolymph with radioactive palmitic acid injected into the foot muscle. Labeled plasma was centrifuged in a density gradient and fractionated. A radioactive lipoprotein fraction of low density (hydrated density in the range of 1.029–1.048g\\/ml was isolated and its lipids were analyzed by TLC-FID. Free fatty acids, triacylglycerols

Claudia F. Garin; Ricardo J. Pollero



Metabolism of apoprotein B in selectively bred baboons with low and high levels of low density lipoproteins  

Microsoft Academic Search

Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) apoprotein (apo)-B turnover rates were mea- sured simultaneously by injecting 1311-labeled VLDL and Iz5I- labeled LDL into fasting baboons (Pupio sp.) selectively bred for high serum cholesterol levels and having either low or high LDL levels. The radioactivities in VLDL, intermediate density lipo- protein (IDL), LDL apoB, and urine were

Rampratap S. Kushwaha; George M. Barnwell; K. D. Carey; Henry C. McGill


Relationship of lipoprotein-associated phospholipase A2 and oxidized low density lipoprotein in carotid atherosclerosis[S  

PubMed Central

Plasma levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and oxidized low density lipoprotein (oxLDL) have been identified as risk factors for cardiovascular disease. Lp-PLA2 is the sole enzyme responsible for the hydrolysis of oxidized phospholipids on LDL particles in atherosclerotic plaques. We have studied the relationship between Lp-PLA2 and oxLDL in carotid endarterectomy (CEA) tissues and in matched plasmas. In extracts from CEA anatomical segments, the levels of oxLDL were significantly associated with the levels of Lp-PLA2 protein (r = 0.497) and activity (r = 0.615). OxLDL and Lp-PLA2 mass/activity were most abundant in the carotid bifurcation and internal segments where plaque was most abundant. In extracts from CEA atheroma, the levels of oxLDL and Lp-PLA2 were significantly correlated (r = 0.634). In matched plasma and atheroma extracts, the levels of Lp-PLA2 were negatively correlated (r = ? 0.578). The ratio of Lp-PLA2 to oxLDL was higher in atheromatous tissue (277:1) than in normal tissue (135:1) and plasma (13:1). Immunohistochemical experiments indicated that in plaques, oxLDL and Lp-PLA2 existed in overlapping but distinctly different distribution. Fluorescence microscopy showed both oxLDL and Lp-PLA2 epitopes on the same LDL particle in plasma but not in plaque. These results suggest that the relationship between Lp-PLA2 and oxLDL in the atherosclerotic plaque is different from that in the plasma compartment.

Vickers, Kasey C.; Maguire, Colin T.; Wolfert, Robert; Burns, Alan R.; Reardon, Michael; Geis, Richard; Holvoet, Paul; Morrisett, Joel D.



Plasma lipases and lipid transfer proteins increase phospholipid but not free cholesterol transfer from lipid emulsion to high density lipoproteins  

Microsoft Academic Search

BACKGROUND: Plasma lipases and lipid transfer proteins are involved in the generation and speciation of high density lipoproteins. In this study we have examined the influence of plasma lipases and lipid transfer protein activities on the transfer of free cholesterol (FC) and phospholipids (PL) from lipid emulsion to human, rat and mouse lipoproteins. The effect of the lipases was verified

Valéria S Nunes; Eder CR Quintão; Patrícia M Cazita; Lila M Harada; Eliana C de Faria; Helena CF Oliveira



Characterization of a Very High Density Lipoprotein Allergen, Dpt 4, from the House Dust Mite Dermatophagoides pteronyssinus  

Microsoft Academic Search

The allergen Dpt 4 from the house dust mite Dermatophagoides pteronyssinus was shown to be a lipoprotein as judged by its Sudan black B staining properties. Ultracentrifugal studies confirmed this finding and showed that Dpt 4 was polydisperse, although the majority of the allergen belonged to a very high density lipoprotein class. Physicochemical studies using gradient polyacrylamide gel electrophoresis showed

G. A. Stewart; A. Butcher; K. J. Turner



Novel lipoprotein density profiling in healthy dogs of various breeds, healthy miniature schnauzers, and miniature schnauzers with hyperlipidemia  

PubMed Central

Background Despite the importance of abnormalities in lipoprotein metabolism in clinical canine medicine, the fact that most previously used methods for lipoprotein profiling are rather laborious and time-consuming has been a major obstacle to the wide clinical application and use of lipoprotein profiling in this species. The aim of the present study was to assess the feasibility of a continuous lipoprotein density profile (CLPDP) generated within a bismuth sodium ethylenediaminetetraacetic acid (NaBiEDTA) density gradient to characterize and compare the lipoprotein profiles of healthy dogs of various breeds, healthy Miniature Schnauzers, and Miniature Schnauzers with primary hypertriacylglycerolemia. A total of 35 healthy dogs of various breeds with serum triacylglycerol (TAG) and cholesterol concentrations within their respective reference intervals were selected for use as a reference population. Thirty-one Miniature Schnauzers with serum TAG and cholesterol concentrations within their respective reference intervals and 31 Miniature Schnauzers with hypertriacylglyceridemia were also included in the study. Results The results suggest that CLPDP using NaBiEDTA provides unique diagnostic information in addition to measurements of serum TAG and cholesterol concentrations and that it is a useful screening method for dogs with suspected lipoprotein metabolism disorders. Using the detailed and continuous density distribution information provided by the CLPDP, important differences in lipoprotein profiles can be detected even among dogs that have serum TAG and cholesterol concentrations within the reference interval. Miniature Schnauzers with serum TAG and cholesterol concentrations within the reference interval had significantly different lipoprotein profiles than dogs of various other breeds. In addition, it was further established that specific lipoprotein fractions are associated with hypertriacylglyceridemia in Miniature Schnauzers. Conclusions The results of the present study suggest that density gradient ultracentrifugation using NaBiEDTA is a useful screening method for the study of lipoprotein profiles in dogs. Therefore, this method could potentially be used for diagnostic purposes for the separation of dogs suspected of having lipoprotein abnormalities from healthy dogs.



High-density lipoprotein cholesterol as an independent risk factor in cardiovascular disease: assessing the data from Framingham to the Veterans Affairs High--Density Lipoprotein Intervention Trial.  


The Framingham Heart Study found that high-density lipoprotein cholesterol (HDL-C) was the most potent lipid predictor of coronary artery disease risk in men and women >49 years of age. The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), in which subjects were randomized to treatment with lovastatin or placebo, also reported a striking benefit of treatment, particularly in patients with HDL-C < or =35 mg/dL at baseline. Treatment with lovastatin was associated with a remarkable 45% reduction in events for this group. The Veterans Affairs HDL Intervention Trial (VA-HIT) randomized subjects to gemfibrozil or placebo. A high proportion of enrolled subjects with low HDL-C also had characteristics of the dysmetabolic syndrome. HDL-C likewise increased by 6% on treatment, total cholesterol was reduced by 4% and triglycerides by 31%. There was no change in low-density lipoprotein cholesterol (LDL-C) levels. These changes in lipid were associated with a cumulative 22% reduction in the trial primary endpoint of all-cause mortality and nonfatal myocardial infarction (MI). Additionally, significant reductions in secondary endpoints including death from coronary artery disease, nonfatal MI, stroke, transient ischemic attack, and carotid endarterectomy were associated with the increase in HDL-C. In VA-HIT, for every 1% increase in HDL-C, there was a 3% reduction in death or MI, a therapeutic benefit that eclipses the benefit associated with LDL-C reduction. PMID:11374850

Boden, W E



Alpha slow-moving high-density-lipoprotein subfraction in serum of a patient with radiation enteritis and peritoneal carcinosis  

SciTech Connect

An alpha slow-moving high-density-lipoprotein (HDL) subfraction was seen in a patient presenting with radiation enteritis and peritoneal carcinosis, who was given long-term cyclic parenteral nutrition. This subfraction, observed in addition to normal HDL, was precipitated with low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) by sodium phosphotungstate-magnesium chloride. The patient's serum lipoproteins were analyzed after fractionation by density gradient ultracentrifugation. The alpha slow-moving HDL floated in the ultracentrifugation subfractions with densities ranging from 1.028 to 1.084 kg/L, and their main apolipoproteins included apolipoprotein E in addition to apolipoprotein A-I. These HDL were larger than HDL2. The pathogenesis of this unusual HDL subfraction is hypothesized.

Peynet, J.; Legrand, A.; Messing, B.; Thuillier, F.; Rousselet, F.



High-density lipoprotein heterogeneity and function in reverse cholesterol transport  

PubMed Central

Purpose of review HDL is a cardioprotective lipoprotein, at least in part, because of its ability to mediate reverse cholesterol transport (RCT). It is becoming increasingly clear that the antiatherogenic effects of HDL are not only dependent on its concentration in circulating blood but also on its biological ‘quality’. This review summarizes our current understanding of how the biological activities of individual subclasses of HDL particles contribute to overall HDL performance in RCT. Recent findings Recent work indicates that apolipoprotein A-I-containing nascent HDL particles are heterogeneous and that such particles exert different effects on the RCT pathway. RCT from macrophages has been examined in detail in mice and the roles of plasma factors (lecithin-cholesterol acyltransferase, cholesterol ester transfer protein, phospholipid transfer protein) and cell factors (ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, scavenger receptor class B type 1) have been evaluated. Manipulation of such factors has consistent effects on RCT and atherosclerosis, but the level of plasma HDL does not reliably predict the degree of RCT. Furthermore, HDL cholesterol or apolipoprotein A-I levels do not necessarily correlate with the magnitude of cholesterol efflux from macrophages; more understanding of the contributions of specific HDL subspecies is required. Summary The antiatherogenic quality of HDL is defined by the functionality of HDL subspecies. In the case of RCT, the rate of cholesterol movement through the pathway is critical and the contributions of particular types of HDL particles to this process are becoming better defined.

Rothblat, George H.; Phillips, Michael C.



Functionalizing low-density lipoprotein nanoparticles for in vivo near-infrared optical imaging of cancer  

NASA Astrophysics Data System (ADS)

Low density lipoproteins (LDL) have long been recognized as a potential delivery system for exogenous agents. Imaging agents or drugs can be attached to LDL through surface loading, protein loading or core loading methods. The LDL delivery system has received considerable attention particularly among cancer biologists as it was observed that numerous cancers over-express the low density lipoprotein receptor (LDLR). In this paper we investigate the utility of LDL to transport optical imaging contrast agents for caner detection. The method of loading fluorophores into the core of LDL is attractive as it behaves like an activatable contrast agent. Surface and protein labeled methods also prove to be effective strategies for tracing LDL nanoparticle activity. The strengths and limitations of the LDL carrier system are discussed and novel approaches for imaging cancer with LDL nanoparticles are highlighted.

Corbin, Ian R.; Chen, Juan; Li, Hui; Cao, Weiguo; Zheng, Gang



Scavenger receptor for malondialdehyde-modified high density lipoprotein on rat sinusoidal liver cells  

SciTech Connect

The presence of a membrane-associated receptor which mediates endocytic uptake of malondialydehyde-modified high density lipoprotein (MDA-HDL) on sinusoidal liver cells is reported. Binding of (/sup 125/I)MDA-HDL to the cells was followed by internalization and degradation in lysosomes. The binding and lysomal degradation of (/sup 125/I)MDA-HDL were effectively inhibited by unlabeled MDA-HDL and acetyl-HDL. However, formaldehyde-treated serum albumin or low density lipoprotein modified either by acetylation or malondialdehyde, ligands known to undergo receptor-mediated endocytosis by sinusoidal liver cells, did not affect the binding of (/sup 175/I)MDA-HDL to the cells. These results indicate that a receptor for MDA-HDL is described as a distinct member among the scavenger receptors for chemically modified proteins.

Murakami, M.; Horiuchi, S.; Takata, K.; Morino, Y.



A dietary portfolio: maximal reduction of low-density lipoprotein cholesterol with diet.  


Over the past two decades, cholesterol-lowering drugs have proven to be effective and have been found to significantly reduce the risk of coronary heart disease (CHD). However, diet and lifestyle factors are still recognized as the first line of intervention for CHD risk reduction by the National Cholesterol Education Program and the American Heart Association, which now advocate use of viscous fibers and plant sterols, and soy protein and nuts, respectively. In a series of metabolically controlled studies, we have combined these four cholesterol-lowering dietary components in the same diet (ie, a dietary portfolio of cholesterol-lowering foods) in an attempt to maximize low-density lipoprotein cholesterol reduction. We have found that the portfolio diet reduced low-density lipoprotein cholesterol by approximately 30% and produced clinically significant reductions in CHD risk. These reductions were the same as found with a starting dose of a first-generation statin drug. PMID:15485596

Kendall, Cyril W C; Jenkins, David J A



Association between Hepatitis C Virus and Very-Low-Density Lipoprotein (VLDL)/LDL Analyzed in Iodixanol Density Gradients  

PubMed Central

Hepatitis C virus (HCV) RNA circulates in the blood of persistently infected patients in lipoviroparticles (LVPs), which are heterogeneous in density and associated with host lipoproteins and antibodies. The variability and lability of these virus-host complexes on fractionation has hindered our understanding of the structure of LVP and determination of the physicochemical properties of the HCV virion. In this study, HCV from an antibody-negative immunodeficient patient was analyzed using three fractionation techniques, NaBr gradients, isotonic iodixanol, and sucrose gradient centrifugation. Iodixanol gradients were shown to best preserve host lipoprotein-virus complexes, and all HCV RNA was found at densities below 1.13 g/ml, with the majority at low density, ?1.08 g/ml. Immunoprecipitation with polyclonal antibodies against human ApoB and ApoE precipitated 91.8% and 95.0% of HCV with low density, respectively, suggesting that host lipoprotein is closely associated with HCV in a particle resembling VLDL. Immunoprecipitation with antibodies against glycoprotein E2 precipitated 25% of HCV with low density, providing evidence for the presence of E2 in LVPs. Treatment of serum with 0.5% deoxycholic acid in the absence of salt produced HCV with a density of 1.12 g/ml and a sedimentation coefficient of 215S. The diameters of these particles were calculated as 54 nm. Treatment of serum with 0.18% NP-40 produced HCV with a density of 1.18 g/ml, a sedimentation coefficient of 180S, and a diameter of 42 nm. Immunoprecipitation analysis showed that ApoB remained associated with HCV after treatment of serum with deoxycholic acid or NP-40, whereas ApoE was removed from HCV with these detergents.

Nielsen, S?ren U.; Bassendine, Margaret F.; Burt, Alastair D.; Martin, Caroline; Pumeechockchai, Wanna; Toms, Geoffrey L.



Correlations of plasma lipoproteins with LDL subfractions by particle size in men and women  

Microsoft Academic Search

Nondenaturing gradient gel electrophoresis of plasma low density lipoprotein (LDL) has been used to identify major LDL subclasses that are influenced by genetic and other factors. In the present paper, this technique has been extended by mea- suring absorbance of lipid- or protein-stained gels as an index of concentration at intervals of 0.05 nm across the entire LDL particle size

Paul T. Williams; Karen M. Vranizan; Ronald M. Krauss


Phenotypic characterization of the Ath1 gene controlling high density lipoprotein levels and susceptibility to atherosclerosis  

Microsoft Academic Search

The Ath-2 gene determines the levels of high density lipoprotein (HDL) lipid in response to a high fat diet challenge as well as susceptibility to diet-induced atherosclerosis in mice (Paigen et al. 1987. Pmc. Natl. Acad. Sci. USA. 84: 3763-3767). As yet, the identity of the Aih-1 gene and how it acts to affect HDL levels are completely unknown. In

Renee C. LeBoeuf; Mark H. Doolittle; Alice Montcalm; Dominique C. Martin; Karen Reue; Aldons J. Lusistf


Exercise Mitigates the Association of Abdominal Obesity with High-density Lipoprotein Cholesterol in Premenopausal Women  

Microsoft Academic Search

Objective To examine the relationship between abdominal obesity, as measured by waist-to-hip ratio (WHR) and high-density lipoprotein cholesterol (HDL-C) level within the context of age, body fatness, exercise, saturated fat intake, and other plasma lipids.Design\\/subjects Subjects were premenopausal, white, non-Hispanic women from the third National Health and Nutrition Examination Survey. Smokers, heavy drinkers, and women who took lipid-altering drugs were




Resveratrol inhibits metal ion-dependent and independent peroxidation of porcine low-density lipoproteins  

Microsoft Academic Search

Resveratrol, a phytoalexin (3, 4?, 5, trihydroxystilbene) present in some red wines, has been reported to inhibit copper-mediated low-density lipoprotein (LDL) oxidation. In this study, we examined the efficiency of this compound in inhibiting metal ion-dependent and independent peroxidation of porcine LDL. At 0.5, 1, or 1.5 ?M, transresveratrol prolonged the lag time preceding the onset of conjugated diene formation

Leila Belguendouz; Lucie Fremont; Alain Linard



Interaction of low density lipoproteins with liver cells in rainbow trout  

Microsoft Academic Search

Liver is the main catabolic tissue for low density lipoprotein in rainbow trout (Gjøen and Berg 1992). We have investigated the interaction of LDL with isolated trout liver cells and liver membranes. 125I-TC labelled trout LDL bound to isolated trout liver cells in a time dependent and saturable manner with an apparant Kd of 20.1 µg\\/ml, suggesting the existence of

Tor Gjøen; Trond Berg



Small low-density lipoprotein particles and endothelium-dependent vasodilation in postmenopausal women  

Microsoft Academic Search

Low concentrations of estrogen may decrease endothelial function in postmenopausal women. Elevated plasma triglycerides after menopause are frequently associated with a small, dense low-density lipoprotein (LDL) phenotype. Small LDL particles that are more susceptible to oxidation can also inhibit endothelium-dependent vasodilation. The purpose of the present study was to investigate whether hypertriglyceridemia-induced small LDL particles are associated with endothelial dysfunction

Akihiko Wakatsuki; Nobuo Ikenoue; Koichi Shinohara; Kazushi Watanabe; Takao Fukaya



Protective effect of high density lipoprotein on endothelium-dependent vasodilatation  

Microsoft Academic Search

Low concentrations of high-density lipoprotein cholesterol (HDL-C) have been associated with increased risk of coronary heart disease (CHD) even when the total cholesterol (TC) and triglyceride (TG) levels are not elevated. The mechanism by which HDL confers protection against atherosclerosis remains speculative. Using high-resolution ultrasound, we measured the dilatation changes of brachial arteries during reactive hyperemia and after sublingual glyceryl

Xiang-Ping Li; Shui-Ping Zhao; Xiang-Yu Zhang; Ling Liu; Mei Gao; Qi-Chang Zhou



Effect of L-carnitine treatment on very low density lipoprotein kinetics in the hyperlipidemic rabbit  

Microsoft Academic Search

This study examined the hypolipidemic effect of 4 weeks of L-carnitine treatment (170 mg\\/kg b.w.\\/day) in New Zealand White rabbits fed a high fat diet (5% corn oil\\/0.5% cholesterol). Specifically, [3H] glycerol and [125I] very low density lipoprotein (VLDL) turnover studies were conducted to examine the effect of treatment on VLDL kinetics. The masses of plasma VLDL-triglycerides (VLDL-TG) and VLDL-apoprotein

Leighton James; A. K. M. Jalaluddin Bhuiyan; David Foster; David Seccombe



Growth modulation of low density lipoprotein receptor sterol sensitivity in cultured human fibroblasts  

Microsoft Academic Search

Sterols regulate low density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase gene\\u000a expressions by end product repression. Studies on cultured cells have shown that growing cells have a higher LDL uptake than\\u000a quiescent cells and that incubation of cells with growth factors or mitogenic compounds leads to sterol-resistant upregulation\\u000a of LDL receptor gene expression. The recent finding that

Loukas Tatidis; Sigurd Vitols



Effects of atorvastatin treatment on the oxidatively modified low density lipoprotein in hyperlipidemic patients  

Microsoft Academic Search

Atorvastatin is an established HMG-CoA reductase inhibitor which effectively reduces the plasma low density lipoprotein (LDL)-cholesterol level in hyperlipidemic patients. The present study was designed to investigate whether atorvastatin treatment can modify the biochemical content of oxidized LDL in hyperlipidemic patients and the ability of oxidized LDL to impair the endothelium-dependent relaxation of blood vessels. With atorvastatin (10 mg\\/day) treatment

Quansheng Zhu; Jason McMaster; David Mymin; Tom Dembinski; Grant Hatch; Patrick C. Choy; Edwin A. Kroeger



Anionic Phospholipids Lose Their Procoagulant Properties When Incorporated into High Density Lipoproteins  

Microsoft Academic Search

Blood coagulation involves a series of enzymatic protein complexes that assemble on the surface of anionic phospholipid. To investigate whether apolipoproteins affect coagulation reactions, they where included during the preparation of anionic phospholipid vesicles using a detergent solubilization-dialysis method. Apolipoprotein components of high-density lipoproteins, especially apolipoprotein A-I, had pronounced anticoagulant effect. The anionic phospholipids lost their procoagulant effect when the

Cecilia Oslakovic; Michael J. Krisinger; Astra Andersson; Matti Jauhiainen; Christian Ehnholm; B. Dahlback



Dissociation of lipid-free apolipoprotein AI from high density lipoproteins  

Microsoft Academic Search

Conditions under which apolipoprotein (apo) A-I dissociates from human high density lipoproteins (HDL) during incubation in vitro have been investigated. Dissociation of apoA-I was demonstrated by non-denaturing gradient gel electropho- resis followed by immunoblotting for apoA-I and by size- exclusion chromatography. It was quantitated after ultracen- trifugation as the loss of apoA-I from the fraction of d < 1.25 g\\/ml.

Hui-Qi Liang; Kerry-Anne Rye; Philip J. Barter


Triglyceride Accumulation and Very Low Density Lipoprotein Secretion by Rat and Goat Hepatocytes In Vitro  

Microsoft Academic Search

Utilization of ( 1-14 C) oleate by freshly isolated rat and goat hepatocytes was compared. Intracellular (14 C) triglyceride accumulation by hepatocytes did not differ between species. At 2 h of in- cubation, rat hepatocytes secreted ap- proximately 25 times more (14C)tri- glyceride than goat hepatocytes. Very low density lipoprotein secretion was greatest by hepatocytes incubated in media containing 4:1

Barry B. Kleppe; Robert J. Aiello; Ric R. Grummer; Louis E. Armentano



Phenolic antioxidants attenuate neuronal cell death following uptake of oxidized low-density lipoprotein  

Microsoft Academic Search

Oxidative stress is implicated in neuronal loss associated with neurodegeneration such as in Parkinson’s disease, Alzheimer’s disease and age-related cognitive decline. Recent reports indicate that the consumption of flavonoid-rich fruits partly reverses the age-related neuronal and cognitive decline. In this study, cultured striatal neurons were exposed to oxidized lipids in the form of low-density lipoprotein (oxLDL) as a model for

Hagen Schroeter; Robert J Williams; Rubeta Matin; Leslie Iversen; Catherine A Rice-Evans



Polymyxin B Enhances Low Density Lipoprotein Catabolism in Hepatic and Extrahepatic Cells  

Microsoft Academic Search

We investigated the effects of polymyxin B (PMB), an antibiotic that binds to endotoxins, on the uptake and degradation of low density lipoproteins (LDLs) in HepG2 cells, a highly differentiated human hepatoma cell line. The results showed that PMB very effectively enhanced the binding, intemalization, and degradation of LDL in HepG2 cells. The PMB-mediated enhancement of LDL uptake was not

Wei Liao; Claes-Henrik Florin



The endothelial cholesterol efflux is promoted by the high-density lipoprotein anionic peptide factor  

Microsoft Academic Search

The prevention of atherosclerosis depends on the high-density lipoprotein (HDL) capacity to stimulate the efflux of unesterified cholesterol (UC). We tested here the effects of 2 HDL apolipoproteins, apo A-I and the 7-kd anionic peptide factor (APF), on the UC efflux by human endothelial ECV 304 cells in culture. Apolipoprotein A-I (10 ?mol\\/L) or APF (3.5 ?mol\\/L) in lipid-free forms

Nicole Domingo; Isabelle Mastellone; Sandra Grès; Valérie Marin; Anne Marie Lorec; Frédéric Tosini; Jeanne Grosclaude; Catherine Farnarier; Françoise Chanussot



Apolipoprotein AI charge and conformation regulate the clearance of reconstituted high density lipoprotein in vivo  

Microsoft Academic Search

While low apolipoprotein A-I (apoA-I) levels are primarily associated with increased high density lipoprotein (HDL) fractional catabolic rate (FCR), the factors that regu- late the clearance of HDL from the plasma are unclear. In this study, the effect of lipid composition of reconstituted HDL particles (LpA-I) on their rate of clearance from rab- bit plasma has been investigated. Sonicated LpA-I

Sylvie Braschi; Marie-Claude Vohl; Daniel L. Sparks


Serum High-Density Lipoprotein Cholesterol and Risk of Non-Hodgkin Lymphoma  

Microsoft Academic Search

Lymphoma patients often exhibit abnormal lipid metabolism. Recent evidence, however, suggests that a decrease in circulating high-density lipoprotein cholesterol (HDL-C)may occur during lymphomagenesis, reflecting underlying etiology such as inflammation. We investigated the relationship between prediagnostic HDL-C and non-Hodgkin lymphoma (NHL)in the Alpha-Tocopherol Beta-Carotene Cancer Pre- vention Study cohort. At baseline, serum HDL-C and total cholesterol concentrations from fasting blood, information

Unhee Lim; Travis Gayles; Hormuzd A. Katki; Stephanie J. Weinstein; Pirjo Pietinen; Philip R. Taylor; Jarmo Virtamo; Demetrius Albanes


Glycated low density lipoprotein catabolism is increased in rabbits with alloxan-induced diabetes mellitus  

Microsoft Academic Search

Summary  Hyperglycaemia in diabetes mellitus is responsible for the process of non-enzymatic glycosylation of different proteins. Since we did not find elevated glycated apolipoprotein B levels in diabetic patients, an altered glycated apolipoprotein B metabolism was suspected in diabetic patients. Experiments in normal rabbits showed that non-reductive (in vitro) glycated low density lipoprotein (gly-LDL) was cleared at a slower rate than

W. Kortlandt; C. Benschop; H. J. M. van Rijn; D. W. Erkelens



Dietary carbohydrates, glycemic load and serum high-density lipoprotein cholesterol concentrations among South Indian adults  

Microsoft Academic Search

Objective:To examine the relationship between dietary carbohydrates, glycemic load and high-density lipoprotein cholesterol (HDL-C) concentrations in Asian Indians, a high-risk group for diabetes and premature coronary artery disease.Subjects\\/methods:The study population comprised of 2043 individuals aged ?20 years randomly selected from Chennai Urban Rural Epidemiological Study (CURES), an ongoing population-based study on a representative population of Chennai (formerly Madras) city in

G Radhika; A Ganesan; R M Sathya; V Sudha; V Mohan



Inhibitors of hepatic microsomal triacylglycerol hydrolase decrease very low density lipoprotein secretion  

Microsoft Academic Search

The presence of elevated circulating triacylglycerol (TG)-rich very low density lipoprotein (VLDL) and apolipoprotein B-100 (apoB-100) levels represents an independent risk factor for coronary artery disease. Triacylglycerol hydrolase catalyzes the mobilization of cytoplasmic TG stores. To test the hypothesis that the enzyme plays a role in the provision of core lipids for the assembly of VLDL, we inhibited the lipase

Dean Gilham; Samuel Ho; Mehdi Rasouli; Paul Martres; Dennis E. Vance; Richard Lehner



High Density Lipoprotein (HDL) Promotes Glucose Uptake in Adipocytes and Glycogen Synthesis in Muscle Cells  

Microsoft Academic Search

BackgroundHigh density lipoprotein (HDL) was reported to decrease plasma glucose and promote insulin secretion in type 2 diabetes patients. This investigation was designed to determine the effects and mechanisms of HDL on glucose uptake in adipocytes and glycogen synthesis in muscle cells.Methods and ResultsActions of HDL on glucose uptake and GLUT4 translocation were assessed with 1-[3H]-2-deoxyglucose and plasma membrane lawn,

Qichun Zhang; Yun Zhang; Haihua Feng; Rui Guo; Lai Jin; Rong Wan; Lina Wang; Cheng Chen; Shengnan Li



Serum High-Density Lipoprotein Cholesterol, Metabolic Profile, and Breast Cancer Risk  

Microsoft Academic Search

Background: The prevalence of metabolic syndrome (obe- sity, glucose intolerance, low serum high-density lipoprotein cholesterol (HDL-C), high serum triglycerides, hyperten- sion) is high and increasing in parallel with an increasing breast cancer incidence worldwide. HDL-C represents an important aspect of the syndrome, yet its role in breast cancer is still undefined. Methods: In two population-based screening surveys during 1977-1983 and

Anne-Sofie Furberg; Tom Wilsgaard; Leslie Bernstein; Inger Thune



Analysis of high density lipoproteins by a modified gradient gel electrophoresis method  

Microsoft Academic Search

A high resolution electrophoretic method has been developed to separate plasma high density lipoprotein (HDL) particles by size using 4-3076 polyacrylamide agarose (PAA) gradient gels, Sudan black B staining, and laser densitometry. Fourteen distinct HDL bands were observed with HDL-1 being designated as the largest particle and HDL-14 as the smallest particle. HDL-1 was similar in size to ferritin (Stokes

Zhengling Li; Judith R. McNamara; Jose M. Ordovas; Ernst J. Schaeferl


Relationship of low-density lipoprotein particle size and measures of adiposity  

Microsoft Academic Search

OBJECTIVE: To determine if obesity measures are related to measures of low-density lipoprotein (LDL) size and LDL subfractions in a population of Mexican-Americans with high prevalence of obesity.METHODS: LDL size phenotypes, based on nondenaturing gradient gel electrophoresis and staining for cholesterol (using Sudan black B), were determined for 313 unrelated Mexican-American participants in the San Antonio Family Heart Study. LDL

DL Rainwater; BD Mitchell; AG Comuzzie; SM Haffner



Decreased Atherosclerosis in Low-Density Lipoprotein Receptor Knockout Mice Transplanted With Abcg1\\/ Bone Marrow  

Microsoft Academic Search

Objective—Recent studies indicate that the ATP-binding cassette transporter ABCG1 can promote cholesterol efflux from macrophages to high-density lipoprotein. This study was designed to assess the in vivo role of macrophage ABCG1 in atherosclerosis. Methods and Results—Bone marrow from Abcg1\\/ mice was transplanted into irradiated Ldlr\\/ recipients, and atherosclerosis was evaluated by aortic root assay after 7 or 11 weeks of

Mollie Ranalletta; Nan Wang; Seongah Han; Laurent Yvan-Charvet; Carrie Welch; Alan R. Tall



Oxidized Low-Density Lipoprotein and Oxidative Stress in the Development of Glomerulosclerosis  

Microsoft Academic Search

Glomerulosclerosis frequently complicates most renal diseases and is characterized by mesangial matrix accumulation. Oxidized low-density lipoprotein (Ox-LDL) could induce oxidative stress and profibrotic gene expression in mesangial cells. This article will review our current understanding of the pathogenetic mechanisms of lipid-mediated glomerulosclerosis, emphasizing the fibrogenic signaling cascades triggered by Ox-LDL. In addition, therapeutic strategies to prevent the development of Ox-LDL-mediated

Hyun Soon Lee; Chi Young Song



Antioxidation of human low density lipoprotein by unconjugated and conjugated bilirubins  

Microsoft Academic Search

We demonstrate here that both unconjugated bilirubin (Bu) and conjugated bilirubin (Bc) can protect human low density lipoprotein (LDL) against oxidation by oxyradicals generated by 2,2?-azo-bis(2-amidinopropane) dihydrochloride at 37°. The oxidation was assessed by agarose gel electrophoresis and was further corroborated by assaying the malondialdehydes and lipid peroxides formed throughout oxidation. On a per mole basis, Bu and less so

Tai-Wing Wu; K. P. Fung; Jun Wu; Chih-Chin Yang; Richard D. Weisel



A Green Tea Catechin Extract Upregulates the Hepatic Low-Density Lipoprotein Receptor in Rats  

Microsoft Academic Search

Green tea extracts have hypocholesterolaemic properties in epidemiological and animal intervention studies. Upregulation of\\u000a the low-density lipoprotein (LDL) receptor may be one mechanism to explain this as it is the main way cholesterol is removed\\u000a from the circulation. This study aimed to determine if a green tea extract could upregulate the hepatic LDL receptor in vivo\\u000a in the rat. A

Christina A. Bursill; Paul D. Roach



Uptake by macrophages of low-density lipoprotein damaged by nitrogen dioxide in air  

Microsoft Academic Search

In order to know whether nitrogen dioxide, an environmental and endogenous free radical toxin, can participate in the formation\\u000a of atherosclerotic lesions, damage to low-density lipoprotein (LDL) by nitrogen dioxide and uptake of the damaged LDL by macrophages\\u000a were investigated. A solution of LDL at pH 7.5 was exposed to an atmosphere of nitrogen dioxide (70 ppm) in air at

Kiyomi Kikugawa; Masatoshi Beppu; Yutaka Okamoto



Characterization of native and oxidized human low-density lipoproteins by the Z-scan technique  

Microsoft Academic Search

The nonlinear optical response of human normal and oxidized by Cu2+ low-density lipoproteins particles (LDL), were investigated by the Z-scan technique as a function of temperature and concentration of LDL particles. The Z-scan signals increase linearly with concentration of normal LDL particles, following the usual Beer–Lambert law in a broad range of concentrations. The oxidized LDL particles do not show

S. L. Gómez; R. F. Turchiello; M. C. Jurado; P. Boschcov; M. Gidlund; A. M. Figueiredo Neto



Circulating Oxidized Low-Density Lipoprotein and Paraoxonase Activity in Preeclampsia  

Microsoft Academic Search

Preeclampsia is one of the most frequent complications of pregnancy, however, little is known about its etiology. The objective of this study was to investigate the association of oxidized low-density lipoprotein (oxLDL) and paraoxonase (PON1) activity in women with either preeclampsia or normotensive (NT) pregnancy. The study groups included 41 pregnant women with preeclampsia and 33 normotensive pregnant women. In

H. Uzun; A. Benian; M. Albayrak



Low-density lipoprotein (LDL) binds to a G-protein coupled receptor in human platelets  

Microsoft Academic Search

We present evidence of a link between low-density lipoprotein (LDL) receptor binding and activation of a platelet G-coupled protein. LDL stimulation induced cytosolic [Ca2+]i mobilization, increase in inositol 1,4,5-triphosphate (IP3) formation and a rapid cytosol-to-membrane translocation of protein kinase C (PKC) enzymatic activity. Pertussis toxin inhibited all the stimulatory effects, whereas cholera toxin had no effect. Using ligand-binding assays, we

Javier Pedreño; Eva Hurt-Camejo; Olov Wiklund; Lina Badimón; Lluis Masana



Platelet Interaction with Bioactive Lipids Formed by Mild Oxidation of Low-Density Lipoprotein  

Microsoft Academic Search

Oxidation of low-density lipoprotein (LDL) generates pro-inflammatory and pro-thrombotic mediators that play a crucial role in cardiovascular and inflammatory diseases. Mildly oxidized LDL (mox-LDL) and minimally modified LDL (mm-LDL) which escape the uptake of macrophage scavenger receptors accumulate in the atherosclerotic intima. Oxidatively modified LDL is also present within the electronegative LDL fraction in blood, which is elevated in patients

Wolfgang Siess



Increased serum and low-density-lipoprotein antioxidant potential after antioxidant supplementation in endurance athletes1  

Microsoft Academic Search

We studied the effect of antioxidant supplemen- tation on acute exercise-induced lipid peroxidation and antioxidant potential measured in serum and low-density-lipoprotein (LDL) samples. Eight endurance athletes repeated a 3 1-km running cx- ercise twice with an interval of 4 wk. During the 4 wk before the runs, the subjects took in a single-blind randomized order either a combination of antioxidant

Tommi J Vasankari; Urho M Kujala; Tuula M Vasankari; Timo Vuorimaa; Markku Ahotupa


A systems genetic analysis of high density lipoprotein metabolism and network preservation across mouse models  

Microsoft Academic Search

We report a systems genetic analysis of high density lipoprotein (HDL) levels in an F2 intercross between inbred strains CAST\\/EiJ and C57BL\\/6J. We previously showed that there are dramatic differences in HDL metabolism in a cross between these strains, and we now report co-expression network analysis of HDL that integrates global expression data from liver and adipose with relevant metabolic

Peter Langfelder; Lawrence W. Castellani; Zhiqiang Zhou; Eric Paul; Richard Davis; Eric E. Schadt; Aldons J. Lusis; Steve Horvath; Margarete Mehrabian


A multiexon deletion in the human low density lipoprotein receptor gene causes familial hypercholesterolemia  

SciTech Connect

Familial hypercholesterolemia (FH) is a widespread human disease. FH is caused by a disturbance in the catabolism of low density lipoproteins (LDL), which results from mutations in the LDL receptor gene (LDLR). The majority of mutations in the LDLR locus is represented by large-scale reorganizations in the above gene. In this study, we describe a novel 5 kb deletion, which eliminates exons 4 to 6 in the LDLR gene. 16 refs., 2 figs., 1 tab.

Mandel`shtam, M.Yu.; Lipovetskii, B.M.; Shvartsman, A.L.; Gaitskhoki, V.S. [Institute of Experimental Medicine, St. Petersburg (Russian Federation)



Tomato lycopene and low density lipoprotein oxidation: A human dietary intervention study  

Microsoft Academic Search

Increase in low density lipoprotein (LDL) oxidation is hypothesized to be causally associated with increasing risk of atherosclerosis\\u000a and coronary heart disease. In recent epidemiological studies, tissue and serum levels of lycopene, a carotenoid available\\u000a from tomatoes, have been found to be inversely related to risk of coronary heart disease. A study was undertaken to investigate\\u000a the effect of dietary

Sanjiv Agarwal; A. Venketeshwer Rao



Studies on oxidized low density lipoproteins. Controlled oxidation and a prostaglandin artifact  

Microsoft Academic Search

Low density lipoproteins (LDL), isolated by ultra- centrifugal flotation, were oxidized (LDLoxID) slowly during dialysis against 0.15 M NaCl and subsequent incubation in 96% air-4% C02 at 37OC. Butylated hydroxytoluene prevented LDL oxidation. LDL preparations from different sera were oxidized at different rates and the degree of lipid peroxidation was con- trolled by varying the incubation time. Mild oxidation did

Hanfang Zhang; W. Bruce Davis; David G. Cornwell; Xunsheng Chen; Ronald L. Whisler


Low-density lipoprotein cholesterol lowering in the prevention of CHD: How low should we go?  

Microsoft Academic Search

Opinion statement  The past 12 years have seen the publication of numerous randomized placebo-controlled studies using statins to lower low-density\\u000a lipoprotein cholesterol (LDLC) to assess the efficacy of cholesterol lowering on cardiovascular events. Initial studies predominantly\\u000a evaluated mortality or nonfatal myocardial infarctions and coronary heart disease (CHD) death in patients with known or presumed\\u000a established coronary disease and moderately elevated to

William L. Isley



A new relationship between total\\/high density lipoprotein cholesterol and polyunsaturated fatty acids  

Microsoft Academic Search

Dietary and plasma fatty acids have been linked to total cholesterol but not to the ratio of total\\/high-density lipoprotein\\u000a cholesterol (TC\\/HDLC). To evaluate the relationship between dietary and plasma levels of polyunsaturated fatty acids (PUFA)\\u000a and TC\\/HDLC, we analyzed cross-sectional and longitudinal data using 519 plasma samples (50% men, 50% women) from subjects\\u000a participating in the Framingham Heart Study and

Edward Siguel



Evolving Concepts of the Role of High-Density Lipoprotein in Protection from Atherosclerosis  

Microsoft Academic Search

High-density lipoprotein (HDL) is classified as a negative risk factor due to the inverse relationship between elevated levels\\u000a of HDL cholesterol and atherosclerosis. The mechanism by which HDL can mediate protection from atherosclerosis is complex\\u000a and multifactorial. The primary role of reverse cholesterol transport in the reduction of risk for coronary artery disease\\u000a is supported by a considerable amount of

John A. Farmer; Joshua Liao



Improved glucose control decreases the interaction of plasma low-density lipoproteins with arterial proteoglycans  

Microsoft Academic Search

The entrapment and retention of plasma low-density lipoproteins (LDL) by arterial proteoglycans (PG) is a process central to atherogenesis. We postulated therefore that accelerated atherosclerosis of diabetic individuals may result from hyperglycemia-associated modifications in LDL that enhance their interaction with arterial PG. To evaluate the role of clinical treatment on this process, LDL-PG binding was evaluated in uncontrolled type 2

Iris J. Edwards; James G. Terry; Audrey D. Bell-Farrow; William T. Cefalu



Stimulation of the apo AI–high density lipoprotein system by dietary soyabean lecithin in humans  

Microsoft Academic Search

The aim of this work was to assess, the effect of a dietary supplement of soyabean lecithin on the apoprotein (apo) AI–high density lipoprotein system in humans. Adult outpatients (three women and seven men, aged 52 ± 5 years) were selected on the basis of a major type IIA hypercholesterolemia (>6.5 mmol\\/L). For each subject, a previous control period of

Elisabeth Polichetti; Anne Janisson; Cécilia Iovanna; Henri Portugal; Nadia Mekki; Anne-Marie Lorec; Anne-Marie Pauli; Antonia Luna; Denis Lairon; Philippe La Droitte; Huguette Lafont; Françoise Chanussot



Indications that paraoxonase-1 contributes to plasma high density lipoprotein levels in familial hypercholesterolemia  

Microsoft Academic Search

HDL-associated paraoxonase type 1 (PON1) can protect LDL and HDL against oxidative modification in vitro and therefore may protect against cardiovascular disease. We investigated the effects of PON1 levels, activity, and genetic variation on high density lipoprotein-cholesterol (HDL-C) levels, circulating oxidized LDL (OxLDL), subclinical in- flammation (high-sensitive C-reactive protein (Hs-CRP)), and carotid atherosclerosis. PON1 genotypes (L55M, Q192R, ? 107C\\/T, ?

Thomas M. van Himbergen; Mark Roest; Jacqueline de Graaf; Eugène H. J. M. Jansen; Hiroaki Hattori; John J. P. Kastelein; Hieronymus A. M. Voorbij; Anton F. H. Stalenhoef



Overexpression of Low Density Lipoprotein (LDL) Receptor Eliminates LDL from Plasma in Transgenic Mice  

Microsoft Academic Search

A complementary DNA encoding the human low density lipoprotein (LDL) receptor under control of the mouse metallothionein-I promoter was injected into fertilized mouse eggs, and a strain of mice expressing high levels of LDL receptors was established. After administration of cadmium, these mice cleared intravenously injected 125I-labeled LDL from blood eight to ten times more rapidly than did normal mice.

Sandra L. Hofmann; David W. Russell; Michael S. Brown; Joseph L. Goldstein; Robert E. Hammer



Inefficient internalization of receptor-bound low density lipoprotein in human carcinoma A-431 cells  

Microsoft Academic Search

Human epithehoid carcinoma A-431 cellsare known to express unusually large numbers of receptors for the polypeptide hormone epidermal growth factor. The current studies demonstrate that thiscelllinealso expresses 5- to 10-fold more low density lipoprotein (LDL) receptors per cellthan either human fibroblastsor Chinese hamster ovary (CHO) cells. As visualized with an LDL-ferritinconjugate, the LDL receptors in A-431 cellsappeared in clustersthat were




Regulation of hepatic secretion of very low density lipoprotein by dietary cholesterol  

Microsoft Academic Search

Male rats were fed a cholesterol-free diet or the same diet supplemented with either 0.05, 0.1, 0.25, 0.5, 1, or 2% C for 21 days to investigate the effects of cholesterol on secretion of very low density lipoprotein (VLDL). Cholester- ol feeding increased plasma and hepatic concentrations of triglyceride (TG) and cholesteryl esters (CE) in a dosede- pendent manner. Plasma

Thomas V. Fungwe; Lauren Cagen; Henry G. Wdcox; Murray Heimberg


Cel I u lar localization and characterization of proteins that bind high density lipoprotein  

Microsoft Academic Search

High density lipoprotein (HDL) stimulates excretion of excess intracellular cholesterol from cells, presumably by in- teracting with a cell-surface receptor. A 110 kDa membrane pro- tein that is a candidate for the HDL receptor has been identified by ligand blot analysis. In this study we determined the cellular localization of this and other HDL-binding proteins and charac- terized their properties.

Bjern Hokland; Armando J. Mendez; John F. Oram


A biochemical and morphologic study of very low density lipoproteins in carbohydrate-induced hypertriglyceridemia  

PubMed Central

On a high carbohydrate, fat-free diet, control and hypertriglyceridemic subject had a three-fold increase in d < 1.006, very low density lipoprotein (VLDL) triglyceride, and somewhat lesser increases in VLDL cholesterol and protein. Cholesterol and protein in 1.006 < d < 1.21 lipoprotein decreased in a reciprocal fashion, suggesting that these components might have been utilized in VLDL production. Electron microscope studies demonstrated a significant increase in the size of lipoprotein particles of the VLDL class and, in three of four subjects, an apparent increase in particle number. The change in particle size correlated with an increase in the triglyceride/protein ratio of the d < 1.006 lipoprotein. Hypertriglyceridemic individuals differed from the control subjects in that they had greater absolute increases in VLDL triglyceride, cholesterol, and protein, and greater decreases in 1.006 < d < 1.21 cholesterol and protein. In addition, they had larger VLDL particles with a higher triglyceride/protein ratio, both before the study and at the peak of the carbohydrate effect. The data suggest that the increase in plasma triglycerides induced by a high carbohydrate diet is usually due to the appearance in plasma of both greater numbers of VLDL particles and larger particles that are relatively richer in triglyceride content than those isolated during the basal state. Images

Ruderman, Neil B.; Jones, Albert L.; Krauss, Ronald M.; Shafrir, Eleazar



Influence of risk factors on peripheral and cerebrovascular disease in men with coronary artery disease, low high-density lipoprotein cholesterol levels, and desirable low-density lipoprotein cholesterol levels  

Microsoft Academic Search

Background The Veterans Administration-HDL Intervention Trial is an ongoing, 20-center, randomized, double-blind, placebo-controlled study aiming to assess the effect of gemfibrozil-improved low high-density lipoprotein cholesterol levels on cardiovascular morbidity and mortality rates. Methods and Results Eligible patients were men with low high-density lipoprotein cholesterol levels and demonstrable coronary heart disease. A total of 2531 patients (average age 63.5 years) were

Vasilios Papademetriou; Puneet Narayan; Hanna Rubins; Dorothea Collins; Sander Robins



Plasma lipoprotein composition in alcoholic hepatitis: accumulation of apolipoprotein E-rich high density lipoprotein and preferential reappearance of "light'-HDL during partial recovery.  


Abnormal lipoproteins accumulate in the plasma of alcoholic hepatitis patients in association with a deficiency of the cholesterol esterifying enzyme, lecithin:cholesterol acyl-transferase. Most of these abnormal lipoproteins are found in the d > 1.006 g/ml density fraction. To investigate the composition and morphology of the lipoproteins at various times during the illness in four patients, we have employed density gradient ultracentrifugation combined with analyses of gradient fractions by polyacrylamide gel electrophoresis, electroimmunoassay, and electron microscopy. At the onset of the illness, plasma cholesteryl esters ranged from 19-34% of total cholesterol; high density lipoprotein (HDL) cholesterol and apoA-I, the major HDL apoprotein, were <10% of normal; and most of the d > 1.006 g/ml triglycerides and phospholipids were found in the LDL density region. A linear correlation (r = 0.964, P < 0.001) was found between the d > 1.006 g/ml apoB concentration and the summation of the triglyceride and esterified cholesterol for that fraction, indicating a constant ratio of apoB to the summation of these two "core lipids". ApoA-I was primarily found in the fraction d > 1.18 g/ml (HDL(3) and VHDL) but not at all in the HDL(2) density range of the gradient. No cholesteryl esters were present in the apoA-I containing fractions. In contrast to normal, large amounts of apoE accumulated in lipoproteins isolated at d 1.055-1.114 g/ml. The apoE-rich fractions contained primarily phospholipids and unesterified cholesterol; they appeared by electron microscopy to be mixtures of spherical particles, vesicular particles, and chains of bilamellar discs. Analyses of the density gradient fractions by SDS polyacrylamide gel electrophoresis under reducing conditions indicated that apoA-II levels and distribution paralleled apoA-I, not apoE, providing evidence against appreciable concentrations of apoE-apoA-II complexes. During partial recovery from alcoholic hepatitis in three patients, the d > 1.006 g/ml unesterified cholesterol and triglyceride levels decreased, while esterified cholesterol, HDL-cholesterol, and apoA-I levels increased. The first HDL fractions to reappear were lipoproteins with HDL(2) density characteristics, as evidenced by simultaneous increases of apoA-I, apoA-II, cholesteryl esters and phospholipids. Lipoproteins with HDL(3) density characteristics appeared later. Long-term (6-10 months) follow-up studies indicated a substantial elevation of HDL cholesterol and apoA-I in three of the four patients that appeared to have resulted from further increases in their HDL(2)-like subspecies. The above results illustrate the diversity of abnormal lipoproteins in alcoholic hepatitis and the ability of density gradient ultra-centrifugation combined with lipid and apolipoprotein quantitation, electron microscopy, and polyacrylamide gel electrophoresis to partially resolve those lipoproteins in the d > 1.006 g/ml plasma fraction.-Weidman, S. W., J. B. Ragland, and S. M. Sabesin. Plasma lipoprotein composition in alcoholic hepatitis: accumulation of apolipoprotein E-rich high density lipoprotein and preferential reappearance of "light"-HDL during partial recovery. PMID:7097121

Weidman, S W; Ragland, J B; Sabesin, S M



Familial cholesteryl ester transfer protein deficiency is associated with triglyceride-rich low density lipoproteins containing cholesteryl esters of probable intracellular origin  

Microsoft Academic Search

The net transfer of core lipids between lipoproteins is facilitated by cholesteryl ester transfer protein (CETP). We have recently documented CETP deficiency in a family with hyperalphalipoproteinemia, due to\\\\a CETP gene splicing defect. The purpose of the present study was to characterize the plasma lipoproteins within the low density lipoprotein (LDL) density range and also the cholesteryl ester fatty acid

Charles L. Bisgaier; Mary V. Siebenkas; Maryanne L. Brown; Akihiro Inazu; Hiroshi Mabuchi; Alan R. Tall


Studies of very low density lipoprotein triglyceride metabolism in an obese population with low plasma lipids: lack of influence of body weight or plasma insulin  

Microsoft Academic Search

Pima Indians have a high prevalence of hyper- insulinemia, obesity, and diabetes, but they have low plasma cholesterol levels, reduced low density lipoprotein synthesis, and little arteriosclerotic heart disease. To in- vestigate lipoprotein metabolism further in this group, very low density lipoprotein (VLDL) metabolism was studied. using ('H)glycerol as an endogenous precursor of tri- glyceride (TG) synthesis, in 1.5 obese

Barbara V. Howard; Loren Zech; Michael Davis; Lynn J. Bennion; Peter J. Savage; M. Nagulesparan; David Bilheimer; Peter H. Bennett; Scott M. Grundy


Total and High-density Lipoprotein Cholesterol in Adults: National Health and Nutrition Examination Survey, 2011-2012  


... and High-density Lipoprotein Cholesterol in Adults: National Health and Nutrition Examination Survey, 2011–2012 On This ... to source, however, is appreciated. National Center for Health Statistics Charles J. Rothwell, M.S., Acting Director Jennifer ...



Technology Transfer Automated Retrieval System (TEKTRAN)

To test the hypothesis whether determination of high-density lipoprotein (HDL) subpopulations provides more power to predict recurrent cardiovascular disease (CVD) events (nonfatal myocardial infarction, coronary heart disease death, and stroke) than traditional risk factors in the Veterans Affairs ...


Rethinking oxidized low-density lipoprotein, its role in atherogenesis and the immune responses associated with it  

Microsoft Academic Search

Summary Atherosclerosis is a chronic inflammatory disease, resulting from hyperlipidemia and a complex interplay of many environmental, metabolic, and genetic risk factors. The unregulated macrophage uptake of cholesterol and lipids through modified forms of low- density lipoprotein (LDL), such as \\

Peter X. Shaw



Lovastatin therapy reduces low density lipoprotein apoB levels in subjects with combined hyperlipide- mia by reducing the production of apoB-containing lipoproteins: implications for the pathophysiology of apoB production  

Microsoft Academic Search

We investigated the metabolism of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) apolipoprotein B (apoB) in seven patients with combined hyperlipidemia (CHL), using lZ5I- labeled VLDL and '311-labeled LDL and compartmental mo- deling, before and during lovastatin treatment. Lovastatin ther- apy significantly reduced plasma levels of LDL cholesterol (142 vs 93 mg\\/dl, P

Yadon Arad; Rajasekhar Ramakrishnan; Henry N. Ginsberg


Endogenous Androgen Deficiency Enhances Diet-Induced Hypercholesterolemia and Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice  

PubMed Central

Background Despite numerous clinical and animal studies, the role of sex steroid hormones on lipoprotein metabolism and atherosclerosis remain controversial. Objective We sought to determine the effects of endogenous estrogen and testosterone on lipoprotein levels and atherosclerosis using mice fed a low-fat diet with no added cholesterol. Methods Male and female low-density lipoprotein receptor-deficient mice were fed an open stock low-fat diet (10% of kcals from fat) for 2, 4, or 17 weeks. Ovariectomy, orchidectomy, or sham surgeries were performed to evaluate the effects of the presence or absence of endogenous hormones on lipid levels, lipoprotein distribution, and atherosclerosis development. Results Female mice fed the study diet for 17 weeks had a marked increase in levels of total cholesterol, triglycerides, apolipoprotein-B containing lipoproteins, and atherosclerosis compared with male mice. Surprisingly, ovariectomy in female mice had no effect on any of these parameters. In contrast, castration of male mice markedly increased total cholesterol concentrations, triglycerides, apolipoprotein B-containing lipoproteins, and atherosclerotic lesion formation compared with male and female mice. Conclusions These data suggest that endogenous androgens protect against diet-induced increases in cholesterol concentrations, formation of proatherogenic lipoproteins, and atherosclerotic lesions formation. Conversely orchidectomy, which decreases androgen concentrations, promotes increases in cholesterol concentrations, proatherogenic lipoprotein formation, and atherosclerotic lesion formation in lowdensity lipoprotein receptor-deficient mice in response to a low-fat diet.

Hatch, Nicholas W.; Srodulski, Sarah J.; Chan, Huei-Wei; Zhang, Xuan; Tannock, Lisa R.; King, Victoria L.



Transfer of cholesteryl ester into high density lipoprotein by cholesteryl ester transfer protein: effect of HDL lipid and apoprotein content  

Microsoft Academic Search

Recombinant high density lipoprotein (rHDL) particles were prepared by cosonication of purified lipids and human apo- proteins and incubated with partly purified cholesteryl ester trans- fer protein (CETP) and low density lipoprotein (LDL) containing \\\\3H)cholesteryl ester. Increasing the triglyceride content relative to cholesteryl ester in rHDL sign&cantly decreased the ability of the particles to accept cholesteryl esters transferred by CETP.

D. L. Sparks; P. H. Pritchard


Long-term effect of low-density lipoprotein apheresis on plasma lipoproteins and coronary heart disease in native vessels and coronary bypass in severe heterozygous familial hypercholesterolemia  

Microsoft Academic Search

Low-density lipoprotein (LDL) apheresis is a potent treatment for patients with coronary heart disease and severe hereditary forms of LDL hypercholesterolemia not adequately responsive to drug treatment. Until now, the beneficial effect of aggressive reduction of LDL cholesterol by LDL apheresis on the course of coronary heart disease has been demonstrated in one 3-year study and several studies lasting 2

Werner O. Richter; Markus G. Donner; Berthold Höfling; Peter Schwandt



Molecular mechanisms of vascular effects of High-density lipoprotein: alterations in cardiovascular disease  

PubMed Central

Low high-density lipoprotein (HDL)-cholesterol levels are associated with an increased risk of coronary artery disease (CAD) and myocardial infarction, which has triggered the hypothesis that HDL, in contrast to low-density lipoprotein (LDL), acts as an anti-atherogenic lipoprotein. Moreover, experimental studies have identified potential anti-atherogenic properties of HDL, including promotion of macrophage cholesterol efflux and direct endothelial-protective effects of HDL, such as stimulation of endothelial nitric oxide production and repair, anti-apoptotic, anti-inflammatory and anti-thrombotic properties. Studies in gene-targeted mice, however, have also indicated that increasing HDL-cholesterol plasma levels can either limit (e.g. apolipoprotein A-I) or accelerate (e.g. Scavenger receptor class B type I) atherosclerosis. Moreover, vascular effects of HDL have been observed to be heterogenous and are altered in patients with CAD or diabetes, a condition that has been termed ‘HDL dysfunction’. These alterations in biological functions of HDL may need to be taken into account for HDL-targeted therapies and considering raising of HDL-cholesterol levels alone is likely not sufficient in this respect. It will therefore be important to further determine, which biological functions of HDL are critical for its anti-atherosclerotic properties, as well as how these can be measured and targeted.

Besler, Christian; Luscher, Thomas F; Landmesser, Ulf



Endoplasmic reticulum localization of the low density lipoprotein receptor mediates presecretory degradation of apolipoprotein B  

PubMed Central

Mutations in the low density lipoprotein (LDL) receptor (LDLR) cause hypercholesterolemia because of inefficient LDL clearance from the circulation. In addition, there is a paradoxical oversecretion of the metabolic precursor of LDL, very low density lipoprotein (VLDL). We recently demonstrated that the LDLR mediates pre-secretory degradation of the major VLDL protein, apolipoprotein B (apoB). Kinetic studies suggested that the degradation process is initiated in the secretory pathway. Here, we evaluated the ability of several LDLR variants that are stalled within the secretory pathway to regulate apoB secretion. Both a naturally occurring mutant LDLR and an LDLR consisting of only the ligand-binding domains and a C-terminal endoplasmic reticulum (ER) retention sequence were localized to the ER and not at the cell surface. In the presence of either of the ER-localized LDLRs, apoB secretion was essentially abolished. When the ligand-binding domain of the truncated receptor was mutated the receptor was unable to block apoB secretion, indicating that the inhibition of apoB secretion depends on the ability of the LDLR to bind to its ligand. These findings establish LDLR-mediated pre-secretory apoB degradation as a pathway distinct from reuptake of nascent lipoproteins at the cell surface. The LDLR provides an example of a receptor that modulates export of its ligand from the ER.

Gillian-Daniel, Donald L.; Bates, Paul W.; Tebon, Angie; Attie, Alan D.



Herpes Simplex Virus Binds to Human Serum Lipoprotein  

Microsoft Academic Search

Summary Binding of herpes simplex virus (HSV) type 1 to the various subclasses of human serum lipoproteins was investigated. Studies were performed with human serum lipoproteins purified by differential ultracentrifugation and artificial proteoliposomes containing only one type of apolipoprotein (Al5 E) by using an enzyme-linked immunosorbent assay technique, column chromatography, and electron microscopy. All tested lipoprotein subclasses (very low, low-,

H. P. Huemer; H. J. Menzel; D. Potratz; B. Brake; D. Falke; G. Utermann; M. P. Dierich



Preparation of high-density lipoproteins labelled exclusively at the cholesteryl ester moiety.  


The in vitro preparation of HDL radiolabelled at the cholesteryl ester moiety was determined by incubating different serum fractions with [3H]cholesteryl linoleate or cholesteryl [14C]oleate dissolved in dimethylsulfoxide (DMSO) and subsequent re-isolation of HDL from the incubation mixture by ultracentrifugation. Using the supernatant obtained by precipitation of apolipoprotein B-containing lipoproteins with phosphotungstate/MgCl2 or using the greater than 1.075 kg/l fraction of sera, the bulk of the added radioactivity could be recovered in the re-isolated HDL fraction, as demonstrated by density gradient ultracentrifugation or by gel chromatography. Incubation experiments using whole sera or the greater than 1.063 kg/l fraction of sera resulted in the preferential association of the labelled cholesteryl linoleate with apolipoprotein B-containing lipoproteins. PMID:7116635

Schriewer, H; Jabs, H U; Schultze, J; Assmann, G



Immunohistochemical detection of a very high density lipoprotein (VHDL) in ovarian follicles of Triatoma infestans.  


The ability of Triatoma infestans ovarian follicles to synthesize a very high-density lipoprotein (VHDL) has been examined by immunohistochemical methods. This kind of lipoprotein can be envisaged as a storage hexameric protein present in the hemolymph of some insect species. VHDL immunoreactivity is observed in oocytes at different stages of maturation. The antigen is present in the oocyte cytoplasm as well as in the follicular epithelial cells. The immunopositive reaction in the apical surface of follicle cells suggests both a VHDL synthesis and a secretion process. Furthermore, VHDL seems to be stored into oocyte in yolk granules. On the contrary, no immunopositive reaction is observed in the intracellular spaces between follicle cells, suggesting that VHDL is not incorporated from hemolymph into the oocyte. PMID:11387873

González, M S; Ronderos, J R; Rimoldi, O J; Brenner, R R



New function for high density lipoproteins. Their participation in intravascular reactions of bacterial lipopolysaccharides.  

PubMed Central

The addition of bacterial lipopolysaccharide (LPS) from Escherichia coli 0111:B4 or Salmonella minnesota R595 to plasma (or serum) resulted in a marked reduction of the hydrated buoyant density of the parent LPS (0111:B4 [d = 1.44 g/cm3] and R595 [d = 1.38 g/cm3]), to d less than 1.2 g/cm3. This reduction in buoyant density to less than 1.2 g/cm3 of the LPS required plasma (or serum) lipid. Delipidation of plasma (or serum) by extraction with n-butanol/diisopropyl ether (40/60, vol:vol) prevented the conversion of the parent LPS to a form with d less than 1.2 g/cm3. Reversal of the effect of delipidation was accomplished by the addition of physiologic concentrations of high density lipoprotein (HDL). In contrast, as much as two times normal serum concentration of low density or very low density lipoprotein were ineffective. The ability of normal plasma (or serum) to inhibit the pyrogenic activity of LPS, lost after delipidation, was also restored after the addition of HDL. Preliminary results suggested that prior modifications of the LPS, probably disaggregation, may be required before interaction with HDL.

Ulevitch, R J; Johnston, A R; Weinstein, D B



High-density lipoprotein cholesterol as a predictor of clinical outcomes in patients achieving low-density lipoprotein cholesterol targets with statins after percutaneous coronary intervention  

PubMed Central

Background A low level of high-density lipoprotein cholesterol (HDL-C) is strongly associated with cardiovascular events. However, the significance of HDL-C after statin therapy on the outcome of patients who have undergone percutaneous coronary intervention (PCI) with drug eluting stents (DES) is unclear. Objectives To investigate the significance of HDL-C after statin therapy on cardiovascular events in patients with coronary artery disease after DES implantation. Methods Patients who underwent PCI with DES from January 2004 to December 2009 were prospectively enrolled. The follow-up lipid panel of 2693 patients (median lab follow-up duration 225?days) who had continued using statins after PCI and who attained low-density lipoprotein cholesterol (LDL-C) <100?mg/dl was analysed. Major adverse cardiac events (MACE), including all-cause death, non-fatal myocardial infarction, and target vessel revascularisation according to follow-up HDL-C level (40?mg/dl for men or 50?mg/dl for women) were compared with the use of propensity scores matching. Results Median follow-up duration was 832?days. 1585 (58.9%) patients had low follow-up HDL-C and 1108 had high follow-up HDL-C. The low follow-up HDL-C group had significantly higher rates of MACE. Low follow-up HDL-C was a significant independent predictor of MACE (adjusted HR 1.404, 95% CI 1.111 to 1.774, p=0.004). In further analysis with propensity scores matching, overall findings were consistent. Conclusions Raising HDL-C levels may be a subsequent goal after achieving target LDL-C levels in patients with DES implantation.

Seo, Suk Min; Choo, Eun-Ho; Koh, Yoon-Seok; Park, Mahn Won; Shin, Dong Il; Choi, Yoon Seok; Park, Hun-Jun; Kim, Dong Bin; Her, Sung Ho; Lee, Jong Min; Park, Chul Soo; Kim, Pum-Joon; Moon, Keon Woong; Chang, Kiyuk; Kim, Hee Yeol; Yoo, Ki Dong; Jeon, Doo Soo; Chung, Wook Sung; Park, Yong Gyu



The role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in comparison with whole egg yolk for sperm cryopreservation in rhesus monkeys  

PubMed Central

Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein (HDL) in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant (glycerol) on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL–sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL–sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in post-thaw survival; while addition of methyl-?-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.

Dong, Qiao-Xiang; Rodenburg, Sarah E; Hill, Dana; VandeVoort, Catherine A



Cross-linking of apoproteins in high density lipoprotein by dimethylsuberimidate inhibits specific lipoprotein binding to membranes  

SciTech Connect

Apoprotein E-free high density lipoproteins (HDL) bind to various cells and cell membrane preparations with properties typical of ligand-receptor interactions. This specific binding can be inhibited by treatment of HDL with tetranitromethane (TNM). During treatment of HDL with TNM, in addition to the expected nitration of tyrosine residues, cross-linking of lipids to apoproteins and of apoproteins to each other occurs. We have recently shown that cross-linking of phospholipids to apoproteins is not responsible for the inhibition of binding. To determine the role of cross-linking of apoproteins to each other in the inhibition, we used the bifunctional reagent dimethylsuberimidate (DMS) to cross-link the apoproteins in HDL3. Over 80% of apoproteins in DMS-HDL3 were cross-linked, as analyzed by SDS-polyacrylamide gel electrophoresis. DMS-HDL3 was similar to control HDL3 in its lipid composition. Gel filtration chromatography did not reveal any significant difference in size between DMS-HDL3 and control HDL3. As determined by competitive binding with 125I-labeled HDL3, DMS-HDL3 was almost completely unable to bind specifically to rat liver plasma membranes and human skin fibroblasts. It is concluded from these results that TNM inhibits the specific binding of HDL3 to membranes by a mechanism that involves cross-linking of apoproteins to each other in HDL3 particles. This observation implies that the specific binding of HDL3 to cells may depend on the native quaternary structure of apoproteins in the HDL particle. Because of its reduced ability to bind to the specific binding sites, DMS-HDL3 may be useful for studies related to the functional aspects of HDL binding sites.

Chacko, G.K.; Mahlberg, F.H.; Johnson, W.J.



Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies  

PubMed Central

Oxidation of low-density lipoprotein (LDL) has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO) is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNF? and IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis.

Vanhamme, Luc; Roumeguere, Thierry; Zouaoui Boudjeltia, Karim



The exchange of unesterified cholesterol between human low-density lipoproteins and rat erythrocyte `ghosts'  

PubMed Central

1. The exchange of unesterified cholesterol molecules between rat erythrocyte `ghosts' and human low-density lipoproteins has been studied under a number of different experimental conditions. 2. The process is pH-dependent, the rate being minimal at about pH5. 3. Cholesterol exchange does not vary greatly with temperature, the rate at 50° being less than twice that at 2°. 4. Large variations in the ionic strength or Ca2+ concentration of the medium have little effect, but the exchange rate is greatly increased in the presence of a wide range of chemical compounds, e.g. urea, alcohols, acetone, dimethyl sulphoxide and tetra-alkyl-ammonium salts. 5. Acetone and dimethyl sulphoxide have a much greater effect at 37° than at 8–10°. 6. It is proposed that hydrophobic bonding is of great importance in maintaining the structure of `ghosts' and lipoproteins. 7. The results are discussed in relation to current theories of membrane and lipoprotein structure.

Bruckdorfer, K. R.; Green, C.



Low Clusterin Levels in High Density Lipoprotein Associate with Insulin Resistance, Obesity, and Dyslipoproteinemia  

PubMed Central

Objective Insulin resistance and obesity are hallmarks of type 2 diabetes and the metabolic syndrome, which confer an increased risk of cardiovascular disease. Recent studies suggest that the protein cargo of high density lipoprotein (HDL) makes important contributions to the lipoprotein’s cardioprotective effects. We used targeted proteomics to determine if obesity and insulin resistance associate with changes in HDL’s protein content in two different groups of men. Methods and Results In a discovery study, we used isotope dilution mass spectrometry to quantify the relative concentrations of five proteins previously implicated in HDL’s cardioprotective effects in three groups of healthy subjects: lean insulin-sensitive, lean insulin-resistant, and obese insulin-resistant. We validated our findings in a different group of subjects. Clusterin concentration in HDL strongly and negatively associated with insulin resistance and body mass index in both populations. HDL clusterin levels were lower in subjects with low HDL and high triglycerides, key components of the metabolic syndrome. There was an inverse correlation between clusterin levels in HDL and VLDL/LDL. Conclusions Clusterin levels in HDL are lower in men with reduced insulin sensitivity, higher body mass index, and an unfavorable lipid profile. Our observations raise the possibility that clusterin depletion contributes to the loss of HDL’s cardioprotective properties.

Hoofnagle, Andrew N.; Wu, Mingyuan; Gosmanova, Albina K.; Becker, Jessica O.; Wijsman, Ellen M.; Brunzell, John D.; Kahn, Steven E.; Knopp, Robert H.; Lyons, Timothy J.; Heinecke, Jay W.



Effect of soybean phytoestrogen intake on low density lipoprotein oxidation resistance.  


The oxidation of low density lipoproteins (LDLs) is thought to take place in the arterial intima when the particles have become isolated from circulating water-soluble antioxidants. We hypothesized that isoflavonoid antioxidants derived from soy could be incorporated into lipoproteins and possibly could protect them against oxidation, which is regarded as atherogenic. Six healthy volunteers received 3 soy bars [containing the isoflavonoid antioxidants genistein (12 mg) and daidzein (7 mg)] daily for 2 weeks. LDLs were isolated from blood drawn at the the end of a 2-week dietary baseline period, after 2 weeks on soy, and after discontinuation of soy. Large increases in plasma isoflavonoid levels occurred during soy feeding, but only minute amounts were stably associated with lipoproteins (less than 1% of plasma isoflavonoids in the LDL fraction). The LDLs were subjected to copper-mediated oxidation in vitro. Compared with off soy values, lag phases of LDL oxidation curves were prolonged by a mean of 20 min (P < 0.02) during soy intake, indicating a reduced susceptibility to oxidation. The results suggest that intake of soy-derived antioxidants, such as genistein and daidzein, may provide protection against oxidative modification of LDL. As only very small amounts of these substances were detected in purified LDL, modified LDL particles may have been produced in vivo by circulating isoflavonoids promoting resistance to oxidation ex vivo. PMID:9501223

Tikkanen, M J; Wähälä, K; Ojala, S; Vihma, V; Adlercreutz, H



Does low-density lipoprotein size add to atherogenic particle number in predicting the risk of fatal myocardial infarction?  


The lipoprotein-related risk of coronary artery disease is determined principally by the balance between atherogenic lipoprotein particles, i.e., the lipoprotein that contain apolipoprotein-B (apo-B), and the antiatherogenic particles, i.e., high-density lipoprotein particles that contain apo-A-I. However, there is also considerable evidence that patients with predominantly small dense low-density lipoprotein (LDL) have more adverse clinical outcomes than do those with large buoyant LDL. The AMORIS study prospectively examined the relative importance of lipoprotein lipids versus apolipoproteins on the risk of fatal myocardial infarction in a large Swedish cohort. This updated analysis includes 69,029 men and 57,167 women who were followed for a mean of 10.3 years. Our objective was to determine whether LDL size as reflected by the LDL cholesterol/apo-B ratio added significant predictive power to apo-B or the apo-B/apo-A-I ratio. Although apo-A-I added significantly to the predictive power of apo-B, categorical and continuous multivariate analyses showed that this is not the case for LDL size. The strongest single lipoprotein-related risk factor was the apo-B/apo-A-I ratio. In conclusion, these results provide further confirmation of the importance of determining apo-B and apo-A-I in routine clinical practice. PMID:16563891

Jungner, Ingmar; Sniderman, Allan D; Furberg, Curt; Aastveit, Are H; Holme, Ingar; Walldius, Goran



Lipid and apolipoprotein distribution as a function of density in equine plasma lipoprotein.  


1. Equine lipoproteins were isolated from plasma by density gradient ultracentrifugation and apolipoprotein composition determined by SDS-polyacrylamide gel electrophoresis. 2. VLDL and IDL were present at low concentration (0.2 mg/ml). Two apoB components of Mr corresponding to human apoB-100 and one apoB-48-like component were represented in VLDL fraction. 3. LDL-1 and LDL-2 subfractions have displayed an almost equal concentration (0.4 mg/ml). Two apoB-100-like components were the major apolipoproteins in each fraction. Small amounts of apoB-48-like component were detectable in LDL-1 and LDL-2. 4. HDL-2 represented a major class of equine lipoproteins (1.8 mg/ml). ApoA-1-like component was the dominant protein in HDL-1, HDL-2 and HDL-3. Dimeric apoA-II-like components were slightly represented in HDL subfractions. 5. HDL-3 displayed the same apolipoprotein pattern as HDL-1 and HDL-2, but two further minor proteins of Mr 20,000 and 14,000 were detected. 6. VHDL represented a minor class of lipoprotein (0.2 mg/ml). ApoA-I-like component was the major apolipoprotein of VHDL. Small amounts of apoA-IV-like, apoE-like, and Mr 55,000 protein were detectable. 7. ApoC-like of Mr lower than 10,000 was represented in all equine lipoprotein classes. PMID:2776430

Le Goff, D; Pastier, D; Hannan, Y; Petit, E; Ayrault-Jarrier, M; Nouvelot, A



Postprandial Changes in High Density Lipoproteins in Rats Subjected to Gavage Administration of Virgin Olive Oil  

PubMed Central

Background and Aims The present study was designed to verify the influence of acute fat loading on high density lipoprotein (HDL) composition, and the involvement of liver and different segments of small intestine in the changes observed. Methods and Results To address these issues, rats were administered a bolus of 5-ml of extra-virgin olive oil and sacrificed 4 and 8 hours after feeding. In these animals, lipoproteins were analyzed and gene expressions of apolipoprotein and HDL enzymes were assessed in duodenum, jejunum, ileum and liver. Using this experimental design, total plasma and HDL phospholipids increased at the 8-hour-time-point due to increased sphingomyelin content. An increase in apolipoprotein A4 was also observed mainly in lipid-poor HDL. Increased expression of intestinal Apoa1, Apoa4 and Sgms1 mRNA was accompanied by hepatic decreases in the first two genes in liver. Hepatic expression of Abcg1, Apoa1bp, Apoa2, Apoe, Ptlp, Pon1 and Scarb1 decreased significantly following fat gavage, while no changes were observed for Abca1, Lcat or Pla2g7. Significant associations were also noted for hepatic expression of apolipoproteins and Pon1. Manipulation of postprandial triglycerides using an inhibitor of microsomal transfer protein -CP-346086- or of lipoprotein lipase –tyloxapol- did not influence hepatic expression of Apoa1 or Apoa4 mRNA. Conclusion All these data indicate that dietary fat modifies the phospholipid composition of rat HDL, suggesting a mechanism of down-regulation of hepatic HDL when intestine is the main source of those particles and a coordinated regulation of hepatic components of these lipoproteins at the mRNA level, independently of plasma postprandial triglycerides.

Martinez-Beamonte, Roberto; Navarro, Maria A.; Acin, Sergio; Guillen, Natalia; Barranquero, Cristina; Arnal, Carmen; Surra, Joaquin; Osada, Jesus



Females with angina pectoris have altered lipoprotein metabolism with elevated cholesteryl ester transfer protein activity and impaired high-density lipoproteins-associated antioxidant enzymes  

PubMed Central

In order to investigate non-invasive biomarkers for angina pectoris (AP), we analyzed the lipid and protein composition in individual lipoproteins from females with angina pectoris (n=22) and age- and gender-matched controls (n=20). In the low-density lipoprotein (LDL) fraction, the triglycerides (TG) and protein content increased in the AP group compared to the control group. The AP group had lower total cholesterol (TC) and elevated TG in the high-density lipoprotein (HDL) fraction. In the AP group, cholesteryl ester transfer protein (CETP) activity was enhanced in HDL and LDL, while lecithin:cholesterol acyltransferase (LCAT) activity in HDL3 was almost depleted. Antioxidant activity was significantly decreased in the HDL3 fraction, with a decrease in the HDL2 particle size. In the HDL3 fraction, paraoxonase and platelet activating factor-acetylhydrolase (PAF-AH) activity were much lower and the levels of CETP and apoC-III were elevated in the AP group. The LDL from the AP group was more sensitive to cupric ion-mediated oxidation with faster mobility. In conclusion, the lipoprotein fractions in the AP group had impaired antioxidant activity and increased TG and apoC-III with structural and functional changes.




High density lipoprotein plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits.  


The effects of in vivo administration of high density lipoprotein-very high density lipoprotein (HDL-VHDL) on the development of aortic fatty streaks were studied in cholesterol-fed rabbits. The rabbits received a 0.5% cholesterol-rich diet for 8 weeks. During this period, the HDL-VHDL group was intravenously administered with 50 mg/week of homologous HDL-VHDL protein; the control group received normal saline (0.9% NaCl). HDL-VHDL fraction was obtained at density range 1.063 to 1.25 gm/ml by ultracentrifugation of normal rabbit plasma. Along the study, plasma lipid levels followed a similar profile in both groups. At the completion of the study, atherosclerotic-like lipid-rich lesions covered 37.9 +/- 6% (X +/- SEM) of the intimal aortic surface in the control group, and 14.9 +/- 2.1% in the treated group (p less than 0.001). The values of total and free cholesterol, esterified cholesterol, and phospholipids deposited within vessel wall were significantly lower in the aortas of the HDL-VHDL treated group than those in the control group. Cholesterol accumulation in the livers was also significantly lower (p less than 0.01) in the treated group than in the control. We concluded that administration of homologous HDL-VHDL lipoprotein fraction to cholesterol-fed rabbits, dramatically inhibited the extent of aortic fatty streaks and lowered lipid deposition in the arterial wall and liver without modification of the plasma lipid levels. PMID:2927083

Badimon, J J; Badimon, L; Galvez, A; Dische, R; Fuster, V



Gradient gel electrophoretic separation of LDL and HDL subclasses on BioRad Mini Protean II and size phenotyping in healthy Macedonians  

Microsoft Academic Search

Background: Lipoprotein subclass determinations provide a more detailed reflection of lipoprotein metabolism and an accurate prediction for risk of cardiovascular disease. Gradient gel electrophoresis for lipoprotein separation on Pharmacia electrophoretic apparatus has been most commonly used for many years. Methods: In this paper, we describe a new method for separating LDL and HDL subclasses by nondenaturing polyacrylamide gradient (3–31%) gel

Sonja B Alabakovska; Bojana B Todorova; Danica D Labudovic; Katerina N Tosheska



Synthetic Nano-Low Density Lipoprotein as Targeted Drug DeliveryVehicle for Glioblastoma Multiforme  

SciTech Connect

This paper discribes a synthetic low density lipoprotein(LDL) made by complexing a 29 amino acid that consists of a lipid bindingdomain and the LDL receptor binding domain with a lipid microemulsion.The nano-LDL particles were intermdiate in size between LDL and HDL andbound to LDL receptors on GBM brain tumor cells. Synthetic nano-LDLuptake by GBM cells was LDL receptor specific and dependent on cellreceptor number. It is suggested that these synthetic particles can serveas a delivery vehicle for hydophobic anti-tumor drugs by targeting theLDL receptor.

Nikanjam, Mina; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Shu,Xiao; Budinger, Thomas F.; Forte, Trudy M.



Effects of fluvastatin therapy on lipids, antioxidants, oxidation of low density lipoproteins and trace metals  

Microsoft Academic Search

Objective: Oxidation of low density lipoproteins (LDL) is thought to be an important step in the development of atherosclerosis. Trace\\u000a metals are involved in oxidative processes. It was of interest to determine whether lipid-lowering therapy with fluvastatin,\\u000a a potent HMGCoA reductase inhibitor, affected LDL oxidation and trace metal levels.\\u000a \\u000a \\u000a \\u000a Methods: Twenty hypercholesterolemic patients were treated with fluvastatin (40?mg twice daily)

W. Leonhardt; T. Kurktschiev; D. Meissner; P. Lattke; C. Abletshauser; G. Weidinger; W. Jaross; M. Hanefeld



Native low density lipoprotein induces pancreatic ? cell apoptosis through generating excess reactive oxygen species  

Microsoft Academic Search

Background  The growing evidences demonstrated hyperlipidemia in obesity and type 2 diabetes is characterized by high levels of free fatty\\u000a acids, low-density lipoprotein (LDL), triglyceride, and cholesterol.\\u000a \\u000a \\u000a \\u000a \\u000a Method and Results  We investigated the effect of LDL particles (LDLs) loading on MIN6 cells derived from pancreatic ? cells. Exposure of MIN6\\u000a cells to LDLs induced apoptosis in dose and time-dependent manner, demonstrated by

Xiuli Lu; Jianli Liu; Xiangyu Cao; Xiao Hou; Xude Wang; Chenguang Zhao; Youliang Wang; Yang Li; Hisao Seo; Bing Gao



The effect of alcohol on serum high density lipoprotein (HDL). A controlled experiment.  


A cross-over study using 11 male subjects and a closely controlled diet, investigated the effect of alcohol on serum high density lipoprotein (HDL) components. Smoking status and body weight remained essentially constant and exercise changes were adjusted for in the analysis. As compared to sucrose, alcohol consumption was associated with a significant elevation in serum apolipoprotein A-I (0.37 mg/dl/g/day of alcohol) with similar effects for serum HDL cholesterol (0.14 mg/dl/g/day of alcohol) and serum apolipoprotein A-II (0.11 mg/dl/g/day of alcohol) achieving borderline levels of statistical significance. PMID:6405757

Fraser, G E; Anderson, J T; Foster, N; Goldberg, R; Jacobs, D; Blackburn, H



Preferential enrichment of large-sized very low density lipoprotein populations with transferred cholesteryl esters  

SciTech Connect

The effect of lipid transfer proteins on the exchange and transfer of cholesteryl esters from rat plasma HDL2 to human very low (VLDL) and low density (LDL) lipoprotein populations was studied. The use of a combination of radiochemical and chemical methods allowed separate assessment of (/sup 3/H)cholesteryl ester exchange and of cholesteryl ester transfer. VLDL-I was the preferred acceptor for transferred cholesteryl esters, followed by VLDL-II and VLDL-III. LDL did not acquire cholesteryl esters. The contribution of exchange of (/sup 3/H)cholesteryl esters to total transfer was highest for LDL and decreased in reverse order along the VLDL density range. Inactivation of lecithin: cholesterol acyltransferase (LCAT) and heating the HDL2 for 60 min at 56 degrees C accelerated transfer and exchange of (/sup 3/H)cholesteryl esters. Addition of lipid transfer proteins increased cholesterol esterification in all systems. The data demonstrate that large-sized, triglyceride-rich VLDL particles are preferred acceptors for transferred cholesteryl esters. It is suggested that enrichment of very low density lipoproteins with cholesteryl esters reflects the triglyceride content of the particles.

Eisenberg, S.



Preparation and Activity Analysis of Recombinant Human High-Density Lipoprotein  

PubMed Central

Abstract Population studies have consistently shown a highly inverse correlation between plasma concentration of high-density lipoprotein and the risk of atherosclerotic cardiovascular disease in humans. High-density lipoprotein (HDL) as a therapeutic target is an intense area of ongoing investigation. Aiming to solve the shortcomings of native HDL application, we prepared recombinant human HDL (rhHDL) that contains a similar composition and has similar functions with native HDL. Six kinds of recombinant human apolipoproteins (rhapo)—rhapoA-I, rhapoA-II, rhapoA-IV, rhapoC-I, rhapoC-II, and rhapoE—were expressed in Pichia pastoris and purified with chromatography. By the facilitation of cholate, six kinds of rhapo penetrated among the phosphatidylcholine acyl chains. After purification by density-gradient centrifugation, rhHDL was acquired. Based on morphological observation, we confirmed that the micellar complexes of rhapo with phosphatidylcholine and cholesterol were prepared. We carried on comparative studies in vitro and in vivo between native HDL and rhHDL. Cellular cholesterol efflux assays showed that rhHDL could promote the efflux of excess cholesterol from macrophages. Furthermore, rhHDL has similar effects with native HDL on the blood lipid metabolism in hyperlipidemic mice. In conclusion, rhHDL has similar effects on antiatherosclerosis with native HDL through reverse cholesterol transport, antioxidative, and antithrombotic properties. It could be used as a therapeutic HDL-replacement agent.

Su, Manman; Chang, Weiqin; Shi, Kaiyao; Wang, Dingding; Wang, Mingxing; Yan, Weiqun



Low-density lipoprotein subfractions and cardiovascular risk in hypertension: relationship to endothelial dysfunction and effects of treatment  

Microsoft Academic Search

Although hypertensive patients are at particular risk of vascular complications, the possible contribution of an atherogenic lipoprotein profile and endothelial dysfunction to this risk is unclear. We investigated this by measuring low-density lipoprotein (LDL) sub-fractions and flow-mediated dilatation (FMD) (reflecting endothelial damage\\/dysfunction) in a cohort of high risk hypertensive patients.We studied 84 hypertensive patients (74 males; mean age 64 years,

Dirk C. Felmeden; Charles G. C. Spencer; Andrew D. Blann; Gregory Y. H. Lip; Gareth D. Beevers



A study of the small spherical high density lipoproteins of patients afflicted with familial 1ecithin:cholesterol acyltransferase deficiency  

Microsoft Academic Search

We studied the effects of the 1ecithin:cholesterol acyl- transferase reaction on the size and composition of the small spherical high density lipoproteins of patients afflicted with fa- milial 1ecithin:cholesterol acyltransferase deficiency. We isolated these lipoproteins by preparative ultracentrifugation and rate zonal ultracentrifugation, determined their diameter by gradient gel electrophoresis, and then calculated their composition by relating measurements of their lipid

Chu Chen; Kenneth Applegate; Weiling C. King; John A. Glomset; Kaare R. Norum; Egil Gjone


Changes in total and high-density lipoprotein cholesterol over 10- and 20-year periods (the Honolulu Heart Program)  

Microsoft Academic Search

Limited data are available on patterns of change in lipids and lipoproteins as persons age. The purpose of this report is to describe the 10-year change in total and high-density lipoprotein (HDL) cholesterol according to suspected determinants in 898 Japanese-American men enrolled in the Honolulu Heart Program. Data are based on examinations that occurred from 1970 to 1972 and at

RobertD Abbott; Katsuhiko Yano; AmyA Hakim; CecilM Burchfiel; DanS Sharp; BeatrizL Rodriguez; J. David Curb



Molecular characterization of quail apolipoprotein very-low-density lipoprotein II: disulphide-bond-mediated dimerization is not essential for inhibition of lipoprotein lipase.  

PubMed Central

As part of the avian reproductive effort, large quantities of triglyceride-rich very-low-density lipoprotein (VLDL) particles are transported by receptor-mediated endocytosis into the female germ cells. Although the oocytes are surrounded by a layer of granulosa cells harbouring high levels of active lipoprotein lipase, non-lipolysed VLDL is transported into the yolk. This is because VLDL particles from laying chickens are protected from lipolysis by apolipoprotein (apo)-VLDL-II, a potent dimeric lipoprotein lipase inhibitor [Schneider, Carroll, Severson and Nimpf (1990) J. Lipid Res. 31, 507-513]. To determine whether this protection depends on dimer formation and constitutes a general mechanism to ensure high levels of yolk triglycerides for embryonic utilization in birds, we have now molecularly characterized apo-VLDL-II in the Japanese quail, a frequently used avian species. Quail apo-VLDL-II shows 72% amino acid identity with the chicken protein, with most replacements being in the C-terminal region. Importantly, quail apo-VLDL-II lacks the single cysteine residue present eight residues from the C-terminus of chicken apo-VLDL-II, which is responsible for dimerization of the chicken lipoprotein lipase inhibitor. Nevertheless, monomeric quail and dimeric chicken apo-VLDL-II display, on a molar basis, identical inhibitory effects on lipoprotein lipase, underscoring the biological importance of their function. Furthermore secondary structure prediction of the 3'-untranslated region of the quail message supports a role for loop structures in the strictly oestrogen-dependent production of the lipoprotein lipase inhibitors. Our findings shed new light on the essential role of this small, hormonally regulated, protein in avian reproduction.

MacLachlan, I; Steyrer, E; Hermetter, A; Nimpf, J; Schneider, W J



AnAlphaSlow-Moving High-Density-Lipoprotein Subfraction in Serumof a Patientwith Radiation Ententis and Pentoneal Carcinosis  

Microsoft Academic Search

An alpha slow-movinghigh-density-lipoprotein (HDL) sub- fraction was seen in a patient presenting with radiation enteritisand pentonealcarcinosis,who was given long-term cyclic parenteral nutrition. This subfraction, observed in additionto normal HDL, was precipitatedwith low-density lipoproteins(LDL) and very-low-densityIlpoproteins(VLDL) by sodiumphosphotungstate-magnesium chloride.The pa. tierit'sserum lipoproteinswere analyzed after fractionation by densitygradientultracentrifugation. The alpha slow-mov- ing HDL floated in the ultracentrifugation subfractionswith densitiesrangingfrom 1.028 to 1.084

Jacqueline Peynet; Alain Legrand; Bernard Messing; Francols Rousselet


Effects of Statins on High-Density Lipoproteins: A Potential Contribution to Cardiovascular Benefit  

PubMed Central

Purpose The objective was to systematically review clinical trial data on the effects of statins on high-density lipoproteins (HDL) and to examine the possibility that this provides cardiovascular benefits in addition to those derived from reductions in low-density lipoproteins (LDL). Methods The PubMed database was searched for publications describing clinical trials of atorvastatin, pravastatin, rosuvastatin, and simvastatin. On the basis of predefined criteria, 103 were selected for review. Results Compared with placebo, statins raise HDL, measured as HDL-cholesterol (HDL-C) and apolipoprotein A-I (apo A-I); these elevations are maintained in the long-term. In hypercholesterolemia, HDL-C is raised by approximately 4% to 10%. The percentage changes are greater in patients with low baseline levels, including those with the common combination of high triglycerides (TG) and low HDL-C. These effects do not appear to be dose-related although there is evidence that, with the exception of atorvastatin, the changes in HDL-C are proportional to reductions in apo B-containing lipoproteins. The most likely explanation is a reduced rate of cholesteryl ester transfer protein (CETP)-mediated flow of cholesterol from HDL. There is some evidence that the statin effects on HDL reduce progression of atherosclerosis and risk of cardiovascular disease independently of reductions in LDL. Conclusion Statins cause modest increases in HDL-C and apo A-I probably mediated by reductions in CETP activity. It is plausible that such changes independently contribute to the cardiovascular benefits of the statin class but more studies are needed to further explore this possibility.

Jones, Peter



The effects of monensin on secretion of very-low-density lipoprotein and metabolism of asialofetuin by cultured rat hepatocytes.  

PubMed Central

Primary cultures of rat hepatocytes were used to study secretion of very-low-density lipoproteins and metabolism of asialofetuin. The ionophore monensin inhibited both secretion of very-low-density lipoproteins and binding and degradation of asialofetuin in a concentration-dependent manner. Secretion as well as receptor binding were markedly decreased after 15 min treatment with monensin. The inhibitory effect of the ionophore was fully reversible, and no effect on protein synthesis was observed at concentrations up to 50 microM. The secretion of apoproteins (B-small, B-large and E) and that of albumin were inhibited to the same extent as was triacylglycerol secretion. Secretion of very-low-density lipoproteins was more sensitive to low concentrations of monensin than was the metabolism of asialofetuin. Maximum inhibition of very-low-density-lipoprotein secretion was obtained at 5-10 microM-monensin, whereas 25 microM was required to obtain maximum inhibition of binding and degradation of asialofetuin. The number of surface receptors for asialofetuin decreased to about half when the cells were exposed to 25 microM-monensin. It is possible that monensin inhibits endo- and exo-cytosis via a similar mechanism, e.g. by disturbing proton gradients. Since secretion of very-low-density lipoproteins was more sensitive to low concentrations of monensin, it is likely that monensin independently inhibits endocytic and secretory functions in cultured hepatocytes.

Rustan, A C; Nossen, J O; Berg, T; Drevon, C A



Evidence for electronegativity of plasma high density lipoprotein-3 as one major determinant of human cholesteryl ester transfer protein activity  

Microsoft Academic Search

Plasma high density lipoprotein3 (HDLs) subfrac- tions with different composition and electric charge proper- ties were isolated by anion exchange chromatography; their ability to exchange cholesteryl esters with low density lipopro- teins (LDL) in the presence of the human cholesteryl ester transfer protein (CETP) was studied. The rate of radiolabeled cholesteryl esters transferred between LDL and HDLs was progressively enhanced

David Masson; Anne Athias; Laurent Lagrod


Small low-density lipoproteins and vascular cell adhesion molecule-1 are increased in association with hyperlipidemia in preeclampsia  

Microsoft Academic Search

The pregnancy disorder preeclampsa is characterized by endothelial cell dysfunction that may be promoted by abnormal increases in circulating lipids, particularly triglycerides and free fatty acids. Serum triglyceride concentration is a major regulatory determinant of low-density lipoprotein (LDL) size and density distribution. Smaller, denser LDL particles have several intrinsic properties capable of inducing endothelial dysfunction. The present nested, case-control study

Carl A. Hubel; Fiona Lyall; Lisa Weissfeld; Robin E. Gandley; James M. Roberts



Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels  

Technology Transfer Automated Retrieval System (TEKTRAN)

Maximal doses of atorvastatin and rosuvastatin are highly effective in lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels; however, rosuvastatin has been shown to be significantly more effective than atorvastatin in lowering LDL cholesterol and in increasing high-density lipo...


Effects of androgen manipulation on postprandial triglyceridaemia, low-density lipoprotein particle size and lipoprotein(a) in men  

Microsoft Academic Search

Although androgenic hormones decrease HDLC concentration, no direct evidence has linked them to atherosclerosis. The present study was undertaken to extend our ability to assess risk associated with androgen induced lipoprotein(Lp) changes by simultaneously gathering information about postprandial triglyceridaemia (PPT), LDL particle size, HDL and Lp(a) in men either taking exogenous androgens or with suppressed endogenous androgen concentrations. The experimental

M. S. Hislop; A. St Clair Gibson; M. I. Lambert; T. D. Noakes; A. D. Marais



Uptake and processing of remnants of chylomicrons and very low density lipoproteins by rat liver  

SciTech Connect

In the rat, chylomicron remnants and very low density lipoprotein (VLDL) remnants are taken up into the liver by high affinity processes and appear to undergo degradation by lysosomes. The relationship of this catabolic process to the known pathways of uptake and degradation of low density lipoproteins (LDL) and the involvement of nonparenchymal cells are addressed in these studies. The authors have utilized both light and electron microscopic radioautography to determine whether the pathway of intracellular transport and catabolism resembles that established for LDL in hepatocytes. Radioiodinated plasma VLDL remnants and lymph chylomicron remnants were injected into femoral veins of rats and the livers were fixed by perfusion 3 to 30 minutes later. Quantitative light microscopic radioautography showed little or no accumulation of grains over Kupffer cells. Electromicroscopic radioautography confirmed these observations and, in addition, demonstrated that very few grains were associated with endothelial cells. The processing of the remnant particles closely resembled that of LDL. Following an initial association of grains with the parenchymal cell plasma membrane, frequently in regions in close proximity to clathrin-coated endocytic pits, the grains were found in endocytic vesicles just beneath the plasma membrane. By 15 minutes the grains were found over multivesicular bodies located in the Golgi-lysosome region of the cell. Thirty minutes after injection, radioautographic grains began to be associated with secondary lysosomes.

Jones, A.L.; Hradek, G.T.; Hornick, C.; Renaud, G.; Windler, E.E.; Havel, R.J.



Novel Changes in Discoidal High Density Lipoprotein Morphology: A Molecular Dynamics Study  

PubMed Central

ApoA-I is a uniquely flexible lipid-scavenging protein capable of incorporating phospholipids into stable particles. Here we report molecular dynamics simulations on a series of progressively smaller discoidal high density lipoprotein particles produced by incremental removal of palmitoyloleoylphosphatidylcholine via four different pathways. The starting model contained 160 palmitoyloleoylphosphatidylcholines and a belt of two antiparallel amphipathic helical lipid-associating domains of apolipoprotein (apo) A-I. The results are particularly compelling. After a few nanoseconds of molecular dynamics simulation, independent of the starting particle and method of size reduction, all simulated double belts of the four lipidated apoA-I particles have helical domains that impressively approximate the x-ray crystal structure of lipid-free apoA-I, particularly between residues 88 and 186. These results provide atomic resolution models for two of the particles produced by in vitro reconstitution of nascent high density lipoprotein particles. These particles, measuring 95 Å and 78 Å by nondenaturing gradient gel electrophoresis, correspond in composition and in size/shape (by negative stain electron microscopy) to the simulated particles with molar ratios of 100:2 and 50:2, respectively. The lipids of the 100:2 particle family form minimal surfaces at their monolayer-monolayer interface, whereas the 50:2 particle family displays a lipid pocket capable of binding a dynamic range of phospholipid molecules.

Catte, Andrea; Patterson, James C.; Jones, Martin K.; Jerome, W. Gray; Bashtovyy, Denys; Su, Zhengchang; Gu, Feifei; Chen, Jianguo; Aliste, Marcela P.; Harvey, Stephen C.; Li, Ling; Weinstein, Gilbert; Segrest, Jere P.



Serum Fructosamine, Total Cholesterol, and High-Density Lipoprotein in Children with Asthma during Glucocorticoid Treatment.  


Background/Aims. Glucocorticoids may have adverse effects on carbohydrate and lipid metabolism. The present study was conducted to investigate possible effects on carbohydrate and lipid metabolism of inhaled and oral glucocorticoids in children with asthma. Methods. Two randomised controlled trials with blinded crossover designs were performed. Active treatment was 400? ? g inhaled budesonide or 5?mg prednisolone orally daily during one week. The budesonide trial included 17 and the prednisolone trial 20 school children. Serum fructosamine, total cholesterol and high-density lipoprotein were assessed. Results. Serum fructosamine was increased during active treatment (prednisolone 252.3? ? M versus placebo 247.3? ? M; P = 0.03 and budesonide 228.1? ? M versus no treatment 223.1? ? M; P = 0.02). Total cholesterol and high-density lipoprotein were not statistically significantly increased. Conclusion. Short-term treatment with oral prednisolone and inhaled budesonide may adversely affect mean blood glucose concentration. Possible long-term consequences require further investigations. PMID:23724225

Schou, A J; Wolthers, O D



Serum Fructosamine, Total Cholesterol, and High-Density Lipoprotein in Children with Asthma during Glucocorticoid Treatment  

PubMed Central

Background/Aims. Glucocorticoids may have adverse effects on carbohydrate and lipid metabolism. The present study was conducted to investigate possible effects on carbohydrate and lipid metabolism of inhaled and oral glucocorticoids in children with asthma. Methods. Two randomised controlled trials with blinded crossover designs were performed. Active treatment was 400??g inhaled budesonide or 5?mg prednisolone orally daily during one week. The budesonide trial included 17 and the prednisolone trial 20 school children. Serum fructosamine, total cholesterol and high-density lipoprotein were assessed. Results. Serum fructosamine was increased during active treatment (prednisolone 252.3??M versus placebo 247.3??M; P = 0.03 and budesonide 228.1??M versus no treatment 223.1??M; P = 0.02). Total cholesterol and high-density lipoprotein were not statistically significantly increased. Conclusion. Short-term treatment with oral prednisolone and inhaled budesonide may adversely affect mean blood glucose concentration. Possible long-term consequences require further investigations.

Schou, A. J.; Wolthers, O. D.



Tumor targeting effects of a novel modified paclitaxel-loaded discoidal mimic high density lipoproteins.  


Abstract Objective: Monocholesterylsuccinate (CHS)-modified paclitaxel-loaded discoidal reconstituted high density lipoproteins (cP-d-rHDL) as novel biomimetic nanocarriers that were developed for tumor targeting delivery to avoid unexpected drug leakage from discoidal reconstituted high density lipoproteins (d-rHDL) during remodeling process associated with lecithin-cholesterol acyltransferase (LCAT). Methods: Their in vitro characterizations and biomimetic properties, simultaneously tumor distribution and pharmacodynamics in tumor bearing mice were elaborately investigated. Results. In vitro characterization results showed that cP-d-rHDL had nano-size diameter, high negative zeta potential and high entrapment efficiency (EE). Furthermore, morphology study indicated that cP-d-rHDL did not remodel in the presence of LCAT, compared with that of paclitaxel-loaded d-rHDL (P-d-rHDL, not modified). And cellular uptake, together with cytotoxicity toward tumor cells of cP-d-rHDL was not affected after interaction with LCAT. Tumor distribution and pharmacodynamics tests revealed that cP-d-rHDL possessed specific targeting property and anti-tumor efficacy. Conclusion: cP-d-rHDL served to restrain remodeling process and drug leakage, at the same time reinforce the targeting effect, and could act as a potential drug delivery system for cancer therapy. PMID:24079327

Wang, Ji; Jia, Junting; Liu, Jianping; He, Hongliang; Zhang, Wenli; Li, Zhenghua



Ath-2, a second gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice.  


Strain C57BL/6J and A/J differ at two genes determining atherosclerosis susceptibility. The first gene, Ath-1, was described earlier and this report characterizes Ath-2. The alleles at Ath-2 are r for resistance and s for susceptibility to atherosclerosis. The resistant phenotype in female mice is characterized by high plasma high density lipoprotein-cholesterol levels (74 mg/dl +/- SEM 2) and very few lesions/mouse after 14 weeks of consumption of an atherogenic diet (0.1 +/- SEM 0.1 in a predetermined region of the aorta). The susceptible phenotype in female mice is characterized by low levels of high density lipoprotein-cholesterol (35 mg/dl +/- SEM 1) and 1.2 lesions/mouse +/- SEM 0.2 in the same region of the aorta. In Ath-2 heterozygotes, resistance is dominant to susceptibility. Recombinant inbred strains derived from C57BL/6 and A were characterized for Apoa 1, Apoa 2 and susceptibility to atherosclerosis. Ath-1 and Ath-2 interact with each other so that resistant alleles at either locus confer a resistant phenotype to the animal. The map position of Ath-2 is not known, but Ath-2 does not map near genes determining the apolipoproteins for A-I, A-II, or E. PMID:2499515

Paigen, B; Nesbitt, M N; Mitchell, D; Albee, D; LeBoeuf, R C



A-IMilano apoprotein. Decreased high density lipoprotein cholesterol levels with significant lipoprotein modifications and without clinical atherosclerosis in an Italian family.  

PubMed Central

Significant hypertriglyceridemia with a very marked decrease of high density lipoproteins (HDL)-cholesterol levels (7-14 mg/dl) was detected in three members (father, son, and daughter) of an Italian family. The three affected individuals did not show any clinical signs of atherosclerosis, nor was the atherosclerotic disease significantly present in the family. Lipoprotein lipase and lecithin:cholesterol acyltransferase activites were normal or slightly reduced. Morphological and compositional studies of HDL in the subjects showed a significant enlargement of the lipoprotein particles (approximately 120 vs. approximately 94 A for control HDL) and a concomitant increase in the triglyceride content. Analytical isoelectric focusing of HDL apoproteins provided evidence for multiple isoproteins in the apoprotein(apo)-A-I range, with nine different bands being detected instead of the usual four bands observed in normal subjects. Two-dimensional immunoelectrophoresis against apo-A antiserum indicated a clear reduction of apo-A in the alpha electrophoretic region, with splitting of the protein "peak." The observation in otherwise clinically healthy subjects of hypertriglyceridemia, reduced HDL-cholesterol, and marked apoprotein abnormalities, without a significant incidence of atherosclerotic disease in the family suggests this is a new disease entity in the field of lipoprotein pathology, very probably related to an altered amino acid composition of the apo-A-I protein (see Weisgraber et al. 1980. J. Clin. Invest. 66: 901-907). Images

Franceschini, G; Sirtori, C R; Capurso, A; Weisgraber, K H; Mahley, R W



Model of human low-density lipoprotein and bound receptor based on CryoEM  

PubMed Central

Human plasma low-density lipoproteins (LDL), a risk factor for cardiovascular disease, transfer cholesterol from plasma to liver cells via the LDL receptor (LDLr). Here, we report the structures of LDL and its complex with the LDL receptor extracellular domain (LDL·LDLr) at extracellular pH determined by cryoEM. Difference imaging between LDL·LDLr and LDL localizes the site of LDLr bound to its ligand. The structural features revealed from the cryoEM map lead to a juxtaposed stacking model of cholesteryl esters (CEs). High density in the outer shell identifies protein-rich regions that can be accounted for by a single apolipoprotein (apo B-100, 500 kDa) leading to a model for the distribution of its ?-helix and ?-sheet rich domains across the surface. The structural relationship between the apo B-100 and CEs appears to dictate the structural stability and function of normal LDL.

Ren, Gang; Rudenko, Gabby; Ludtke, Steven J.; Deisenhofer, Johann; Chiu, Wah; Pownall, Henry J.



Administration of hydrogen-saturated saline decreases plasma low-density lipoprotein cholesterol levels and improves high-density lipoprotein function in high-fat diet-fed hamsters.  


Hydrogen (dihydrogen; H(2)) has an antiatherosclerotic effect in apolipoprotein (apo) E knockout mice. The goals of this study were to further characterize the effects of H(2) on the content, composition, and biological activities of plasma lipoproteins in golden hamsters. Plasma analysis by enzymatic method and fast protein liquid chromatography showed that 4-week intraperitoneal injection of hydrogen-saturated saline remarkably decreased plasma total cholesterol and low-density lipoprotein (LDL) cholesterol levels in high-fat diet-fed hamsters. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of apolipoproteins from ultracentrifugally isolated plasma lipoproteins revealed a marked decrease of apo B100 and apo B48 in LDL. A profound decrease of apo E level in very low-density lipoprotein was also observed. Besides, we determined the functional quality of high-density lipoprotein (HDL) particles isolated from H(2)-treated and control mice. H(2) significantly improved HDL functionality assessed in 2 independent ways, namely, (1) stimulation of cholesterol efflux from macrophage foam cells by measuring HDL-induced [(3)H]cholesterol efflux and (2) protection against LDL oxidation as a measure of Cu(2+)-induced thiobarbituric acid reactive substances formation. Administration of hydrogen-saturated saline decreases plasma LDL cholesterol and apo B levels and improves hyperlipidemia-injured HDL functions, including the capacity of enhancing cellular cholesterol efflux and playing antioxidative properties, in high-fat diet-fed hamsters. PMID:22153840

Zong, Chuanlong; Song, Guohua; Yao, Shutong; Li, Luqin; Yu, Yang; Feng, Lei; Guo, Shoudong; Luo, Tian; Qin, Shucun



Adrenal Cell Aldosterone Production Is Stimulated by Very-Low-Density Lipoprotein (VLDL)  

PubMed Central

Very low-density lipoproteins (VLDL) are a class of large lipoprotein synthesized in the liver. The key function of VLDL, in vivo, is to carry triglyceride from the liver to adipose tissue. As a steroidogenic organ, the adrenal gland mainly uses lipoproteins as sources of cholesterol. Although VLDL receptors have been detected in the human adrenal, the function of VLDL in the adrenal gland remains unknown. Herein, we used primary cultures of human and bovine adrenal cells and the adrenocortical cell line H295R as models to determine the effects of VLDL on adrenal steroidogenesis. Our studies revealed that VLDL significantly increased aldosterone synthesis in all of the models tested. This increase was largely due to VLDL's stimulation of the expression of steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2). VLDL increased CYP11B2 mRNA expression in a concentration-dependent manner. Effects of VLDL on CYP11B2 transcript levels were not additive with angiotensin II or potassium but were additive with the cAMP pathway agonists ACTH and forskolin. Nifedipine completely inhibited the effects of VLDL on CYP11B2 mRNA, suggesting that calcium is the main signal transduction pathway used by VLDL in adrenal cells. Indeed, VLDL increased cytosolic free calcium levels. An in vivo study conducted in sucrose-fed rats showed a positive correlation between elevated triglyceride (VLDL) levels in plasma and CYP11B2 expression in the adrenal. In conclusion, we have shown that VLDL can stimulate aldosterone synthesis in adrenocortical cells by increasing StAR and CYP11B2 expression, an event likely mediated by a calcium-initiated signaling cascade.

Xing, Yewei; Rainey, William E.; Apolzan, John W.; Francone, Omar L.; Harris, Ruth B. S.



The preferential uptake of very-low-density lipoprotein cholesteryl ester by rat liver in vivo.  


The removal from the blood and the uptake by the liver of injected very-low-density lipoprotein (VLDL) preparations that had been radiolabelled in their apoprotein and cholesteryl ester moieties was studied in lactating rats. Radiolabelled cholesteryl ester was removed from the blood and taken up by the liver more rapidly than sucrose-radiolabelled apoprotein. Near-maximum cholesteryl ester uptake by the liver occurred within 5 min of the injection of the VLDL. At this time, apoprotein B uptake by the liver was only about 25% of the maximum. Maximum uptake of the injected VLDL apoprotein B label was not achieved until at least 15 min after injection, by which time the total uptakes of cholesteryl ester and apoprotein B label were very similar. The results suggest that preferential uptake of the lipoprotein cholesteryl ester by the liver occurred before endocytosis of the entire lipoprotein complex. The fate of the injected VLDL cholesteryl ester after its uptake by the liver was also monitored. Radiolabel associated with the hepatic cholesteryl ester fraction fell steadily from its early maximum level, the rate of fall being faster and more extensive when the fatty acid, rather than the cholesterol, moiety of the ester was labelled. By 30 min after the injection of VLDL containing [3H]cholesteryl ester, over one-third of the injected label was already present as [3H]cholesterol in the liver. When VLDL containing cholesteryl [14C]oleate was injected, a substantial proportion (about 25%) of the injected radiolabelled fatty acid appeared in the hepatic triacylglycerol fraction within 60 min: very little was present in the plasma triacylglycerol fraction at this time. PMID:2268298

Holder, J C; Zammit, V A; Robinson, D S



A Potential Neuroprotective Role of Apolipoprotein E-containing Lipoproteins through Low Density Lipoprotein Receptor-related Protein 1 in Normal Tension Glaucoma*  

PubMed Central

Glaucoma is an optic neuropathy and the second major cause of blindness worldwide next to cataracts. The protection from retinal ganglion cell (RGC) loss, one of the main characteristics of glaucoma, would be a straightforward treatment for this disorder. However, the clinical application of neuroprotection has not, so far, been successful. Here, we report that apolipoprotein E-containing lipoproteins (E-LPs) protect primary cultured RGCs from Ca2+-dependent, and mitochondrion-mediated, apoptosis induced by glutamate. Binding of E-LPs to the low density lipoprotein receptor-related protein 1 recruited the N-methyl-d-aspartate receptor, blocked intracellular Ca2+ elevation, and inactivated glycogen synthase kinase 3?, thereby inhibiting apoptosis. When compared with contralateral eyes treated with phosphate-buffered saline, intravitreal administration of E-LPs protected against RGC loss in glutamate aspartate transporter-deficient mice, a model of normal tension glaucoma that causes glaucomatous optic neuropathy without elevation of intraocular pressure. Although the presence of ?2-macroglobulin, another ligand of the low density lipoprotein receptor-related protein 1, interfered with the neuroprotective effect of E-LPs against glutamate-induced neurotoxicity, the addition of E-LPs overcame the inhibitory effect of ?2-macroglobulin. These findings may provide a potential therapeutic strategy for normal tension glaucoma by an LRP1-mediated pathway.

Hayashi, Hideki; Eguchi, Yuko; Fukuchi-Nakaishi, Yuko; Takeya, Motohiro; Nakagata, Naomi; Tanaka, Kohichi; Vance, Jean E.; Tanihara, Hidenobu



Serum Paraoxonase 1 Activity Is Associated with Fatty Acid Composition of High Density Lipoprotein  

PubMed Central

Introduction. Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ?6 fatty acids of HDL. Conclusion. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health.

Boshtam, Maryam; Pourfarzam, Morteza; Ani, Mohsen; Naderi, Gholam Ali; Basati, Gholam; Mansourian, Marjan; Dinani, Narges Jafari; Asgary, Seddigheh; Abdi, Soheila



Optical Characterization of Europium Tetracycline Complex in the presence of Low Density Lipoprotein and its Applications  

NASA Astrophysics Data System (ADS)

Development of native Low Density Lipoprotein (LDL) biosensors is of great importance in clinical analysis because the LDL concentration, which is the main carrier of cholesterol, in the plasma, is a fundamental parameter for the prevention and diagnosis of a number of clinical disorders such as heart disease, hypertension and atherosclerosis. The optical properties of the Europium-Tetracycline Complex (EuTc) were investigated for the solutions containing LDL in their compositions. In this paper we show an enhancement in the europium luminescence of EuTc complex in the presence of LDL. The time-resolved fluorescence spectroscopy experimental results of the pure EuTc sample and samples with LDL (EuTc:LDL) reveal an increase in the europium emission lifetime in the lipoprotein-doped samples with respect to the pure EuTc sample. A calibration curve, reasonably well described by a linear function between 0 and 3 mg/mL of LDL, was obtained. The obtained limit of detection was 0.23 mg/mL. Sixteen blood plasma samples all of them contend approximately 90 mg/dL of LDL were studied and the LDL concentrations were calculated with our method. The average LDL concentration obtained was 94 mg/dL. The results show that the EuTc complex can be used as a sensor to determine LDL with fast response, compact design, and reproducible results.

de Oliveira Silva, Flávia Rodrigues; Monteiro, Andrea Moreira; Neto, Antônio M. Figueiredo; Gidlund, Magnus A.; Gomes, Laércio; Junior, Nilson Dias Vieira; Courrol, Lilia Coronato



Effects of estrogen on very low-density lipoprotein triglyceride metabolism in fed and fasted chicks  

SciTech Connect

A single injection of estrogen into growing chicks resulted in a marked elevation in plasma triglyceride (TG) followed by phospholipid (PL) and cholesterol (CH) in both fed and fasted chicks. Estrogen caused a development of massive fatty liver in fed chicks. Hepatic malic enzyme and glucose-6-phosphate dehydrogenase activities also increased significantly in fed chicks and, to a small extent, in fasted chicks. Very low density lipoproteins (VLDL) were barely detectable in the fasted control plasma. However, the VLDL concentration increased markedly upon estrogen injection, becoming the most prevalent lipoprotein in the plasma. The administration of estrogen resulted in an increase in oleic acid and a decrease in linoleic acid content except in the cholesteryl ester of VLDL and LDL. VLDL of estrogenized birds had {beta}-mobility on agarose gel electrophoresis, and they eluted in two peaks on agarose gel filtration chromatography. Both peaks on gel filtration exhibited the same {beta}-mobility on agarose gel electrophoresis. Nevertheless, the apoprotein composition of these two peaks were substantially different from each other; apo B was not present in the first peak VLDL. VLDL-TG kinetic studies conducted in vivo, using {sup 14}C-TG-VLDL prepared endogenously from control and estrogenized chicks revealed that VLDL-TG produced from the former had a higher fractional catabolic rate (FCR) than VLDL-TG from the latter.

Park, J.R.



Cholesteryl ester accumulation in macrophages incubated with low density lipoprotein pretreated with cigarette smoke extract  

SciTech Connect

Although cigarette smoking is one of the major risk factors for atherosclerosis and coronary heart disease, the precise mechanisms of its adverse effects have not been fully elucidated. We incubated low density lipoprotein (LDL) with cigarette smoke (CS) extract and examined the incorporation of the lipoprotein by macrophages in vitro. When incubated with macrophages, LDL pretreated with CS extract (100 micrograms/ml) stimulated cholesteryl (/sup 14/C)oleate synthesis approximately equal to 12.5-fold that with unmodified LDL and transformed macrophages to cells rich in lipid droplets positively stained with oil red O. Enhancement in cholesteryl ester synthesis was dependent on the concentration of CS-modified LDL and exhibited saturation kinetics. When subjected to electrophoreses, CS-modified LDL migrated to a more anionic position than did unmodified LDL and showed extensive fragmentation of apolipoprotein B. This LDL modification depended upon the incubation time and concentration of the CS extract. Superoxide dismutase inhibited modification of LDL by 52%, suggesting that superoxide anion is, at least in part, involved. These results suggest that CS extract alters LDL into a form recognized and incorporated by macrophages. Such modification if it occurs in vivo, could explain the increased incidence of atherosclerosis and coronary heart disease in smokers.

Yokode, M.; Kita, T.; Arai, H.; Kawai, C.; Narumiya, S.; Fujiwara, M.



Calcium as a Crucial Cofactor for Low Density Lipoprotein Receptor Folding in the Endoplasmic Reticulum*  

PubMed Central

The family of low density lipoprotein (LDL) receptors mediate uptake of a plethora of ligands from the circulation and couple this to signaling, thereby performing a crucial role in physiological processes including embryonic development, cancer development, homeostasis of lipoproteins, viral infection, and neuronal plasticity. Structural integrity of individual ectodomain modules in these receptors depends on calcium, and we showed before that the LDL receptor folds its modules late after synthesis via intermediates with abundant non-native disulfide bonds and structure. Using a radioactive pulse-chase approach, we here show that for proper LDL receptor folding, calcium had to be present from the very early start of folding, which suggests at least some native, essential coordination of calcium ions at the still largely non-native folding phase. As long as the protein was in the endoplasmic reticulum (ER), its folding was reversible, which changed only upon both proper incorporation of calcium and exit from the ER. Coevolution of protein folding with the high calcium concentration in the ER may be the basis for the need for this cation throughout the folding process even though calcium is only stably integrated in native repeats at a later stage.

Pena, Florentina; Jansens, Annemieke; van Zadelhoff, Guus; Braakman, Ineke



Anti-oxidant properties of high-density lipoprotein and atherosclerosis  

PubMed Central

SUMMARY High-density lipoprotein (HDL) is one of the major carriers of cholesterol in the blood. It attracts particular attention because, in contrast with other lipoproteins, many physiological functions of HDL influence the cardiovascular system in favourable ways unless HDL is modified pathologically.The best known function of HDL is the capacity to promote cellular cholesterol efflux from peripheral cells and deliver cholesterol to the liver for excretion, thereby playing a key role in reverse cholesterol transport. The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High anti-oxidant and anti-inflammatory activities of HDL are associated with protection from cardiovascular disease.Atheroprotective activities, as well as a functional deficiency of HDL, ultimately depend on the protein and lipid composition of HDL. Conversely, these activities are compromised in many pathological states associated with inflammation.The focus of the present review is on the anti-oxidant and anti-inflammatory functions of HDL and its individual components in relation to protection from atherosclerosis.

Podrez, Eugene A



Role of dietary supplements in lowering low-density lipoprotein cholesterol: a review.  


Coronary heart disease (CHD) remains a major source of morbidity and mortality. As the epidemic of obesity, diabetes, and hypertension continues to grow among young adults, the population at risk for atherosclerotic CHD is ever increasing. More than a century of laboratory and human findings link cholesterol levels with a propensity to develop atherosclerosis. Low-density lipoprotein (LDL) is the major atherogenic lipoprotein, and numerous clinical trials have shown the efficacy of lowering LDL-cholesterol (LDL-C) for reducing CHD risk. New trial data have resulted in LDL-C goals being lowered over time and expansion of the population of patients that are candidates for LDL-lowering therapy to decrease their lifetime risk of CHD. Although statins are relatively safe and well tolerated, there are still significant numbers of patients who cannot tolerate them and many others who only require mild LDL-C reduction and prefer nonprescription alternatives to statin therapy. A number of dietary supplements and functional foods have been suggested to reduce LDL-C levels, but only a few have withstood the rigors of randomized controlled trials. Here we review the evidence in support of dietary supplements and their LDL-C-lowering effects. We also review supplements that, after initial excitement about their purported effect, were not found to lower LDL-C significantly. PMID:21122657

Nijjar, Prabhjot S; Burke, Frances M; Bloesch, Annette; Rader, Daniel J



The effects of physical exercise on plasma prebeta-1 high-density lipoprotein.  


The impact of physical exercise on high-density lipoprotein (HDL) metabolism is recognized as a major mechanism of coronary artery disease (CAD) risk reduction. Prebeta-1 HDL subparticle species play a pivotal role in initiating reverse cholesterol transport (RCT). We examined the effect of acute physical exercise on plasma prebeta-1 HDL levels. Nineteen nonsmoking, healthy men (n = 11) and women (n = 8) not receiving lipid-altering medications completed dietary surveys, and had percent body fat determinations, and fasting blood drawn for measurements of plasma lipids, lipoproteins, apolipoprotein A-I (Apo A-I), and absolute and percent prebeta-1 HDL. Each subject completed cardiopulmonary exercise stress testing to Vo(2max) followed by a 4-km course of run-jogging. Laboratory measurements were repeated from blood drawn immediately after exercise. Mean +/- SD values were determined for age, percent body fat, dietary calories, dietary cholesterol, dietary fat, and plasma lipids, lipoproteins, Apo A-I, and absolute and percent prebeta-1 HDL using 1-way analysis of variance (ANOVA). One-way ANOVA comparisons were made for measurements of plasma lipids, lipoproteins, Apo A-I, and absolute and percent prebeta HDL measurements taken before and after exercise for all subjects combined. Entry characteristics showed the following (mean +/-SD): age, 24 +/- 5.8 years; body mass index (BMI), 22.4 +/- 2.6; percent body fat, 13 +/- 5.7; and Vo(2max), 49.1 +/- 7.9 mL O(2)/kg/min. Exercise significantly increased absolute plasma prebeta HDL (0.10 +/- 0.05 to 0.130 +/- 0.07 microg/mL, P =.039) and decreased plasma HDL-triglycerides (23.3 +/- 10.8 to 12.5 +/- 5.6 mg/dL, P =.012). Our findings indicate that prebeta-1 HDL and HDL-triglyceride metabolism are significant components of the effect of acute exercise on RCT. These findings have important relevance for studies pertaining to exercise-related effects on HDL metabolism as pertains to CAD risk reduction. PMID:12701055

Jafari, Mahtab; Leaf, David Alexander; Macrae, Holden; Kasem, Julie; O'conner, Patricia; Pullinger, Clive; Malloy, Marry; Kane, John P



Patients with early rheumatoid arthritis exhibit elevated autoantibody titers against mildly oxidized low-density lipoprotein and exhibit decreased activity of the lipoprotein-associated phospholipase A2  

PubMed Central

Rheumatoid arthritis is a chronic inflammatory disease, associated with an excess of cardiovascular morbidity and mortality due to accelerated atherosclerosis. Oxidized low-density lipoprotein (oxLDL), the antibodies against oxLDL and the lipoprotein-associated phospholipase A2 (Lp-PLA2) may play important roles in inflammation and atherosclerosis. We investigated the plasma levels of oxLDL and Lp-PLA2 activity as well as the autoantibody titers against mildly oxLDL in patients with early rheumatoid arthritis (ERA). The long-term effects of immunointervention on these parameters in patients with active disease were also determined. Fifty-eight ERA patients who met the American College of Rheumatology criteria were included in the study. Patients were treated with methotrexate and prednisone. Sixty-three apparently healthy volunteers also participated in the study and served as controls. Three different types of mildly oxLDL were prepared at the end of the lag, propagation and decomposition phases of oxidation. The serum autoantibody titers of the IgG type against all types of oxLDL were determined by an ELISA method. The plasma levels of oxLDL and the Lp-PLA2 activity were determined by an ELISA method and by the trichloroacetic acid precipitation procedure, respectively. At baseline, ERA patients exhibited elevated autoantibody titers against all types of mildly oxLDL as well as low activity of the total plasma Lp-PLA2 and the Lp-PLA2 associated with the high-density lipoprotein, compared with controls. Multivariate regression analysis showed that the elevated autoantibody titers towards oxLDL at the end of the decomposition phase of oxidation and the low plasma Lp-PLA2 activity are independently associated with ERA. After immunointervention autoantibody titers against all types of oxLDL were decreased in parallel to the increase in high-density lipoprotein-cholesterol and high-density lipoprotein-Lp-PLA2 activity. We conclude that elevated autoantibody titers against oxLDL at the end of the decomposition phase of oxidation and low plasma Lp-PLA2 activity are feature characteristics of patients with ERA, suggesting an important role of these parameters in the pathophysiology of ERA as well as in the accelerated atherosclerosis observed in these patients.

Lourida, Evangelia S; Georgiadis, Athanasios N; Papavasiliou, Eleni C; Papathanasiou, Athanasios I; Drosos, Alexandros A; Tselepis, Alexandros D



Introduction to High-Density Lipoprotein, Dyslipidemia, and Coronary Heart Disease  

Microsoft Academic Search

\\u000a Alterations in plasma lipoproteins are major risk factors for coronary heart disease caused by atherosclerosis. The purpose\\u000a of this chapter is to provide the reader with an overview of lipids, lipoprotein composition, lipoprotein metabolism, and\\u000a lipoprotein disorders, with particular relevance to coronary heart disease risk (CHD). This chapter will then provide a framework\\u000a for the reader to understand the remaining

Ernst J. Schaefer


Cholesteryl ester synthesis in macrophages: stimulation by p-very low density lipoproteins from cholesterol-fed animals of several species  

Microsoft Academic Search

Animals fed cholesterol accumulate several types of cholesterol-rich lipoproteins in their plasma and ulti- mately develop cholesteryl ester deposition in tissue macrophages. Previous studies in the cholesterol-fed dog have shown that one class of cholesterol-rich lipoproteins, P-migrating very low density lipoproteins (P-VLDI,, density < 1.006 g\\/ml), possesses a unique ability to produce cellular cholesteryl ester accumulation when incubated with mouse

Robert W. Mahley; Thomas L. Innerarity; Michael S. Brown; Y. K. Ho; Joseph L. Goldstein


The complex fate in plasma of gadolinium incorporated into high-density lipoproteins used for magnetic imaging of atherosclerotic plaques.  


We have previously reported enhancing the imaging of atherosclerotic plaques in mice using reconstituted high density lipoproteins (HDL) as nanocarriers for the MRI contrast agent gadolinium (Gd). This study focuses on the underlying mechanisms of Gd delivery to atherosclerotic plaques. HDL, LDL, and VLDL particles containing Gd chelated to phosphatidyl ethanolamine (DTPA-DMPE) and a lipidic fluorophore were used to demonstrate the transfer of Gd-phospholipids among plasma lipoproteins in vitro and in vivo. To determine the basis of this transfer, the roles of phospholipid transfer protein (PLTP) and lipoprotein lipase (LpL) in mediating the migration of Gd-DTPA-DMPE among lipoproteins were investigated. The results indicated that neither was an important factor, suggesting that spontaneous transfer of Gd-DTPA-DMPE was the most probable mechanism. Finally, two independent mouse models were used to quantify the relative contributions of HDL and LDL reconstituted with Gd-DTPA-DMPE to plaque imaging enhancement by MR. Both sets of results suggested that Gd-DTPA-DMPE originally associated with LDL was about twice as effective as that injected in the form of Gd-HDL, and that some of Gd-HDL's effectiveness in vivo is indirect through transfer of the imaging agent to LDL. In conclusion, the fate of Gd-DTPA-DMPE associated with a particular type of lipoprotein is complex, and includes its transfer to other lipoprotein species that are then cleared from the plasma into tissues. PMID:23617731

Barazza, Alessandra; Blachford, Courtney; Even-Or, Orli; Joaquin, Victor A; Briley-Saebo, Karen C; Chen, Wei; Jiang, Xian-Cheng; Mulder, Willem J M; Cormode, David P; Fayad, Zahi A; Fisher, Edward A



Purification and properties of a very high density lipoprotein from the hemolymph of the honeybee Apis mellifera.  


A larval-specific very high density lipoprotein (VHDL) has been isolated from the hemolymph of the honeybee Apis mellifera. VHDL was isolated by a combination of density gradient ultracentrifugation and gel filtration. The purified protein is a dimer of Mr 160,000 apoproteins as shown by chemical cross-linking with dimethyl suberimidate. N-Terminal sequence analysis indicates that the two polypeptide chains are identical. The holoprotein contains 10% lipid by weight and 2.6% covalently bound carbohydrate. A native Mr 330,000 species was obtained by gel permeation chromatography. Antiserum directed against VHDL was used to show that VHDL is distinct from other hemolymph proteins and appears to constitute a novel lipoprotein of unknown function. However, the lipoprotein is present in high amounts in hemolymph only at the end of larval life, suggesting a potential role in lipid transport and/or storage protein metabolism during metamorphosis. PMID:3109474

Shipman, B A; Ryan, R O; Schmidt, J O; Law, J H



Effect of oxidized low-density lipoprotein concentration polarization on human smooth muscle cells' proliferation, cycle, apoptosis and oxidized low-density lipoprotein uptake  

PubMed Central

To clarify the effect of concentration polarization of oxidative modification of low-density lipoproteins (ox-LDLs) on human smooth muscle cells (SMCs), the proliferation, ox-LDL uptake and apoptosis with SMCs cultured on permeable (the permeable group) or non-permeable membranes (the non-permeable group) were analysed by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay, spectrofluorometry and flow cytometry using a parallel-plate flow chamber technique. The concentration polarization of ox-LDLs at the surface of the cultured cell monolayer was assessed by confocal laser microscopy. The results showed that concentration polarization of ox-LDLs could indeed occur at the cultured cell monolayer surface of the permeable group, leading to an enhanced wall concentration of ox-LDLs that was over 15 per cent higher than the bulk concentration of the perfusion solution at a pressure of 100 mmHg. When concentration of ox-LDLs in the perfusion solution was less than or equal to 100 µg ml–1, SMCs' proliferation was induced, while cell apoptosis was induced when its concentration was above 150 µg ml–1. The uptake of ox-LDLs by the cultured cells was significantly higher for the permeable group than for the non-permeable group. In addition, the ox-LDL-induced cell death and apoptosis were much more severe in the permeable group than that in the non-permeable group. Therefore, the experimental study suggests that concentration polarization of ox-LDLs plays an adverse role in the vascular system owing to its toxicity to vascular cells, in turn enhance ox-LDL infiltration into the arterial wall and accelerate SMC apoptosis.

Ding, Zufeng; Liu, Shijie; Yang, Bo; Fan, Yubo; Deng, Xiaoyan



Association between low density lipoprotein and rheumatoid arthritis genetic factors with low density lipoprotein levels in rheumatoid arthritis and non-rheumatoid arthritis controls.  


OBJECTIVES: While genetic determinants of low density lipoprotein (LDL) cholesterol levels are well characterised in the general population, they are understudied in rheumatoid arthritis (RA). Our objective was to determine the association of established LDL and RA genetic alleles with LDL levels in RA cases compared with non-RA controls. METHODS: Using data from electronic medical records, we linked validated RA cases and non-RA controls to discarded blood samples. For each individual, we extracted data on: first LDL measurement, age, gender and year of LDL measurement. We genotyped subjects for 11 LDL and 44 non-HLA RA alleles, and calculated RA and LDL genetic risk scores (GRS). We tested the association between each GRS and LDL level using multivariate linear regression models adjusted for age, gender, year of LDL measurement and RA status. RESULTS: Among 567 RA cases and 979 controls, 80% were female and mean age at the first LDL measurement was 55 years. RA cases had significantly lower mean LDL levels than controls (117.2 vs 125.6 mg/dl, respectively, p<0.0001). Each unit increase in LDL GRS was associated with 0.8 mg/dl higher LDL levels in both RA cases and controls (p=3.0×10(-7)). Each unit increase in RA GRS was associated with 4.3 mg/dl lower LDL levels in both groups (p=0.01). CONCLUSIONS: LDL alleles were associated with higher LDL levels in RA. RA alleles were associated with lower LDL levels in both RA cases and controls. As RA cases carry more RA alleles, these findings suggest a genetic basis for epidemiological observations of lower LDL levels in RA. PMID:23716066

Liao, Katherine P; Diogo, Dorothée; Cui, Jing; Cai, Tianxi; Okada, Yukinori; Gainer, Vivian S; Murphy, Shawn N; Gupta, Namrata; Mirel, Daniel; Ananthakrishnan, Ashwin N; Szolovits, Peter; Shaw, Stanley Y; Raychaudhuri, Soumya; Churchill, Susanne; Kohane, Isaac; Karlson, Elizabeth W; Plenge, Robert M



Lecithin:Cholesterol Acyltransferase-Mediated Modification of Discoidal Peripheral Lymph High Density Lipoproteins: Possible Mechanism of Formation of Cholesterol-Induced High Density Lipoproteins (HDLc) in Cholesterol-Fed Dogs  

Microsoft Academic Search

Peripheral lymph high density lipoproteins (HDL) of the cholesterol-fed dog differ in a number of characteristics from plasma HDL of the same animal. Their high content of free cholesterol, phospholipid, apoprotein E, and apoprotein A-IV, their greater heterogeneity in size, and the presence of many discoidal particles suggest that a portion of lymph HDL is assembled within the interstitial fluid.

L. Dory; C. H. Sloop; L. M. Boquet; R. L. Hamilton; P. S. Roheim



Genetic Diagnosis of Familial Hypercholesterolemia in a South European Outbreed Population: Influence of Low Density Lipoprotein (LDL) Receptor Gene Mutations on Treatment Response to Simvastatin in Total, LDL, and High-Density Lipoprotein Cholesterol  

Microsoft Academic Search

The aims of this study were to examine the presence of mu- tations in the low-density lipoprotein receptor gene among subjects clinically diagnosed with familial hypercholesterol- emia and to analyze whether the molecular diagnosis helps to predict the response to simvastatin treatment in our familial hypercholesterolemia population. Fifty-five probands and 128 related subjects with familial hypercholesterolemia were studied. Genetic diagnosis



The effect of concentrated n-3 fatty acids versus gemfibrozil on plasma lipoproteins, low density lipoprotein heterogeneity and oxidizability in patients with hypertriglyceridemia.  


We evaluated in a double-blind randomized trial with a double-dummy design in 28 patients with primary hypertriglyceridemia, the effect of gemfibrozil (1200 mg/day) versus Omacor (4 g/day), a drug containing the n-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), on lipid and lipoprotein levels, low density lipoprotein (LDL) subfraction profile and LDL oxidizability. Both Omacor and gemfibrozil therapy resulted in a similar significant decrease in serum triglyceride (TG), very low density lipoprotein (VLDL) triglyceride and VLDL cholesterol concentrations and an increase in high density lipoprotein (HDL) and LDL cholesterol concentrations. The increase in LDL cholesterol was due to a significant increase in cholesterol content of the relatively buoyant LDL subfractions LDL1, LDL2 and LDL3, whereas the relative contribution of the dense LDL subfractions LDL4 and LDL5 to total LDL tended to decrease. So, both therapies resulted in a more buoyant LDL subfraction profile, reflected by a significant increase of the value of parameter K (+10.3% on Omacor vs. +26.5% on gemfibrozil therapy, gemfibrozil vs Omacor P>0.05). Cu(2+)-induced oxidation of LDL was measured by continuous monitoring of conjugated dienes. After 12 weeks of Omacor treatment LDL appeared more prone to oxidative modification in vitro than LDL after gemfibrozil treatment, as measured by the significantly decreased lag time, preceding the onset of the lipid peroxidation. In both groups the rate of oxidation did not change with therapy. The amount of dienes formed during oxidation increased significantly on Omacor treatment, but not on gemfibrozil treatment. Plasma thiobarbituric acid reactive substances were higher after Omacor and lower after gemfibrozil treatment, although not significantly. We conclude that both Omacor and gemfibrozil have favorable effects on lipid and lipoprotein concentrations and the LDL subfraction profile. However, Omacor increased the susceptibility of LDL to oxidation, whereas gemfibrozil did not affect the resistance of LDL to oxidative modification in vitro. The clinical relevance of these changes remains to be established in the light of other postulated favorable effects of n-3 fatty acids on the course of cardiovascular disease. PMID:11058707

Stalenhoef, A F; de Graaf, J; Wittekoek, M E; Bredie, S J; Demacker, P N; Kastelein, J J



Exercise-mediated changes in high-density lipoprotein: Impact on form and function.  


The goal of this systematic review was to assess the current understanding of the effects of exercise intervention on high-density lipoprotein (HDL) cholesterol (HDL-C) and changes in HDL function as well as modification of these effects by genomic factors. The reviewed studies demonstrate that exercise has modest effects on HDL-C with limited data suggesting an effect on HDL function. Genetic polymorphisms in proteins associated with HDL metabolism play a role in modifying the HDL-C response to exercise and possibly its function. Exercise as an intervention for patients at risk for cardiovascular events can lead to small improvements in HDL-C and potential changes in HDL function. There is an important modifier effect of genetics in determining these changes. PMID:24016485

Blazek, Alisa; Rutsky, Jessica; Osei, Kwame; Maiseyeu, Andrei; Rajagopalan, Sanjay



Whole-genome sequence-based analysis of high-density lipoprotein cholesterol.  


We describe initial steps for interrogating whole-genome sequence data to characterize the genetic architecture of a complex trait, levels of high-density lipoprotein cholesterol (HDL-C). We report whole-genome sequencing and analysis of 962 individuals from the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) studies. From this analysis, we estimate that common variation contributes more to heritability of HDL-C levels than rare variation, and screening for mendelian variants for dyslipidemia identified individuals with extreme HDL-C levels. Whole-genome sequencing analyses highlight the value of regulatory and non-protein-coding regions of the genome in addition to protein-coding regions. PMID:23770607

Morrison, Alanna C; Voorman, Arend; Johnson, Andrew D; Liu, Xiaoming; Yu, Jin; Li, Alexander; Muzny, Donna; Yu, Fuli; Rice, Kenneth; Zhu, Chengsong; Bis, Joshua; Heiss, Gerardo; O'Donnell, Christopher J; Psaty, Bruce M; Cupples, L Adrienne; Gibbs, Richard; Boerwinkle, Eric



Tailoring of biomimetic high-density lipoprotein nanostructures changes cholesterol binding and efflux.  


Gold nanoparticles (Au NPs) were employed as templates to synthesize spherical, high-density lipoprotein (HDL) biomimics (HDL Au NPs) of different sizes and surface chemistries. The effect of size and surface chemistry on the cholesterol binding properties and the ability of the HDL Au NPs to efflux cholesterol from macrophage cells were measured. Results demonstrate that Au NPs may be utilized as templates to generate nanostructures with different physical characteristics that mimic natural HDL. Furthermore, the properties of the HDL Au NPs may be tailored to modulate the ability to bind cholesterol in solution and efflux cholesterol from macrophages. From the conjugates tested, the optimum size and surface chemistry for preparing functional Au NP-templated HDL biomimics were identified. PMID:22117189

Luthi, Andrea J; Zhang, Heng; Kim, Dongwoo; Giljohann, David A; Mirkin, Chad A; Thaxton, C Shad



Serum oxidized low-density lipoprotein level and risk of cognitive impairment in older women.  


We investigated the association between serum level of oxidized low-density lipoprotein (oxLDL) and risk of cognitive impairment (dementia or mild cognitive impairment) among 572 nondemented community-dwelling women from a prospective cohort study of aging. After 5 years of follow-up, 228 (39.9%) developed cognitive impairment; and this did not differ by tertile of baseline oxLDL level (highest compared with lowest tertile 38.2% vs. 39.5%; odds ratio, 0.90; 95% confidence interval, 0.63-1.43). Multivariate adjustment produced similar results (odds ratio, 0.91; 95% confidence interval, 0.60-1.39). These findings suggest that increased levels of serum oxLDL are not associated with a greater risk of incident cognitive impairment in older women. PMID:22483339

Koyama, Alain; Stone, Katie; Yaffe, Kristine



High-density-lipoprotein cholesterol and types of alcoholic beverages consumed among men and women.  

PubMed Central

OBJECTIVES. Differences by sex in the relationship between high-density-lipoprotein (HDL) cholesterol and consumption of alcoholic beverages were examined in 1516 individuals. METHODS. Questionnaires and blood-sample data from cross-sectional surveys were analyzed. RESULTS. Both beer and liquor were independently associated with increased HDL cholesterol in the total group, in men, and in women after covariates were controlled for. Wine was associated with a significant increase in HDL cholesterol in women only. CONCLUSIONS. Among women and men, amount may be more important than type of alcoholic beverage consumed. The independent effect of wine on HDL cholesterol among men remains unclear since few men in this population consumed wine exclusively or in large quantities.

Parker, D R; McPhillips, J B; Derby, C A; Gans, K M; Lasater, T M; Carleton, R A



In vivo tumor imaging in mice with near-infrared: low density lipoprotein conjugates  

NASA Astrophysics Data System (ADS)

Near-infrared (NIR) fluorescence imaging possesses many advantages as an in vivo non-invasive optical imaging modality for studying diseases in preclinical models. In this study, low density lipoprotein(LDL) fraction was quickly isolated from human plasma by modified heparin-citrate precipitation method and then conjugated to near infrared fluorescence dye ICG-Der-02 with excitation and emission wavelengths at 760nm and 830nm, respectively. The conjugates LDL-ICG-Der-02 were intravenously injected into the mice bearing different tumor models. And real time series fluorescence tumor images at different intervals of post-injection were in vivo acquired by a self-built NIR reflectance fluorescence imaging system. Results demonstrated that LDL-ICG-Der-02 conjugates could efficiently target to the tumor sites that over-expressed LDL receptors and could be completely eliminated at last.

Chen, Xinyang; Deng, Dawei; Liu, Fei; Li, Hui; Qian, Zhiyu; Gu, Yueqing



Pharmacogenetics of paraoxonase activity: elucidating the role of high-density lipoprotein in disease.  


PON1 is a key component of high-density lipoproteins (HDLs) and is at least partially responsible for HDL's antioxidant/atheroprotective properties. PON1 is also associated with numerous human diseases, including cardiovascular disease, Parkinson's disease and cancer. In addition, PON1 metabolizes a broad variety of substrates, including toxic organophosphorous compounds, statin adducts, glucocorticoids, the likely atherogenic L-homocysteine thiolactone and the quorum-sensing factor of Pseudomonas aeruginosa. Numerous cardiovascular and antidiabetic pharmacologic agents, dietary macronutrients, lifestyle factors and antioxidant supplements affect PON1 expression and enzyme activity levels. Owing to the importance of PON1 to HDL function and its individual association with diverse human diseases, pharmacogenomic interactions between PON1 and the various factors that alter its expression and activity may represent an important therapeutic target for future investigation. PMID:24024900

Kim, Daniel Seung; Marsillach, Judit; Furlong, Clement E; Jarvik, Gail P



Turnover products of the apo very low density lipoprotein II messenger RNA from chicken liver.  

PubMed Central

The mature apo Very Low Density Lipoprotein II (apo VLDLII) mRNA appears in chicken liver within a few hours after estrogen administration. Apart from this mRNA species, shorter RNA molecules hybridizing to apo VLDLII sequences have been detected in rooster liver upon estrogen stimulation. These molecules are present in the non-polyadenylated fraction of the total cellular- and polysomal RNA. Northern blotting and electron microscopy of R-loops were employed to show that these shorter RNA molecules are truncated at their 3'-end. The 3'-termini were further characterized by nuclease S1 analyses, and are located predominantly in the 3' untranslated region of the mRNA. Using a secondary structure model (Shelness and Williams, J. Biol. Chem. 260, 8637-8646, 1985), we show that the 3' termini map mainly in unpaired regions of the structure. Images

Bakker, O; Arnberg, A C; Noteborn, M H; Winter, A J; Ab, G



Oxidized low-density lipoprotein (Ox-LDL) impacts on erythrocyte viscoelasticity and its molecular mechanism.  


The oxidized low-density lipoprotein (Ox-LDL) plays an important role in atherosclerosis, yet it remains unclear if it damages circulating erythrocytes. In this study, erythrocyte deformability and its membrane proteins after Ox-LDL incubations are investigated by micropipette aspiration, thiol radical measurement, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Results show that Ox-LDL incubation reduces the erythrocyte deformability, decreases free thiol radical contents in erythrocytes, and induces the cross-linking among membrane proteins. SDS-PAGE analysis reveals a high molecular weight (HMW) complex as well as new bands between spectrins and band 3 and reduced ratios between band 3 and other major membrane skeletal proteins. Analyses indicate that Ox-LDL makes erythrocytes harder to deform through a molecular mechanism by which the oxidation of free thiol radicals forms disulfide bonds among membrane skeletal proteins. PMID:19747680

Wang, Xiang; Yang, Li; Liu, Yao; Gao, Wei; Peng, Weiyan; Sung, K-L Paul; Sung, Lanping Amy



Low-density lipoprotein (LDL)-antioxidant biflavonoids from Garcinia madruno.  


Six biflavonoids were isolated from G. madruno, one of which, 7''-O-(6''''-acetyl)-glucoside of morelloflavone, is a new compound identified on the basis of 1D, 2D NMR (HMQC and HMBC) spectroscopic methods and chemical evidence. The antioxidant activity of the biflavonoids against low-density lipoprotein (LDL) peroxidation induced with Cu²?, was studied by means of a TBARS assay. The antioxidant potential of a biflavonoid fraction (BF) was also evaluated and correlated with its biflavonoid content. The flavanone-(3?8'')-flavone biflavonoids displayed antioxidant activity, particularly morelloflavone, which was significantly more potent than quercetin, with a CE?? of 12.36 ?g/mL. Lipid peroxidation, was also significantly reduced in the presence of the BF (EC?? = 11.85 ?g/mL). These results suggest that the BF is an excellent antioxidant. PMID:23698056

Osorio, Edison; Londoño, Julián; Bastida, Jaume



Synthetic high-density lipoproteins exert cardioprotective effects in myocardial ischemia/reperfusion injury.  


Human high-density lipoproteins (HDLs) protect the heart against ischemia/reperfusion injury. In the present study, the cardioprotective effects of synthetic high-density lipoproteins (sHDLs) made of phosphatidylcholine and apolipoprotein A-I were investigated in isolated rat hearts, which underwent a 20-min low-flow ischemia followed by a 30-min reperfusion. The administration of sHDL during the 10 min immediately before ischemia caused a rapid, dose-dependent improvement of postischemic cardiac function: at the maximum dose (2.0 mg of sHDL protein/ml), left ventricular developed pressure (LVDP) recovered to 71.0 +/- 3.2 versus 40.5 +/- 3.8 mm Hg in saline-treated hearts, and coronary perfusion pressure (CPP) increased to 100.3 +/- 6.2 versus 132.0 +/- 9.0 mm Hg. The preservation of postischemic cardiac function was associated with a dose-dependent reduction of creatine kinase release into the coronary effluent. sHDLs administered in the first 10 min postischemia also exerted a significant, dose-dependent improvement of postischemic LVDP, CPP, and creatine kinase release, but the cardioprotective effect was less than when sHDLs were given preischemia. The preservation of postischemic cardiac function by sHDL was mediated through a reduction of cardiac tumor necrosis factor-alpha content and an enhanced cardiac production of prostaglandin E2 and I2. The present experimental data indicate that sHDLs may provide a novel therapeutic approach to clinical conditions in which myocardial ischemia/reperfusion occurs, such as acute coronary syndromes, cardiac surgery, or revascularization procedures. PMID:14566009

Rossoni, Giuseppe; Gomaraschi, Monica; Berti, Ferruccio; Sirtori, Cesare R; Franceschini, Guido; Calabresi, Laura



Cholesterol esters selectively taken up from high-density lipoproteins are hydrolyzed extralysosomally.  


High-density lipoprotein (HDL) cholesterol esters (CE) are taken up by many cells without parallel uptake of HDL apoproteins. This selective uptake is mediated by reversible incorporation of HDL CE into a plasma membrane pool, from which the CE are internalized. We now show that selectively taken up CE are directed to an extralysosomal destination where they are hydrolyzed and available to the steroidogenic pathway. Cultured human fibroblasts take up HDL CE predominantly by selective uptake. Wolman's disease fibroblasts, which are deficient in lysosomal cholesterol esterase, effectively hydrolyzed CE from HDL, but not CE taken up in low density lipoproteins (LDL); normal fibroblasts hydrolyzed both effectively. Analogously, the lysosomotropic agent chloroquine effectively blocked hydrolysis of LDL CE but not HDL CE. A similar effect of chloroquine was seen in primary cultures of rat adrenal cells, which are very active in selective uptake. More than 50% of HDL CE taken up by adrenal cells appeared in the medium as corticosterone. To examine the subcellular destination of selectively taken up CE, non-hydrolyzable tracers of HDL and LDL CE were simultaneously injected into rats. On fractionation of adrenal glands 24 h after injection, 83% of the HDL CE tracer and 48% of the LDL CE tracer were recovered in cytoplasmic lipid droplets; that LDL tracer in the lipid droplets was accounted for by selective uptake of CE from LDL. Thus, selectively taken up cholesterol esters are processed by a mechanism distinct from the classical endosomal/lysosomal pathway, and are delivered to a cytoplasmic compartment. PMID:2317530

Sparrow, C P; Pittman, R C



Metabolism of triglyceride-rich nascent rat hepatic high density lipoproteins  

SciTech Connect

Nascent high density lipoprotein (HDL) and nascent very low density lipoprotein (VLDL) were isolated from rat livers that had been perfused with (3H)glycerol to label the triglyceride. When injected into intact rats, the labeled HDL-triglyceride disappeared as rapidly as the VLDL-triglyceride, with only 10% of the injected label remaining in the plasma after 30 min. The protein moiety of nascent HDL was labeled with (35S)methionine in a similar fashion and the labeled nascent HDL was separated into nonretained (NR) and retained (R) fractions by heparin-Sepharose affinity chromatography. When injected into rats, 55% of the injected label in nascent fraction NR and 72% of that in nascent fraction R was recovered from plasma at 30 min, compared to only 10% of the triglyceride label from unfractionated nascent HDL, indicating dissociation of triglyceride and apolipoprotein clearance. The plasma decay curves for both triglyceride and protein were biexponential. By 5 min, 15% of the 35S label remaining in plasma represented apoE and apoC that had been transferred from nascent HDL fractions NR and R to the d less than 1.063 g/ml fraction of plasma. Plasma HDL was labeled in vivo with (35S)methionine, separated into fractions NR and R, and the clearance of the two plasma HDL fractions was compared with that of the corresponding nascent HDL fractions. Except for a faster rate of removal of the nascent HDL fractions during the first 5 min, the serum decay curves were very similar.

Winkler, K.E.; Marsh, J.B. (Medical College of Pennsylvania, Philadelphia (USA))



Chitin-glucan fiber effects on oxidized low-density lipoprotein: a randomized controlled trial  

PubMed Central

Background/objectives: Elevated oxidized low-density lipoprotein (OxLDL) may promote inflammation, and is associated with increased risk of atherosclerotic coronary heart disease and worsening complications of diabetes mellitus. The primary objective of this study was to evaluate the efficacy of chitin-glucan (CG), alone and in combination with a potentially anti-inflammatory olive oil (OO) extract, for reducing OxLDL in subjects with borderline to high LDL cholesterol (LDL-C) levels. Subjects/methods: This 6-week, randomized, double-blind, placebo-controlled study of a novel, insoluble fiber derived from the Aspergillus niger mycelium, CG, evaluated 130 subjects free of diabetes mellitus with fasting LDL-C 3.37–4.92?mmol/l and glucose ?6.94?mmol/l. Participants were randomly assigned to receive CG (4.5?g/day; n=33), CG (1.5?g/day; n=32), CG (1.5?g/day) plus OO extract (135?mg/day; n=30), or matching placebo (n=35). Results: Administration of 4.5?g/day CG for 6 weeks significantly reduced OxLDL compared with placebo (P=0.035). At the end of study, CG was associated with lower LDL-C levels relative to placebo, although this difference was statistically significant only for the CG 1.5?g/day group (P=0.019). CG did not significantly affect high-density lipoprotein cholesterol, triglycerides, glucose, insulin or F2-isoprostane levels. Adverse events did not substantively differ between treatments and placebo. Conclusions: In this 6-week study, CG (4.5?g/day) reduced OxLDL, an effect that might affect the risk for atherosclerosis.

Bays, H E; Evans, J L; Maki, K C; Evans, M; Maquet, V; Cooper, R; Anderson, J W



Metabolic fate of sphingomyelin of high-density lipoprotein in rat plasma  

SciTech Connect

The metabolic fate of high density lipoprotein (HDL) sphingomyelin in plasma was studied in rats over a 24-hr period after injection of HDL containing sphingomyelin which was {sup 14}C-labeled in the stearic (18:0) or lignoceric acid (24:0) moiety and {sup 3}H-labeled in the choline methyl groups. Decay of label in plasma followed three phases. The first two phases were similar for both isotopes and both types of sphingomyelin (t1/2 approximately 10 and 110 min). However, during the third phase (from 10 hr after injection), {sup 3}H label disappeared more slowly than {sup 14}C label from 18:0 sphingomyelin, whereas the {sup 3}H/{sup 14}C ratio remained relatively constant when 24:0 sphingomyelin was used. Intact, doubly-labeled 18:0 sphingomyelin disappeared from HDL rapidly (t1/2 = 38 min) by tissue uptake and by transfer to very low density lipoprotein (VLDL). VLDL contained up to 12% of the sphingomyelin 1 hr after injection. This is the first demonstration of a transfer in vivo of sphingomyelin from HDL to VLDL. A similarly rapid transfer was also observed in vitro. Some nontritiated, ({sup 14}C)18:0 or ({sup 14}C)24:0 sphingomyelin was redistributed more slowly into HDL. Doubly-labeled phosphatidylcholine appeared in VLDL and HDL within 1 hr after injection and reached 1.8 and 2.1% of the injected {sup 14}C and {sup 3}H in VLDL at 1 hr, and 4.8 and 6.9% in HDL at 3 hr, respectively.

Bentejac, M.; Bugaut, M.; Delachambre, M.C.; Lecerf, J. (Universite de Dijon-BP 138 (France))



Age-associated decrease of high-density lipoprotein-mediated reverse cholesterol transport activity.  


High-density lipoproteins (HDL) are considered atheroprotective in contrast to low-density lipoproteins (LDL), which are atherogenic in their oxidized form. A growing body of evidence suggests that HDL exert part of their antiatherogenic effect by counteracting LDL oxidation as well as their proinflammatory effect. However, a number of studies, carried over the past 30 years, have shown that cholesterol efflux plays a major role in the atheroprotective effects of HDL and cholesterol homeostasis. These studies have further identified the scavenger receptor type B-I (SR-BI), the adenosine triphosphate (ATP)-binding cassette transporters ATP-binding cassette subfamily A1 (ABCA1), ATP-binding cassette subfamily G1 (ABCG1) and ABCG4, the liver X receptor/retinoid X receptor (LXR/RXR) and peroxisome proliferator-activated receptorgamma(PPAR gamma) transcription factors, the HDL components apolipoprotein A-I (apoA-I), lecithin-cholesterol acyltransferase (LCAT), and phospholipids as additional mediators of cholesterol transport. Cholesterol efflux occurs via three independent pathways: (1) aqueous diffusion, (2) nonspecific efflux via SR-BI receptors, and (3) specific efflux via cholesterol-responsive members of the ABC superfamily. Whereas aqueous diffusion and scavenger receptor class B, type I (SR-BI)-mediated efflux transport free cholesterol to a wide variety of cholesterol acceptors (particles containing phospholipids, HDL, and lipidated apo-lipoproteins; LDL, etc), the ABCA1 pathway mediates the transport of cholesterol in a unidirectional manner, mainly to lipid-poor apoA-I. In contrast, the ABCG1 pathway is responsible for the transport of cholesterol to all the subfamily members of HDL. Although HDL-mediated cholesterol efflux is apoA-I-dependent, recent studies have suggested an involvement of the enzyme paraoxonase 1 (PON1). Cholesterol efflux is carried on by a number of factors such as genetic mutations, smoking, stress, and high-fat diets. It is attenuated with aging due to changes in the composition and structure of HDL, especially the phosphatidylcholine/sphingomyelin ratio, the fluidity of the phospholipidic layer, the concentration of apoA-I, and the activity of PON1. This review summarizes the findings that cholesterol homeostasis is disrupted with aging as a consequence of dysfunctional cholesterol efflux and the impairment of physiological functions. PMID:19405812

Berrougui, Hicham; Khalil, Abdelouahed



High-density lipoproteins: A consensus statement from the National Lipid Association.  


For >4 decades it has been recognized that elevated serum levels of high-density lipoprotein cholesterol (HDL-C) are associated with reduced risk of cardiovascular disease (CVD) and its sequelae. Many prospective observational studies performed around the world have confirmed an inverse relationship between HDL-C and cardiovascular risk in people irrespective of sex, race, or ethnicity. Consequently, it was assumed that, by extension, raising HDL-C through lifestyle modification and pharmacologic intervention would reduce risk of CVD. Animal studies are consistent with this assumption. Lipid treatment guidelines around the world promoted the recognition of HDL-C as a therapeutic target, especially in high-risk patients. Some post hoc analyses from randomized controlled trials also suggest that raising HDL-C beneficially affects the risk of CVD. However, a number of recent randomized studies putatively designed to test the "HDL hypothesis" have failed to show benefit. The results of these trials have caused many clinicians to question whether HDL-C is a legitimate therapeutic target. In response to the many questions and uncertainties raised by the results of these trials, the National Lipid Association convened an expert panel to evaluate the current status of HDL-C as a therapeutic target; to review the current state of knowledge of HDL particle structure, composition, and function; and to identify the salient questions yet to be answered about the role of HDL in either preventing or contributing to atherosclerotic disease. The expert panel's conclusions and clinical recommendations are summarized herein. The panel concludes that, although low HDL-C identifies patients at elevated risk, and much investigation suggests that HDL may play a variety of antiatherogenic roles, HDL-C is not a therapeutic target at the present time. Risk stratified atherogenic lipoprotein burden (low-density lipoprotein cholesterol and non-HDL-C) should remain the primary and secondary targets of therapy in patients at risk, as described by established guidelines. The National Lipid Association emphasizes that rigorous research into the biology and clinical significance of low HDL-C should continue. The development of novel drugs designed to modulate the serum levels and functionality of HDL particles should also continue. On the basis of an enormous amount of basic scientific and clinical investigation, a considerable number of reasons support the need to continue to investigate the therapeutic effect of modulating HDL structure and function. PMID:24079290

Toth, Peter P; Barter, Philip J; Rosenson, Robert S; Boden, William E; Chapman, M John; Cuchel, Marina; D'Agostino, Ralph B; Davidson, Michael H; Davidson, W Sean; Heinecke, Jay W; Karas, Richard H; Kontush, Anatol; Krauss, Ronald M; Miller, Michael; Rader, Daniel J



Beneficial effect of gemfibrozil on the chemical composition and oxidative susceptibility of low density lipoprotein: a randomized, double-blind, placebo-controlled study  

Microsoft Academic Search

Previous reports have shown that administration of fibrates can reduce coronary events and also improve plasma lipid levels. Oxidative modification of low density lipoprotein has been implicated in the pathogenesis of atherosclerosis, and the resistance of low density lipoprotein (LDL) to in vitro oxidation has been found to be correlated with the extent of atherosclerosis. We performed a double-blind, placebo-controlled

Hiroshi Yoshida; Toshitsugu Ishikawa; Makoto Ayaori; Hideki Shige; Toshimitsu Ito; Michio Suzukawa; Haruo Nakamura



Effect of niacin and etofibrate association on subjects with coronary artery disease and serum high-density lipoprotein cholesterol <35 mg/dl.  


Niacin treatment (alone) was compared with etofibrate and niacin combination to treat patients with high-density lipoprotein <35 mg/dl and without hypertriglyceridemia. The niacin and etofibrate combination proved to be safe and increased high-density lipoprotein cholesterol levels to 48%, which was 3 times higher than that obtained with niacin alone. PMID:10073791

Spósito, A C; Caramelli, B; Serrano, C V; Mansur, A P; Ramires, J A



Onset of lipoprotein-supported steroidogenesis in differentiating granulosa cells of rats: cellular events involved in mediating FSH-enhanced uptake of low-density lipoproteins  

SciTech Connect

Luteal cells use lipoproteins as the main source of cholesterol in steroidogenesis. However, little is known about the mechanisms underlying hormonal control of lipoprotein uptake. Thus, the authors tested the hypothesis that FSH and androgens regulate low density lipoprotein (LDL)-supported steroidogenesis in maturing granulosa cells by affecting receptor-mediated endocytosis of LDL at a cellular level. For this, immature ovarian granulosa cells were cultured with or without hormones, compactin (de novo synthesis inhibitor), or unlabeled or labeled (/sup 125/I or gold particles) LDL. Nonhormone-treated cultures produced little progestin; FSH and FSH/androstenedione stimulated steroid secretion. Progestin production by hormone-, but not nonhormone-, treated cultures was decreased by compactin, suggesting that de novo synthesis provided sterol for steroidogenesis. EM quantitation of cells exposed to gold-LDL at 37/sup 0/C revealed that, compared to nonhormone-treated cells, FSH-treated cells (1) bound and internalized more gold-LDL, (2) had a smaller percentage of gold-LDL at their surfaces, (3) displayed a faster apparent rate of LDL internalization and delivery to lysosomes, and (4) contained more gold-labeled lysosomes. Data from biochemical studies in which /sup 125/I-LDL was used supported the morphological findings. In conclusion, this study demonstrates that FSH has important effects at the cellular level on LDL uptake, which seem to underlie the striking increase in progestin production accompanying granulosa cell differentiation.

Foster, J.D.



Efficacy of Low-Density Lipoprotein Apheresis in Patients with Peripheral Arterial Occlusive Disease Undergoing Hemodialysis Treatment  

Microsoft Academic Search

Background: Low-density lipoprotein (LDL) apheresis is effective in the treatment of peripheral arterial occlusive disease (PAOD). In the present study, we attempted to determine whether LDL apheresis is effective even for PAOD patients undergoing hemodialysis, who tend to be refractory to any treatment, and if so, to determine the mechanism of its efficacy. Methods: Serum levels of lipids and vascular

Satoshi Morimoto; Yutaka Yano; Kei Maki; Katsunori Sawada; Toshiji Iwasaka



Low density lipoproteins extracted from hen egg yolk by an easy method: cryoprotective effect on frozen–thawed bull semen  

Microsoft Academic Search

Hen egg yolk is widely used as a cryoprotective agent in semen freezing extenders in order to protect the spermatozoa against cold shock. The protective action of yolk is largely presumed to be due to low density lipoproteins (LDL). In recent years, arguments concerning the presence of cryoprotective antagonists in egg yolk, have reinforced interest in the use of only

M Moussa; V Martinet; A Trimeche; D Tainturier; M Anton



Significance of the variant and full-length forms of the very low density lipoprotein receptor in brain  

Microsoft Academic Search

The very low density lipoprotein receptor (VLDLR) is a newly described receptor which binds to apolipoprotein E (apoE) specifically. The authors designed a synthetic peptide of 17 amino acids representing the N-terminus of the putative first ligand binding domain of human VLDLR, this being a unique domain for VLDLR. When the synthetic peptide was used as the antigen, two different

Yasuhiro Nakamura; Munehiko Yamamoto; Eriko Kumamaru



The Role of Cholesteryl Ester Transfer Protein and Phospholipid Transfer Protein in the Remodeling of Plasma High-Density Lipoproteins  

Microsoft Academic Search

Recent studies demonstrated that alterations in the size distribution of high-density lipoproteins (HDLs) constitute reliable markers for the risk of coronary artery disease. These observations suggested that the determination of the size distribution of HDL subpopulations by using polyacrylamide gradient gel electrophoresis might constitute an effective tool in clinical practice for the detection of patients with elevated risk. During the

Laurent Lagrost



Human low density lipoprotein subfractions separated by gradient gel electrophoresis: composition, distribution, and alterations induced by cholesteryl ester transfer protein  

Microsoft Academic Search

Low density lipoprotein (LDL) subfractions were studied in sera from 208 normolipidemic, 22 hypercholester- olemic, and 33 hypertriglyceridemic subjects. Whole serum without preliminary ultracentrifugation was submitted to elec- trophoresis in a nondenaturing polyacrylamide gel. Three main LDL patterns were observed in normolipidemic sera: type 1, characterized by the presence of only one major band; type 2, characterized by the presence

Philippe Gambert; Catherine Bouzerand-Gambert; Anne Athias; Michel Farnier; Christian Lallemant


Inverse relation between the concentration of low-density- lipoprotein vitamin E and severity of coronary artery disease13  

Microsoft Academic Search

Oxidation of low-density lipoprotein (LDL) is believed to play an important role in atherogenesis, and antioxidant vitamins are thought to protect against coronary artery disease (CAD). We investigated whether the vitamin E concentrations in serum and LDL were associated with the severity of CAD as assessed by a semiquantitative scoring system in which coronary angiograms are analyzed for the number

Jan Regnstrom; Jan Nilsson; Peter Moldeus; Kerstin Strom; Anders Hamsten


Statin Use in Patients With Extremely Low Low-Density Lipoprotein Levels Is Associated With Improved Survival  

Microsoft Academic Search

Background—Aggressive lipid management has recently become the standard of care for patients with coronary heart disease. The safety and effectiveness of statin usage for patients with extremely low low-density lipoprotein (LDL) levels are less clear, however. The aim of this study was to investigate the safety and clinical outcomes of statin treatment in patients with LDL cholesterol levels below 60

Nicholas J. Leeper; Reza Ardehali; Emil M. deGoma; Paul A. Heidenreich



Physical inactivity interacts with an endothelial lipase polymorphism to modulate high density lipoprotein cholesterol in the GOLDN study  

Technology Transfer Automated Retrieval System (TEKTRAN)

BACKGROUND: Plasma high density lipoprotein (HDL) cholesterol (HDL-C) concentration is highly heritable but is also modifiable by environmental factors including physical activity. HDL-C response to exercise varies among individuals, and this variability may be associated with genetic polymorphism...