Sample records for density lipoprotein subclass

  1. Unusual high-density lipoprotein subclass distribution during late pregnancy.

    PubMed

    Silliman, K; Tall, A R; Kretchmer, N; Forte, T M

    1993-12-01

    Plasma lipoprotein distribution during late pregnancy is unusual since high-density lipoprotein (HDL) levels are increased in the presence of hypertriglyceridemia; the latter is usually associated with decreases in HDL levels. To determine whether there is a relationship between late-pregnancy lipid levels and specific HDL subclasses, HDL size distribution was determined by nondenaturing gradient gel electrophoresis (GGE) in a group of 36 women at 35 to 36 weeks of gestation and again at 6 weeks' postpartum, and in a group of 10 nonpregnant women. At 35 to 36 weeks of gestation, plasma triglyceride (TG) and cholesterol concentrations were significantly increased over postpartum levels (218 +/- 62 v 112 +/- 69 mg/dL and 234 +/- 48 v 197 +/- 36 mg/dL, respectively). During late pregnancy, apolipoprotein A-I (apo A-I) and HDL cholesterol concentrations were also increased relative to postpartum levels (211 +/- 42 v 168 +/- 20 mg/dL and 63 +/- 13 v 53 +/- 11 mg/dL, respectively). GGE analysis indicated that at 35 to 36 weeks of gestation, 86% of the subjects had a substantial increase of the most buoyant and largest of the HDL species, HDL2b; postpartum and nonpregnant HDL subclass distribution was characterized by the predominance of HDL3a, which are smaller, more dense HDL. The shift in the HDL subclass distribution during late pregnancy was associated with significant positive correlations between HDL2b and apo A-I (r = .50, P < .05) and HDL cholesterol (r = .60, P < .001). There were significant elevations in the concentrations of cholesteryl ester transfer protein (CETP) and estrogen during late pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8246775

  2. Inheritance of low-density lipoprotein subclass patterns: results of complex segregation analysis.

    PubMed Central

    Austin, M A; King, M C; Vranizan, K M; Newman, B; Krauss, R M

    1988-01-01

    Heterogeneity in the size of low-density lipoprotein (LDL) particles was used to identify two distinct patterns based on gradient gel electrophoresis analysis. These two phenotypes, LDL subclass pattern A and pattern B, were characterized by a predominance of large, buoyant LDL particles and small, dense LDL particles, respectively. The inheritance of these LDL subclass patterns was investigated in a sample of 61 healthy families including 301 individuals. LDL subclass pattern B was present in 31% of the subjects, with the prevalence varying by gender, age, and (in women) menopausal status. Complex segregation analysis suggested a major locus controlling LDL subclass patterns. The model providing the best fit to the data included a dominant mode of inheritance with a frequency of .25 for the allele determining LDL subclass pattern B and reduced penetrance for men under age 20 and for premenopausal women. Thus, the allele for the LDL subclass pattern characterized by a predominance of small, dense LDL particles appears to be very common in the population, although not usually expressed until adulthood in men and until after menopause in women. The presence of a major gene controlling LDL subclass could explain much of the familial aggregation of lipid and apolipoprotein levels and may be involved in increased risk of coronary heart disease. PMID:3195585

  3. Ability of non-high-density lipoprotein cholesterol and calculated intermediate-density lipoprotein to identify nontraditional lipoprotein subclass risk factors in dialysis patients

    Microsoft Academic Search

    Sharina S Belani; Anne C Goldberg; Daniel W Coyne

    2004-01-01

    Background: Non-high-density lipoprotein cholesterol (non-HDL-C) and calculated intermediate-density lipoprotein cholesterol (IDL-C) have been proposed as surrogate markers to estimate apolipoprotein B-containing lipoproteins. The purpose of this study was to determine the validity of non-HDL-C and calculated IDL-C to predict nontraditional lipoprotein risk factors among dialysis patients and to compare the prevalence of these nontraditional risk factors between dialysis modalities. Methods:

  4. Identification of multiple subclasses of plasma low density lipoproteins in normal humans

    Microsoft Academic Search

    Ronald M. Krauss; David J. Burke

    1982-01-01

    Density gradient ultracentrifugation of low density lipoproteins (LDL) from 12 normal subjects showed multiple, distinct isopycnic bands. Each band could be assigend to one of four density intervals and the boundaries of these intervals were consistent among all the subjects. Analytic ultracentrifuge flotation (S\\/sub f\\/°) rates were assigned to the four density intervals, and there was a strong correlation between

  5. The associations of high-density lipoprotein subclasses with insulin and glucose levels, physical activity, resting heart rate, and regional adiposity in men with coronary artery disease: The stanford coronary risk intervention project baseline survey

    Microsoft Academic Search

    Paul T. Williams; William L. Haskell; Karen M. Vranizan; Ronald M. Krauss

    1995-01-01

    We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the associations of high-density lipoprotein (HDL) subclasses with adiposity, physical activity, resting heart rate (an indicator of sympathetic drive), and plasma insulin and glucose levels in 97 men with angiographically documented coronary artery disease. These men neither smoked nor used medications known to affect lipoproteins. The absorbency of protein stain was

  6. Fluorometric sedimentation equilibrium for lipoprotein sub-class analysis. 

    E-print Network

    Henriquez, Ronald Rene

    2009-05-15

    Studies??????..???????????.. 36 2.3.1 Statistical Methods for Classifying CVD versus non-CVD Samples?????????????? 36 2.3.2 Measuring the Lipid Content of Lipoprotein Subclasses?????????????????. 37 2.3.3 Special Study: Effects of Statin... the Lipid Content of Lipoprotein Subclasses?????????????????. 61 3.2.2 Statistical Methods for Classifying CVD versus non- CVD samples ???????????????... 66 3.2.3 Special Study: Effects of Statin Therapy on Lipoprotein Profiles?????????????.. 74...

  7. Small, dense, low-density lipoprotein and atherosclerosis

    Microsoft Academic Search

    H. Robert Superko

    2000-01-01

    Disorders of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclass distribution are more common contributors\\u000a to coronary artery disease (CAD) than is elevated low-density lipoprotein cholesterol (LDLC). Recent research has emphasized\\u000a the importance of LDL and HDL subclass distribution in patient management and response to treatments. Laboratory determination\\u000a of LDL and HDL subclass distribution involves analytic ultracentrifugation or polyacrylalmide gradient

  8. Apolipoprotein E-enriched lipoprotein subclasses in normolipidemic subjects

    Microsoft Academic Search

    Joyce Corey Gibson; Ardon Rubinstein; Phillip R. Bukberg; W. Virgil Brown

    This study was undertaken to objectively define the lipoprotein association of apoE without ultracentrifugation and represents a description of three distinct apoE-containing lipoprotein (LP) subclasses in normal human plasma. The li- poproteins of whole plasma were fractionated in a continuous manner by molecular sieve chromatography using 4% agarose and the elution profile of apoE was compared to that of apoB,

  9. Sleep Apnea Is Related to the Atherogenic Phenotype, Lipoprotein Subclass B

    PubMed Central

    Luyster, Faith S.; Kip, Kevin E.; Drumheller, Oliver J.; Rice, Thomas B.; Edmundowicz, Daniel; Matthews, Karen; Reis, Steven E.; Strollo, Patrick J.

    2012-01-01

    Study Objectives: Sleep apnea has been implicated as an independent risk factor for atherosclerotic coronary artery disease (CAD). An association between the severity of sleep apnea and total cholesterol levels has previously been reported. However, the association with small dense low density lipoprotein (LDL) cholesterol concentration (subclass B), one of the strongest predictors of atherosclerosis, is unknown. We examined the relationship between sleep apnea and LDL subclass B, considering body size. Methods: This is a cross-sectional observational cohort of participants enrolled in a cardiovascular health study. Sleep apnea was assessed with a validated portable monitor. Lipid panels included total cholesterol, triglycerides, high density lipoprotein cholesterol, LDL cholesterol, and LDL subclasses A, B, and A/B. Sleep apnea was analyzed categorically using the apnea hypopnea index (AHI). Results: A total of 519 participants were evaluated. Mean age was 58.7 ± 7.4 years; BMI was 29.6 ± 5.7; 65% were female; 59% were Caucasian, and 37% were African American. Among participants with abnormal waist circumference by ATP III criteria, moderate to severe sleep apnea (AHI ? 25) was not independently associated with LDL subclass B. In contrast, among participants with normal waist circumference, moderate to severe sleep apnea was associated with 4.5-fold odds of having LDL subclass B. Conclusions: Sleep apnea is independently associated with an atherogenic phenotype (LDL subclass B) in non-obese individuals. The association between sleep apnea and LDL subclass B in those with normal waist circumference may account, in part, for the increased risk of atherosclerosis and subsequent vascular events. Citation: Luyster FS; Kip KE; Drumheller OJ; Rice TB; Edmundowicz D; Matthews K; Reis SE; Strollo PJ. Sleep apnea is related to the atherogenic phenotype, lipoprotein subclass B. J Clin Sleep Med 2012;8(2):155-161. PMID:22505860

  10. Hypertriglyceridemia and unusual lipoprotein subclass distributions associated with late pregnancy

    Microsoft Academic Search

    T. M. Forte; N. Kretchmer; K. Silliman

    1991-01-01

    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

  11. Reduced beta-strand content in apoprotein B-100 in smaller and denser low-density lipoprotein subclasses as probed by Fourier-transform infrared spectroscopy.

    PubMed Central

    Tanfani, F; Galeazzi, T; Curatola, G; Bertoli, E; Ferretti, G

    1997-01-01

    The secondary structure of apolipoprotein B-100 in low-density lipoprotein (LDL) subfractions was analysed by Fourier-transform IR spectroscopy. LDLs were isolated in three density ranges by gradient centrifugation of human plasma from healthy volunteers. The spectra revealed differences in the lipid content and composition of the three LDL fractions. The secondary structure of apolipoprotein B-100 was the same in the two fractions corresponding to the large less-dense LDL particles, whereas a lower content of beta-strands was found in the third fraction corresponding to the smaller denser LDL particles. Analysis of the spectroscopic data suggests that, in the same set of LDL subfractions, the particle size is probably the cause of the observed differences in apolipoprotein B-100 secondary structure. PMID:9148747

  12. Modified Low-Density Lipoproteins and High-Density Lipoproteins

    Microsoft Academic Search

    Elisabeth Koller; Ivo Volf; Aner Gurvitz; Franz Koller

    2006-01-01

    It has long been known that the oxidative state of the various plasma lipoproteins modulates platelet aggregability, thereby contributing to atherogenesis. Low-density lipoprotein (LDL), occurring in vivo both in the native and oxidised forms, interacts directly with platelets, by binding to specific receptors. While the identity of the receptors for native LDL and some subfractions of high-density lipoproteins (HDL) remains

  13. Hypertriglyceridemia and unusual lipoprotein subclass distributions associated with late pregnancy

    SciTech Connect

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

    1991-03-15

    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.

  14. Involvement of the Ca(2+)-dependent phosphorylation of a 20 kDa protein in the proliferative effect of high-density lipoproteins (subclass 3) on the adenocarcinoma cell line A549.

    PubMed Central

    Tazi, K A; Bonnafous, M; Favre, G; Soula, G; Le Gaillard, F

    1995-01-01

    Previous studies from our laboratory demonstrated that high-density lipoproteins (subclass 3; HDL3) bind to sites specific for apolipoprotein AI on the human adenocarcinoma cell line A549 and that HDL3 binding promotes a mitogenic effect [Favre, Tazi, Le Gaillard, Bennis, Hachem and Soula (1993) J. Lipid Res. 34, 1093-1106]. In the present study, we have examined the cell proteins that showed modified phosphorylation after binding of HDL3 to specific sites, and the roles of Ca2+ and protein kinase C. Native HDL3 (but not tetranitromethane-modified HDL3) and Ca2+ ionophore A23187 strongly enhanced the phosphorylation of a 20 kDa protein (x 3.6) and, to a lower extent, the phosphorylation of 24 and 28 kDa proteins (x 2.2 and 2.6 respectively). The two effectors were equally able to stimulate cell growth. Down-regulation of protein kinase C by a 24 h incubation of cells with phorbol myristate acetate prevented the effects of HDL3 on the phosphorylation of 24 and 28 kDa proteins. However, the extent of phosphorylation of the 20 kDa protein was not affected. In contrast, activation of protein kinase C by a short incubation with phorbol myristate acetate resulted in inhibition of proliferation and an increase in 24 and 28 kDa (but not 20 kDa) protein phosphorylation. These results suggest that HDL3 putative receptors exert their proliferative effect on A549 cells through activation of a Ca(2+)-dependent protein kinase. This kinase activity is not modulated by phorbol ester and thus may be a calmodulin kinase or an isoenzyme of protein kinase C that is independent of phorbol ester. It allows a subsequent 20 kDa protein to be phosphorylated. Images Figure 1 Figure 2 Figure 3 PMID:7733897

  15. Lipoprotein subclass analysis by immunospecific density 

    E-print Network

    Lester, Sandy Marie

    2009-05-15

    Apolipoprotein C-1 (apo C-1) enriched HDL has been described as an atherogenic form of HDL associated with an increased risk for cardiovascular disease (CVD). The objective of the present study was to develop a rapid method for the separation...

  16. Apo E-containing lipoproteins in low or high density lipoprotein deficiency.

    PubMed

    Gibson, J C; Rubinstein, A; Brown, W V; Ginsberg, H N; Greten, H; Norum, R; Kayden, H

    1985-01-01

    Apolipoprotein (apo) E-containing subfractions of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and high density lipoprotein (HDL) have been described in normolipidemic and hyperlipidemic subjects. These lipoproteins exist, however, in the presence of large amounts of apo A-I- and apo B-containing lipoproteins so that it has been difficult to assess the independence of these apo E-containing subclasses from the major lipoprotein classes. The present study has approached this question by taking advantage of three hypolipidemic states in which one or more of the major apolipoproteins is deficient or absent. After separating lipoproteins from whole plasma by molecular sieve chromatography followed by radioimmunoassay of column fractions, we found that two subjects with abetalipoproteinemia had no apo E-containing lipoproteins the size of VLDL or IDL and all the plasma apo E was in a fraction of large HDL. Two subjects with Tangier disease and two with familial apo A-I/C-III deficiency had extremely low levels of HDL cholesterol and of apo A-I-containing lipoproteins. In spite of the absence of classical HDL, a major fraction of apo E-containing lipoproteins was reproducibly observed at the elution volume characteristic of large HDL and was identical to that found in normal subjects. These data thus suggest the existence of apo E-containing lipoproteins that are the size of HDL and are not dependent upon the presence of either apo B or apo A-I. While studies in normal subjects indicate that apo E is associated with other apolipoproteins in HDL, further investigations will be needed to determine the full composition of these apo E-containing lipoproteins in the lipoprotein-deficient patients described in this report. PMID:3925935

  17. 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

    Stan?áková, 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

    2011-01-01

    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. PMID:21421807

  18. Glycation impairs high-density lipoprotein function

    Microsoft Academic Search

    C. C. Hedrick; S. R. Thorpe; M.-X. Fu; C. M. Harper; J. Yoo; S.-M. Kim; H. Wong; A. L. Peters

    2000-01-01

    Aims\\/hypothesis. To examine the effects of incubation of high-density lipoprotein (HDL) under hyperglycaemic conditions on several functions\\u000a of HDL in vitro.¶Methods. Human HDL (5 mg protein) was incubated for 1 week at 37 °C in the presence or absence of 25 mmol\\/l glucose. Additional samples\\u000a of human HDL were incubated in butylated hydroxytoluene to control for oxidation.¶Results. High-density lipoprotein incubated

  19. Hypertriglyceridemia during late pregnancy is associated with the formation of small dense low-density lipoproteins and the presence of large buoyant high-density lipoproteins.

    PubMed

    Silliman, K; Shore, V; Forte, T M

    1994-08-01

    Late pregnancy is a unique metabolic state where there are transient increases in the concentrations of plasma triglyceride (TG), cholesterol, and apolipoprotein (apo) B. Despite the hypertriglyceridemic environment, we recently reported that there is an unusual shift in high-density lipoprotein (HDL) subclass distribution from smaller HDL subclasses to the largest, most buoyant HDL2b subclass. In the present investigation, we determined whether the subclasses of low-density lipoprotein (LDL) also change during this transient hyperlipidemic state and whether such changes were associated with plasma TG and apolipoprotein concentrations. Thirty-six Hispanic subjects at 35 to 36 weeks' gestation and at 6 weeks' postpartum were studied. At 35 to 36 weeks of gestation, plasma concentrations of TG, cholesterol, and apo B were increased (218 +/- 62, 234 +/- 48, and 130 +/- 35 mg/dL, respectively) over levels at 6 weeks' postpartum (112 +/- 69, 197 +/- 36, and 97 +/- 25 mg/dL respectively). However, lipoprotein(a) [Lp(a)] concentrations were not changed during pregnancy compared with postpartum. LDL subclass patterns (A, B, or I) were determined by nondenaturing polyacrylamide gradient gel electrophoresis in our group of 36 pregnant women. During late pregnancy, 97% of subjects were categorized as LDL subclass patterns B or I, indicating that small, dense LDL particles predominated. This predominance of small, dense LDL was associated with plasma TG concentration, where there was a significant inverse relationship (r = -.45, P < .01) between the LDL peak particle diameter and plasma TG concentration. In an apparent anomaly, there were significant increases in the concentrations of HDL cholesterol (HDL-C) and HDL2 mass, even though small, dense LDL particles predominated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8052144

  20. High-density lipoproteins protect endothelial cells from apoptosis induced by oxidized low-density lipoproteins

    Microsoft Academic Search

    A. Blanco-Molina; D. Martín-Escalante; D. Bravo; J. A. González-Reyes; J. López-Miranda; J. M. Ordovfis; F. López-Segura; J. A. Jiménez-Péreperez; F. Pérez-Jiménez

    2000-01-01

    Summary Endothelial lesion by oxidized low-density liproproteins (LDL) is one of the first stages in the development of atherosclerosis. The effect of these lipoproteins can range from a functional lesion of the endothelium to death of the endothelial cells by apoptosis. High-density lipoproteins (HDL) are one of the factors which can have a protective effect against the development of atheromatous

  1. Low-Density Lipoprotein Apheresis

    PubMed Central

    2007-01-01

    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

  2. Apo E-Containing Lipoproteins in Low or High Density Lipoprotein Deficiency

    Microsoft Academic Search

    Joyce Corey Gibson; Ardon Rubinstein; W. Virgil Brown; Henry N. Ginsberg; Heiner Greten; Robert Norum; Herbert Kayden

    Apolipoprotein (apo) E-containing subtractions of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and high density lipoprotein (HDL) have been described in normolipidemic and hyperlipidemic subjects. These lipopro- teins exist, however, in the presence of large amounts of apo A-l- and apo B-contain- ing lipoproteins so that it has been difficult to assess the independence of these apo E-containing

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

    Microsoft Academic Search

    M. Hersberger; A. Eckardstein

    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,

  4. Atherosclerosis regression: Is low-density lipoprotein or high-density lipoprotein the answer?

    Microsoft Academic Search

    Stephen J. Nicholls; E. Murat Tuzcu; Steven E. Nissen

    2007-01-01

    Lowering low-density lipoprotein cholesterol is the cornerstone of risk modification in patients with established coronary\\u000a artery disease. Considerable attention is currently focused on developing pharmacologic agents that promote the biologic activity\\u000a of high-density lipoprotein. Advances in imaging of the artery wall provide the opportunity to evaluate the impact of medical\\u000a therapies on serial changes in plaque burden. A number of

  5. Proteomic analysis of electronegative low-density lipoprotein[S

    PubMed Central

    Bancells, Cristina; Canals, Francesc; Benítez, Sònia; Colomé, Nuria; Julve, Josep; Ordóñez-Llanos, Jordi; Sánchez-Quesada, José Luis

    2010-01-01

    Low density lipoprotein is a heterogeneous group of lipoproteins that differs in lipid and protein composition. One copy of apolipoprotein (apo)B accounts for over 95% of the LDL protein, but the presence of minor proteins could disturb its biological behavior. Our aim was to study the content of minor proteins in LDL subfractions separated by anion exchange chromatography. Electropositive LDL [LDL(+)] is the native form, whereas electronegative LDL [LDL(?)] is a minor atherogenic fraction present in blood. LC-ESI MS/MS analysis of both LDL fractions identified up to 28 different proteins. Of these, 13 proteins, including apoB, were detected in all the analyzed samples. LDL(?) showed a higher content of most minor proteins. Statistical analysis of proteomic data indicated that the content of apoE, apoA-I, apoC-III, apoA-II, apoD, apoF, and apoJ was higher in LDL(?) than in LDL(+). Immunoturbidimetry, ELISA, or Western blot analysis confirmed these differences. ApoJ and apoF presented the highest difference between LDL(+) and LDL(?) (>15-fold). In summary, the increased content of several apolipoproteins, and specifically of apoF and apoJ, could be related to the physicochemical characteristics of LDL(?), such as apoB misfolding, aggregation, and abnormal lipid composition. PMID:20699421

  6. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol are risk factors for cardiovascular disease and blood triglycerides reflect key metabolic processes including sensitivity to insulin. Blood lipoprotein and lipid concentrations are heritable. To date, the identification o...

  7. Beginning to understand high-density lipoproteins.

    PubMed

    Santos-Gallego, Carlos G; Badimon, Juan J; Rosenson, Robert S

    2014-12-01

    This article reconciles the classic view of high-density lipoproteins (HDL) associated with low risk for cardiovascular disease (CVD) with recent data (genetics studies and randomized clinical trials) casting doubt over the widely accepted beneficial role of HDL regarding CVD risk. Although HDL cholesterol has been used as a surrogate measure to investigate HDL function, the cholesterol content in HDL particles is not an indicator of the atheroprotective properties of HDL. Thus, more precise measures of HDL metabolism are needed to reflect and account for the beneficial effects of HDL particles. Current and emerging therapies targeting HDL are discussed. PMID:25432389

  8. Intracellular trafficking of pigeon b -very low density lipoprotein and low density lipoprotein at low and high concentrations in pigeon macrophages

    Microsoft Academic Search

    Nancy L. Jones; Jerry A. Saunders; Revill R. Mallory

    Foam cell formation occurs in vitro at lipoprotein concentrations above 50 m g\\/ml in pigeon macrophages. Hypothetically, intracellular trafficking of lipoproteins at higher concentrations may differ from uptake of lipoproteins associated with low concentrations, revealing a separate atherogenic endocytic pathway. Macrophage intracellular traf- ficking of pigeon b -very low density lipoprotein ( b -VLDL) and low density lipoprotein (LDL) at

  9. Nanotechnology for Synthetic High Density Lipoproteins

    PubMed Central

    Luthi, Andrea J.; Patel, Pinal C.; Ko, Caroline H.; Mutharasan, R. Kannan; Mirkin, Chad A.; Thaxton, C. Shad

    2014-01-01

    Atherosclerosis is the disease mechanism responsible for coronary heart disease (CHD), the leading cause of death worldwide. One strategy to combat atherosclerosis is to increase the amount of circulating high density lipoproteins (HDL), which transport cholesterol from peripheral tissues to the liver for excretion. The process, known as reverse cholesterol transport, is thought to be one of the main reasons for the significant inverse correlation observed between HDL blood levels and the development of CHD. This article highlights the most common strategies for treating atherosclerosis using HDL. We further detail potential treatment opportunities that utilize nanotechnology to increase the amount of HDL in circulation. The synthesis of biomimetic HDL nanostructures that replicate the chemical and physical properties of natural HDL provides novel materials for investigating the structure-function relationships of HDL and for potential new therapeutics to combat CHD. PMID:21087901

  10. [Autoantibodies to low-density lipoproteins].

    PubMed

    Khliustov, V N

    1997-09-01

    Our task was to isolate autoantibodies to low-density lipoproteins (LDLP) and characterize them. CNBr-Sepharose and LDLP-based immunoadsorbent were prepared. Autoantibodies were isolated from a pool of human sera from donors by affinity chromatography in a column with immunoadsorbent. Analysis of the eluates from the immunoadsorbents by disk electrophoresis in 9% polyacrylamide gel with sodium dodecyl sulfate and beta-mercaptoethanol revealed 5 components: the second component corresponds to heavy immunoglobulin chains and the fourth to light ones. Analysis of eluates in immunophoresis with monospecific antisera precipitating IgG, IgA, and IgM detected all these immunoglobulins. Enzyme immunoassay of immunoglobins in autoantibody preparations showed the following values: 41% of IgG, 7% of IgA, and 52% of IgM. PMID:9377026

  11. Excessive centrifugal fields damage high density lipoprotein.

    PubMed

    Munroe, William H; Phillips, Martin L; Schumaker, Verne N

    2015-06-01

    HDL is typically isolated ultracentrifugally at 40,000 rpm or greater, however, such high centrifugal forces are responsible for altering the recovered HDL particle. We demonstrate that this damage to HDL begins at approximately 30,000 rpm and the magnitude of loss increases in a rotor speed-dependent manner. The HDL is affected by elevated ultracentrifugal fields resulting in a lower particle density due to the shedding of associated proteins. To circumvent the alteration of the recovered HDL, we utilize a KBr-containing density gradient and a lowered rotor speed of 15,000 rpm to separate the lipoproteins using a single 96 h centrifugation step. This recovers the HDL at two density ranges; the bulk of the material has a density of about 1.115 g/ml, while lessor amounts of material are recovered at >1.2 g/ml. Thus, demonstrating the isolation of intact HDL is possible utilizing lower centrifuge rotor speeds. PMID:25910941

  12. Very low-density lipoprotein metabolism in hypothyroid horses

    Microsoft Academic Search

    Nicholas Frank

    2002-01-01

    The central hypothesis of this thesis is that hypothyroidism alters the metabolism of blood lipoproteins in horses. More specifically, our goal was to determine the effect of hypothyroidism on very low-density lipoprotein (VLDL) metabolism. Thyroid glands were surgically removed (thyroidectomy) from horses to create a hypothyroid state and blood lipids were examined. Results revealed a significant 9-fold rise in mean

  13. Very low density lipoprotein apolipoprotein B metabolism in humans

    Microsoft Academic Search

    Th. Demant; J. Shepherd; C. J. Packard

    1988-01-01

    Summary The human plasma lipoproteins encompass a broad spectrum of particles of widely varying physical and chemical properties whose metabolism is directed by their protein components. Apolipoprotein B100 (apo B100) is the major structural protein resident in particles within the Svedberg flotation range 0–400. The largest of these, the very low density lipoprotein (VLDL), rich in triglyceride, are metabolised by

  14. Negatively Cooperative Binding of High-Density Lipoprotein to the HDL Receptor SR-BI

    E-print Network

    Xu, Shangzhe

    Scavenger receptor class B, type I (SR-BI), is a high-density lipoprotein (HDL) receptor, which also binds low-density lipoprotein (LDL), and mediates the cellular selective uptake of cholesteryl esters from lipoproteins. ...

  15. Nanobiotechnology applications of reconstituted high density lipoprotein

    PubMed Central

    2010-01-01

    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

  16. Lipoprotein Lipase Enhances the Binding of Chylomicrons to Low Density Lipoprotein Receptor-Related Protein

    Microsoft Academic Search

    U. Beisiegel; W. Weber; G. Bengtsson-Olivecrona

    1991-01-01

    Chylomicron catabolism is known to be initiated by the enzyme lipoprotein lipase (triacylglycero-protein acylhydrolase, EC 3.1.1.34). Chylomicron remnants, produced by lipolysis, are rapidly taken up by the liver via an apolipoprotein E (apoE)-mediated, receptor-dependent process. The low density lipoprotein (LDL) receptor-related protein (LRP) has been suggested as the potential apoE receptor. We have analyzed the binding of human chylomicrons to

  17. Modified low density lipoproteins in the pathogenesis of atherosclerosis.

    PubMed

    Laurman, W

    1994-01-01

    A fatty streak, the earliest atherosclerotic lesion consists mostly of lipid-laden macrophages. The mechanism leading to accumulation of cholestrol ester in macrophages in vivo is unknown, but it may result from the uptake of modified low density lipoproteins that enter from blood or are modified within the arterial wall. In this review I discuss the major types of modified low density lipoproteins with a special focus on their chemical nature. PMID:7921905

  18. Plasma lipoprotein distribution of liposomal nystatin is influenced by protein content of high-density lipoproteins.

    PubMed

    Cassidy, S M; Strobel, F W; Wasan, K M

    1998-08-01

    The plasma lipoprotein distribution of free nystatin (Nys) and liposomal nystatin (L-Nys) in human plasma samples with various lipoprotein lipid and protein concentrations and compositions was investigated. To assess the lipoprotein distributions of Nys and L-Nys, human plasma was incubated with Nys and L-Nys (equivalent to 20 microg/ml) for 5 min at 37 degreesC. The plasma was subsequently partitioned into its lipoprotein and lipoprotein-deficient plasma fractions by step-gradient ultracentrifugation, and each fraction was analyzed for Nys content by high-pressure liquid chromatography. The lipid and protein contents and compositions of each fraction were determined with enzymatic kits. Following the incubation of Nys and L-Nys in human plasma the majority of Nys recovered within the lipoprotein fractions was recovered from the high-density lipoprotein (HDL) fraction. Incorporation of Nys into liposomes consisting of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol significantly increased the percentage of drug recovered within the HDL fraction. Furthermore, it was observed that as the amount of HDL protein decreased the amounts of Nys and L-Nys recovered within this fraction decreased. These findings suggest that the preferential distribution of Nys and L-Nys into plasma HDL may be a function of the HDL protein concentration. PMID:9687378

  19. Structures of Discoidal High Density Lipoproteins

    PubMed Central

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

    2010-01-01

    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. PMID:19948731

  20. Reliability of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B measurement

    Microsoft Academic Search

    John H. Contois; G. Russell Warnick; Allan D. Sniderman

    2011-01-01

    There is little understanding of the reliability of laboratory measurements among clinicians. Low-density lipoprotein cholesterol (LDL-C) measurement is the cornerstone of cardiovascular risk assessment and prevention, but it is fraught with error. Therefore, we have reviewed issues related to accuracy and precision for the measurement of LDL-C and the related markers non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B. Despite the

  1. Non-high-density lipoprotein cholesterol: A target of lipid-lowering in dialysis patients

    Microsoft Academic Search

    Christoph Wanner; Vera Krane

    2003-01-01

    Background: The finding of an increased prevalence and levels of atherogenic lipoproteins in the context of normal plasma total and low-density lipoprotein (LDL) cholesterol (LDL-C) levels in hemodialysis (HD) patients highlights the need to look beyond the basic assessment of plasma concentrations of total cholesterol and LDL-C. Measurement of atherogenic lipoproteins (remnant lipoprotein particles [RLPs], particularly intermediate-density lipoprotein [IDL]), is

  2. Lipoproteins, apolipoproteins, and low-density lipoprotein size among diabetics in the Framingham offspring study.

    PubMed

    Siegel, R D; Cupples, A; Schaefer, E J; Wilson, P W

    1996-10-01

    Diabetes mellitus has been shown to be associated with lipid abnormalities. Prior studies have indicated that women with diabetes have a risk of coronary heart disease similar to that of men. We compared lipid parameters in diabetic and nondiabetic participants in cycle 3 of the Framingham Offspring Study. Values for plasma total cholesterol (TC), triglyceride, lipoprotein, cholesterol, apolipoprotein (apo) A1, B, apo and lipoprotein(a) [Lp(a)] and low-density lipoprotein (LDL) particle size were analyzed in 174 diabetic and 3,757 nondiabetic subjects. Data from a total of 2,025 men and 2,042 women participating in the third examination (1983 to 1987) of the Framingham Offspring Study were subjected to statistical analysis. Male and female diabetics showed lower high-density lipoprotein (HDL) cholesterol, higher triglycerides, higher very-low-density lipoprotein (VLDL) cholesterol, lower apo A1, and higher LDL particle scores, indicating smaller size, than nondiabetics. Female diabetics also showed significantly higher TC and apo B values than nondiabetics. The results remained statistically significant after controlling for obesity and menopausal status. The presence of small dense LDL particles (pattern B) was highly associated with diabetes and hypertriglyceridemia in both sexes, and the relative odds for pattern B remained significant in women but not in men after adjustment for age and hypertriglyceridemia. No differences in apo E isoform distribution were found for diabetics and nondiabetics. Diabetes was not associated with elevated LDL cholesterol levels. In conclusion, diabetics have lower HDL cholesterol and higher triglyceride levels and are more likely to have small dense LDL particles. Diabetes is not a secondary cause of elevated LDL cholesterol. Lipid screening of diabetics should include full quantification of lipids for proper assessment of potential atherosclerotic risk. PMID:8843183

  3. Non-oxidative modification of native low-density lipoprotein by oxidized low-density lipoprotein.

    PubMed

    Yang, M; Leake, D S; Rice-Evans, C A

    1996-06-01

    The oxidative modification of low-density lipoprotein (LDL) has been implicated in the pathogenesis of atherosclerosis, although little is known as yet about the precise mechanism of oxidation in vivo. The studies presented here demonstrate that, in the absence of cells or transition metals, oxidized LDL can modify native LDL through co-incubation in vitro such as to increase its net negative charge, in a concentration-dependent manner. The interaction is not inhibited by peroxyl radical scavengers or metal chelators, precluding the possibility that the modification of native LDL by oxidized LDL is through an oxidative process. Studies with radioiodinated oxidized LDL showed no transfer of radioactivity to the native LDL, demonstrating that fragmentation of protein and the transfer of some of the fragments does not account for the modified charge on the native LDL particle. The adjacency of native to oxidized LDL in the arterial wall may be a potential mechanism by which the altered recognition properties of the apolipoprotein B-100 may arise rapidly without oxidation or extensive modification of the native LDL lipid itself. PMID:8687375

  4. Oxygen-Mediated Heterogeneity of Apo-Low-Density Lipoprotein

    Microsoft Academic Search

    Joseph Schuh; Gordon F. Fairclough; Rudy H. Haschemeyer

    1978-01-01

    Mild oxidation of human serum low-density lipoprotein (LDL) converts the apoprotein from a nearly homogeneous component of high apparent molecular weight to a mixture of apparently lower molecular weight polypeptide components, as characterized by sodium dodecyl sulfate\\/ polyacrylamide gel electrophoresis. This protein alteration, which correlates temporally with increases in the formation of lipid oxidation products and in the fluorescence of

  5. Recycling of vitamin E in human low density lipoproteins

    Microsoft Academic Search

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

    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

  6. The Role of High-Density Lipoprotein Cholesterol in Atherothrombosis

    Microsoft Academic Search

    BRIAN G. CHOI; GEMMA VILAHUR; JUAN F. V ILES-GONZALEZ; JUAN J. BADIMON

    2006-01-01

    Despite considerable progress in the development of new therapies to control atherosclerosis and its complications, coronary he art disease (CHD) remains the number one cause of death in the Western world. While low high-density lipoprotein (HDL) has been associated with increased risk for CHD, raising HDL to reduce risk of disease has yet to be accepted as a standard therapeutic

  7. Different methods for particle diameter determination of low density and high density lipoproteins-Comparison and evaluation 

    E-print Network

    Vaidyanathan, Vidya

    2009-05-15

    Predominance of small dense Low Density Lipoprotein (LDL) is associated with a two to threefold increase in risk for Coronary Heart Disease (CVD). Small, dense HDL (High Density Lipoprotein) particles protect small dense LDL from oxidative stress...

  8. Effects of human low and high density lipoproteins on the binding of rat intermediate density lipoproteins to rat liver membranes

    SciTech Connect

    Brissette, L.; Nol, S.P.

    1986-05-25

    Upon incubation with rat liver membranes, radioiodinated rat intermediate density lipoproteins (IDL) interacted with at least two binding sites having a low and a high affinity as demonstrated by the curvilinear Scatchard plots obtained from the specific binding data. The purpose of our work was to identify the nature of these binding sites. Human low density lipoproteins (LDL), contain apolipoprotein B only, and human high density lipoproteins (HDL3), containing neither apolipoprotein B nor E, were both capable of decreasing the specific binding of rat /sup 125/I-IDL. The Scatchard analysis clearly revealed that only the low affinity component was affected by the addition of these human lipoproteins. In fact, the low affinity binding component gradually decreased as the amount of human LDL or HDL3 increased in the binding assay. At a 200-fold excess of human LDL or HDL3, the low affinity binding was totally masked, and the Scatchard plot of the specific /sup 125/I-IDL binding became linear. Only the high affinity binding component was left, enabling a precise measurement of its binding parameters. In a series of competitive displacement experiments in which the binding assay contained a 200-fold excess of human LDL or HDL3, only unlabeled rat IDL effectively displaced the binding of rat /sup 125/I-IDL. We conclude that the low affinity binding of rat IDL to rat liver membranes is due to weak interactions with unspecified lipoprotein binding sites. The camouflage of these sites by human lipoproteins makes possible the study of IDL binding to the high affinity component which likely represents the combined effect of IDL binding to both the remnant and the LDL receptors.

  9. Experimental hypothyroidism modulates the expression of the low density lipoprotein receptor by the liver.

    PubMed

    Scarabottolo, L; Trezzi, E; Roma, P; Catapano, A L

    1986-03-01

    The effect of experimental hypothyroidism on the catabolism of plasma lipoproteins and on the expression of low density lipoprotein receptors by the liver was investigated in rats made hypothyroid by surgery. The animals developed mild hypercholesterolemia, mainly due to an increase of plasma low density lipoprotein, while other lipoprotein classes were only marginally affected. Kinetic studies using [125I]LDL indicated that a decreased fractional catabolic rate of the lipoprotein was responsible for this finding in agreement with the in vitro observation of a reduced binding of lipoproteins to liver membranes from hypothyroid rats and with the demonstration, by ligand blotting analysis, of a decreased expression of lipoprotein receptors in liver membranes. These data suggest that hypothyroidism affects lipoprotein distribution also by decreasing the catabolism of low density lipoproteins by the liver. PMID:3964353

  10. Effects of probucol on the in vivo plasma clearance of human low density lipoproteins in rabbits and on the expression of lipoprotein receptors in vitro.

    PubMed

    Trezzi, E; Roma, P; Bernini, F; Fumagalli, R; Catapano, A L

    1984-09-01

    The purpose of this study was to investigate the effects of probucol on the plasma levels of low density lipoproteins in rabbits and whether the resulting decrease of low density lipoproteins was related to the effects of probucol on the expression of lipoprotein receptors. Probucol administration effectively lowered plasma cholesterol in normal rabbits. Both low density and high density lipoprotein cholesterol decreased, as well as apo B in the former fraction. Probucol had no effect on the fractional catabolic rate of low density lipoprotein while the flux of this lipoprotein decreased to about 50%. Moreover both the binding of lipoproteins to liver membranes and the in vitro uptake of low density lipoprotein by human skin fibroblasts were not affected by the drug. These findings are consistent with an effect of probucol on low density lipoprotein synthesis. PMID:6093829

  11. 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

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

    2010-03-01

    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. 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. PMID:19783527

  12. 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

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

    2010-01-01

    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. PMID:19783527

  13. A step towards quantitative lipoprotein density profiling analysis: applied Rayleigh scattering

    E-print Network

    Nowlin, Michael

    2009-05-15

    an ultracentrifuge plays a key role in the area of preventative medicine in regards to atherosclerosis. Two of the most critical lipoprotein characteristics, diameter and density, are well preserved with the proper isopycnic gradient. Currently, lipoprotein particles...

  14. Intracellular oxidative modification of low density lipoprotein by endothelial cells

    Microsoft Academic Search

    Toshimi Satoh; Osamu Tokunaga

    2002-01-01

    We investigated intracellular oxidative modification of low density lipoprotein (IOM-LDL) by endothelial cells (ECs) and the role of ferritin in this process. IOM-LDL was examined by immunocytochemistry with an anti-oxidized phosphatidylcholine antibody and by lipid peroxidation assay. Incubation of LDL-treated ECs (human umbilical vein endothelial cells, passage 3) with ferritin produced cytoplasmic immunostain with the antibody, especially in large or

  15. Low-Density Lipoprotein-Lowering Medication and Platelet Function

    Microsoft Academic Search

    Patrizia Ferroni; Stefania Basili; Francesca Santilli; Giovanni Davì

    2006-01-01

    Elevated low-density lipoprotein (LDL) cholesterol (LDL-C) levels represent one of the most important risk factors for atherosclerosis and therefore cardiovascular morbidity and mortality. LDL-C operates at different levels and through various classic and non-classic mechanisms. In particular, increased or modified LDL enhances platelet function and increases sensitivity of platelets to several naturally occurring agonists. Agents that lower LDL-C in hypercholesterolemic

  16. Synthesis, transport, and processing of apolipoproteins of high density lipoproteins

    Microsoft Academic Search

    Wilhelm Stoffel

    Cell biology methods have greatly influenced the elucidation of the biosynthetic pathways of apolipoproteins. In vitro and tissue culture systems allow the study, to a large extent, of the process of synthesis, intracellular processing, secretion, and extracellular processing of the major high density lipoprotein apoproteins apoA-I and A-I1 and also of a minor component, apoA-IV. Whereas the latter apoprotein is

  17. A prominent large high-density lipoprotein at birth enriched in apolipoprotein C-I identifies a new group of infancts of lower birth weight and younger gestational age

    SciTech Connect

    Kwiterovich Jr., Peter O.; Cockrill, Steven L.; Virgil, Donna G.; Garrett, Elizabeth; Otvos, James; Knight-Gibson, Carolyn; Alaupovic, Petar; Forte, Trudy; Farwig, Zachlyn N.; Macfarlane, Ronald D.

    2003-10-01

    Because low birth weight is associated with adverse cardiovascular risk and death in adults, lipoprotein heterogeneity at birth was studied. A prominent, large high-density lipoprotein (HDL) subclass enriched in apolipoprotein C-I (apoC-I) was found in 19 percent of infants, who had significantly lower birth weights and younger gestational ages and distinctly different lipoprotein profiles than infants with undetectable, possible or probable amounts of apoC-I-enriched HDL. An elevated amount of an apoC-I-enriched HDL identifies a new group of low birth weight infants.

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

    Microsoft Academic Search

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

    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,

  19. Kinetics of tryptophan oxidation in plasma lipoproteins by myeloperoxidase-generated HOCl

    Microsoft Academic Search

    Andreas Jerlich; Michal Hammel; Fabienne Nigon; M. John Chapman; R. Jorg Schaur

    The relative susceptibility of the apoprotein components of human lipoproteins (high-density lipoprotein (HDL) and low-density lipoprotein (LDL)) and their subclasses to oxidation by the myeloperoxidase\\/H2O2\\/Cl 2 system in vitro was studied by measuring the decrease in rate of tryptophan fluorescence. Whereas the lipoprotein- modification rate showed a saturation type of dependence on the concentration of myeloperoxidase, a biphasic dependence on

  20. Dot-blot assay for the low density lipoprotein receptor

    SciTech Connect

    Maggi, F.M.; Catapano, A.L.

    1987-01-01

    We describe a new method for detecting the interaction of low density lipoprotein with its receptor using unmodified nitrocellulose as support for membrane protein. The method is specific and sensitive down to 3 micrograms of membrane protein. Unlabeled LDL, but not HDL, competes with /sup 125/I-labeled LDL for binding, and binding is abolished by pretreatment of the membranes with pronase and is dependent upon the presence of Ca2+. Furthermore, modification of arginine or lysine residues on LDL abolishes the lipoprotein interaction with the receptor protein supported on the nitrocellulose. When the membranes are solubilized with octyl glucoside, purification steps of the receptor can be directly followed with no interference of the detergent, therefore eliminating the need for its removal. The increased expression of LDL receptors on liver membranes from estradiol-treated rats was also demonstrated. We suggest, therefore, that this method can be used to detect the presence of LDL receptors on minute amounts of membrane protein.

  1. Changes in non-high-density lipoprotein cholesterol levels and triglyceride\\/high-density lipoprotein cholesterol ratios among patients randomized to aripiprazole versus olanzapine

    Microsoft Academic Search

    John W. Newcomer; Jonathan M. Meyer; Ross A. Baker; James M. Eudicone; Andrei Pikalov; Estelle Vester-Blokland; Robert D. McQuade; David T. Crandall; William H. Carson; Ronald N. Marcus; Gilbert L'Italien

    2008-01-01

    ObjectiveNon-high-density lipoprotein cholesterol (non-HDL-C) and the triglyceride to high-density lipoprotein cholesterol ratio (TG:HDL-C) are predictors of cardiovascular risk. This post-hoc analysis assessed changes in these parameters during treatment with the atypical antipsychotics olanzapine or aripiprazole using pooled data from three randomized, long-term clinical studies in patients with schizophrenia.

  2. Apoprotein composition of very low density lipoproteins of human serum.

    PubMed Central

    Kane, J P; Sata, T; Hamilton, R L; Havel, R J

    1975-01-01

    Methods for quantitation of the major apoproteins of human serum very low density lipoprotein have been developed employing tetramethylurea, which delipidates the lipoprotein and selectively precipitates apolipoprotein B. Six soluble apoproteins are separated by electrophoresis in polyacrylamide gel. One of these is a previously unrecognized species of R-alanine (R4-alanine), more anionic than the R3-alanine polypeptide. Conditions of staining have been found which yield reproducibly linear chromogenic response with native lipoprotein and with each purified apoprotein. Recovery of protein in the seven species measured accounts for over 97% of the total in the very low density lipoprotein of normolipidemic individuals and in most samples from individuals with endogenous hyperlipemia. The mean content of apolipoprotein B in 43 samples from normolipidemic subjects was 36.9(+/-1.2 SEM)% of total protein, The distribution of the major soluble apoproteins as mean (+/-SEM) percentage of the soluble fraction was : R-serine, 5.3+/-o.5; arginine-rich, 20.6+/-1.0; R-glutamic, 10.6+/-0.4; R2-alanine, 28.3+/-0.7; R3-alanine, 26.9+/-0.5; and R4-alanine, 8.0+/-0.5. Distribution of the apoproteins was a function of particle diameter of very low density lipoprotein in fractions separated by gel permeation chromatography and by density gradient ultracentrifugation. In fractions below 700-800 A, apolipoprotein B comprised an increasing percentage of the total protein with decreasing particle diameter. Among the soluble proteins the percentage of the arginine-rich and R-serine polypeptides increased and that of the R-glutamic polypeptide declined progressively with decreasing particle size. Apoprotein distribution was similar in fractions of similar particle size from normolipidemic and hyperlipemic subjects with the exception that all fractions from the hyperlipemic subjects contained more R-serine and some, more arginine rich polypeptide. Even in the absence of chylomicrons, the distribution of soluble apoproteins in particles of diameters greater than 700-800 A was usually similar to that of the smallest particles. This suggests that the largest particles may include products of the partial catabolism of chylomicrons. Images PMID:172534

  3. 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...

  4. Oxidised low density lipoproteins induce iron release from activated myoglobin.

    PubMed

    Rice-Evans, C; Green, E; Paganga, G; Cooper, C; Wrigglesworth, J

    1993-07-12

    Recent reports have detected the presence of iron in human atherosclerotic lesions [Biochem. J. 286 (1992) 901-905]. This study provides evidence for a biochemical mechanism whereby iron is released from myoglobin by low density lipoprotein (LDL) which has become oxidised by the ferryl myoglobin species. The haem destabilisation and iron release are inhibited by monohydroxamate compounds and desferrioxamine through their ability to inhibit the propagation of LDL oxidation. Thus, iron may derive from the myoglobin released from ruptured cells in the oxidising environment of the atherosclerotic lesion. PMID:8391992

  5. Very-Low-Density Lipoprotein-Induced Triglyceride Accumulation in Human Mesangial Cells Is Mainly Mediated by Lipoprotein Lipase

    Microsoft Academic Search

    Jing Li; Hang Li; Yu-bing Wen; Xue-wang Li

    2008-01-01

    Background: Very-low-density lipoprotein (VLDL) in vitro can induce foam cell formation in human mesangial cells. Lipoprotein lipase (LPL) expressed in the arterial wall plays a key role in atherogenesis by actions of enzymolysis and ‘molecular bridge’, and, thereby, leads to the formation of lipid-loaded foam cells. It is known that LPL is expressed by glomerular mesangial cells. This study was

  6. A positive relationship between Apo ?2 allele and high-density lipoprotein cholesterol

    Microsoft Academic Search

    Yung-Chieh Yen; Bih-Ching Shu; Chien-Shu Wang; Ming-Jen Yang; Wei-Tsung Kao; Chun-Hua Shih; For-Wey Lung

    2006-01-01

    This study explored the relationship between ApoE genotypes and the fasting serum levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triacylglycerol in an elderly Chinese population. A total of 500 subjects aged 65 to 74 years were randomly selected in southern Taiwan from April to June 2001. Two hundred fifty-six participants, who agreed

  7. Rationale for Use of Non–High-Density Lipoprotein Cholesterol Rather Than Low-Density Lipoprotein Cholesterol as a Tool for Lipoprotein Cholesterol Screening and Assessment of Risk and Therapy

    Microsoft Academic Search

    Philip H Frost; Richard J Havel

    1998-01-01

    The plasma level of low-density lipoprotein (LDL) cholesterol is the “gold standard” for estimating the lipoprotein-related risk for complications of atherosclerotic vascular disease. LDL cholesterol concentrations are commonly estimated by the Friedewald formula that requires only the measurement (after overnight fasting) of plasma cholesterol and triglycerides along with high-density lipoprotein (HDL) cholesterol. This value, however, is not in fact a

  8. Beyond Low-Density Lipoprotein Cholesterol Respective Contributions of Non-High-Density Lipoprotein Cholesterol Levels, Triglycerides, and the Total Cholesterol\\/High-Density Lipoprotein Cholesterol Ratio to Coronary Heart Disease Risk in Apparently Healthy Men and Women

    Microsoft Academic Search

    B. J. Arsenault; J. S. Rana; E. S. G. Stroes; J. P. Després; P. K. Shah; J. J. P. Kastelein; N. J. Wareham; S. M. Boekholdt; K. T. Khaw

    2009-01-01

    OBJECTIVES: This study was designed to test the hypothesis that at any low-density lipoprotein cholesterol (LDL-C) level, other lipid parameters such as non-high-density lipoprotein cholesterol (HDL-C) levels, triglyceride (TG) levels, and the total cholesterol (TC)\\/HDL-C are still associated with an increased coronary heart disease (CHD) risk. BACKGROUND: Although LDL-C is considered to be the primary target of lipid-lowering therapy, other

  9. Protein carbamylation renders high-density lipoprotein dysfunctional

    PubMed Central

    2012-01-01

    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. PMID:21235354

  10. High density lipoprotein metabolism in low density lipoprotein receptor-deficient mice.

    PubMed

    Rinninger, Franz; Heine, Markus; Singaraja, Roshni; Hayden, Michael; Brundert, May; Ramakrishnan, Rajasekhar; Heeren, Joerg

    2014-09-01

    The LDL receptor (LDLR) and scavenger receptor class B type I (SR-BI) play physiological roles in LDL and HDL metabolism in vivo. In this study, we explored HDL metabolism in LDLR-deficient mice in comparison with WT littermates. Murine HDL was radiolabeled in the protein ((125)I) and in the cholesteryl ester (CE) moiety ([(3)H]). The metabolism of (125)I-/[(3)H]HDL was investigated in plasma and in tissues of mice and in murine hepatocytes. In WT mice, liver and adrenals selectively take up HDL-associated CE ([(3)H]). In contrast, in LDLR(-/-) mice, selective HDL CE uptake is significantly reduced in liver and adrenals. In hepatocytes isolated from LDLR(-/-) mice, selective HDL CE uptake is substantially diminished compared with WT liver cells. Hepatic and adrenal protein expression of lipoprotein receptors SR-BI, cluster of differentiation 36 (CD36), and LDL receptor-related protein 1 (LRP1) was analyzed by immunoblots. The respective protein levels were identical both in hepatic and adrenal membranes prepared from WT or from LDLR(-/-) mice. In summary, an LDLR deficiency substantially decreases selective HDL CE uptake by liver and adrenals. This decrease is independent from regulation of receptor proteins like SR-BI, CD36, and LRP1. Thus, LDLR expression has a substantial impact on both HDL and LDL metabolism in mice. PMID:24954421

  11. In vivo assimilation of low density lipoproteins by a fibrosarcoma tumour line in mice.

    PubMed

    Norata, G; Canti, G; Ricci, L; Nicolin, A; Trezzi, E; Catapano, A L

    1984-12-01

    A tumour line inoculated in mice showed high affinity binding for lipoproteins in vitro. Studies in vivo demonstrated that the assimilation of human low density lipoprotein (LDL) by the tumour was very high. Both receptor and non-receptor mediated catabolism of the lipoprotein by the tumour increased as compared to other tissues known to be sites of lipoprotein catabolism (liver, spleen etc.). These findings suggest that lipoproteins may be useful markers for tumours as well as carriers for cytotoxic drugs to target tissues in vivo. PMID:6095991

  12. Role of oxidized low-density lipoprotein in the atherosclerosis of uremia

    Microsoft Academic Search

    Tilman B. Drueke; THAO NGUYEN KHOA; Ziad A. Massy; VÉRONIQUE WITKO-SARSAT; BERNARD LACOUR; BÉATRICE DESCAMPS-LATSCHA

    2001-01-01

    Role of oxidized low-density lipoprotein in the atherosclerosis of uremia. Lipoprotein oxidation is involved in the genesis of atherosclerosis. In chronic renal failure (CRF), oxidative stress is enhanced because of an imbalance between pro-oxidant and antioxidant systems. Oxidative modifications of low-density lipoproteins (LDLs) occur not only at the level of lipid moiety, but also of protein moiety. We have shown

  13. High-density lipoprotein subfractions--what the clinicians need to know.

    PubMed

    Pirillo, Angela; Norata, Giuseppe Danilo; Catapano, Alberico Luigi

    2013-01-01

    Although the inverse relationship between plasma levels of high-density lipoprotein (HDL) and cardiovascular disease has been largely demonstrated, many observations have suggested that the assessment of HDL functionality might be more informative than a simple measurement of HDL-cholesterol plasma levels. HDLs are a class of structurally and functionally heterogeneous particles; in atherosclerosis-related diseases, changes in HDL subfraction levels and functions are frequently observed. Circulating levels of large HDL particles are decreased in dyslipidaemic conditions, while levels of small dense HDL particles are increased in patients with coronary heart disease. Furthermore, specific genetic defects in proteins involved in HDL metabolism significantly impact the distribution of HDL subpopulations. Finally, many drugs used for dyslipidaemia induce changes in HDL subfractions strictly related to cardiovascular disease. Although several methods exist to evaluate HDL subclass levels, most of them are not easily applicable in clinical practice, due to the costs and high variability. However, the possibility to measure the levels of specific HDL subfractions in patients with atherosclerosis-related diseases might help to better define their cardiovascular risk. PMID:23428644

  14. Association between low density lipoprotein and rheumatoid arthritis genetic factors with low density lipoprotein levels in rheumatoid arthritis and non-rheumatoid arthritis controls

    E-print Network

    Liao, K. P.

    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 ...

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

    Microsoft Academic Search

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

    2011-01-01

    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

  16. 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

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

    2001-01-01

    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

  17. Association between the severity of obstructive sleep apnea and the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol

    Microsoft Academic Search

    Yoshiyuki Kawano; Akira Tamura; Junichi Kadota

    The positive association between the ratio of serum low-density lipoprotein cholesterol (LDL-C) to serum high-density lipoprotein cholesterol (HDL-C) and cardiovascular events has recently been receiving much attention. However, the association between the severity of obstructive sleep apnea (OSA) and this ratio has not yet been investigated. Accordingly, we sought to clarify this association and the effect of continuous positive airway

  18. Fitness, Heart Disease, and High-Density Lipoproteins: A Look at the Relationships.

    ERIC Educational Resources Information Center

    McCunney, Robert J.

    1987-01-01

    The role of fitness in preventing coronary heart disease is explored. Research on high-density lipoprotein, which has been found to be one of the most critical determinants of risk, is reviewed. The relationship between fitness, high-density lipoprotein, and coronary heart disease is assessed, and clinical implications are spelled out. (MT)

  19. EFFECTS OF PASSIVE SMOKE ON HIGH DENSITY LIPOPROTEIN CHOLESTEROL IN COLLEGE AGED INDIVIDUALS

    Microsoft Academic Search

    Julie Wick; Jenna Grotthus; Brett Gressick; Jerry Thao

    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

  20. Counteracting Effects of High Density Lipoprotein-Cholesterol Subfractions on Statin-Induced Growth Arrest

    Microsoft Academic Search

    Masahiro Fujino; Shin-ichiro Miura; Hiroyuki Tanigawa; Yoshino Matsuo; Keijiro Saku

    2005-01-01

    An important issue in atherosclerosis is the timing of intimal microvascular formation and its relation to the initiation of plaque formation. Monocytes and endothelial cells (ECs) are important cell components in these steps. Statins not only reduce atherogenic low density lipoprotein cholesterol, they also increase high density lipoprotein-cholesterol (HDL). Although a higher concentration of statin has an anti-proliferative effect, HDL

  1. The interaction between ruptured erythrocytes and low-density lipoproteins.

    PubMed

    Paganga, G; Rice-Evans, C; Rule, R; Leake, D

    1992-06-01

    Low-density lipoproteins (LDL) are oxidatively modified on interaction with haem proteins. The interaction of ruptured erythrocytes with LDL induces oxidative damage as detected by alterations in electrophoretic mobility and the peroxidation of the polyunsaturated fatty acyl chains. Difference spectroscopy reveals that the amplification of the oxidative process by the haem protein is related to the transition of the oxidation state of the haemoglobin in the erythrocyte lysate from the oxy [X-FeII-O2] to the ferryl [X-FeIV = O] form. The incorporation of the lipid-soluble antioxidant, butylated hydroxy toluene, at specific time points during the LDL-erythrocyte interaction prolongs the lag phase to oxidation and eliminates the oxy-to-ferryl conversion of the haemoglobin. The timescale of this haem conversion is related to the antioxidant status of the LDL. PMID:1607013

  2. High-density lipoprotein synthesis and metabolism (Review).

    PubMed

    Zhou, Lingyan; Li, Congcong; Gao, Ling; Wang, Aihong

    2015-09-01

    High density lipoproteins (HDL) are heterogeneous particles regarding their size and composition. They have vital functions in reverse cholesterol transport (RCT). RCT occurs when lipid-free apolipoprotein AI recruits cholesterol and phospholipid to form nascent HDL particles. Adenosine triphosphate?binding cassette transporters and scavenger receptor class B type I were found to be associated with the synthesis of HDL. Experimental studies have identified several potential anti?atherogenic effects of HDL, including promotion of macrophage cholesterol outflow as well as anti?inflammatory and anti?thrombotic effects. HDL can also transport microRNAs. This review mainly summarizes the present knowledge of HDL synthesis and metabolism. PMID:26082200

  3. Oxidized low density lipoprotein, stem cells, and atherosclerosis

    PubMed Central

    2012-01-01

    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. PMID:22747902

  4. Targeted Deletion of Hepatocyte ABCA1 Leads to Very Low Density Lipoprotein Triglyceride Overproduction and Low Density Lipoprotein Hypercatabolism*

    PubMed Central

    Chung, Soonkyu; Timmins, Jenelle M.; Duong, MyNgan; Degirolamo, Chiara; Rong, Shunxing; Sawyer, Janet K.; Singaraja, Roshni R.; Hayden, Michael R.; Maeda, Nobuyo; Rudel, Lawrence L.; Shelness, Gregory S.; Parks, John S.

    2010-01-01

    Loss of ABCA1 activity in Tangier disease (TD) is associated with abnormal apoB lipoprotein (Lp) metabolism in addition to the complete absence of high density lipoprotein (HDL). We used hepatocyte-specific ABCA1 knock-out (HSKO) mice to test the hypothesis that hepatic ABCA1 plays dual roles in regulating Lp metabolism and nascent HDL formation. HSKO mice recapitulated the TD lipid phenotype with postprandial hypertriglyceridemia, markedly decreased LDL, and near absence of HDL. Triglyceride (TG) secretion was 2-fold higher in HSKO compared with wild type mice, primarily due to secretion of larger TG-enriched VLDL secondary to reduced hepatic phosphatidylinositol 3-kinase signaling. HSKO mice also displayed delayed clearance of postprandial TG and reduced post-heparin plasma lipolytic activity. In addition, hepatic LDLr expression and plasma LDL catabolism were increased 2-fold in HSKO compared with wild type mice. Last, adenoviral repletion of hepatic ABCA1 in HSKO mice normalized plasma VLDL TG and hepatic phosphatidylinositol 3-kinase signaling, with a partial recovery of HDL cholesterol levels, providing evidence that hepatic ABCA1 is involved in the reciprocal regulation of apoB Lp production and HDL formation. These findings suggest that altered apoB Lp metabolism in TD subjects may result from hepatic VLDL TG overproduction and increased hepatic LDLr expression and highlight hepatic ABCA1 as an important regulatory factor for apoB-containing Lp metabolism. PMID:20178985

  5. Lipoprotein receptors in copper-deficient rats: high density lipoprotein binding to liver membranes

    SciTech Connect

    Hassel, C.A.; Lei, K.Y.; Marchello, J.A.

    1986-03-05

    In copper-deficient rats, the observed hyperlipoproteinemia was mainly due to the elevation in high density lipoproteins (HDL). This study was designed to determine whether an impairment in the binding of HDL to liver membrane is responsible for the hyperlipoproteinemia. Sixty male Sprague-Dawley rats were randomly divided into 2 treatments, namely copper (Cu) deficient and adequate (less than 1 and 8 mg Cu/kg of diet). After 8 weeks, plasma, heart and liver tissues were obtained. Reduction in liver Cu content and elevation in heart to body weight ratio and plasma cholesterol confirmed that rats fed the test diet were Cu-deficient. Plasma HDL isolated from both Cu-deficient and control rats were iodinated and bound to liver membranes prepared from rats of each treatment. Binding of /sup 125/I-HDL was competitively inhibited by unlabelled rat HDL from both treatments, but not by human LDL. Scatchard analysis of specific binding data showed that maximal /sup 125/I-HDL binding (per mg membrane protein) to membranes prepared from Cu-deficient rats was not lower than controls. Furthermore, the amount of /sup 125/I-HDL from deficient rats specifically bound to liver membranes prepared from either treatment was not less than the amount of /sup 125/I-HDL from control rats bound to the same membranes. The data suggest that the hyperlipoproteinemia in Cu-deficient rats may not have resulted from a decrease in the number of hepatic HDL binding sites.

  6. Proprotein convertases in high-density lipoprotein metabolism.

    PubMed

    Choi, Seungbum; Korstanje, Ron

    2013-01-01

    The proprotein convertase subtilisin/kexins (PCSKs) are a serine endopeptidase family. PCSK members cleave amino acid residues and modulate the activity of precursor proteins. Evidence from patients and animal models carrying genetic alterations in PCSK members show that PCSK members are involved in various metabolic processes. These studies further revealed the molecular mechanism by which genetic alteration of some PCSK members impairs normal molecular and physiological functions, which in turn lead to cardiovascular disease. High-density lipoprotein (HDL) is anti-atherogenic as it removes excessive amount of cholesterol from blood and peripheral tissues. Several PCSK members are involved in HDL metabolism. PCSK3, PCSK5, and PCSK6 process two triglyceride lipase family members, endothelial lipase and lipoprotein lipase, which are important for HDL remodeling. Recent studies in our lab found evidence that PCSK1 and PCSK9 are also involved in HDL metabolism. A mouse model carrying an amino acid substitution in PCSK1 showed an increase in serum apolipoprotein A1 (APOA1) level. Another mouse model lacking PCSK9 showed a decrease in APOE-containing HDL. In this review, we summarize the role of the five PCSK members in lipid, glucose, and bile acid (BA) metabolism, each of which can influence HDL metabolism. We propose an integrative model in which PCSK members regulate HDL metabolism through various molecular mechanisms and metabolic processes and genetic variation in some PCSK members may affect the efficiency of reverse cholesterol transport. PCSK members are considered as attractive therapeutic targets. A greater understanding of the molecular and physiological functions of PCSK members will improve therapeutic strategies and drug efficacy for cardiovascular disease where PCSK members play critical role, with fewer adverse effects. PMID:24252756

  7. Differential density lipoprotein profiling for the characterization of Lipoprotein(a) 

    E-print Network

    Espinosa Garcia, Irma Leticia

    2006-10-30

    Lipoprotein(a) (Lp(a)) has been described as an emerging risk factor for cardiovascular disease. The complexity of the Lp(a) molecule sets a challenge for the determination of the risk it represents for the cardiovascular ...

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

    Microsoft Academic Search

    Anders Nykjaer; Thomas E. Willnow

    2002-01-01

    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

  9. Non-High-Density Lipoprotein Cholesterol and Apolipoprotein B in the Prediction of Coronary Heart Disease in Men

    Microsoft Academic Search

    Tobias Pischon; Cynthia J. Girman; Frank M. Sacks; Nader Rifai; Meir J. Stampfer; Eric B. Rimm

    Background—Apolipoprotein B (apoB) plasma levels reflect the concentration of proatherogenic lipoproteins very low-density lipoprotein and low-density lipoprotein (LDL), whereas non-high-density lipoprotein cholesterol (non- HDL-C) levels reflect the concentration of cholesterol transported by these particles. Methods and Results—The aim of our study was to compare apoB, non-HDL-C, LDL cholesterol (LDL-C), and other lipid markers as predictors of coronary heart disease (CHD)

  10. Cholesteryl Ester Hydroperoxides Are Biologically Active Components of Minimally Oxidized Low Density Lipoprotein*S?

    PubMed Central

    Harkewicz, Richard; Hartvigsen, Karsten; Almazan, Felicidad; Dennis, Edward A.; Witztum, Joseph L.; Miller, Yury I.

    2008-01-01

    Oxidation of low density lipoprotein (LDL) occurs in vivo and significantly contributes to the development of atherosclerosis. An important mechanism of LDL oxidation in vivo is its modification with 12/15-lipoxygenase (LO). We have developed a model of minimally oxidized LDL (mmLDL) in which native LDL is modified by cells expressing 12/15LO. This mmLDL activates macrophages inducing membrane ruffling and cell spreading, activation of ERK1/2 and Akt signaling, and secretion of proinflammatory cytokines. In this study, we found that many of the biological activities of mmLDL were associated with cholesteryl ester (CE) hydroperoxides and were diminished by ebselen, a reducing agent. Liquid chromatography coupled with mass spectroscopy demonstrated the presence of many mono- and polyoxygenated CE species in mmLDL but not in native LDL. Nonpolar lipid extracts of mmLDL activated macrophages, although to a lesser degree than intact mmLDL. The macrophage responses were also induced by LDL directly modified with immobilized 12/15LO, and the nonpolar lipids extracted from 12/15LO-modified LDL contained a similar set of oxidized CE. Cholesteryl arachidonate modified with 12/15LO also activated macrophages and contained a similar collection of oxidized CE molecules. Remarkably, many of these oxidized CE were found in the extracts of atherosclerotic lesions isolated from hyperlipidemic apoE–/– mice. These results suggest that CE hydroperoxides constitute a class of biologically active components of mmLDL that may be relevant to proinflammatory activation of macrophages in atherosclerotic lesions. PMID:18263582

  11. Molecular motion and conformation of cholesteryl esters in reconstituted high density lipoprotein by deuterium magnetic resonance.

    PubMed

    Parmar, Y I; Gorrissen, H; Wassall, S R; Cushley, R J

    1983-02-10

    Reconstituted high density lipoprotein has been prepared by sonication and preparative ultracentrifugation of mixtures containing the apoprotein of high density lipoprotein, egg phosphatidylcholine, cholesteryl oleate, and acyl chain deuterated cholesteryl palmitate in aqueous buffer. The resulting structures have a size and chemical composition very similar to native high density lipoprotein. Deuterium NMR spectra and longitudinal relaxation times were obtained at approximately 25 degrees C. The variation of the 2H NMR line width with chain position is consistent with an average conformation such that the ester acyl chain is extended. In addition, 2H NMR line widths and longitudinal relaxation times indicate that the ester acyl chains possess significant mobility. PMID:6822546

  12. Plasma lipoprotein concentration as an indicator of fatness in broilers: Development and use of a simple assay for plasma very low density lipoproteins

    Microsoft Academic Search

    H. D. Griffin; C. C. Whitehead

    1982-01-01

    1. A turbidimetric assay for plasma very low density lipoproteins (VLDL) was developed, based on their selective precipitation with heparin and Mg.2. Measurements of plasma VLDL concentration using the turbidimetric method showed a correlation of 0–98 with plasma VLDL plus low density lipoprotein triglyceride concentration estimated chemically.3. Correlations between plasma VLDL concentration measured turbidimetrically and body fat content were similar

  13. Tiliroside and gnaphaliin inhibit human low density lipoprotein oxidation.

    PubMed

    Schinella, Guillermo R; Tournier, Horacio A; Máñez, Salvador; de Buschiazzo, Perla M; Del Carmen Recio, María; Ríos, José Luis

    2007-01-01

    Two flavonoids, gnaphaliin and tiliroside, isolated from Helichrysum italicum, were studied in vitro for their capacity to inhibit Cu(2+)-induced human low density lipoprotein (LDL) and diluted plasma oxidation. LDL oxidation was monitored by conjugated diene, thiobarbituric acid-reactive substances (TBARS) formation and electrophoretic mobility on agarose gel. Gnaphaliin and tiliroside increased the lag-phase for diene conjugate production in a dose-dependent manner. The reduction of TBARS production confirmed the antioxidant activity of gnaphaliin and tiliroside with 50% inhibitory concentration (IC(50)) values of 8.0+/-3.9 microM and 7.0+/-2.6 microM respectively. Furthermore, the flavonoids negated the Cu(2+)-induced increase in electrophoretic mobility of LDL. Antioxidant activity of gnaphaliin and tiliroside was significantly different when diluted plasma was oxidised by adding 1 mM CuSO(4). Although both flavonoids again reduced the TBARS production, tiliroside showed higher activity than gnaphaliin (IC(50)=10.6+/-2.5 microM vs. IC(50)>50 microM). In conclusion, tiliroside and gnaphaliin are antioxidants against in vitro Cu(2+)-induced LDL oxidation in the same order of magnitude compared to that of the reference drug, probucol. PMID:17084992

  14. Stability of discoidal high-density lipoprotein particles

    NASA Astrophysics Data System (ADS)

    Maleki, Mohsen; Fried, Eliot

    Motivated by experimental and numerical studies revealing that discoidal high-density lipoprotein (HDL) particles may adopt flat elliptical and nonplanar saddle-like configurations, it is hypothesized that these might represent stabilized configurations of initially unstable flat circular particles. A variational description is developed to explore the stability of a flat circular discoidal HDL particle. While the lipid bilayer is modeled as two-dimensional fluid film endowed with surface tension and bending elasticity, the apoA-I belt is modeled as one-dimensional inextensible twist-free chain endowed with bending elasticity. Stability is investigated using the second variation of the underlying energy functional. Various planar and nonplanar instability modes are predicted and corresponding nondimensional critical values of salient dimensionless parameters are obtained. The results predict that the first planar and nonplanar unstable modes occur due to in-plane elliptical and transverse saddle-like perturbations. Based on available data, detailed stability diagrams indicate the range of input parameters for which a flat circular discoidal HDL particle is linearly stable or unstable.

  15. Pluronic block copolymers inhibit low density lipoprotein self-association.

    PubMed

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

    2012-10-01

    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

  16. Ethanol enhances de novo synthesis of high density lipoprotein cholesterol

    SciTech Connect

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

    1984-05-01

    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.

  17. Targeting high-density lipoproteins: update on a promising therapy.

    PubMed

    Verdier, Céline; Martinez, Laurent O; Ferrières, Jean; Elbaz, Meyer; Genoux, Annelise; Perret, Bertrand

    2013-11-01

    Numerous epidemiological studies have demonstrated the atheroprotective roles of high density lipoproteins (HDL), so that HDL is established as an independent negative risk factor. The protective effect of HDL against atherosclerosis is mainly attributed to their capacity to bring peripheral excess cholesterol back to the liver for further elimination into the bile. In addition, HDL can exert other protective functions on the vascular wall, through their anti-inflammatory, antioxidant, antithrombotic and cytoprotective properties. HDL-targeted therapy is thus an innovative approach against cardiovascular risk and atherosclerosis. These pleiotropic atheroprotective properties of HDL have led experts to believe that "HDL-related therapies" represent the most promising next step in fighting against atherosclerosis. However, because of the heterogeneity of HDL functions, targeting HDL is not a simple task and HDL therapies that lower cardiovascular risk are NOT yet available. In this paper, an overview is presented about the therapeutic strategies currently under consideration to raise HDL levels and/or functions. Recently, clinical trials of drugs targeting HDL-C levels have disappointingly failed, suggesting that HDL functions through specific mechanisms should be targeted rather than increasing per se HDL levels. PMID:24074699

  18. Acrolein impairs the cholesterol transport functions of high density lipoproteins.

    PubMed

    Chadwick, Alexandra C; Holme, Rebecca L; Chen, Yiliang; Thomas, Michael J; Sorci-Thomas, Mary G; Silverstein, Roy L; Pritchard, Kirkwood A; Sahoo, Daisy

    2015-01-01

    High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway. PMID:25849485

  19. Acrolein Impairs the Cholesterol Transport Functions of High Density Lipoproteins

    PubMed Central

    Chadwick, Alexandra C.; Holme, Rebecca L.; Chen, Yiliang; Thomas, Michael J.; Sorci-Thomas, Mary G.; Silverstein, Roy L.; Pritchard, Kirkwood A.; Sahoo, Daisy

    2015-01-01

    High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway. PMID:25849485

  20. High-density lipoprotein, beta cells, and diabetes .

    PubMed

    von Eckardstein, Arnold; Widmann, Christian

    2014-08-01

    High-density lipoproteins (HDLs) exert a series of potentially beneficial effects on many cell types including anti-atherogenic actions on the endothelium and macrophage foam cells. HDLs may also exert anti-diabetogenic functions on the beta cells of the endocrine pancreas, notably by potently inhibiting stress-induced cell death and enhancing glucose-stimulated insulin secretion. HDLs have also been found to stimulate insulin-dependent and insulin-independent glucose uptake into skeletal muscle, adipose tissue, and liver. These experimental findings and the inverse association of HDL-cholesterol levels with the risk of diabetes development have generated the notion that appropriate HDL levels and functionality must be maintained in humans to diminish the risks of developing diabetes. In this article, we review our knowledge on the beneficial effects of HDLs in pancreatic beta cells and how these effects are mediated. We discuss the capacity of HDLs to modulate endoplasmic reticulum stress and how this affects beta-cell survival. We also point out the gaps in our understanding on the signalling properties of HDLs in beta cells. Hopefully, this review will foster the interest of scientists in working on beta cells and diabetes to better define the cellular pathways activated by HDLs in beta cells. Such knowledge will be of importance to design therapeutic tools to preserve the proper functioning of the insulin-secreting cells in our body. PMID:24903496

  1. Oxidized lipids in the diet are incorporated by the liver into very low density lipoprotein in rats

    Microsoft Academic Search

    Ilona Staprans; Joseph H. Rapp; Xian-Mang Pan; Kenneth R. Feingold

    Previous studies have shown that the quantity of oxidized lipids in the diet directly correlates with the level of oxidized chylomicrons in mesenteric lymph and the level of oxidized lipids in endogenous lipoproteins such as very low density lipoprotein (VLDL) and low density lipoprotein (LDL). The aim of the present study was to determine whether oxidized fatty acids in the

  2. Effect of a Moderate Fat Diet With and Without Avocados on Lipoprotein Particle Number, Size and Subclasses in Overweight and Obese Adults: A Randomized, Controlled Trial

    PubMed Central

    Wang, Li; Bordi, Peter L.; Fleming, Jennifer A.; Hill, Alison M.; Kris?Etherton, Penny M.

    2015-01-01

    Background Avocados are a nutrient?dense source of monounsaturated fatty acids (MUFA) that can be used to replace saturated fatty acids (SFA) in a diet to lower low density lipoprotein cholesterol (LDL?C). Well?controlled studies are lacking on the effect of avocado consumption on cardiovascular disease (CVD) risk factors. Methods and Results A randomized, crossover, controlled feeding trial was conducted with 45 overweight or obese participants with baseline LDL?C in the 25th to 90th percentile. Three cholesterol?lowering diets (6% to 7% SFA) were fed (5 weeks each): a lower?fat diet (LF: 24% fat); 2 moderate?fat diets (34% fat) provided similar foods and were matched for macronutrients and fatty acids: the avocado diet (AV) included one fresh Hass avocado (136 g) per day, and the moderate?fat diet (MF) mainly used high oleic acid oils to match the fatty acid content of one avocado. Compared with baseline, the reduction in LDL?C and non?high?density lipoprotein (HDL) cholesterol on the AV diet (?13.5 mg/dL, ?14.6 mg/dL) was greater (P<0.05) than the MF (?8.3 mg/dL, ?8.7 mg/dL) and LF (?7.4 mg/dL, ?4.8 mg/dL) diets. Furthermore, only the AV diet significantly decreased LDL particle number (LDL?P, ?80.1 nmol/L, P=0.0001), small dense LDL cholesterol (LDL3+4, ?4.1 mg/dL, P=0.04), and the ratio of LDL/HDL (?6.6%, P<0.0001) from baseline. Conclusions Inclusion of one avocado per day as part of a moderate?fat, cholesterol?lowering diet has additional LDL?C, LDL?P, and non?HDL?C lowering effects, especially for small, dense LDL. Our results demonstrate that avocados have beneficial effects on cardio?metabolic risk factors that extend beyond their heart?healthy fatty acid profile. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01235832. PMID:25567051

  3. Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery.

    PubMed Central

    Simon, B C; Cunningham, L D; Cohen, R A

    1990-01-01

    The direct vasoactive effects of native and oxidatively modified low density lipoproteins as well as their effects on endothelium-dependent relaxations to 5-hydroxytryptamine were studied in isolated rings of pig right coronary artery. Slowly developing contractions were caused by native low density lipoproteins (100 micrograms protein/ml). The contractions were more pronounced in the absence than in the presence of the trace metal chelator, EDTA, and coincided with the formation of lipid peroxides during the response. The lipophilic antioxidant, butylated hydroxytoluene, prevented the oxidation of, and contraction to, native low density lipoproteins. Low density lipoproteins oxidized by exposure to copper contracted coronary arteries more rapidly with a threshold of only 1 micrograms protein/ml, but with a similar maximal contraction at 100 micrograms protein/ml. Superoxide dismutase inhibited the contraction to native low density lipoproteins, but not to oxidized low density lipoproteins. Catalase blocked contractions to both native and oxidized low density lipoproteins. Contractions to oxidized low density lipoproteins were unaffected by indomethacin, but were abolished by removal of the endothelium or by inhibitors of endothelium-derived relaxing factor. Oxidized low density lipoproteins but not native low density lipoproteins inhibited endothelium-dependent relaxations to 5-hydroxytryptamine. Thus, oxidized low density lipoproteins caused endothelium-dependent coronary artery contractions which are mediated by a hydroperoxide. Contractions to native low density lipoproteins are due to their oxidation in the organ chamber by the superoxide anion radical. Oxidized, but not native, low density lipoproteins impair normal endothelial cell vasodilator function in vitro. Oxidized low density lipoproteins, important in the pathogenesis of atherosclerosis, may directly contribute to the increased risk of vasospasm seen in hypercholesterolemia and atherosclerosis. PMID:2365828

  4. Compositional and functional changes of low-density lipoprotein during hemodialysis in patients with ESRD1

    Microsoft Academic Search

    Andreas Ambrosch; Ute Domroese; Sabine Westphal; Jutta Dierkes; Wolfgang Augustin; Klaus H. Neumann; Claus Luley

    1998-01-01

    Compositional and functional changes of low-density lipoprotein during hemodialysis in patients with ESRD.BackgroundThis study focused on the effects of hemodialysis on the atherogenic properties of low density lipoprotein (LDL) in patients with end-stage renal disease (ESRD). The impact of cholesterol ester transfer protein (CETP) activity and lipolysis on LDL composition, particularly the changes during hemodialysis, was investigated.MethodsBlood was drawn from

  5. Non-High-Density Lipoprotein Cholesterol Level as a Predictor of Cardiovascular Disease Mortality

    Microsoft Academic Search

    Yadong Cui; Roger S. Blumenthal; Jodi A. Flaws; Maura K. Whiteman; Patricia Langenberg; Paul S. Bachorik; Trudy L. Bush

    Background: Non-high-density lipoprotein choles- terol (non-HDL-C) contains all known and potential ath- erogenic lipid particles. Therefore, non-HDL-C level may be as good a potential predictor of risk for cardiovascu- lar disease (CVD) as low-density lipoprotein choles- terol (LDL-C). Objectives: Todeterminewhethernon-HDL-Clevelcould be useful in predicting CVD mortality and to compare the predictive value of non-HDL-C and LDL-C levels. Methods: Data are

  6. Should we change our lipid management strategies to focus on non-high-density lipoprotein cholesterol?

    Microsoft Academic Search

    J. S. Rana; S. M. Boekholdt

    2010-01-01

    Purpose of review Despite aggressive low-density lipoprotein cholesterol lowering, patients continue to be at significant risk of cardiovascular events. Assessment of non-high-density lipoprotein cholesterol (non-HDL-C) provides a measure of cholesterol contained in all atherogenic particles. In the third Adult Treatment Panel guidelines, non-HDL-C was introduced as a secondary target of therapy. Recent findings A combined post-hoc analysis of data from

  7. Interaction of very-low-density, intermediate-density, and low-density lipoproteins with human arterial wall proteoglycans.

    PubMed

    Anber, V; Millar, J S; McConnell, M; Shepherd, J; Packard, C J

    1997-11-01

    The specific interaction of lipoproteins with arterial wall constituents, particularly proteoglycans (APG), is believed to play an important role in the development of atherosclerosis. The objective of this study was to examine the interaction of apolipoprotein B (apoB) containing lipoprotein subfractions (VLDL1, Sf 60 to 400; VLDL2, Sf 20 to 60; IDL1, Sf 16 to 20; IDL2, Sf 12 to 16; LDLA, Sf 8 to 12; and LDLB, Sf 0 to 8) prepared by cumulative density gradient centrifugation with chondroitin sulfate-rich APG. Eighteen subjects were studied, and a similar pattern of interaction between the lipoprotein species and APG was found in all. The order of reactivity (as measured by increased turbidity due to insoluble complex formation) was IDL Sf 12 to 16 > or = LDL Sf 8 to 12 > LDL Sf 0 to 8 > IDL Sf 16 to 20 > VLDL Sf 20 to 60 > VLDL Sf 60 to 400. When the subjects were divided on the basis of their LDL subfraction profile, the extent of insoluble complex formation was highest in the group in which small, dense LDLIII was predominant; intermediate in the group whose LDL was mainly LDLII; and lowest in the group with a high proportion of LDLI (the mean reactivity, AU at 600 nm. of APG with IDL Sf 12 to 16 and LDL Sf 8 to 12 was 0.66; 0.62 and 0.46, 0.43 and 0.20, and 0.21 for the three groups, respectively). Fibrate lipid-lowering treatment decreased the percentage of LDLIII and increased the percentage of LDLI within total LDL and reduced the reactivity of all apoB-containing lipoprotein fractions toward APG. Sialic acid content varied in different lipoprotein subfractions, being the highest in VLDL and lowest in LDL. However, across lipoprotein species, it did not significantly correlate with APG-binding reactivity, suggesting that other factors are important in determining the interaction of lipoproteins with APG. Modification of LDL arginine and lysine residues abolished the ability of the lipoprotein to interact with APG, a finding that supports the hypothesis that the interaction is dependent on key positively charged amino acids on apoB. These findings demonstrate that (1) the overall reactivity of apoB-containing lipoproteins is greatest in individuals with small, dense LDL and (2) within an individual, IDL of Sf 12 to 16 is the most reactive species, and this may in part explain the positive correlation between IDL and risk of coronary heart disease. PMID:9409221

  8. Biomimetic High-Density Lipoproteins from a Gold Nanoparticle Template

    NASA Astrophysics Data System (ADS)

    Luthi, Andrea Jane

    For hundreds of years the field of chemistry has looked to nature for inspiration and insight to develop novel solutions for the treatment of human diseases. The ability of chemists to identify, mimic, and modifiy small molecules found in nature has led to the discovery and development of many important therapeutics. Chemistry on the nanoscale has made it possible to mimic natural, macromolecular structures that may also be useful for understanding and treating diseases. One example of such a structure is high-density lipoprotein (HDL). The goal of this work is to use a gold nanoparticle (Au NP) as a template to synthesize functional mimics of HDL and characterize their structure and function. Chapter 1 details the structure and function of natural HDL and how chemistry on the nanoscale provides new strategies for mimicking HDL. This Chapter also describes the first examples of using nanoparticles to mimic HDL. Chapter 2 reports the synthesis and characterization of biomimetic HDL using different sizes of Au NPs and different surface chemistries and how these variables can be used to tailor the properties of biomimetic HDL. From these studies the optimal strategy for synthesizing biomimetic HDL was determined. In Chapter 3, the optimization of the synthesis of biomimetic HDL is discussed as well as a full characterization of its structure. In addition, the work in this chapter shows that biomimetic HDL can be synthesized on a large scale without alterations to its structure or function. Chapter 4 focuses on understanding the pathways by which biomimetic HDL accepts cholesterol from macrophage cells. The results of these studies demonstrate that biomimetic HDL is able to accept cholesterol by both active and passive pathways of cholesterol efflux. In Chapter 5 the preliminary results of in vivo studies to characterize the pharmacokinetics and pharmacodynamics of biomimetic HDL are presented. These studies suggest that biomimetic HDL traffics through tissues prone to atherosclerosis and that it has the potential to remove cholesterol from macrophages in the body.

  9. FT-IR spectroscopy of lipoproteins—A comparative study

    NASA Astrophysics Data System (ADS)

    Krilov, Dubravka; Balarin, Maja; Kosovi?, Marin; Gamulin, Ozren; Brnjas-Kraljevi?, Jasminka

    2009-08-01

    FT-IR spectra, in the frequency region 4000-600 cm -1, of four major lipoprotein classes: very low density lipoprotein (VLDL), low density lipoprotein (LDL) and two subclasses of high density lipoproteins (HDL 2 and HDL 3) were analyzed to obtain their detailed spectral characterization. Information about the protein domain of particle was obtained from the analysis of amide I band. The procedure of decomposition and curve fitting of this band confirms the data already known about the secondary structure of two different apolipoproteins: apo A-I in HDL 2 and HDL 3 and apo B-100 in LDL and VLDL. For information about the lipid composition and packing of the particular lipoprotein the well expressed lipid bands in the spectra were analyzed. Characterization of spectral details in the FT-IR spectrum of natural lipoprotein is necessary to study the influence of external compounds on its structure.

  10. Delay of copper-catalyzed oxidation of low density lipoprotein by in vitro enrichment with choline or ethanolamine plasmalogens

    Microsoft Academic Search

    Günther Jürgens; Astrid Fell; Gerhard Ledinski; Qi Chen; Fritz Paltauf

    1995-01-01

    Low density lipoprotein (LDL) isolated from human serum of different donors was enriched with plasmalogens and their diacyl analogs in order to investigate a possible effect of these phospholipids on the rate of lipid peroxidation in this lipoprotein. LDL was incubated with either vesicles of choline plasmalogen or phosphatidylcholine in presence of lipoprotein- deficient serum, or with liposomes of ethanolamine

  11. Novel fluorescent probe for low density lipoprotein, based on the enhancement of Europium emission band

    NASA Astrophysics Data System (ADS)

    Courrol, L. C.; Monteiro, A. M.; Silva, F. R. O.; Gomes, L.; Vieira, N. D., Jr.; Gidlund, M. A.; Figueiredo Neto, A. M.

    2007-05-01

    We report here the observation of the enhancement of Europium-tetracycline complex emission in Low Density Lipoprotein (LDL) solutions. Europium emission band of tetracycline solution containing Europium (III) chloride hexahydrate was tested to obtain effective enhancement in the presence of native LDL and oxidized LDL. Europium emission lifetime in the presence of lipoproteins was measured, resulting in a simple method to measure the lipoproteins quantity in an aqueous solution at physiological pH. This method shows that the complex can be used as a sensor to determine the different states of native and oxidized LDL in biological fluids.

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

    PubMed

    Pieper-Fürst, Ursula; Lammert, Frank

    2013-07-01

    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

  13. Low density lipoprotein delays clearance of triglyceride-rich lipoprotein by human subcutaneous adipose tissue.

    PubMed

    Bissonnette, Simon; Salem, Huda; Wassef, Hanny; Saint-Pierre, Nathalie; Tardif, Annie; Baass, Alexis; Dufour, Robert; Faraj, May

    2013-05-01

    Delayed clearance of triglyceride-rich lipoprotein (TRL) by white adipose tissue (WAT) promotes hypertriglyceridemia and elevated apoB-lipoproteins, which are primarily in the form of LDL. This study examines whether LDL promotes delayed clearance of TRL by WAT. Following the ingestion of a (13)C-triolein-labeled high-fat meal, obese women with high plasma apoB (> median 0.93 g/l, N = 11, > 98% as IDL/LDL) had delayed clearance of postprandial (13)C-triglyceride and (13)C-NEFA over 6 h compared with controls. AUC6 h of plasma (13)C-triglyceride and (13)C-NEFA correlated with plasma apoB but not with LDL diameter or adipocyte area. There was no group difference in (13)C-triolein oxidation rate, which suggests lower (13)C-NEFA storage in peripheral tissue in women with high apoB. Ex vivo/in vitro plasma apoB correlated negatively with WAT (3)H-lipid following a 4 h incubation of women's WAT with synthetic (3)H-triolein-TRL. LDL-differentiated 3T3-L1 adipocytes had lower (3)H-TRL hydrolysis and (3)H-NEFA storage. Treatment of women's WAT with their own LDL decreased (3)H-TRL hydrolysis and (3)H-NEFA uptake. Finally, LDL, although not an LPL substrate, reduced LPL-mediated (3)H-TRL hydrolysis as did VLDL and HDL. Exposure to LDL decreases TRL clearance by human WAT ex vivo. This may promote production of apoB-lipoproteins and hypertriglyceridemia through a positive-feedback mechanism in vivo. PMID:23417739

  14. Low density lipoprotein delays clearance of triglyceride-rich lipoprotein by human subcutaneous adipose tissue

    PubMed Central

    Bissonnette, Simon; Salem, Huda; Wassef, Hanny; Saint-Pierre, Nathalie; Tardif, Annie; Baass, Alexis; Dufour, Robert; Faraj, May

    2013-01-01

    Delayed clearance of triglyceride-rich lipoprotein (TRL) by white adipose tissue (WAT) promotes hypertriglyceridemia and elevated apoB-lipoproteins, which are primarily in the form of LDL. This study examines whether LDL promotes delayed clearance of TRL by WAT. Following the ingestion of a 13C-triolein-labeled high-fat meal, obese women with high plasma apoB (> median 0.93 g/l, N = 11, > 98% as IDL/LDL) had delayed clearance of postprandial 13C-triglyceride and 13C-NEFA over 6 h compared with controls. AUC6 h of plasma 13C-triglyceride and 13C-NEFA correlated with plasma apoB but not with LDL diameter or adipocyte area. There was no group difference in 13C-triolein oxidation rate, which suggests lower 13C-NEFA storage in peripheral tissue in women with high apoB. Ex vivo/in vitro plasma apoB correlated negatively with WAT 3H-lipid following a 4 h incubation of women's WAT with synthetic 3H-triolein-TRL. LDL-differentiated 3T3-L1 adipocytes had lower 3H-TRL hydrolysis and 3H-NEFA storage. Treatment of women's WAT with their own LDL decreased 3H-TRL hydrolysis and 3H-NEFA uptake. Finally, LDL, although not an LPL substrate, reduced LPL-mediated 3H-TRL hydrolysis as did VLDL and HDL. Exposure to LDL decreases TRL clearance by human WAT ex vivo. This may promote production of apoB-lipoproteins and hypertriglyceridemia through a positive-feedback mechanism in vivo. PMID:23417739

  15. Development of Capture Assays for Different Modifications of Human Low-Density Lipoprotein

    Microsoft Academic Search

    Gabriel Virella; M. Brooks Derrick; Virginia Pate; Charlyne Chassereau; Suzanne R. Thorpe; Maria F. Lopes-Virella

    2005-01-01

    Antibodies to malondialdehyde (MDA)-modified low-density lipoprotein (LDL), copper-oxidized LDL (oxLDL), N(carboxymethyl) lysine (CML)-modified LDL, and advanced glycosylation end product (AGE)-modified LDL were obtained by immunization of rabbits with in vitro-modified human LDL preparations. After absorption of apolipoprotein B (ApoB) antibodies, we obtained antibodies specific for each modified lipoprotein with unique patterns of reactivity. MDA-LDL antibodies reacted strongly with MDA-LDL and

  16. Effect of glycation of high density lipoproteins on their physicochemical properties and on paraoxonase activity

    Microsoft Academic Search

    G. Ferretti; T. Bacchetti; C. Marchionni; L. Caldarelli; G. Curatola

    2001-01-01

    We investigated the effect of incubation of high density lipoprotein (HDL) under hyperglycaemic conditions on lipid composition,\\u000a physicochemical properties and activity of paraoxonase (PON), a calcium-dependent enzyme associated with HDL that contributes\\u000a to the antiatherogenicity of this lipoprotein. HDL incubated for three days with various glucose concentrations (0–100 mM)\\u000a had significant increases in thiobarbituric acid-reactive substances (TBARS) and conjugated dienes

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

    Microsoft Academic Search

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

    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

  18. Alzheimer's amyloid ? interaction with normal human plasma high density lipoprotein: association with apolipoprotein and lipids

    Microsoft Academic Search

    Alexei R Koudinov; Temirbolat T Berezov; Asok Kumar; Natalia V Koudinova

    1998-01-01

    We report studies of the interaction of Alzheimer's amyloid beta protein (A?) with normal human plasma high density lipoprotein (HDL), aiming to clarify to which lipoprotein (LP) structural constituent (apolipoprotein or lipid) soluble A? is primarily bound. Purified HDLs were incubated with biotinylated A?1–40 followed by LP repurification by size exclusion (SE) HPLC. SDS–PAGE, immunoblot and N-terminal sequence analysis of

  19. Metabolic behavior in rats of a nonprotein microemulsion resembling low-density lipoprotein

    Microsoft Academic Search

    Raul C. Maranhão; Thais B. Cesara; Suzana R. Pedroso-Mariani; Mario H. Hirata; Carlos H. Mesquita

    1993-01-01

    A protein-free microemulsion (LDE) with a lipid composition resembling that of low-density lipoprotein (LDL) was used in metabolic\\u000a studies in rats to compare LDE with the native lipoprotein. LDE labeled with radioactive lipids was injected into the bloodstream\\u000a of male Wistar rats, and plasma kinetics of the labeled lipids were followed on plasma samples collected at regular intervals\\u000a for 12

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

    SciTech Connect

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

    1987-03-02

    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 ..mu..M. Incubation of rat plasma low-density lipoproteins (LDL) with 200 ..mu..M 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.

  1. Impact of hydrogenated fat on high density lipoprotein subfractions and metabolism

    Microsoft Academic Search

    A. H. Lichtenstein; M. Jauhiainen; S. McGladdery; L. M. Ausman; S. M. Jalbert; M. Vilella-Bach; C. Ehnholm; J. Frohlich; E. J. Schaefer

    Relative to saturated fatty acids, trans -fatty acids\\/ hydrogenated fat-enriched diets have been reported to in- crease low density lipoprotein (LDL) cholesterol levels and either decrease or have no effect on high density lipopro- tein (HDL) cholesterol levels. To better understand the ef- fect of trans -fatty acids\\/hydrogenated fat on HDL choles- terol levels and metabolism, 36 subjects (female, n

  2. Serum amyloid A-containing human high density lipoprotein 3. Density, size, and apolipoprotein composition.

    PubMed

    Coetzee, G A; Strachan, A F; van der Westhuyzen, D R; Hoppe, H C; Jeenah, M S; de Beer, F C

    1986-07-25

    Serum amyloid A protein (apo-SAA), an acute phase reactant, is an apolipoprotein of high density lipoproteins (HDL), in particular the denser subpopulation HDL3. The structure of HDL3 isolated from humans affected by a variety of severe disease states was investigated with respect to density, size, and apolipoprotein composition, using density gradient ultracentrifugation, gradient gel electrophoresis, gel filtration, and solid phase immunoadsorption. Apo-SAA was present in HDL particles in increasing amounts as particle density increased. Apo-SAA-containing HDL3 had bigger radii than normal HDL3 of comparable density. Purified apo-SAA associated readily with normal HDL3 in vitro, giving rise to particles containing up to 80% of their apoproteins as apo-SAA. The addition of apo-SAA resulted in a displacement of apo-A-I and an increase in particle size. Acute phase HDL3 represented a mixture of particles, polydisperse with respect to apolipoprotein content; for example, some particles were isolated that contained apo-A-I, apo-A-II, and apo-SAA, whereas others contained apo-A-I and apo-SAA but no apo-A-II. We conclude that apo-SAA probably associates in the circulation of acute phase patients with existing HDL particles, causing the remodeling of the HDL shell to yield particles of bigger size and higher density that are relatively depleted of apo-A-I. PMID:3525531

  3. Comparison of high density lipoprotein and serum cholesterol levels in a European and an African community.

    PubMed

    Ononogbu, I C

    1979-09-01

    Serum and high density lipoprotein cholesterol concentrations have been measured in 210 men and women in a London community and in a Nsukka community. Mean serum cholesterol concentrations were higher in London than in Nsukka. High density lipoprotein cholesterol was, however, higher in Nsukka than in London. Whereas the difference in serum cholesterol reached a statistical level when all the age groups were considered together, there was no statistical difference when the two populations were considered in terms of the young (20-39 year age group) and the middle aged (40-59 year age group). Difference in high density lipoprotein cholestrol, however, reached a statistical level in these two age groups. PMID:227428

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

    Microsoft Academic Search

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

    1994-01-01

    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).

  5. Strategies for Modifying High-Density Lipoprotein Cholesterol: A Role for Nicotinic Acid

    Microsoft Academic Search

    Michael Schachter

    2005-01-01

    Summary  Statin-mediated lowering of low-density lipoprotein cholesterol (LDL-C) is regarded as the foundation of lipid-modifying therapy.\\u000a However, the residual cardiovascular risk for statin-treated patients remains high, indicating the need for therapeutic intervention\\u000a against other lipid targets as well as non-lipid risk factors. Low levels of high-density lipoprotein cholesterol (HDL-C)\\u000a are established as a strong independent risk factor for cardiovascular disease. Intervention

  6. High-density lipoprotein subfractions in normolipidemic individuals without clinical atherosclerosis lipoprotein subfractions in an adult population.

    PubMed

    Sodré, Fabio L; Castanho, Vera S; Castilho, Lucia N; de Barros-Mazon, Silvia; de Faria, Eliana C

    2006-01-01

    This study evaluated the serum concentrations of lipids, lipoproteins, apolipoproteins, and high-density lipoprotein (HDL) subfractions in Brazilian adults. We analyzed the distribution of lipids in HDL2 and HDL3 in a normolipidemic population without evidence of established cardiovascular disease (CVD). A total of 93 males and 92 females, healthy and normolipidemic, volunteered to be submitted to a clinical examination, a blood collection, and to answer a questionnaire aimed at determining signs and symptoms of atherosclerotic disease. Their fasting plasma lipid, lipoproteins, apolipoproteins, and the cholesterol and triglyceride concentrations in HDL2 and HDL3, isolated by microultracentrifugation, were determined by enzymatic-colorimetric methods. The interpercentile intervals (2.5-97.5) for the population were established as being 5-18 mg/dL in men and 4-28 mg/dL in women for HDL2 cholesterol (HDL2chol) and 1-57 mg/dL in men and 2-61 mg/dL in women for HDL3 cholesterol (HDL3chol). HDL2 triglyceride levels (HDL2Tg) in men were 1-26 mg/dL and in women 2-28 mg/dL; moreover, the HDL3 triglyceride (HDL3Tg) intervals were established as 4-46 mg/dL for both sexes. The determination of reference ranges for lipids in HDL subfractions in populations without clinical atherosclerosis, is an useful tool for metabolic, diagnostic, and therapeutic approaches. We determined the intervals for HDL2chol, HDL3chol, HDL2Tg, and HDL3Tg. There were variations with sex and/or age for HDL2chol, HDL3chol, and HDL2Tg in the studied population. PMID:16721834

  7. The effect of tocopherol on high-density lipoprotein cholesterol. A clinical observation.

    PubMed

    Hermann, W J; Ward, K; Faucett, J

    1979-11-01

    A significant redistribution of cholesterol in lipoproteins following ingestion of large doses of D,L-alpha tocopherol (vitamin E) is documented. In persons with decreased high-density lipoprotein (HDL) cholesterol a complex response occurs, which includes cholesterol redistribution in favor of the HDL fraction, with decreases in very-low-density lipoprotein (VLDL) levels and total triglycerides. The response was studied in five persons with average cholestrol distributions and five persons with cholesterol distributions associated with high risk of coronary heart disease. The mean elevation of the HDL cholesterol concentration in the former group was 168% of the initial value, while the latter group experienced post-therapy levels 375% of initial levels. PMID:228547

  8. Investigations on the transport and metabolism of high density lipoprotein cholesteryl esters in African green monkeys

    SciTech Connect

    Sorci-Thomas, M.G.

    1984-01-01

    The metabolic fate of circulating high density lipoprotein cholesteryl esters was studied in African green monkeys to determine the significance of the lipid transfer reaction on the catabolism of lipoprotein cholesteryl esters. A method of doubly labeling both moieties of lipoprotein cholesteryl esters with (/sup 3/He)cholesteryl oleate and cholesteryl (/sup 14/C)oleate was developed for the purpose of studying plasma cholesteryl ester metabolism in vivo. In these studies the total plasma (/sup 3/He)cholesterol turnover resulted in production rates, which ranged from 10-17 mg/kg day, similar to previously reported values in African green monkeys and in normal lipoproteinemic humans. In contrast to the production rates calculated from the decay of plasma /sup 3/He-radioactivity, the production rates calculated from lipoproteins labeled with cholesteryl (/sup 14/C)oleate were approximately 2-3 times greater. In addition to these studies, a plasma cholesteryl ester transacylation activity was demonstrated in vitro when HDL containing doubly labeled cholesteryl esters were incubated with fresh plasma. These results demonstrated that high density lipoprotein cholesteryl esters undergo transacylation in vitro, resulting in release and reesterification of free (/sup 3/H)cholesterol.

  9. The Relationship between Thyrotropin and Low Density Lipoprotein Cholesterol Is Modified by Insulin Sensitivity in Healthy Euthyroid Subjects

    Microsoft Academic Search

    STEPHAN J. L. BAKKER; JAN C. TER MAATEN; CORRIE POPP-SNIJDERS; JORIS P. J. SLAETS; ROBERT J. HEINE; RIJK O. B. GANS

    High levels of TSH are associated with an increased cardiovascular risk. Many cardiovascular risk factors cluster within the insulin re- sistance syndrome. It is not known whether levels of TSH cluster as well. We conducted this research to test the hypothesis that TSH, insulin sensitivity, and levels of low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) are

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

    PubMed

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

    2013-03-01

    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

  11. [The alternative view on diagnostic of hyperlipoproteinemia, cholesterol lipoproteins of low density and effect of statins: a lecture].

    PubMed

    Tupoleva, T A; Tikhomirov, D S; Grumbkova, L O; Ignatova, E N; Romanova, T Iu; Filatov, F P; Garanzha, T A

    2015-01-01

    The effect of statins occur in several stages: 1) inhibition in hepatocytes of synthesis of functionally specific pool of spirit cholesterol, polar mono-layer of lipoproteins of very low density; 2) activation of hydrolysis of triglycerides in lipoproteins of very low density, formation of apoE/B-100-ligand and absorption of lipoproteins of very low density by insulin-depended cells; 3) decreasing of content of and spirit cholesterol-lipoproteins of very low density in blood plasma; 4) activation of hydrolysis of triglycerides in lipoproteins of low density, formation of apoB-100-ligand and absorption of lipoproteins of low density by insulin-independent cells; 5) decreasing of level of and increasing of content of lipoproteins of high density. During first weeks of effect of statins occurs decreasing of concentration of triglycerides and unesterified spirit cholesterol-lipoproteins of very low density in blood plasma. Then, slower and more durational decreasing of level of spirit cholesterol-lipoproteins of low density occurs. The value of spirit cholesterol-lipoproteins of low density is primarily determined by content of palmitic saturated fatty acid in food, its endogenous synthesis from glucose and concentration of palmitic triglycerides and lipoproteins of very low density of the same name in blood plasma. The effect of preparations is biologically valid and corresponds to alternative hypolipidemic preparations. All these preparations have an effect following a common algorithm: they activate, using different mechanisms, receptor absorption of lipoproteins of very low density or lipoproteins of low density by cells. The level of spirit cholesterol-lipoproteins of low density in full measure depends on content of triglycerides in blood. The concentration of spirit cholesterol in blood plasma has a reliable diagnostic significance only under physiological content of triglycerides. The main criterion of diagnostic and control of hypolipidemic therapy biologically is content of triglycerides. The comprehension of differences in effect of hypolipidemic preparations within framework of common algorithm permits rationally combine them under treatment of both primary inheritable phenotypes of glucolipoproteins and secondary symptomatic types of glucolipoproteins under obligatory observation of strict dietary treatment. PMID:25874302

  12. Fasting during Ramadan induces a marked increase in high-density lipoprotein cholesterol and decrease in low-density lipoprotein cholesterol.

    PubMed

    Adlouni, A; Ghalim, N; Benslimane, A; Lecerf, J M; Saile, R

    1997-01-01

    We demonstrated for the first time in a Moroccan population that fasting during Ramadan, the ninth lunar month of the Muslims' year, affected lipid and lipoprotein metabolism in a group of 32 healthy adult male volunteers. This investigation was conducted to study the changes in serum total cholesterol, triglycerides, cholesterol in high-density lipoprotein (HDL) and low-density lipoprotein (LDL), glucose, and body weight during Ramadan. The results showed a significant decrease (7.9%, p < 0.001) in serum total cholesterol concentration during Ramadan as compared with the prefasting period. Also, we obtained a significant decrease of serum triglyceride concentration (30%, p < 0.001) during Ramadan fasting as compared to the period before Ramadan. The reduction of both serum triglycerides and total cholesterol was maintained 1 month after Ramadan. By the end of Ramadan, serum HDL cholesterol had markedly increased (14.3%, p < 0.001) and remained elevated 1 month after Ramadan in contrast to LDL cholesterol which showed a significant decrease (11.7%, p < 0.0001) also maintained 1 month after Ramadan. Mean body weight declined by 2.6% (p < 0.01) on day 29 of Ramadan, whereas during Ramadan, the diet pattern used by our subjects showed an increase of total energy intake due to carbohydrates (+ 1.4% of total energy), proteins (+ 0.4% of total energy) but not fat (-0.7% of total energy) compared to a usual diet used throughout the rest of the year. Moreover, the fat diet is high in monounsaturated (p < 0.05) and polyunsaturated fatty acid in contrast to saturated fatty acid which significantly (p < 0.05) decreased during Ramadan. These findings suggest that feeding behavior that occurs during Ramadan beneficially affects plasma lipids and lipoproteins. PMID:9363296

  13. Overexpression of apolipoprotein E in transgenic mice: marked reduction in plasma lipoproteins except high density lipoprotein and resistance against diet-induced hypercholesterolemia.

    PubMed Central

    Shimano, H; Yamada, N; Katsuki, M; Shimada, M; Gotoda, T; Harada, K; Murase, T; Fukazawa, C; Takaku, F; Yazaki, Y

    1992-01-01

    Apolipoprotein E (apoE) has a high affinity to cell-surface low density lipoprotein (LDL) receptor. To determine the role of apoE in plasma lipoprotein metabolism, transgenic mouse lines with integrated rat apoE gene under the control of the metallothionein promoter were established. We found that a high expressor line produced rat apoE mainly in the liver, and the gene product was almost entirely associated with plasma lipoproteins. The plasma level of rat apoE in homozygotes for the transgene was 17.4 mg/dl after zinc induction (vs. 4.56 mg/dl of mouse apoE in controls). In this group, plasma cholesterol and triglyceride levels were 43% and 68% reduced as compared with controls, respectively. Heterozygotes showed decreases in both lipids to a lesser extent. Gel filtration chromatography showed that lipid reduction was mainly due to decreased very low density lipoproteins (VLDL) and LDL. Especially in zinc-treated homozygotes, VLDL had almost disappeared, and a remarkable decrease in LDL and a slight decrease in high density lipoprotein were also observed. Consistently, the plasma level of apoB, a structural protein of VLDL and LDL, was 78% lower than that of controls, indicating a marked reduction in lipoproteins containing apoB. Furthermore, the transgenic mice, in contrast to controls, did not develop hypercholesterolemia when fed a high cholesterol diet. These results demonstrated that overexpression of apoE reduces plasma cholesterol and triglyceride levels and prevents diet-induced hypercholesterolemia. From dramatic and dose-related decreases in plasma lipoproteins in transgenic mice, we conclude that apoE plays a key role in plasma lipoprotein metabolism. Images PMID:1542669

  14. High-density lipoproteins: an emerging target in the prevention of cardiovascular disease

    Microsoft Academic Search

    Belinda A Cutri; Neil J Hime; Stephen J Nicholls

    2006-01-01

    High-density lipoproteins (HDLs) have been well established to protect against the development of atherosclerotic cardiovascular disease. It has become apparent that in addition to the promotion of reverse cholesterol transport, HDLs possess a number of additional functional properties that may contribute to their beneficial influence on the arterial wall. A number of exciting therapeutic strategies have been developed that target

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

    Microsoft Academic Search

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

    1993-01-01

    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

  16. Glycated Low Density Lipoproteins Modify Platelet Properties: A Compositional and Functional Study

    Microsoft Academic Search

    G. Ferretti; R. A. RABINI; T. BACCHETTI; A. VIGNINI; E. SALVOLINI; F. RAVAGLIA; G. CURATOLA; L. MAZZANTI

    2002-01-01

    The interaction between low density lipoproteins (LDL) and platelets might play a central role in the development of ath- erosclerosis in diabetes. The aim of the present study was to investigate whether the glycation of LDL is associated with modifications of their physico-chemical and functional prop- erties and to study the action of glycated LDL (glycLDL) on platelets. LDL and

  17. A rare polymorphism in the low density lipoprotein (LDL) gene that affects mRNA splicing

    Microsoft Academic Search

    M. Bourbon; X. M. Sun; A. K. Soutar

    2007-01-01

    Familial hypercholesterolaemia (FH) is usually caused by mutations in the low density lipoprotein (LDL) receptor gene (LDLR) that impair clearance of LDL from the circulation. The increased risk of premature coronary heart disease associated with FH can be reduced by dietary advice and treatment with lipid-lowering drug therapy, but it is important to identify affected individuals at an early stage.

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

    Microsoft Academic Search

    Earl S. Ford; Simin Liu

    2001-01-01

    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

  19. Scavenger Receptor Class B Type I Protein as an Independent Predictor of High-Density Lipoprotein

    E-print Network

    Terasaki, Mark

    Scavenger Receptor Class B Type I Protein as an Independent Predictor of High-Density Lipoprotein, Kentucky 40507 Context: In mice, scavenger receptor class B, type I (SR-BI) receptor protein deficiency, is the scavenger re- ceptor, class B, type I (SR-BI) receptor. SR-BI was isolated and characterized

  20. Radioiodination of low density lipoprotein initiates lipid peroxidation: protection by use of antioxidants

    Microsoft Academic Search

    Andrew S. Khouw; Sampath Parthasarathy; Joseph L. Witztuml

    It is now apparent that low density lipoprotein (LDL) is very susceptible to lipid peroxidation and that the resulting oxidized LDL has altered biological properties. Radia- tion, particularly of longer duration and lower intensities, initi- ates lipid peroxidation, yet radioiodination with 1251 and 1311 is a frequently used method to label LDL for biological studies. To test the possibility that

  1. Lysosomal cholesterol derived from mildly oxidized low density lipoprotein is resistant to efflux

    Microsoft Academic Search

    Patricia G. Yancey; W. Gray Jerome

    In atherosclerotic lesions, macrophages store lipid in cytoplasmic inclusions and lysosomes. Regression studies show that lysosomal lipid is not as easily cleared as cytoplasmic inclusion lipid. Macrophages enriched with mildly oxidized low density lipoprotein (oxLDL) accumu- late cholesteryl ester (CE) and free cholesterol (FC) in lyso- somes. We examined whether lysosomal stores of choles- terol from oxLDL are cleared from

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

    Microsoft Academic Search

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

    1987-01-01

    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

  3. Total and High-Density Lipoprotein Cholesterol in Adults with Mental Retardation.

    ERIC Educational Resources Information Center

    Rimmer, James H.; Kelly, Luke E.

    1990-01-01

    The study evaluated the total cholesterol and high density lipoprotein cholesterol of 40 adults (mean age 37.5 years) with mental retardation residing at an intermediate care facility. Results indicated that 59 percent of the males and 68 percent of the females were at moderate to high risk for coronary heart disease. (DB)

  4. Non-high density lipoprotein cholesterol is the best discriminator of myocardial infarction in young individuals

    Microsoft Academic Search

    Loukianos S. Rallidis; Christos Pitsavos; Demosthenes B. Panagiotakos; Loukas Sinos; Christodoulos Stefanadis; Dimitrios T. Kremastinos

    2005-01-01

    Background:Several studies have shown that non-high density lipoprotein (HDL) cholesterol is a strong and independent predictor of cardiovascular events. We investigated whether non-HDL cholesterol can discriminate young individuals with myocardial infarction (MI) from age- and sex-matched controls.

  5. Tobacco smoking, estrogen receptor   gene variation and small low density lipoprotein level

    Microsoft Academic Search

    Amanda M. Shearman; Serkalem Demissie; L. Adrienne Cupples; Inga Peter; Christopher H. Schmid; Jose M. Ordovas; Michael E. Mendelsohn; David E. Housman

    2005-01-01

    High levels of small low density lipoprotein (LDL) particles are a major risk factor for cardiovascular morbidity and mortality. Both estrogens and smoking, with known anti-estrogenic effects, alter the atherogenic lipid pro- file. We tested for a role of interaction between smoking and estrogen receptor a gene (ESR1) variation in association with plasma concentration of atherogenic small LDL particles and

  6. 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 ...

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

    Microsoft Academic Search

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

    2009-01-01

    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

  8. Comparison of HOCl traps with myeloperoxidase inhibitors in prevention of low density lipoprotein oxidation

    Microsoft Academic Search

    Andreas Jerlich; Gerhard Fritz; Hadi Kharrazi; Michal Hammel; Sylvia Tschabuschnig; Otto Glatter; R. Jörg Schaur

    2000-01-01

    In this study, the production of the highly toxic oxidant hypochlorous acid (HOCl) by the phagocytic enzyme myeloperoxidase (MPO) was quantitated and the concomitant alterations of low density lipoprotein (LDL) were analyzed in view of the potential role of LDL in atherosclerosis. Using the monochlorodimedone assay, it was found that HOCl is produced in micromolar concentrations. The kinetics of the

  9. Polyunsaturated fatty acids downregulate the low density lipoprotein receptor of human HepG2 cells

    Microsoft Academic Search

    Sebely Pal; Andrew M Thomson; Cynthia D. K Bottema; Paul D Roach

    2002-01-01

    The aim of the study was to investigate the effect of different fatty acids on the low density lipoprotein (LDL) receptor of cultured human liver HepG2 cells. Previous studies investigating the effect of fatty acids on LDL expression have reported conflicting findings and are limited to measurements of LDL receptor binding activity. Therefore, this study is unique in that the

  10. Enzymatic Modification of Plasma Low Density Lipoproteins in Rabbits: A Potential Treatment for Hypercholesterolemia

    NASA Astrophysics Data System (ADS)

    Labeque, Regine; Mullon, Claudy J. P.; Ferreira, Joao Paulo M.; Lees, Robert S.; Langer, Robert

    1993-04-01

    Phospholipase A_2 (EC 3.1.1.4) hydrolyzes certain phospholipids of low density lipoprotein (LDL). Plasma clearance of phospholipase A_2-modified human LDL is up to 17 times faster than that of native human LDL in hypercholesterolemic rabbits. Modification of blood lipoproteins of hypercholesterolemic rabbits was performed by using an extracorporeal circuit containing immobilized phospholipase A_2. After 90-min treatments, nearly 30% decreases in plasma cholesterol concentrations were observed. Erythrocyte, leukocyte, and platelet counts showed no net change after treatment. This technique does not require any fluid replacement or sorbent regeneration and offers a potential approach for lowering serum cholesterol and LDL levels.

  11. Plasma phospholipid transfer protein-mediated reactions are impaired by hypochlorite-modification of high density lipoprotein

    Microsoft Academic Search

    Pirkko J Pussinen; Jari Metso; Ritva Keva; Birgit Hirschmugl; Wolfgang Sattler; Matti Jauhiainen; Ernst Malle

    2003-01-01

    The two main functions of phospholipid transfer protein (PLTP) are the transfer of phospholipids between plasma lipoproteins and the conversion of high density lipoprotein (HDL), where pre?-HDL particles are generated. HDL is considered an anti-atherogenic lipoprotein due to its function in the reverse cholesterol transport, where pre?-HDL accepts cellular membrane cholesterol from peripheral tissues. However, the anti-atherogenic properties of native

  12. Tissue distribution of high-density lipoprotein labeled with radioiodinated cholesterol.

    PubMed

    Counsell, R E; Schappa, L W; Korn, N; Huler, R J

    1980-09-01

    This preliminary study was undertaken in order to explore possible methods for enhancing the target organ specificity of radioiodinated cholesterol. 19-[125I]cholesterol (IC) was rapidly incorporated and transported in high-density lipoproteins (HDL) following i.v. admnistration to rats, and thus behaved like cholesterol in this regard. Incorporation of IC into HDL (IC-HDL) before administration produced little change in the tissue distribution profile except for a reduction in the amount of radioactivity appearing in the thyroid. This suggested that the lipoprotein carrier may have afforded protection from metabolic dehalogenation of IC. When rats were pretreated with 4-aminopyrazolo-(3,4d)-pyrimidine to drastically reduce the circulating lipoprotein levels, a fourfold enhancement in adrenal uptake was observed following administration of IC-HDL. This finding was consistent with the current view that the rat adrenal contains high-affinity and saturable receptors for HDL. PMID:7411217

  13. Distribution of Brevetoxin (PbTx-3) in Mouse Plasma: Association with High-Density Lipoproteins

    PubMed Central

    Woofter, Ricky T.; Spiess, Page C.; Ramsdell, John S.

    2005-01-01

    We investigated the brevetoxin congener PbTx-3 to determine its distribution among carrier proteins, including albumin and blood lipoproteins. Using a radiolabeled brevetoxin tracer (PbTx-3), we found that 39% of the radiolabel remained associated with components in mouse plasma after > 15 kDa cutoff dialysis. Of this portion, only 6.8% was bound to serum albumin. We also examined the binding of brevetoxin to various lipoprotein fractions. Plasma, either spiked with PbTx-3 or from mice treated for 30 min with PbTx-3, was fractionated into different-sized lipoproteins by iodixanol gradient ultracentrifugation. Each fraction was then characterized and quantified by agarose gel electrophoresis and brevetoxin radioimmunoassay, respectively. In both the in vitro and in vivo experiments, the majority of brevetoxin immunoreactivity was restricted to only those gradient fractions that contained high-density lipoproteins (HDLs). Independent confirmation of brevetoxin binding to HDLs was provided by high molecular weight (100 kDa cutoff) dialysis of [3H]PbTx-3 from lipoprotein fractions as well as a scintillation proximity assay using [3H]PbTx-3 and purified human HDLs. This information on the association of brevetoxins with HDLs provides a new foundation for understanding the process by which the toxin is delivered to and removed from tissues and may permit more effective therapeutic measures to treat intoxication from brevetoxins and the related ciguatoxins. PMID:16263501

  14. Apolipoprotein-mediated cellular cholesterol\\/phospholipid efflux and plasma high density lipoprotein level in mice

    Microsoft Academic Search

    Maki Tsujita; Shigehiro Tomimoto; Kuniko Okumura-Noji; Mitsuyo Okazaki; Shinji Yokoyama

    2000-01-01

    Helical apolipoprotein(apo)s generate pre-?-high density lipoprotein (HDL) by removing cellular cholesterol and phospholipid upon the interaction with cells. To investigate its physiological relevance, we studied the effect of an in vitro inhibitor of this reaction, probucol, in mice on the cell–apo interaction and plasma HDL levels. Plasma HDL severely dropped in a few days with probucol-containing chow while low density

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

    Microsoft Academic Search

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

    1993-01-01

    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

  16. Stimulating effect of biologically modified low density lipoproteins on ADP-induced aggregation of washed platelets persists in absence of specific binding

    Microsoft Academic Search

    Ivo Volf; Astrid Roth; Thomas Moeslinger; Julian Cooper; Werner Schmid; Manfred Zehetgruber; Elisabeth Koller

    2000-01-01

    Oxidized low density lipoproteins are closely associated with atherosclerosis and also might be directly involved in thrombosis because they have been shown to mediate a stimulating effect on human platelets. In this work, we used biologically modified low density lipoproteins (i.e., low density lipoproteins sufficiently oxidized to show specificity for the macrophage scavenger receptor system) to examine if specific binding

  17. Low density lipoprotein fraction assay for cardiac disease risk

    DOEpatents

    Krauss, Ronald M. (Berkeley, CA); Blanche, Patricia J. (Berkeley, CA); Orr, Joseph (San Pablo, CA)

    1999-01-01

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

  18. Hepatic deficiency of low density lipoprotein receptor-related protein-1 reduces high density lipoprotein secretion and plasma levels in mice.

    PubMed

    Basford, Joshua E; Wancata, Lauren; Hofmann, Susanna M; Silva, R A Gangani D; Davidson, W Sean; Howles, Philip N; Hui, David Y

    2011-04-15

    The low density lipoprotein receptor-related protein-1 (LRP1) is known to serve as a chylomicron remnant receptor in the liver responsible for the binding and plasma clearance of apolipoprotein E-containing lipoproteins. Previous in vitro studies have provided evidence to suggest that LRP1 expression may also influence high density lipoprotein (HDL) metabolism. The current study showed that liver-specific LRP1 knock-out (hLrp1(-/-)) mice displayed lower fasting plasma HDL cholesterol levels when compared with hLrp1(+/+) mice. Lecithin:cholesterol acyl transferase and hepatic lipase activities in plasma of hLrp1(-/-) mice were comparable with those observed in hLrp1(+/+) mice, indicating that hepatic LRP1 inactivation does not influence plasma HDL remodeling. Plasma clearance of HDL particles and HDL-associated cholesteryl esters was also similar between hLrp1(+/+) and hLrp1(-/-) mice. In contrast, HDL secretion from primary hepatocytes isolated from hLrp1(-/-) mice was significantly reduced when compared with that observed with hLrp1(+/+) hepatocytes. Biotinylation of cell surface proteins revealed decreased surface localization of the ATP-binding cassette, subfamily A, member 1 (ABCA1) protein, but total cellular ABCA1 level was not changed in hLrp1(-/-) hepatocytes. Finally, hLrp1(-/-) hepatocytes displayed reduced binding capacity for extracellular cathepsin D, resulting in lower intracellular cathepsin D content and impairment of prosaposin activation, a process that is required for membrane translocation of ABCA1 to facilitate cholesterol efflux and HDL secretion. Taken together, these results documented that hepatic LRP1 participates in cellular activation of lysosomal enzymes and through this mechanism, indirectly modulates the production and plasma levels of HDL. PMID:21343303

  19. Hepatic Deficiency of Low Density Lipoprotein Receptor-related Protein-1 Reduces High Density Lipoprotein Secretion and Plasma Levels in Mice*

    PubMed Central

    Basford, Joshua E.; Wancata, Lauren; Hofmann, Susanna M.; Silva, R. A. Gangani D.; Davidson, W. Sean; Howles, Philip N.; Hui, David Y.

    2011-01-01

    The low density lipoprotein receptor-related protein-1 (LRP1) is known to serve as a chylomicron remnant receptor in the liver responsible for the binding and plasma clearance of apolipoprotein E-containing lipoproteins. Previous in vitro studies have provided evidence to suggest that LRP1 expression may also influence high density lipoprotein (HDL) metabolism. The current study showed that liver-specific LRP1 knock-out (hLrp1?/?) mice displayed lower fasting plasma HDL cholesterol levels when compared with hLrp1+/+ mice. Lecithin:cholesterol acyl transferase and hepatic lipase activities in plasma of hLrp1?/? mice were comparable with those observed in hLrp1+/+ mice, indicating that hepatic LRP1 inactivation does not influence plasma HDL remodeling. Plasma clearance of HDL particles and HDL-associated cholesteryl esters was also similar between hLrp1+/+ and hLrp1?/? mice. In contrast, HDL secretion from primary hepatocytes isolated from hLrp1?/? mice was significantly reduced when compared with that observed with hLrp1+/+ hepatocytes. Biotinylation of cell surface proteins revealed decreased surface localization of the ATP-binding cassette, subfamily A, member 1 (ABCA1) protein, but total cellular ABCA1 level was not changed in hLrp1?/? hepatocytes. Finally, hLrp1?/? hepatocytes displayed reduced binding capacity for extracellular cathepsin D, resulting in lower intracellular cathepsin D content and impairment of prosaposin activation, a process that is required for membrane translocation of ABCA1 to facilitate cholesterol efflux and HDL secretion. Taken together, these results documented that hepatic LRP1 participates in cellular activation of lysosomal enzymes and through this mechanism, indirectly modulates the production and plasma levels of HDL. PMID:21343303

  20. 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.

    PubMed

    Boden, W E

    2000-12-21

    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

  1. Effect of oxidation on the structure of human low- and high-density lipoproteins.

    PubMed

    Oliveira, Cristiano L P; Santos, Priscila R; Monteiro, Andrea M; Figueiredo Neto, Antonio M

    2014-06-17

    This work presents a controlled study of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) structural changes due to in vitro oxidation with copper ions. The changes were studied by small-angle x-ray scattering (SAXS) and dynamic light scattering (DLS) techniques in the case of LDL and by SAXS, DLS, and Z-scan (ZS) techniques in the case of HDL. SAXS data were analyzed with a to our knowledge new deconvolution method. This method provides the electron density profile of the samples directly from the intensity scattering of the monomers. Results show that LDL particles oxidized for 18 h show significant structural changes when compared to nonoxidized particles. Changes were observed in the electrical density profile, in size polydispersity, and in the degree of flexibility of the APO-B protein on the particle. HDL optical results obtained with the ZS technique showed a decrease of the amplitude of the nonlinear optical signal as a function of oxidation time. In contrast to LDL results reported in the literature, the HDL ZS signal does not lead to a complete loss of nonlinear optical signal after 18 h of copper oxidation. Also, the SAXS results did not indicate significant structural changes due to oxidation of HDL particles, and DLS results showed that a small number of oligomers formed in the sample oxidized for 18 h. All experimental results for the HDL samples indicate that this lipoprotein is more resistant to the oxidation process than are LDL particles. PMID:24940777

  2. Structural investigation of reconstituted high density lipoproteins by scanning tunnelling microscopy

    NASA Astrophysics Data System (ADS)

    Culot, C.; Durant, F.; Lazarescu, S.; Thiry, P. A.; Vanloo, B.; Rosseneu, M. Y.; Lins, L.; Brasseur, R.

    2004-05-01

    Being able to participate in the reverse cholesterol transport (RCT), high density lipoproteins (HDL) are known to be anti-atherogenic. In order to understand such a process, it is thus essential to have a detailed knowledge of the structure and molecular organisation of HDL. Reconstituted nascent high density lipoproteins (r-HDL), consisting of synthetic phospholipids together with different apolipoproteins (apo A-I, A-IV and E), were thus analysed by scanning tunnelling microscopy (STM). Both shape and dimensions of the discoidal HDL particles measured by this technique were found in good agreement with the data available from the literature. The accuracy of the STM pictures presented in this paper enables for the first time the visualisation of the molecular organisation of such macromolecules. The arrangement of the protein as antiparallel helical segments, is consistent with the general mode of organisation of apolipoprotein/phospholipid discoidal particles previously reported.

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

    NASA Astrophysics Data System (ADS)

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

    2007-07-01

    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.

  4. Relationship between smoking habits and low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides in a hypercholesterolemic adult cohort, in relation to gender and age

    Microsoft Academic Search

    G. E. Schuitemaker; G. J. Dinant; G. A. van der Pol; J. W. J. van Wersch

    2002-01-01

    Elevated total cholesterol, the related low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides,\\u000a and smoking habits are risk factors for cardiovascular disease. The objective of this study was to investigate the influence\\u000a of habitual smoking on these parameters in 492 hypercholesterolemic men and women, aged between 26 and 66 years. Relative\\u000a differences between smokers and non-smokers in the mean values of total cholesterol,

  5. High-density lipoprotein subfractions and risk of coronary artery disease

    Microsoft Academic Search

    John Morgan; Christina Carey; Anne Lincoff; David Capuzzi

    2004-01-01

    Numerous studies have shown that levels of high-density lipoprotein (HDL) cholesterol are inversely related to coronary artery\\u000a disease risk. The HDL subfractions, however, seem to differ in their capacity to confer protection, with the large HDL2 subfraction\\u000a appearing to be more important than the small HDL3 subfraction. Lipid-modifying drugs differ in their HDL-raising efficacy,\\u000a and they also differ in how

  6. A novel oxidized low-density lipoprotein-binding protein from Pseudomonas aeruginosa

    Microsoft Academic Search

    Jayasimha Rao; Antonio DiGiandomenico; Jason Unger; Yongde Bao; Renata K. Polanowska-Grabowska; Joanna B. Goldberg

    2008-01-01

    A novel protein, PA0122, has been identified in Pseudomonas aeruginosa and shown to bind to oxidized low-density lipoprotein (Ox-LDL). The PA0122 gene was recognized based on gene expression pattern differences between two strains of P. aeruginosa isolated from the sputum of an individual with cystic fibrosis (CF). There was an approximately eightfold increase in PA0122 expression in the non-mucoid strain

  7. The Clinical Relevance of Low-Density-Lipoproteins Size Modulation by Statins

    Microsoft Academic Search

    Manfredi Rizzo; Kaspar Berneis

    2006-01-01

    The predominance of small, dense low density lipoproteins (LDL) has been accepted as an emerging cardiovascular risk factor\\u000a by the National Cholesterol Education Program Adult Treatment Panel III; in fact, LDL size seems to be an important predictor\\u000a of cardiovascular events and progression of coronary heart disease. Several studies have also shown that the therapeutical\\u000a modulation of LDL size is

  8. Carotid artery stiffness, high-density lipoprotein cholesterol and inflammation in men with pre-hypertension

    Microsoft Academic Search

    K S Heffernan; R H Karas; J T Kuvin; S Y Jae; V J Vieira; B Fernhall

    2009-01-01

    Low circulating levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased risk for cardiovascular events. HDL-C has a variety of poorly understood atheroprotective effects, including altering lipid metabolism and reducing inflammation. Increased arterial stiffness is an important predictor of subsequent cardiovascular risk. Therefore, in this study, we sought to determine whether HDL-C levels are associated with carotid arterial stiffness.

  9. Characterization of nascent high density lipoprotein subfractions from perfusates of rat liver

    Microsoft Academic Search

    K. Elise Wider; Julian B. Marsh

    Nascent high density lipoprotein (HDL) (1.063 < d < 1.21 g\\/ml) was isolated from recirculating rat liver perfusates and separated by heparin-Sepharose chromatography into a nonretained fraction (NR) and a fraction (R) that eluted with 0.5 M NaCI. Fractions NR and R contained 70% and 30% of the nascent HDL protein, respectively. ApoB-containing par- ticles were removed from fraction R

  10. Effect of bicarbonate on iron-mediated oxidation of low-density lipoprotein

    Microsoft Academic Search

    Hirofumi Arai; Barbara S. Berlett; P. Boon Chock; Earl R. Stadtman

    2005-01-01

    Oxidation of low-density lipoprotein (LDL) may play an important role in atherosclerosis. We studied the effects of bicarbonate\\/CO2 and phosphate buffer systems on metal ion-catalyzed oxidation of LDL to malondialdehyde (MDA) and to protein carbonyl and MetO derivatives. Our results revealed that LDL oxidation in mixtures containing free iron or heme derivatives was much greater in bicarbonate\\/CO2 compared with phosphate

  11. Total antioxidant activity of low density lipoproteins and the relationship with alpha-tocopherol status.

    PubMed

    Miller, N J; Paganga, G; Wiseman, S; Van Nielen, W; Tijburg, L; Chowienczyk, P; Rice-Evans, C A

    1995-05-29

    A rapid method is described for measuring the antioxidant activity of low density lipoproteins. Studies were undertaken on individuals attending a hyperlipidaemia clinic, an unsupplemented group and a group after supplementation with 300 mg dl-alpha-tocopherol acetate for nine weeks. The results show a positive correlation between the antioxidant activity and alpha-tocopherol content of LDL in the supplemented group. PMID:7781772

  12. Utility of Atherosclerosis Imaging in the Evaluation of High-Density Lipoprotein–Raising Therapies

    Microsoft Academic Search

    Raphaël Duivenvoorden; Zahi A. Fayad

    2011-01-01

    Decreased level of high density-lipoprotein cholesterol (HDL-C) is a rigorous predictor for future cardiovascular events.\\u000a Much effort is being made to develop HDL-C–raising pharmacotherapies in the attempt to avert the pandemic of atherosclerotic\\u000a disease. Important properties by which HDL-C–raising compounds are effective involve improvement of cholesterol uptake from\\u000a macrophages in plaque for transport back to the liver, improvement of endothelial

  13. Proteomic analysis of human macrophages exposed to hypochlorite-oxidized low-density lipoprotein

    Microsoft Academic Search

    Jeong Han Kang; Hyun Su Ryu; Hyun Tae Kim; Su Jin Lee; Ung-Kyu Choi; Yong Bok Park; Tae-Lin Huh; Myung-Sook Choi; Tae-Cheon Kang; Soo Young Choi; Oh-Shin Kwon

    2009-01-01

    The invasion of monocytes through the endothelial wall of arteries and their transformation from macrophage into form cells has been implicated as a critical initiating event in atherogenesis. Human THP-1 monocytic cells can be induced to differentiate into macrophages by phorbol myristate acetate (PMA) treatment, and can be converted into foam cells by exposure to oxidized low-density lipoprotein (oxLDL). To

  14. Protective effect of oleuropein, an olive oil biophenol, on low density lipoprotein oxidizability in rabbits

    Microsoft Academic Search

    E. Coni; R. Di Benedetto; M. Di Pasquale; R. Masella; D. Modesti; R. Mattei; E. A. Carlini

    2000-01-01

    On the basis of the results obtained with pilot studies conducted in vitro on human low density lipoprotein (LDL) and on cell cultures (Caco-2), which had indicated the ability of certain molecules\\u000a present in olive oil to inhibit prooxidative processes, an in vivo study was made of laboratory rabbits fed special diets. Three different diets were prepared: a standard diet

  15. Influence of an atherogenic diet on the structure of swine low density lipoproteins

    Microsoft Academic Search

    Henry J. Pownall; Richard L. Jackson; Robert I. Roth; Antonio M. Gotto; Josef R. Patsch; Fred A. Kummerow

    Five groups of three swine each were fed a basal diet supplemented with 15% tallow and either 0.0, 1.0, 1.5, 2.076, or 2.5% cholesterol. The animals were studied over a period of 9 weeks to observe changes in plasma lipids and low density lipoproteins (LDL). At the end of the study period, LDL was analyzed by rate zonal ultracentrifugation, characterized

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

    Microsoft Academic Search

    Edward Siguel

    1996-01-01

    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

  17. Effect of methylglyoxal on the physico-chemical and biological properties of low-density lipoprotein

    Microsoft Academic Search

    Casper G. Schalkwijk; Mario A. Vermeer; Coen D. A. Stehouwer; Johan te Koppele; Hans M. G. Princen; Victor W. M. van Hinsbergh

    1998-01-01

    In patients with diabetes, non-enzymatic glycation of low-density lipoprotein (LDL) has been suggested to be involved in the development of atherosclerosis. ?-Dicarbonyl compounds were identified as intermediates in the non-enzymatic glycation and increased levels were reported in patients with diabetes. We studied the effect of the ?-dicarbonyl compound methylglyoxal (MG) on the physicochemical and biological properties of LDL. MG dose-dependently

  18. Impaired Cellular Cholesterol Efflux By Oxysterol-Enriched High Density Lipoproteins

    Microsoft Academic Search

    Laurence Gesquière; Nadine Loreau; Denis Blache

    1997-01-01

    One of the proposed antiatherogenicity role of high-density lipoproteins (HDL) is believed to stimulate removal of cholesterol from the peripheral cells back to the liver for excretion. We have investigated the effects of oxidation-related modifications of HDL on their ability to stimulate cholesterol efflux from cultured cells. Human HDL (HDL3, 1.13 < d < 1.21 g\\/ml) have been modified either

  19. A Hepatic Lipase (LIPC) Allele Associated with High Plasma Concentrations of High Density Lipoprotein Cholesterol

    Microsoft Academic Search

    Rudy Guerra; Jinping Wang; Scott M. Grundy; Jonathan C. Cohen

    1997-01-01

    Genetic factors strongly influence interindividual variation in plasma high density lipoprotein cholesterol (HDL-C) levels, but the specific genetic polymorphisms that confer heritable variation in HDL-C levels have not been identified. In this study we examined the relationship between polymorphism in LIPC, the gene encoding hepatic lipase, and plasma HDL-C concentrations using a sequential approach comprising linkage analysis, DNA sequencing, and

  20. Age-dependent associations of smoking and drinking with non–high-density lipoprotein cholesterol

    Microsoft Academic Search

    Ichiro Wakabayashi; Klaus Groschner

    2010-01-01

    Serum high-density lipoprotein (HDL) cholesterol levels are influenced by habitual smoking and drinking. Non-HDL cholesterol is known to be a potent predictor of cardiovascular disease. However, it remains to be determined whether the associations of non-HDL cholesterol with smoking and drinking differ with age. The objectives of this study were to investigate relationships among smoking, drinking, and non-HDL cholesterol and

  1. A modified formula for calculating low-density lipoprotein cholesterol values

    Microsoft Academic Search

    Yunqin Chen; Xiaojin Zhang; Baishen Pan; Xuejuan Jin; Haili Yao; Bin Chen; Yunzeng Zou; Junbo Ge; Haozhu Chen

    2010-01-01

    BACKGROUND: The Friedewald formula (FF) is useful for calculating serum low-density lipoprotein cholesterol (LDL-C) values, but has a remarkable deviation and limitation especially in hypertriglyceridemia. We modify the formula which is now more suitable for LDL-C calculation. METHODS: 2180 cases were classified into three groups according to their TG concentrations (A: n = 1220; B: 200-400 mg\\/dl, n = 480;

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

    Microsoft Academic Search

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

    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

  3. Relation of high-density lipoprotein cholesterol concentration to type of diabetes and its control

    Microsoft Academic Search

    A L Kennedy; T R Lappin; T D Lavery; D R Hadden; J A Weaver; D A Montgomery

    1978-01-01

    Serum cholesterol and high-density lipoprotein (HDL) cholesterol concentrations were measured in 192 diabetics (94 with juvenile-onset and 98 with maturity-onset diabetes) and 177 non-diabetic controls. Hb A1C, an index of blood sugar control, was also measured in the diabetics. Serum cholesterol concentrations were similar in all the diabetics and controls, but HDL cholesterol concentrations were lower in patients with maturity-onset

  4. Sex difference in the regulation of plasma high density lipoprotein cholesterol by genetic and environmental factors

    Microsoft Academic Search

    Heikki Kauma; Markku J. Savolainen; Riitta Heikkilä; Asko O. Rantala; Mauno Lilja; Antti Reunanen; Y. Antero Kesäniemi

    1996-01-01

    Association between high density lipoprotein (HDL) cholesterol concentration and restriction fragment length polymorphisms at the cholesteryl ester transfer protein (CETP) gene locus was studied in a random population-based cohort of 526 Caucasian subjects (259 men, mean age 50.9 years, and 267 women, mean age 51.8 years). HDL cholesterol concentration was adjusted for age, body mass index, alcohol consumption, smoking and

  5. Comparison of two methods of estimation of low density lipoprotein cholesterol, the direct versus friedewald estimation

    Microsoft Academic Search

    Suchanda Sahu; Rajinder Chawla; Bharti Uppal

    2005-01-01

    Current recommendations of the Adult Treatment Panel and Adolescents Treatment Panel of National Cholesterol Education Program\\u000a make the low-density lipoprotein cholesterol (LDL-C) levels in serum the basis of classification and management of hypercholesterolemia.\\u000a A number of direct homogenous assays based on surfactant\\/solubility principles have evolved in the recent past. This has made\\u000a LDL-C estimation less cumbersome than the earlier used

  6. Utility of non-high-density lipoprotein cholesterol in hemodialyzed patients

    Microsoft Academic Search

    Laura Schreier; Ana I González; Alicia Elbert; Gabriela Berg; Regina Wikinski

    2004-01-01

    Non-high-density lipoprotein-cholesterol (HDL-C) is proposed as a strong predictor of cardiovascular disease (CVD). Measuring non-HDL-C, as total cholesterol minus HDL-C, is convenient for routine practice because, among other advantages, fasting is not required. There are limited data of non-HDL-C in end-stage renal disease patients. We applied non-HDL-C calculation to 50 chronic renal patients receiving maintenance hemodialysis (HD) and 20 healthy

  7. Thinking beyond low-density lipoprotein cholesterol: strategies to further reduce cardiovascular risk

    Microsoft Academic Search

    Rakesh K Sharma; Vibhuti N Singh; Hanumanth K Reddy

    Several large statin trials and meta-analyses have demonstrated a reduction in low-density lipoprotein cholesterol (LDL-C) and cardiovascular morbidity and mortality. Some trials have also highlighted the significance of residual cardiovascular risk after treatment of LDL-C to target levels. This reflects the complex nature of residual cardiovascular risk. This residual risk is partially due to low HDL-C and high triglycerides (TG)

  8. Small dense low-density lipoprotein cholesterol concentration and carotid atherosclerosis

    Microsoft Academic Search

    Tetsuo Shoji; Sawako Hatsuda; Shoko Tsuchikura; Kayo Shinohara; Eiji Kimoto; Hidenori Koyama; Masanori Emoto; Yoshiki Nishizawa

    2009-01-01

    Low-density lipoprotein cholesterol (LDL-C) and the small dense LDL (SdLDL) phenotype are both predictors for ischemic heart disease. We examined whether cholesterol of SdLDL (SdLDL-C) is more closely associated with carotid artery intima-media thickness (CA-IMT), a surrogate measure of atherosclerosis, than LDL-C and other lipid parameters. The subjects were 326 consecutive participants including those with dyslipidemia, diabetes mellitus, hypertension, chronic

  9. Purification and Characterization of a Bovine Acetyl Low Density Lipoprotein Receptor

    Microsoft Academic Search

    Tatsuhiko Kodama; Pranhitha Reddy; Chiharu Kishimoto; Monty Krieger

    1988-01-01

    The acetyl low density lipoprotein (LDL) receptor is expressed on macrophages and some endothelial cells and mediates macrophage--foam cell formation in culture. A 220-kDa acetyl LDL binding protein was partially purified from bovine liver membranes and was used to make a specific monoclonal antibody. The 220-kDa protein immunoprecipitated by this antibody retained binding activity, and the antibody was used to

  10. Protective effect of olive oil and its phenolic compounds against low density lipoprotein oxidation

    Microsoft Academic Search

    Montserrat Fitó; María Isabel Covas; Rosa M. Lamuela-Raventós; Joan Vila; Jaume Torrents; Carmen de la Torre; Jaume Marrugat

    2000-01-01

    The protective effect of phenolic compounds from an olive oil extract, and of olive oils with (extra-virgin) and without (refined)\\u000a phenolic components, on low density lipoprotein (LDL) oxidation was investigated. When added to isolated LDL, phenolics [0.025–0.3\\u000a mg\\/L caffeic acid equivalents (CAE)] increased the lag time of conjugated diene formation after copper-mediated LDL oxidation\\u000a in a concentration-dependent manner. Concentrations of

  11. Formation of F 2-isoprostanes in oxidized low density lipoprotein: Inhibitory effect of hydroxytyrosol

    Microsoft Academic Search

    Marco Salami; Claudio Galli; Leonardo De Angelis; Francesco Visioli

    1995-01-01

    Oxidatively-modified low-density lipoproteins (LDL) contribute to the onset of the atherosclerotic disease. A recently discovered marker of lipid peroxidation is a series of prostaglandin F2-like compounds, the prostaglandin isomers isoprostanes, that are generated from arachidonic acid through cyclooxygenase-independent pathways following free radical injury and are endowed with potent biological activities. The incidence of cardiovascular disease in the Mediterranean area is

  12. Subpopulations of high density lipoproteins in homozygous and heterozygous Tangier disease

    Microsoft Academic Search

    Bela F Asztalos; Margaret E Brousseau; Judith R McNamara; Katalin V Horvath; Paul S Roheim; Ernst J Schaefer

    2001-01-01

    Tangier disease (TD) is characterized by severe high-density lipoproteins (HDL) deficiency, hypercatabolism of HDL constituents, impaired cellular cholesterol efflux, and mutations in the gene of ATP-binding cassette 1 (ABC-1). In the present study, we determined plasma lipid and apolipoprotein levels, and HDL subpopulations, in 110 subjects from a large TD kindred in which the proband was homozygous for an A?C

  13. Dietary effects on oxidation of low-density lipoprotein and atherogenesis

    Microsoft Academic Search

    Pietro Galassetti; Andria Pontello

    2006-01-01

    Oxidization of low-density lipoprotein (LDL) particles leads to formation of atherosclerotic lesions and increased risk of\\u000a cardiovascular disease (CVD) via a complex cascade of biochemical events occurring mostly within the arterial wall. Multiple\\u000a dietary factors impact LDL oxidation levels, such as fat-rich meals, hyper- and hypocaloric diets, and specific nutrients\\u000a (vitamins E, C, and beta-carotene; mono- and polyunsaturated fatty acids;

  14. Circulating Oxidized Low-Density Lipoprotein and Paraoxonase Activity in Preeclampsia

    Microsoft Academic Search

    H. Uzun; A. Benian; M. Albayrak

    2005-01-01

    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

  15. Predicting the structure of apolipoprotein A-I in reconstituted high-density lipoprotein disks.

    PubMed Central

    Phillips, J C; Wriggers, W; Li, Z; Jonas, A; Schulten, K

    1997-01-01

    In reconstituted high-density lipoproteins, apolipoprotein A-I and phosphatidylcholines combine to form disks in which the amphipathic alpha-helices of apolipoprotein A-1 bind to the edge of a lipid bilayer core, shielding the hydrophic lipid tails from the aqueous environment. We have employed experimental data, sequence analysis, and molecular modeling to construct an atomic model of such a reconstituted high-density lipoprotein disk consisting of two apolipoprotein A-I proteins and 160 palmitoyloleoylphosphatidylcholine lipids. The initial globular domain (1-47) of apolipoprotein A-I was excluded from the model, which was hydrated with an 8-A shell of water molecules. Molecular dynamics and simulated annealing were used to test the stability of the model. Both head-to-tail and head-to-head forms of a reconstituted high-density lipoprotein were simulated. In our simulations the protein contained and adhered to the lipid bilayer while providing good coverage of the lipid tails. Images FIGURE 1 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 7 FIGURE 8 PMID:9370429

  16. VALUE OF HIGH-DENSITY LIPOPROTEIN (HDL) SUBPOPULATIONS IN PREDICTING RECURRENT CARDIOVASCULAR EVENTS IN THE VETERANS AFFAIRS HDL INTERVENTION TRIAL

    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 ...

  17. Properties and metabolic fate of two very low density lipoprotein subfractions from rhesus monkey serum.

    PubMed

    Lusk, L; Chung, J; Scanu, A M

    1982-02-15

    Physical, chemical and physiological approaches were used to examine the properties of two very low density lipoproteins, VLDL-I (slow-beta), and VLDL-II (pre-beta), which were isolated by agarose column chromatography from the serum of rhesus monkeys fed either Purina Chow or one of four hyperlipidemic diets containing 0.5-20% cholesterol suspended in either coconut oil, peanut oil, mixed coconut oil and butter fat or lard. In the coconut oil-fed hyperlipidemic animals, the majority of the apolar lipids of VLDL-I was represented by cholesteryl esters. The small percentage of triacylglycerol (15%) had a fatty acid composition which resembled that of the fatty acid in each of the diets. In turn, VLDL-II had a triacylglycerol-rich core and differed from VLDL-I in apolipoprotein distribution (VLDL-I: low molecular weight apolipoprotein B, 36%; apolipoprotein E, 64%; and VLDL-II: high molecular weight apolipoprotein B, 38%; apolipoprotein E, 3%; and apolipoprotein C, 65%). Both VLDLs were hydrolyzed in vitro by milk lipoprotein lipase by first-order kinetics although VLDL-I exhibited a slightly slower reaction rate. When an oral dose of [3H]retinol was given to one of the animals, both VLDLs became labeled but the specific activity of VLDL-I was six times higher than that of VLDL-II and the other lipoproteins. We conclude that VLDL-I represents a cholesteryl ester-rich lipoprotein probably of intestinal origin, whereas VLDL-II may be a particle of hepatic derivation modified by its interaction with the other plasma lipoproteins. PMID:7066352

  18. Regulation of very low density lipoprotein apo B metabolism by dietary fat saturation and chain length in the guinea pig

    Microsoft Academic Search

    Ghada Abdel-Fattah; Maria Luz Fernandez; Donald J. McNamara

    1998-01-01

    Studies investigated the effects of dietary fatty acid composition and saturation on the regulation of very low density lipoprotein\\u000a (VLDL) apo B flux, clearance, and conversion to low density lipoprotein (LDL) in guinea pigs fed semipurified diets containing\\u000a 15% (w\\/w) corn oil (CO), lard (LA), or palm kernel oil (PK). Plasma cholesterol levels were highest with dietary PK (3.1±1.0\\u000a mmol\\/L)

  19. Dietary supplementation with ?-carotene, but not with lycopene, inhibits endothelial cell-mediated oxidation of low-density lipoprotein

    Microsoft Academic Search

    Tammy R Dugas; Diane W Morel; Earl H Harrison

    1999-01-01

    Carotenoids may protect low-density lipoprotein from oxidation, a process implicated in the development of atherosclerosis. Our previous studies showed that in vitro enrichment of low-density lipoprotein (LDL) with ?-carotene protected it from cell-mediated oxidation. However, in vitro enrichment with either lutein or lycopene actually enhanced oxidation of the LDL. In the present studies we have examined the impact of LDL

  20. Estimation oftheConcentration of Low-Density Lipoprotein Cholesterol inPlasma, Without UseofthePreparative Ultracentrifuge

    Microsoft Academic Search

    William T. Friedewald; Robert I. Levy; Donald S. Fredrickson

    1972-01-01

    A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf- 0.20)is presented. The method involves measure- ments of fasting plasma total cholesterol, tri- glyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Cornparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded

  1. Apolipoprotein B and non-high density lipoprotein cholesterol and the risk of coronary heart disease in Chinese

    Microsoft Academic Search

    Kuo-Liong Chien; Hsiu-Ching Hsu; Ta-Chen Su; Ming-Fong Chen; Yuan-Teh Lee; Frank B. Hu

    2007-01-01

    The aim of our study was to compare apolipo- protein B (apoB), non-high density lipoprotein cholesterol (nonHDL-C), low density lipoprotein cholesterol (LDL-C), and other lipid markers as predictors of coronary heart dis- ease (CHD) in Chinese. Overall, 122 individuals developed CHD during a median 13.6 years of follow-up in 3,568 adult participants from a community-based cohort. The multivari- ate relative

  2. Effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: a review

    Microsoft Academic Search

    Terry A. Jacobson; Sara B. Glickstein; Jonathan D. Rowe; Paresh N. Soni

    This exploratory, hypothesis-generating literature review evaluated potentially differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and non-HDL-C in published studies of ?-3 fatty acid (OM3) supplementation or prescription OM3 ethyl esters (P-OM3s). Placebo-adjusted changes in mean lipid parameters were compared in randomized, controlled trials in subjects treated

  3. The acute effect of 30 min of moderate exercise on high density lipoprotein cholesterol in untrained middle-aged men

    Microsoft Academic Search

    Lyle M. Hubinger; Laurel Traeger Mackinnon

    1992-01-01

    Summary  Fifteen middle-aged, untrained (defined as no regular exercise) men (mean age 49.9 years, range 42–67) cycled on a cycle ergometer at 50 rpm for 30 min at an intensity producing 60% predicted maximum heart rate [(f\\u000ac,max), wheref\\u000ac, max = 220 - age]. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (Tg) concentrations were

  4. [The difference of conformation of apoB-100 in lipoproteins of low and very low density. The modified lipoproteins and destructive inflammation in intima of arteries: a lecture].

    PubMed

    Titov, V N; Ameliyushkina, V A; Kotkina, T I; Aripovskiy, A V

    2014-02-01

    The formation of ligand occurs in phylogenetically earlier lipoproteins of very low density and later lipoproteins of very low density when apoB- 100 takes active conformation in association with essential polyenoic fatty acids, in form of ethers with alcohol cholesterol, palmitic and oleic triglycerides. In lipoproteins of low density apoB-100-domain-ligand is formed, in lipoproteins of very low density apoE/B-100-ligand is formed. The ligand lipoproteins absorb cells using apoE/B-100 and apoB-100 receptor endocytosis. In cases of excess of palmitic triglycerides. and lipoproteins of very low density of the same name in blood, damage of primary structure of post-heparin, hepatic lipoprotein lipase and co-enzymes apoC-II and apoC-II, phenotype E2/E2 blood accumulates pre-ligand lipoproteins rich in triglycerides. In case of pathology of apoB-100-receptor post-ligand lipoproteins of low density with low content of triglycerides are cumulated. All non-ligand lipoproteins in a physiological way denature neutrophils. The presence of pathology induces modification in case of action of other agents (glyco-toxins). The pre-lipoproteins form in the intima of arteries soft voluminous plaques and such destructive inflammatory process as athero-thrombosis. The post-lipoproteins form flat plaques and destructive inflammatory atheromatosis. The atherosclerosis can be labeled as disease ofconformation. The surplus of palmitic saturated fatty acids in food, phenotype E2/E2 and deletion of gene apoB-100-receptor are causes of intima lesion. The non-ligand lipoproteins form destructive process, dying foam cells and macrophages--inflammatory component. The atheromatosis is a result of realization of biological function of endoecology, support of "purity" of intercellular medium. PMID:25069231

  5. Current guidelines for high-density lipoprotein cholesterol in therapy and future directions.

    PubMed

    Subedi, Bishnu H; Joshi, Parag H; Jones, Steven R; Martin, Seth S; Blaha, Michael J; Michos, Erin D

    2014-01-01

    Many studies have suggested that a significant risk factor for atherosclerotic cardiovascular disease (ASCVD) is low high-density lipoprotein cholesterol (HDL-C). Therefore, increasing HDL-C with therapeutic agents has been considered an attractive strategy. In the prestatin era, fibrates and niacin monotherapy, which cause modest increases in HDL-C, reduced ASCVD events. Since their introduction, statins have become the cornerstone of lipoprotein therapy, the benefits of which are primarily attributed to decrease in low-density lipoprotein cholesterol. Findings from several randomized trials involving niacin or cholesteryl ester transfer protein inhibitors have challenged the concept that a quantitative elevation of plasma HDL-C will uniformly translate into ASCVD benefits. Consequently, the HDL, or more correctly, HDL-C hypothesis has become more controversial. There are no clear guidelines thus far for targeting HDL-C or HDL due to lack of solid outcomes data for HDL specific therapies. HDL-C levels are only one marker of HDL out of its several structural or functional properties. Novel approaches are ongoing in developing and assessing agents that closely mimic the structure of natural HDL or replicate its various functions, for example, reverse cholesterol transport, vasodilation, anti-inflammation, or inhibition of platelet aggregation. Potential new approaches like HDL infusions, delipidated HDL, liver X receptor agonists, Apo A-I upregulators, Apo A mimetics, and gene therapy are in early phase trials. This review will outline current therapies and describe future directions for HDL therapeutics. PMID:24748800

  6. Influence of caveolin-1 on cellular cholesterol efflux mediated by high-density lipoproteins.

    PubMed

    Frank, P G; Galbiati, F; Volonte, D; Razani, B; Cohen, D E; Marcel, Y L; Lisanti, M P

    2001-05-01

    Caveolin-1 is a principal structural component of caveolae membranes. These membrane microdomains participate in the regulation of signaling, transcytosis, and cholesterol homeostasis at the plasma membrane. In the present study, we determined the effect of caveolin-1 expression on cellular cholesterol efflux mediated by high-density lipoprotein (HDL). We evaluated this effect in parental NIH/3T3 cells as well as in two transformed NIH/3T3 cell lines in which caveolin-1 protein levels are dramatically downregulated. Compared with parental NIH/3T3 cells, these two transformed cell lines effluxed cholesterol more rapidly to HDL. In addition, NIH/3T3 cells harboring caveolin-1 antisense also effluxed cholesterol more rapidly to HDL. However, this effect was not due to changes in total cellular cholesterol content. We further showed that chronic HDL exposure reduced caveolin-1 protein expression in NIH/3T3 cells. HDL exposure also inhibited caveolin-1 promoter activity, suggesting a direct negative effect of HDL on caveolin-1 gene transcription. Moreover, we showed that HDL-induced downregulation of caveolin-1 prevents the uptake of oxidized low-density lipoprotein in human endothelial cells. These data suggest a novel proatherogenic role for caveolin-1, i.e., regarding the uptake and/or transcytosis of modified lipoproteins. PMID:11287334

  7. Single Step Reconstitution of Multifunctional High-Density Lipoprotein-Derived Nanomaterials Using Microfluidics

    PubMed Central

    Kim, YongTae; Fay, Francois; Cormode, David P.; Sanchez-Gaytan, Brenda L.; Tang, Jun; Hennessy, Elizabeth J.; Ma, Mingming; Moore, Kathryn; Farokhzad, Omid C.; Fisher, Edward Allen; Mulder, Willem J. M.; Langer, Robert; Fayad, Zahi A.

    2014-01-01

    High-density lipoprotein (HDL) is a natural nanoparticle that transports peripheral cholesterol to the liver. Reconstituted high-density lipoprotein (rHDL) exhibits antiatherothrombotic properties and is being considered as a natural treatment for cardiovascular diseases. Furthermore, HDL nanoparticle platforms have been created for targeted delivery of therapeutic and diagnostic agents. The current methods for HDL reconstitution involve lengthy procedures that are challenging to scale up. A central need in the synthesis of rHDL, and multifunctional nanomaterials in general, is to establish large-scale production of reproducible and homogeneous batches in a simple and efficient fashion. Here, we present a large-scale microfluidics-based manufacturing method for single-step synthesis of HDL-mimicking nanomaterials (µHDL). µHDL is shown to have the same properties (e.g., size, morphology, bioactivity) as conventionally reconstituted HDL and native HDL. In addition, we were able to incorporate simvastatin (a hydrophobic drug) into µHDL, as well as gold, iron oxide, quantum dot nanocrystals or fluorophores to enable its detection by computed tomography (CT), magnetic resonance imaging (MRI), or fluorescence microscopy, respectively. Our approach may contribute to effective development and optimization of lipoprotein-based nanomaterials for medical imaging and drug delivery. PMID:24079940

  8. Possible involvement of very low density lipoproteins in steroidogenesis in the human ovary.

    PubMed

    Murata, M; Tamura, A; Kodama, H; Hirano, H; Takahashi, O; Tanaka, T

    1998-08-01

    To determine whether human luteal cells can utilize very low density lipoproteins (VLDL)-carried cholesterol for steroidogenesis, we investigated the expression of VLDL receptor mRNA in human ovarian tissues and progesterone production by human luteinized granulosa cells after the addition of VLDL. The production of progesterone in the presence of human chorionic gonadotrophin (HCG) was increased significantly (P < 0.05) by VLDL (2479 +/- 1477 ng/10(5) cells, mean +/- SD, n = 6) and low density lipoproteins (LDL) (2726 +/- 1287), in comparison with the level in the absence of these lipoproteins (1350 +/- 739). Northern blot analysis revealed that the levels of expression of VLDL and LDL receptor mRNA in granulosa cells were almost equal to those in whole ovarian tissue. VLDL receptor mRNA was abundant in granulosa cells of preovulatory follicles and cells of the corpus luteum. Preovulatory thecal cells and stromal cells expressed lower amounts of VLDL receptor mRNA than granulosa cells of preovulatory follicles and cells of the corpus luteum. From the present study, it might be suggested that VLDL is utilized for steroidogenesis in human luteinized granulosa cells. PMID:9733438

  9. Unique Features of High-Density Lipoproteins in the Japanese: In Population and in Genetic Factors

    PubMed Central

    Yokoyama, Shinji

    2015-01-01

    Despite its gradual increase in the past several decades, the prevalence of atherosclerotic vascular disease is low in Japan. This is largely attributed to difference in lifestyle, especially food and dietary habits, and it may be reflected in certain clinical parameters. Plasma high-density lipoprotein (HDL) levels, a strong counter risk for atherosclerosis, are indeed high among the Japanese. Accordingly, lower HDL seems to contribute more to the development of coronary heart disease (CHD) than an increase in non-HDL lipoproteins at a population level in Japan. Interestingly, average HDL levels in Japan have increased further in the past two decades, and are markedly higher than in Western populations. The reasons and consequences for public health of this increase are still unknown. Simulation for the efficacy of raising HDL cholesterol predicts a decrease in CHD of 70% in Japan, greater than the extent by reducing low-density lipoprotein cholesterol predicted by simulation or achieved in a statin trial. On the other hand, a substantial portion of hyperalphalipoproteinemic population in Japan is accounted for by genetic deficiency of cholesteryl ester transfer protein (CETP), which is also commonly unique in East Asian populations. It is still controversial whether CETP mutations are antiatherogenic. Hepatic Schistosomiasis is proposed as a potential screening factor for historic accumulation of CETP deficiency in East Asia. PMID:25849946

  10. The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis?

    PubMed Central

    Vergeer, Menno; Holleboom, Adriaan G.; Kastelein, John J. P.; Kuivenhoven, Jan Albert

    2010-01-01

    There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for this “HDL hypothesis”. In vitro studies suggest that HDL has a wide range of anti-atherogenic properties but validation of these functions in humans is absent to date. A significant number of animal studies and clinical trials support an atheroprotective role for HDL; however, most of these findings were obtained in the context of marked changes in other plasma lipids. Finally, genetic studies in humans have not provided convincing evidence that HDL genes modulate cardiovascular risk. Thus, despite a wealth of information on this intriguing lipoprotein, future research remains essential to prove the HDL hypothesis correct. PMID:20371550

  11. Phenotypes and Genotypes of High Density Lipoprotein Cholesterol in Exceptional Longevity

    PubMed Central

    Milman, Sofiya; Atzmon, Gil; Crandall, Jill; Barzilai, Nir

    2014-01-01

    A change in the lipoprotein profile is a metabolic hallmark of aging and has been the target for modern medical developments. Although pharmaceutical interventions aimed at lipid lowering substantially decrease the risk of cardiovascular disease, they have much less impact on mortality and longevity. Moreover, they have not affected death from other age-related diseases. In this review we focus on high density lipoprotein (HDL) cholesterol, the levels of which are either elevated or do not decrease as would be expected with aging in centenarians, and which are associated with lower prevalence of numerous age-related diseases; thereby, suggesting a potential HDL-mediated mechanism for extended survival. We also provide an update on the progress of identifying longevity-mediating lipid genes, describe approaches to discover longevity genes, and discuss possible limitations. Implicating lipid genes in exceptional longevity may lead to drug therapies that prevent several age-related diseases, with such efforts already on the way. PMID:24350928

  12. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage

    SciTech Connect

    Frei, B. (Department of Nutrition, Harvard School of Public Health, Boston, MA (Unites States))

    1991-12-01

    The authors exposed human blood plasma and low-density lipoprotein (LDL) to many different oxidative challenges and followed the temporal consumption of endogenous antioxidants in relation to the initiation of oxidative damage. Under all types of oxidizing conditions, ascorbic acid completely protects lipids in plasma and LDL against detectable peroxidative damage as assessed by a specific and highly sensitive assay for lipid peroxidation. Ascorbic acid proved to be superior to the other water-soluble plasma antioxidants bilirubin, uric acid, and protein thiols as well as to the lipoprotein-associated antioxidants alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene. Although these antioxidants can lower the rate of detectable lipid peroxidation, they are not able to prevent its initiation. Only ascorbic acid is reactive enough to effectively intercept oxidants in the aqueous phase before they can attack and cause detectable oxidative damage to lipids.

  13. Relation of gemfibrozil treatment and high-density lipoprotein subpopulation profile with cardiovascular events in the Veterans Affairs High-Density Lipoprotein Intervention Trial.

    PubMed

    Asztalos, Bela F; Collins, Dorothea; Horvath, Katalin V; Bloomfield, Hanna E; Robins, Sander J; Schaefer, Ernst J

    2008-01-01

    The significant cardiovascular disease (CVD) event reduction in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) could not be fully explained by the 6% increase in high-density lipoprotein (HDL) cholesterol with the fibrate gemfibrozil. We examined whether measurement of HDL subpopulations provided additional information relative to CVD risk reduction. The HDL subpopulations were characterized by 2-dimensional gel electrophoresis in subjects who were treated with gemfibrozil (n = 754) or placebo (n = 741). In this study, samples obtained at the 3-month visit were used; and data were analyzed prospectively using CVD events (coronary heart disease death, myocardial infarction, or stroke) during the 5.1 years of follow-up. Analyses in the gemfibrozil arm showed that subjects with recurrent CVD events had significantly higher prebeta-1 and had significantly lower alpha-1 and alpha-2 HDL levels than those without such events. Prebeta-1 level was a significant positive predictor; alpha-1 and alpha-2 levels were significant negative risk factors for future CVD events. alpha-2 level was superior to HDL cholesterol level in CVD-risk assessment after adjustment for established risk factors. Gemfibrozil treatment was associated with 3% to 6% decreases in the small, lipid-poor prebeta-1 HDL and in the large, lipid-rich alpha-1 and alpha-2 HDL and with increases in the small alpha-3 (3%) and prealpha-3 (16%) HDLs. Although the use of gemfibrozil has been associated with reduction in CVD events in VA-HIT, HDL subpopulation analysis indicates that gemfibrozil-mediated improvement in CVD risk might not be the result of its effects on HDL. It is quite possible that much of the cardiovascular benefits of gemfibrozil are due to a much wider spectrum of effects on metabolic processes that is not reflected by changes in blood lipids and HDL subpopulations. PMID:18078862

  14. Oxidation of low-density lipoprotein with hypochlorite causes transformation of the lipoprotein into a high-uptake form for macrophages.

    PubMed

    Hazell, L J; Stocker, R

    1993-02-15

    Oxidation of low-density lipoprotein (LDL) lipid is thought to represent the initial step in a series of oxidative modification reactions that ultimately transform this lipoprotein into an atherogenic high-uptake form that can cause lipid accumulation in cells. We have studied the effects of hypochlorite, a powerful oxidant released by activated monocytes and neutrophils, on isolated LDL. Exposure of LDL to reagent hypochlorite (NaOCl) at 4 degrees C resulted in immediate and preferential oxidation of amino acid residues of apoprotein B-100, the single protein associated with LDL. Neither lipoprotein lipid nor LDL-associated antioxidants, except ubiquinol-10, represented major targets for this oxidant. Even when high concentrations of NaOCl were used, only low levels of lipid hydroperoxides could be detected with the highly sensitive h.p.l.c. post-column chemiluminescence detection method. Lysine residues of apoprotein B-100 quantitatively represented the major target, scavenging some 68% of the NaOCl added, with tryptophan and cysteine together accounting for an additional 10% of the oxidant. Concomitant with the loss of LDL's amino groups, chloramines were formed and the anionic surface charge of the lipoprotein particle increased, indicated by a 3-4-fold increase in electrophoretic mobility above that of native LDL on agarose gels. While both these changes could be initially reversed by physiological reductants such as ascorbic acid and methionine, incubation of the NaOCl-modified LDL at 37 degrees C resulted in increasing resistance of the modified lysine residues against reductive reversal. Exposure of mouse peritoneal macrophages to NaOCl-oxidized LDL resulted in increased intracellular concentrations of cholesterol and cholesteryl esters. These findings suggest that lipid-soluble antioxidants associated with LDL do not efficiently protect the lipoprotein against oxidative damage mediated by hypochlorite, and that extensive lipid oxidation is not a necessary requirement for oxidative LDL modification that leads to a high-uptake form of the lipoprotein. PMID:8439285

  15. Oxidation of low-density lipoprotein with hypochlorite causes transformation of the lipoprotein into a high-uptake form for macrophages.

    PubMed Central

    Hazell, L J; Stocker, R

    1993-01-01

    Oxidation of low-density lipoprotein (LDL) lipid is thought to represent the initial step in a series of oxidative modification reactions that ultimately transform this lipoprotein into an atherogenic high-uptake form that can cause lipid accumulation in cells. We have studied the effects of hypochlorite, a powerful oxidant released by activated monocytes and neutrophils, on isolated LDL. Exposure of LDL to reagent hypochlorite (NaOCl) at 4 degrees C resulted in immediate and preferential oxidation of amino acid residues of apoprotein B-100, the single protein associated with LDL. Neither lipoprotein lipid nor LDL-associated antioxidants, except ubiquinol-10, represented major targets for this oxidant. Even when high concentrations of NaOCl were used, only low levels of lipid hydroperoxides could be detected with the highly sensitive h.p.l.c. post-column chemiluminescence detection method. Lysine residues of apoprotein B-100 quantitatively represented the major target, scavenging some 68% of the NaOCl added, with tryptophan and cysteine together accounting for an additional 10% of the oxidant. Concomitant with the loss of LDL's amino groups, chloramines were formed and the anionic surface charge of the lipoprotein particle increased, indicated by a 3-4-fold increase in electrophoretic mobility above that of native LDL on agarose gels. While both these changes could be initially reversed by physiological reductants such as ascorbic acid and methionine, incubation of the NaOCl-modified LDL at 37 degrees C resulted in increasing resistance of the modified lysine residues against reductive reversal. Exposure of mouse peritoneal macrophages to NaOCl-oxidized LDL resulted in increased intracellular concentrations of cholesterol and cholesteryl esters. These findings suggest that lipid-soluble antioxidants associated with LDL do not efficiently protect the lipoprotein against oxidative damage mediated by hypochlorite, and that extensive lipid oxidation is not a necessary requirement for oxidative LDL modification that leads to a high-uptake form of the lipoprotein. Images Figure 6 PMID:8439285

  16. Changes in remnant and high-density lipoproteins associated with hormone therapy and progression of coronary artery disease in postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of hormone therapy (HT) on the plasma concentration of remnant lipoprotein cholesterol (RLP-C) and high density lipoprotein (HDL) subpopulations and the contribution of HT-related changes in these lipoproteins to the progression of coronary heart disease (CHD) were examined in 256 postmen...

  17. Oxidisability of low density lipoproteins in patients with carotid or femoral artery atherosclerosis.

    PubMed

    Andrews, B; Burnand, K; Paganga, G; Browse, N; Rice-Evans, C; Sommerville, K; Leake, D; Taub, N

    1995-01-01

    Oxidation of low density lipoprotein (LDL) is implicated in the pathogenesis of atherosclerosis. In this study the susceptibility to oxidation of LDL (from patients with atherosclerosis) is related to the progression of the disease. LDL were isolated from 37 patients with demonstrable atherosclerotic plaques. The susceptibility of LDL to oxidation (induced by an exogenous oxidative stress) was assessed by measuring the breakdown products of lipid peroxidation, the increased formation of conjugated dienes, and changes in surface charge of the apolipoprotein B (apo B). Progression of the atherosclerotic plaque was assessed by measuring the maximum velocity of blood through the narrowest portion of the vessel at inclusion and after one year. Twenty-nine of the 37 samples taken were found to have LDL that were partially oxidised, whereas 8 samples showed LDL whose state of oxidation was within the normal range. Progression of the atherosclerotic plaque occurred in 19 (66%) of the 29 patients whose lipoproteins were partially oxidised compared with only 2 (25%) of the 8 patients with normal lipoproteins (P = 0.055, Fisher's exact test). These data support an association between the progression of atherosclerotic plaques in carotid and femoral vessels and the susceptibility to oxidation of LDL. PMID:7772070

  18. Autoantibodies to the low density lipoprotein receptor in a subject affected by severe hypercholesterolemia.

    PubMed Central

    Corsini, A; Roma, P; Sommariva, D; Fumagalli, R; Catapano, A L

    1986-01-01

    We studied a 32-yr-old man with a benign paraproteinemia (IgA) affected by severe nonfamilial hypercholesterolemia. In vitro experiments demonstrated that lipoprotein-deficient serum (LPDS) from the patient inhibited the binding of low density lipoprotein (LDL) to human skin fibroblasts cultured in vitro (up to 70%) whereas LPDS from controls had no effect. Removal of IgA from the patient's serum by immunoprecipitation with mono-specific antisera abolished the inhibition of LDL binding. IgA isolated from the serum of the patient by affinity chromatography inhibited, in a dose-dependent manner, the binding of LDL to human skin fibroblasts in vitro, thus showing an IgA-mediated effect. Ligand-blotting experiments demonstrated that the paraprotein directly interacts with the LDL receptor, thus inhibiting the binding of the lipoprotein. Treatment of the receptor protein with reducing agents blocked the interaction of the antibody with the LDL receptor. From these data we speculate that this autoantibody may be responsible for the severe nonfamilial hypercholesterolemia of the patient. Images PMID:3760193

  19. Postprandial Changes in High Density Lipoproteins in Rats Subjected to Gavage Administration of Virgin Olive Oil

    PubMed Central

    Martínez-Beamonte, Roberto; Navarro, María A.; Acin, Sergio; Guillén, Natalia; Barranquero, Cristina; Arnal, Carmen; Surra, Joaquín; Osada, Jesus

    2013-01-01

    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. PMID:23383120

  20. Decreased susceptibility of low-density lipoproteins to in-vitro oxidation after dextran-sulfate LDL-apheresis treatment

    Microsoft Academic Search

    Norbert Leitinger; Christian Pirich; Ingrid Blazek; Georg Endler; Helmut Sinzinger

    1996-01-01

    Low-density lipoproteins (LDL)-apheresis is a well established treatment of severe hypercholesterolemia resulting in fast clinical improvement and angiographically proven regression after 6 months of therapy. The underlying mechanisms, beside lipoprotein removal, are still under debate. Recently, oxidized LDL were shown to be of key importance in foam cell formation and atherosclerotic lesion development. We examined the influence of dextran-sulfate LDL-apheresis

  1. Early Increase in Autoantibodies Against Human Oxidized Low-Density Lipoprotein in Hypertensive Patients After Blood Pressure Control

    Microsoft Academic Search

    Sergio A. Brandão; Maria C Izar; Simone M. Fischer; Andreza O. Santos; Carlos M. Monteiro; Rui M. Póvoa; Tatiana Helfenstein; Antonio C. Carvalho; Andrea M. Monteiro; Eduardo Ramos; Magnus Gidlund; Antonio M. Figueiredo Neto; Francisco A. Fonseca

    2010-01-01

    BackgroundOxidized lipoproteins and antioxidized low-density lipoprotein (anti-oxLDL) antibodies (Abs) have been detected in plasma in response to blood pressure (BP) elevation, suggesting the participation of the adaptive immune system. Therefore, treatment of hypertension may act on the immune response by decreasing oxidation stimuli. However, this issue has not been addressed. Thus, we have here analyzed anti-oxLDL Abs in untreated (naive)

  2. Hypochlorite-modified low-density lipoprotein induces the apoptotic machinery in Jurkat T-cell lines

    Microsoft Academic Search

    Ulrike Resch; Michaela Semlitsch; Astrid Hammer; Heidrun Susani-Etzerodt; Henning Walczak; Wolfgang Sattler; Ernst Malle

    2011-01-01

    Myeloperoxidase is abundantly present in inflammatory diseases where activation of monocytes\\/macrophages and T-cell-mediated immune response occurs. The potent oxidant hypochlorous acid (HOCl), generated by the myeloperoxidase–H2O2–chloride system of activated phagocytes, converts low-density lipoprotein (LDL) into a proinflammatory lipoprotein particle. Here, we investigated the apoptotic effect of HOCl–LDL, an in vivo occurring LDL modification, on human T-cell lymphoblast-like Jurkat cells. Experiments

  3. Pre-beta-very low density lipoproteins as precursors of beta-very low density lipoproteins. A model for the pathogenesis of familial dysbetalipoproteinemia (type III hyperlipoproteinemia).

    PubMed Central

    Chappell, D A

    1988-01-01

    The physical, chemical, and receptor binding properties of very low density lipoprotein (VLDL) fractions from familial dysbetalipoproteinemic (dys-beta) subjects, homozygous for apolipoprotein (apo-) E2 (E2/2 phenotype), and subjects with the E3/3 phenotype were studied to gain insights into the pathogenesis of dysbetalipoproteinemia, a disorder characterized by the presence of beta-VLDL in the plasma. Pre-beta-VLDL from dys-beta subjects were larger (27 vs. 17 x 10(6) D) and more triglyceride rich (68 vs. 43% dry weight) than beta-VLDL. Pre-beta-VLDL predominated in the Sf greater than 100 flotation fraction, whereas beta-VLDL predominated in the Sf 20-60 fraction. Because lipolysis converts large VLDL (Sf greater than 100) in vivo to smaller, more cholesteryl ester-rich VLDL (Sf 20-60), it is likely that pre-beta-VLDL are precursors of beta-VLDL. Although beta-VLDL were not found in type V hyperlipidemic E3/3 subjects, they were induced by intravenous heparinization, suggesting that lipolysis of pre-beta-VLDL in vivo can result in beta-VLDL formation. Similarly, heparinization of a dys-beta subject produced more beta-VLDL, at the expense of pre-beta-VLDL. The pre-beta-VLDL from normolipidemic and type V hyperlipidemic E3/3 subjects, respectively, had 90 and 280 times the affinity for the apo-B,E(LDL) receptor than did the pre-beta-VLDL from dys-beta subjects. Heparin-induced beta-VLDL from type V hyperlipidemic subjects had a sixfold higher binding affinity than did heparin-induced beta-VLDL from dys-beta subjects. These data suggest that pre-beta-VLDL from E2/2 subjects interact poorly with lipoprotein receptors in vivo, decreasing their receptor-mediated clearance and increasing their conversion to beta-VLDL during lipolytic processing. Images PMID:2841358

  4. Fluorescence quenching by iodide ions of low density lipoproteins from normolipidemic and hypercholesterolemic type IIa subjects. Effect of low density lipoprotein-cholesterol and low density lipoprotein non-apolipoprotein-B.

    PubMed

    Dang, Q Q; Douste-Blazy, P; Camare, R; Galy, D

    1984-12-01

    In order to evaluate the effect of hypercholesterolemia on the surface properties of low density lipoproteins (LDL), the quenching by iodide ions of the native fluorescence of human plasma LDL was studied on normolipidemic and hypercholesterolemic type IIa subjects. A significant difference (P less than 0.001) was found between these two groups (20 patients with type IIa hyperlipoproteinemia, 18 normolipidemic subjects). Furthermore, the fluorescence quenching (F0-F1)/F0 (F0 and F1 fluorescence intensity respectively in the absence and in the presence of iodide ions is negatively correlated with the relative LDL-cholesterol level (LDL-cholesterol/LDL-apoprotein). In contrast, this quenching is positively correlated with the relative LDL-non-apo-B level (LDL-non-apo-B/LDL apo). It is suggested that the greater the LDL-cholesterol level, the more embedded are the tryptophyl residues in the hydrophobic core. In contrast, the greater the LDL-non-apo-B level, the more exposed are the tryptophyl to the aqueous environment. Thus, a significant conformation change of the superficial apolipoproteins occurs, which could affect the immunological properties of the LDL and their affinity to the LDL receptors. PMID:6532567

  5. [The role of oxidative processes in augmentation of atherogenity of low density lipoprotein particles].

    PubMed

    Kumskova, E M; Aksenov, D V; Konovalova, G G; Tikhaze, A K; Lankin, V Z

    2012-01-01

    We investigated action of natural dicarbonyl compounds which are formed in atherosclerosis and diabetes on properties of low density lipoproteins (LDL) such as surface charge, conformational changes of apoB100, susceptibility to oxidation. and aggregation rate. It was found that malonic dialdehyde (MDA) compared with glyoxal and methylglyoxal is more effective modificating agent of protein part of LDL particle. Nevertheless glyoxal and methylglyoxal-dependent modification of LDL can accelerate processes of further free radical peroxidation increasing atherogenity of LDL particles. PMID:22839672

  6. Non-oxidative modification of low density lipoprotein by ruptured myocytes.

    PubMed

    Bourne, L C; Lamb, D J; Collis, C S; O'Brien, M; Leake, D S; Rice-Evans, C

    1997-09-15

    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 not the macrophage uptake suggesting that LDL can be modified by mechanisms that are independent of oxidative processes by intracellular constituents of cardiac myocytes. PMID:9323039

  7. Practical approaches to low density lipoprotein oxidation: whys, wherefores and pitfalls.

    PubMed

    Rice-Evans, C; Leake, D; Bruckdorfer, K R; Diplock, A T

    1996-10-01

    The purpose of this review is to bring together the different approaches for studying the oxidation of low density lipoproteins and try to identify some critical factors which will permit greater comparability between laboratories. These issues are discussed both in terms of the variety of exogenous mediators of oxidation applied (transition metal ions, haem proteins, azo initiators, peroxynitrite, cells etc.) and their raisons d'être, as well as the methodologies (formation of conjugated dienes, hydroperoxides, decomposition products of lipid peroxidation, altered surface charge, macrophage uptake) applicable to the different stages of the oxidation and the factors underlying their accurate execution and interpretation. PMID:8889494

  8. Synthetic Nano-Low Density Lipoprotein as Targeted Drug DeliveryVehicle for Glioblastoma Multiforme

    SciTech Connect

    Nikanjam, Mina; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Shu,Xiao; Budinger, Thomas F.; Forte, Trudy M.

    2006-06-14

    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.

  9. Effects of exercise with varying energy expenditure on high-density lipoprotein-cholesterol

    Microsoft Academic Search

    Paul S. Visich; Fredric L. Goss; Paul M. Gordon; Robert J. Robertson; Vijay Warty; Bart G. Denys; Kenneth F. Metz

    1996-01-01

    To investigate the effect of varying energy expenditure on acute high-density lipoprotein-cholesterol (HDL-C) changes, 12 healthy endurance-trained men completed three- counterbalanced running trials at different energy expenditures: trial 1, 1690.3 (24.4) kJ [mean (SD)]; trial 2, 2529.1 (24.0) kJ; trial 3, 3384.3 (36.6) kJ, with exercise intensity at 75% of maximal oxygen consumption. For each trial, blood samples were collected

  10. High levels of human apolipoprotein AI and high density lipoproteins in transgenic mice do not enhance efflux of cholesterol from a depot of injected lipoproteins

    Microsoft Academic Search

    Olga Stein; Yedida Dabach; Gideon Hollander; Mazal Ben-Naim; Gideon Halperin; Yechezkiel Stein

    1999-01-01

    The role of high density lipoprotein (HDL) and apolipoprotein A-I (apo A-I)in promoting cholesterol efflux from cultured cells and attenuation of development of atherosclerosis in transgenic (tg) animals has been well documented. The aim of the present study was to determine whether high levels of human (h) apo A-I will enhance cholesterol removal in vivo. h apo A-I in sera

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

    PubMed

    Suzukawa, M; Abbey, M; Howe, P R; Nestel, P J

    1995-03-01

    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 subjects. 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 plasma triglyceride, and increased LDL-cholesterol (+6%, P < 0.01 compared to corn oil). LDL particles were larger (P < 0.01) after fish oil compared to baseline and LDL size was inversely correlated with plasma triglyceride (P < 0.001) both before and after fish oil supplementation, and positively correlated with high density lipoprotein cholesterol (P < 0.01). Fish oil reduced lag time before onset of copper-induced LDL oxidation (-25%, P < 0.001) and significantly increased production of thiobarbituric acid-reactive substances (TBARS) during oxidation, compared with corn oil. Corn oil had no significant effect on lag time and oxidation rate. Fish oil increased macrophage uptake of copper-oxidized LDL and of macrophage-modified LDL. Corn oil was without effect. Additionally, macrophages that were supplemented with fish oil fatty acids in vitro displayed a significantly (P < 0.001) higher capacity to oxidize LDL than either control cells or cells supplemented with corn oil fatty acids. We conclude that from the standpoint of atherosclerosis, fish oil fatty acids adversely raise the susceptibility of LDL to copper-induced and macrophage-mediated oxidation but that the increase in plasma LDL cholesterol concentration reflects an increase in size that may be favorable. PMID:7775859

  12. Emerging low-density lipoprotein therapies: Microsomal triglyceride transfer protein inhibitors.

    PubMed

    Goldberg, Anne C

    2013-01-01

    Microsomal triglyceride transfer protein, which is localized in the endoplasmic reticulum of enterocytes and hepatocytes, is necessary for the formation of chylomicron and very low-density lipoprotein particles. Lomitapide is a small molecule microsomal triglyceride transfer protein inhibitor that was recently approved by the Food and Drug Administration as an adjunct to a low-fat diet and other lipid-lowering therapies for reducing low-density lipoprotein cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia (FH). Results from clinical trials of lomitapide have demonstrated its ability to reduce atherogenic lipoprotein concentrations in this population. Most recently, in a phase 3 clinical trial of 29 men and women with homozygous FH (mean baseline LDL-C, 336 mg/dL) who were on stable doses of concomitant lipid therapies and a low-fat diet, lomitapide was gradually titrated over 26 weeks (from 5 to 60 mg/d), followed by 52 weeks at the maximum tolerated dose. LDL-C decreased from baseline by 50% at 26 weeks, and reductions were maintained through the end of the study. Gastrointestinal disorders were the most frequent side effects and the most common reason for failure to tolerate lomitapide dose escalation. Few patients had elevated aspartate or alanine aminotransferases; bilirubin and alkaline phosphatase levels were unaffected; and hepatic fat increased by ? 10 g/100 g. In conclusion, recent data support the LDL-C-lowering efficacy of low-dose titrated lomitapide in patients with homozygous FH; however, concerns regarding increased hepatic fat will need to be addressed in long-term safety studies. PMID:23642324

  13. Novel mutations of low-density lipoprotein receptor gene in china patients with familial hypercholesterolemia.

    PubMed

    Fan, Liang-Liang; Lin, Min-Jie; Chen, Ya-Qin; Huang, Hao; Peng, Dao-Quan; Xia, Kun; Zhao, Shui-Ping; Xiang, Rong

    2015-05-01

    Familial hypercholesterolaemia (FH) is an autosomal dominant genetic disorder, associated with elevated level of serum low-density lipoprotein-cholesterol (LDL-C), which can lead to premature cardiovascular disease (CVD). Mutations in low density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) have been identified to be the underlying cause of this disease. Genetic research of FH has already been extensively studied all over the world. However, reports of FH mutations in the Chinese population are still limited. In this paper, 20 unrelated FH families were enrolled to detect the candidate gene variants in Chinese FH population by DNA direct sequencing. We identified 12 LDLR variants in 13 FH probands. Importantly, we first reported two unique mutations (c.2000_2000 delG/p.C667LfsX6 and c.605T>C/p.F202S) in LDLR gene. Our discoveries expand the spectrum of LDLR mutations and contribute to the genetic diagnosis and counseling for FH patients. PMID:25846081

  14. Standardization of a Method to Evaluate the Antioxidant Capacity of High-Density Lipoproteins

    PubMed Central

    de Juan-Franco, Elena; Pérez, Antonio; Ribas, Vicent; Sánchez-Hernández, Juan Antonio; Blanco-Vaca, Francisco; Ordóñez-Llanos, Jordi; Sánchez-Quesada, José Luis

    2009-01-01

    Background: A method to evaluate the antioxidant capacity of high-density lipoprotein (HDL) was developed and standardized. Methods: This method measure conjugated diene (CD) formation and electrophoretic mobility of low-density lipoprotein (LDL) in agarose gels in the presence and absence of HDL. HDL was isolated from 1 mL of plasma within 24 hours and oxidation assays were performed within 6 hours. Oxidation was induced by adding CuSO4. The lag phase increase in CD kinetics and the inhibition of electrophoretic mobility were defined as the HDL antioxidant capacity. Results: The optimal conditions for the CD assay were 2.5 ?M CuSO4, LDL at 0.1 g apoB/L, HDL at 0.1 g apoA-I/L, at 37°C and for 3h 50 min. Agarose electrophoresis at 100 V, at 4°C for 50 min was then performed immediately. CD formation variability was 21.1% for inter-assay CV and 12.7% for intra-assay CV. Electrophoretic mobility was 26.5% for inter-assay CV and 2.4% for intra-assay CV. Correlation analysis showed a significant association between the antioxidant capacity of HDL and its neutral/polar lipid ratio. Conclusions: The method herein described measures of the HDL antioxidant capacity in a reproducible and rapid manner that can be applied to a relatively high number of samples. PMID:23675165

  15. Lowering low-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus.

    PubMed

    Bays, Harold E

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, insulin resistance, and/or progressive loss of ?-cell function. T2DM patients are at increased risk of micro- and macrovascular disease, and are often considered as representing an atherosclerotic coronary heart disease (CHD) risk equivalent. Interventions directed at glucose and lipid level control in T2DM patients may reduce micro- and macrovascular disease. The optimal T2DM agent is one that lowers glucose levels with limited risk for hypoglycemia, and with no clinical trial evidence of worsening CHD risk. Lipid-altering drugs should preferably reduce low-density lipoprotein cholesterol and apolipoprotein B (apo B) and have evidence that the mechanism of action reduces CHD risk. Statins reduce low-density lipoprotein cholesterol and apo B and have evidence of improving CHD outcomes, and are thus first-line therapy for the treatment of hypercholesterolemia. In patients who do not achieve optimal lipid levels with statin therapy, or who are intolerant to statin therapy, add-on therapy or alternative therapies may be indicated. Additional available agents to treat hypercholesterolemic patients with T2DM include bile acid sequestrants, fibrates, niacin, and ezetimibe. This review discusses the use of these alternative agents to treat hypercholesterolemia in patients with T2DM, either as monotherapy or in combination with statin therapy. PMID:25045281

  16. Lowering low-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus

    PubMed Central

    Bays, Harold E

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, insulin resistance, and/or progressive loss of ?-cell function. T2DM patients are at increased risk of micro- and macrovascular disease, and are often considered as representing an atherosclerotic coronary heart disease (CHD) risk equivalent. Interventions directed at glucose and lipid level control in T2DM patients may reduce micro- and macrovascular disease. The optimal T2DM agent is one that lowers glucose levels with limited risk for hypoglycemia, and with no clinical trial evidence of worsening CHD risk. Lipid-altering drugs should preferably reduce low-density lipoprotein cholesterol and apolipoprotein B (apo B) and have evidence that the mechanism of action reduces CHD risk. Statins reduce low-density lipoprotein cholesterol and apo B and have evidence of improving CHD outcomes, and are thus first-line therapy for the treatment of hypercholesterolemia. In patients who do not achieve optimal lipid levels with statin therapy, or who are intolerant to statin therapy, add-on therapy or alternative therapies may be indicated. Additional available agents to treat hypercholesterolemic patients with T2DM include bile acid sequestrants, fibrates, niacin, and ezetimibe. This review discusses the use of these alternative agents to treat hypercholesterolemia in patients with T2DM, either as monotherapy or in combination with statin therapy. PMID:25045281

  17. 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...

  18. Passage of Low-density Lipoproteins Through Bruch’s Membrane and Choroid

    PubMed Central

    Cankova, Zdravka; Huang, Jiahn-Dar; Kruth, Howard S.; Johnson, Mark

    2011-01-01

    Plasma lipoproteins are thought to transport cholesterol, vitamins and carotenoids to the retinal pigment epithelium (RPE) for ultimate use by the photoreceptors. However, to reach the RPE, these lipoprotein particles must cross Bruch’s membrane. We examined the reflection coefficient of Bruch’s membrane (BrM) to low-density lipoprotein (LDL). Bruch’s membrane and choroid were removed from 47 bovine eyes. Specimens were placed in a Ussing chamber and perfused with phosphate-buffered saline (PBS) with (31 specimens) or without (16 specimens) fluorescent low-density lipoproteins (DiI-LDL). The hydraulic conductivity of the tissue was determined for both calf and cow eyes. In the perfusions with DiI-LDL, the fluorescence intensity emitted by DiI-LDL in the efflux was measured and the reflection coefficient of BrM/choroid preparations to DiI-LDL determined. Leakage tests were done to confirm tissue integrity. Several specimens were examined using scanning electron microscopy (SEM) to examine tissue integrity before and after perfusion. Leak testing confirmed that BrM was intact both before and after perfusion. The average hydraulic conductivity of BrM/choroid perfusion of calf eyes with PBS alone was 1.42 ± 0.55 ×10?9 m/s/Pa (mean ± SD, n = 11). The average hydraulic conductivity of the cow eyes was 4.94 ± 1.48 ×10?10 m/s/Pa (n = 5), nearly a 3-fold decrease with age. While the flow rate remained constant during the PBS perfusions, it decreased as a function of time during perfusion with DiI-LDLs. Our major finding was of fluorescence in the effluent collected in all perfusions with DiI-LDLs, demonstrating passage of LDL through the tissue. The average reflection coefficient of calf BrM/choroid preparations to DiI-LDL was 0.58 ± 0.25 (n = 23); a similar distribution of reflection coefficients was seen in tissue from cow eyes (0.51 ± 0.33, n = 8). Our data suggested that the DiI-LDL was modestly hindered and/or captured by the tissue. This might explain the progressive decrease of hydraulic conductivity with continued perfusion of DiI-LDL. PMID:22063729

  19. Hepatitis C Virus Stimulates Low-Density Lipoprotein Receptor Expression To Facilitate Viral Propagation

    PubMed Central

    Syed, Gulam Hussain; Tang, Huihui; Khan, Mohsin; Hassanein, Tarek; Liu, Jingwen

    2014-01-01

    ABSTRACT Lipids play a crucial role in multiple aspects of hepatitis C virus (HCV) life cycle. HCV modulates host lipid metabolism to enrich the intracellular milieu with lipids to facilitate its proliferation. However, very little is known about the influence of HCV on lipid uptake from bloodstream. Low-density lipoprotein receptor (LDLR) is involved in uptake of cholesterol rich low-density lipoprotein (LDL) particles from the bloodstream. The association of HCV particles with lipoproteins implicates their role in HCV entry; however, the precise role of LDLR in HCV entry still remains controversial. Here, we investigate the effect of HCV infection on LDLR expression and the underlying mechanism(s) involved. We demonstrate that HCV stimulates LDLR expression in both HCV-infected Huh7 cells and in liver tissue from chronic hepatitis C patients. Fluorescence activated cell sorting and immunofluorescence analysis revealed enhanced cell surface and total expression of LDLR in HCV-infected cells. Increased LDLR expression resulted in the enhanced uptake of lipoprotein particles by HCV-infected cells. Analysis of LDLR gene promoter identified a pivotal role of sterol-regulatory element binding proteins (SREBPs), in the HCV-mediated stimulation of LDLR transcription. In addition, HCV negatively modulated the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that facilitates LDLR degradation. Ectopic expression of wild-type PCSK9 or gain-of-function PCSK9 mutant negatively affected HCV replication. Overall, our results demonstrate that HCV regulates LDLR expression at transcriptional and posttranslational level via SREBPs and PCSK9 to promote lipid uptake and facilitate viral proliferation. IMPORTANCE HCV modulates host lipid metabolism to promote enrichment of lipids in intracellular environment, which are essential in multiple aspects of HCV life cycle. However, very little is known about the influence of HCV on lipid uptake from the bloodstream. LDLR is involved in uptake of cholesterol rich lipid particles from bloodstream. In this study, we investigated the effect of HCV on LDLR expression and the underlying mechanism triggered by the virus to modulate LDLR expression. Our observations suggest that HCV upregulates LDLR expression at both the protein and the transcript levels and that this upregulation likely contributes toward the uptake of serum lipids by infected hepatocytes. Abrogation of HCV-mediated upregulation of LDLR inhibits serum lipid uptake and thereby perturbs HCV replication. Overall, our findings highlight the importance of serum lipid uptake by infected hepatocytes in HCV life cycle. PMID:24352472

  20. Isolation and characterization of an apoA-ii- containing lipoprotein (LP-A-ii:B complex) from plasma very low density lipoproteins of patients with Tangier disease and type V hyperlipoproteinemia

    Microsoft Academic Search

    P. Alaupovic; C. Knight-Gibson; C. S. Wang; D. Downs; E. Koren; H. B. Brewer; R. E. Greg

    Previous studies have shown that very low density lipoproteins (VLDL) from patients with Tangier disease are less effective as a substrate for human milk lipoprotein lipase (LPL) than VLDL from normal controls as assessed by measuring the first order rate constant (k,) of triglyceride hydrolysis. Tangier VLDL also has a higher content of apolipoprotein (apo) A-I1 than normal VLDL. To

  1. A step towards quantitative lipoprotein density profiling analysis: applied Rayleigh scattering 

    E-print Network

    Nowlin, Michael

    2009-05-15

    Ultracentrifugation and imaging techniques of human blood serum are precise and information-rich methods for obtaining information about an individual’s lipoprotein particle content. The information derived from lipoprotein separations via...

  2. Streptococcal Serum Opacity Factor Increases Hepatocyte Uptake of Human Plasma High Density Lipoprotein-Cholesterol1

    PubMed Central

    Gillard, Baiba K.; Rosales, Corina; Pillai, Biju K.; Lin, Hu Yu; Courtney, Harry S.; Pownall, Henry J.

    2010-01-01

    Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM), that contains the cholesterol esters (CE) of up to ~400,000 HDL particles and apo E as its major protein. Similar SOF reaction products are obtained with HDL, total plasma lipoproteins and whole plasma. We hypothesized that hepatic uptake of CERM-CE via multiple apo E dependent receptors would be faster than that of HDL-CE. We tested our hypothesis using human hepatoma cells and lipoprotein receptor-specific Chinese hamster ovary (CHO) cells. [3H]CE uptake by HepG2 and Huh7 cells from HDL after SOF treatment, which transfers >90% of HDL-CE to CERM, was respectively 2.4 and 4.5 times faster than from control HDL. CERM-[3H]CE uptake was inhibited by LDL and HDL, suggestive of uptake by both the LDL receptor (LDL-R) and scavenger receptor class B type I (SR-BI). Studies in CHO cells specifically expressing LDL-R and SR-BI confirmed CERM-[3H]CE uptake by both receptors. RAP and heparin inhibit CERM-[3H]CE but not HDL-[3H]CE uptake thereby implicating LRP-1 and cell surface proteoglycans in this process. These data demonstrate that SOF treatment of HDL increases CE uptake via multiple hepatic apo E receptors. In so doing, SOF might increase hepatic disposal of plasma cholesterol in a way that is therapeutically useful. PMID:20879789

  3. Role of high density lipoproteins in the biodistribution of two radioiodinated probes in the rat

    SciTech Connect

    Pohland, R.C.; Counsell, R.E.

    1985-01-01

    Two radioiodinated probes, /sup 125/I-cholesteryl oleate (/sup 125/I-CO), a derivative of a natural constituent of lipoproteins, and 1-(2-chlorophenyl)-1-(4(/sup 125/I)iodophenyl)-2,2-dichlorethane (/sup 125/I-DDD), an analog of the adrenolytic drug o,p'-DDD (mitotane), were selected to study the role of lipoproteins in drug disposition and to examine the ability of these vehicles to direct foreign molecules to specific tissues. In vivo and in vitro techniques were utilized to associate these probes with rat high density lipoproteins (HDL). Tissue distribution studies indicated that prior incorporation of /sup 125/I-CO into rat HDL increased the uptake of /sup 125/I-CO by rat adrenal, which was dramatically enhanced when this preparation was administered to animals made hypolipidemic with 4-aminopyrazolo(3,4-d)-pyrimidine (4-APP). Acetylation of HDL labeled with /sup 125/I-CO provided evidence that the observed uptake into the adrenal was via a receptor-mediated process. In contrast with these results, prior association of /sup 125/I-DDD with rat HDL failed to alter the ability of this compound to accumulate in adrenal tissue of normal or hypolipidemic animals. Polyacrylamide gel electrophoresis (PAGE) was utilized to examine the stability of the association of /sup 125/I-CO and /sup 125/I-DDD with rat HDL. These results suggested that /sup 125/I-CO was associated with the lipophilic core of HDL, whereas /sup 125/I-DDD appeared to be partially associated with the surface components of HDL. Saturation of surface components with stable o,p'-DDD offered data to suggest that this binding to apoproteins may disrupt the normal receptor-mediated uptake process.

  4. Starvation of low-density lipoprotein-derived cholesterol induces bradyzoite conversion in Toxoplasma gondii

    PubMed Central

    2014-01-01

    Background Lacking enzymes for sterol synthesis, the intracellular protozoan Toxoplasma gondii scavenges cholesterol from host cells to multiply. T. gondii has a complex life cycle consisting of two asexual stages; the proliferative stage (tachyzoite), and the latent stage characterized by tissue cysts (bradyzoite). In vitro, bradyzoite development can be induced by mimicking host immune response stressors through treatment with IFN-?, heat shock, nitric oxide, and high pH. However, the extent to which host nutrients contribute to stage conversion in T. gondii is unknown. In this study, we examined the impact of host cholesterol levels on stage conversion in this parasite. Methods Growth of T. gondii tachyzoites (ME49 strain) was investigated in Chinese hamster ovary (CHO) cells using various concentrations of low-density lipoprotein (LDL), oleic acid, or glucose. Squalestatin, which is an inhibitor of squalene synthase and is, therefore, an inhibitor of sterol synthesis, was used to treat the CHO cells. Tachyzoite to bradyzoite conversion rates were analyzed by indirect fluorescent antibody tests. Results Parasite growth was significantly enhanced by addition of exogenous LDL, whereas no such enhancement occurred with oleic acids or glucose. In ME49, growth inhibition from squalestatin treatment was not obvious. Although growth of the RH strain was unaffected by squalestatin in the presence of lipoprotein, in its absence growth of this strain was suppressed. The frequency of BAG1-positive vacuoles in ME49 increased under lipoprotein-free conditions. However, addition of exogenous LDL did not increase tachyzoite to bradyzoite conversion in this strain. Furthermore, treatment with squalestatin did not enhance stage conversion. Conclusion Our results suggest that LDL-derived cholesterol levels play a crucial role in bradyzoite conversion in T. gondii. PMID:24885547

  5. Characterization of the binding of human low-density lipoprotein to primary monolayer cultures of rat hepatocytes.

    PubMed Central

    Salter, A M; Saxton, J; Brindley, D N

    1986-01-01

    The binding of human low-density lipoprotein labelled with 125I to rat hepatocytes in monolayer culture was measured at 4 degrees C. Evidence for two different specific binding sites was obtained. Binding to Site 1 was characterized by: being displaced by dextran sulphate or heparin; being dependent on Ca2+; having a Kd value of about 15 micrograms of protein/ml; not being significantly displaced by a 20-fold excess unlabelled low-density lipoprotein that had been reductively methylated; being displaced by approx. 40% by a 20-fold protein excess of unlabelled human high-density lipoprotein, HDL3, and increasing with time in culture when newborn-calf serum was present in the medium. The binding to Site 2 had the following properties: it was not displaced by sulphated polysaccharides; it was only partially Ca2+-dependent, and the presence of EDTA increased the Kd value; the apparent Kd value in the presence of Ca2+ was approx. 30 micrograms of protein/ml, which was significantly higher than for Site 1; it was displaced by approx. 30% with a 20-fold excess of low-density lipoprotein that had been methylated; it was displaced by unlabelled HDL3 to a similar extent to Site 1; it did not increase significantly with time in culture. The characteristics of binding to Sites 1 and 2 are discussed in relation to the receptors for low-density lipoproteins that have previously been described in various cell types. It is proposed that the experimental system described in this paper is suitable for studying the regulation of the binding of low-density lipoproteins to hepatocytes. PMID:2434075

  6. Structure of human plasma low-density lipoproteins: molecular organization of the central core.

    PubMed Central

    Atkinson, D; Deckelbaum, R J; Small, D M; Shipley, G G

    1977-01-01

    Human plasma low density lipoprotein (LDL) exhibits a thermal transition over the temperature range 20-40 degrees. This transition is associated with a structural change within the lipoprotein particle and is reflected in the small-angle x-ray scattering profiles from LDL. The scattering profile of the quasispherical LDL particle at 10 degrees shows a relatively intense maximum at 1/36 A-1 which is absent from the scattering of LDL at 45 degrees. Theoretical calculations, using model electron density distributions, have been carried out to describe the packing of arrangement of the cholesterol esters, based on perturbations of the molecular packing of crystalline cholesteryl myristate, adequately reproduces the high relative intensity of the x-ray scattering maximum at 1/36 A-1. The perturbations of the packing in the crystal structure of cholesteryl myristate involve "melting" of the hydrocarbon chains of the esters together with translations of pairs of molecules parallel to the molecular long axis. The interaction of opposing steroid moieties, with C18 and C19 angular methyl groups interlocked, exhibited in the crystal structure is retained in the perturbed arrangement. At 45 degrees, thermally induced disorder of this arrangement averages the electron density of the central core. The x-ray scattering profiles of particles with a homogeneous electron density in the core region do not show a high relative intensity of the subsidiary maxima in the 1/36 A-1 region, in agreement with experimental observation. The results of these calculations support the concept that the thermal transition observed for LDL is due to a smectic leads to disordered transition of the cholesterol esters in the core of the LDL particle. PMID:191827

  7. Toxicity of oxidized low density lipoproteins for vascular smooth muscle cells and partial protection by antioxidants.

    PubMed

    Guyton, J R; Lenz, M L; Mathews, B; Hughes, H; Karsan, D; Selinger, E; Smith, C V

    1995-12-01

    Oxidized low density lipoprotein (oxLDL) is known to be toxic to a variety of cell types, but relatively little is known about the toxic effects of oxLDL on vascular smooth muscle cells (SMC). We found that LDL oxidized by incubation with 5 microM cupric ions was toxic to cultured porcine SMC when administered at concentrations of 25 micrograms protein/ml and higher. The toxicity was demonstrated whether cells were proliferating or not, and was more evident in the presence of 0.4% lipoprotein-deficient serum than in 10%. Because of recent evidence that 7-ketocholesterol and 7-hydroxycholesterol are toxic species in copper-oxidized LDL, inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase was hypothesized as a mechanism of toxicity. However, mevalonic acid, the product of this enzyme, failed to protect against the toxicity of either oxLDL or the pure oxysterols. Alpha-tocopherol, alpha-tocopherol acetate, probucol, butylated hydroxytoluene, and deferoxamine provided partial protection to SMC exposed to oxLDL. These results suggested a toxic role for newly initiated lipid peroxidation, either in cells or in media oxLDL. Cellular lipid peroxidation appeared more likely, since no further oxidation of media oxLDL was demonstrated in the presence or absence of antioxidants. Overall, the results suggest that toxicity of copper-oxidized LDL for SMC is multifactorial and differs from the previously described toxicity of iron-oxidized LDL for fibroblasts. PMID:8770318

  8. Translation of two aggregated low-density lipoproteins within blood plasma: a mathematical model.

    PubMed

    Hadjinicolaou, Maria; Protopapas, Eleftherios

    2015-01-01

    Arteriosclerosis is a disease in which the artery walls get thicker and harder. Atherosclerosis is a specific form of arteriosclerosis which allows less blood to travel through the artery and increases blood pressure. Low-density lipoproteins (LDLs) and their ability to aggregate are important in atherosclerosis. In the present study we develop a mathematical model that describes the translation of two aggregated LDSs through blood plasma. We model the two aggregated LDLs as an inverted oblate spheroid and the flow as a creeping steady incompressible axisymmetric one. The mathematical tools that we used are the Kelvin inversion and the semi-separation of variables in the spheroidal coordinate systems. The stream function is given as a series expansion of even order terms of combinations of Gegenbauer functions of angular and radial dependence. The analytical solution is expected to give insight into the study of the various chemical precipitation methods used for the precipitation of lipoproteins, as this is the first step for the measurement of their concentration within blood plasma. PMID:25417024

  9. Optical Characterization of Europium Tetracycline Complex in the presence of Low Density Lipoprotein and its Applications

    NASA Astrophysics Data System (ADS)

    de Oliveira Silva, Flávia Rodrigues; Monteiro, Andrea Moreira; Neto, Antônio M. Figueiredo; Gidlund, Magnus A.; Gomes, Laércio; Junior, Nilson Dias Vieira; Courrol, Lilia Coronato

    2008-04-01

    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.

  10. High density lipoprotein-based contrast agents for multimodal imaging of atherosclerosis

    PubMed Central

    Skajaa, Torjus; Cormode, David P.; Falk, Erling; Mulder, Willem J. M.

    2010-01-01

    Lipoproteins, natural nanoparticles, have a well-recognized biological role and are highly suitable as a platform for delivering imaging agents. The ease with which both the exterior and interior of the particles can be modified permits the creation of multifunctional nanoparticles for imaging as well as the delivery of therapeutics. Importantly, their endogenous nature may make them biocompatible, biodegradable and allows them to avoid the recognition of the reticuloendothelial system. In particular, high density lipoproteins (HDL) are of interest, because of their small size they can easily cross the endothelium and penetrate the underlying tissue. We summarize here the progress in establishing HDL as a vector for delivering a variety of diagnostically active materials to vulnerable atherosclerotic plaques in mouse models of atherosclerosis. By loading various types of image-enhancing compounds into either the core or surface of HDL, they can be visualized by different imaging modalities (MRI, CT, optical). By re-routing of HDL away from plaque macrophages, imaging of biological processes in diseases besides atherosclerosis may also be achieved. PMID:19815819

  11. Characterization of lipid composition and high-density lipoprotein function in HIV-infected individuals on stable antiretroviral regimens.

    PubMed

    Munger, Alana M; Chow, Dominic C; Playford, Martin P; Parikh, Nisha I; Gangcuangco, Louie Mar A; Nakamoto, Beau K; Kallianpur, Kalpana J; Ndhlovu, Lishomwa C; Shikuma, Cecilia M; Mehta, Nehal N

    2015-02-01

    There is an increase in the cardiovascular disease (CVD) morbidity in individuals infected with HIV that may be due to inflammatory lipid modulation not captured by traditional lipid measures. The objective of this study was to perform advanced lipoprotein phenotyping inclusive of the high-density lipoprotein (HDL) cholesterol efflux capacity and lipoprotein particle concentration and size in a well-phenotyped group of 118 patients infected with HIV. We used simple and multivariable analyses to determine the associations between advanced lipoprotein parameters and known cardiometabolic risk factors. Participants were on stable antiretroviral therapy (ART) and had benign traditional lipid panels [median total cholesterol, low-density lipoprotein (LDL)-C, HDL-C, and triglycerides of 178?mg/dl, 108?mg/dl, 44?mg/dl, and 122.5?mg/dl, respectively]. However, advanced lipoprotein phenotyping demonstrated an elevation of LDL particle number (median of 1,233?nmol/liter) and a decrease in LDL size (median of 20.4?nm), along with a decrease in protective, large HDL particles (median of 3.15??mol/liter) and reduced HDL cholesterol efflux capacity in comparison to controls of other studies. HDL cholesterol efflux capacity was associated with HDL levels (?=0.395, p<0.001), small LDL particle concentration (?=-0.198, p=0.031), insulin sensitivity by the Matsuda index (?=0.218, p=0.029), and the Framingham Risk Score (?=-0.184, p=0.046). We demonstrate an atherogenic lipoprotein profile by NMR spectroscopy and HDL efflux measurement in a group of HIV-infected patients on stable ART with normal lipid panels. PMID:25416403

  12. Lipoprotein lipase- and hepatic triglyceride lipase-promoted very low density lipoprotein degradation proceeds via an apolipoprotein E-dependent mechanism

    PubMed Central

    Medh, Jheem D.; Fry, Glenna L.; Bowen, Susan L.; Ruben, Stacie; Wong, Howard; Chappell, David A.

    2009-01-01

    Apolipoprotein E (apoE) is the primary recognition signal on triglyceride-rich lipoproteins responsible for interacting with low density lipoprotein (LDL) receptors and LDL receptor-related protein (LRP). It has been shown that lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) promote receptor-mediated uptake and degradation of very low density lipoproteins (VLDL) and remnant particles, possibly by directly binding to lipoprotein receptors. In this study we have investigated the requirement for apoE in lipase-stimulated VLDL degradation. We compared binding and degradation of normal and apoE-depleted human VLDL and apoE knockout mouse VLDL in human foreskin fibroblasts. Surface binding at 37°C of apoE knockout VLDL was greater than that of normal VLDL by 3-and 40-fold, respectively, in the presence of LPL and HTGL. In spite of the greater stimulation of surface binding, lipase-stimulated degradation of apoE knockout mouse VLDL was significantly lower than that of normal VLDL (30, 30, and 80%, respectively, for control, LPL, and HTGL treatments). In the presence of LPL and HTGL, surface binding of apoE-depleted human VLDL was, respectively, 40 and 200% of normal VLDL whereas degradation was, respectively, 25 and 50% of normal VLDL. LPL and HTGL stimulated degradation of normal VLDL in a dose-dependent manner and by a LDL receptor-mediated pathway. Maximum stimulation (4-fold) was seen in the presence LPL (1 µg/ml) or HTGL (3 µg/ml) in lovastatin-treated cells. On the other hand, degradation of apoE-depleted VLDL was not significantly increased by the presence of lipases even in lovastatin-treated cells. Surface binding of apoE-depleted VLDL to metabolically inactive cells at 4°C was higher in control and HTGL-treated cells, but unchanged in the presence of LPL. Degradation of prebound apoE-depleted VLDL was only 35% as efficient as that of normal VLDL. Surface binding of apoE knockout or apoE-depleted VLDL was to heparin sulfate proteoglycans because it was completely abolished by heparinase treatment. However, apoE appears to be a primary determinant for receptor-mediated VLDL degradation. PMID:11060356

  13. Influence of Low Density Lipoprotein (LDL) Subfraction Profile and LDL Oxidation on Endothelium-Dependent and Independent Vasodilation in Patients with Type 2 Diabetes

    Microsoft Academic Search

    K. C. B. Tan; W. S. CHOW AI; M. T. CHAU; L. LEONG; K. S. L. LAM

    1999-01-01

    Recent studies have suggested that hypercholesterolemia is asso- ciated with endothelial dysfunction. In patients with type 2 diabetes mellitus, dyslipidemia is mainly characterized by hypertriglyceride- mia, low high density lipoprotein, and a preponderance of small dense low density lipoprotein (LDL) particles. We have examined the rela- tionships among LDL subfractions, the susceptibility of LDL to oxi- dation in vitro, and

  14. High-density Lipoprotein Increases the Uptake of Oxidized Low Density Lipoprotein via PPAR?/CD36 Pathway in Inflammatory Adipocytes

    PubMed Central

    Zhong, Qiaoqing; Zhao, Shuiping; Yu, Bilian; Wang, Xing; Matyal, Robina; Li, Yunping; Jiang, Zhisheng

    2015-01-01

    Aim: Previous studies have demonstrated that the dysregulated-secretion of adipokines by adipocytes may contribute to obesity-associated atherosclerosis (As) and high density lipoprotein (HDL) may protect against atherogenesis through multiple pathways. This study was to explore the effect of HDL on the oxLDL uptake in inflammatory adipocytes stimulated by endotoxin lipopolysaccharide (LPS) and the possible mechanism. Methods and Results: 3T3-L1 adipocytes were cultured and induced to differentiation and maturation. Acute inflammation in adipocytes was induced by LPS (100 ng/ml) for 6 hours. The adipocytes were pretreated with HDL in various concentrations (10, 50, 100 ?g/ml) for 16 hours or with specific PPAR? antagonist (GW9662, 10 ?M) or agonist (Rosiglitazone, 10 ?M) for 30 min before administration of LPS. The results showed that LPS significantly increased the release of inflammation-related adipokines, such as monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor 1 (PAI-1), tumor necrosis factor-alpha (TNF-?), interleukin (IL)-8 and IL-6, while decreasing the release of leptin and adiponectin. Meanwhile, LPS reduced the uptake and degradation of 125I-oxLDL, and down-regulated the expression of PPAR? and CD36. Pretreatment with HDL dose-dependently affected the release of IL-8 and IL-6 and the reduced uptake and degradation of oxLDL of adipocytes stimulated by LPS, accompanied with marked upregulation of PPAR? and CD36 expression. Pretreatment with GW9662 markedly inhibited the upregulation of CD36 expression mediated by HDL (100 ?g/ml), while the effects of Rosiglitazone were opposite to GW9662. Conclusions: HDL may increase oxLDL uptake of inflammatory adipocytes stimulated by LPS via upregulation of PPAR?/CD36 pathway, which may be a new mechanism of anti-atherosclerosis mediated by HDL. PMID:25678844

  15. Anti-oxidized low-density lipoprotein antibodies in myeloperoxidase–positive vasculitis patients preferentially recognize hypochlorite-modified low density lipoproteins

    PubMed Central

    Slot, M C; Theunissen, R; van Paassen, P; Damoiseaux, J G M C; Cohen Tervaert, J W

    2007-01-01

    Many patients surviving vasculitis are prone to accelerated atherosclerosis and often have enhanced levels of antibodies to oxidized low-density lipoprotein (oxLDL). To measure anti-oxLDL antibodies, oxidation of LDL is achieved with copper (Cu) or malondialdehyde (MDA). Because, in vivo, LDL may be oxidized with myeloperoxidase (MPO) or its product hypochlorite, we measured anti-hypochlorite LDL antibodies in patients with vasculitis, haemodialysis patients and healthy controls. A newly developed enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies to oxLDL as modified by hypochlorite. Results are compared with data obtained by standard LDL oxidation using MDA–LDL or Cu–LDL as substrate. Results were compared between anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients (n = 93), haemodialysis (HD) patients (n = 59) and healthy controls (HC; n = 43). Furthermore, patients with MPO–ANCA-associated vasculitis (n = 47) were compared with patients with proteinase 3 (PR3)–ANCA associated vasculitis (n = 46). Optimal cut-off points were determined by receiver operator characteristic (ROC) curve analysis. Anti-oxLDL antibodies are enhanced in AAV patients (MDA–LDL and hypochlorite–LDL) and in HD patients (hypochlorite–LDL), when compared to HC. Furthermore, patients with MPO–ANCA-associated vasculitis had higher levels of antibodies to hypochlorite–LDL than patients with PR3–ANCA-associated vasculitis. Our newly developed assay, in which hypochlorite–LDL is used as substrate, seems a more sensitive assay than traditional assays to measure oxLDL antibodies. Furthermore, our results suggest that enhanced MPO-mediated LDL oxidation occurs in patients with MPO–ANCA. PMID:17521320

  16. Phosphatidylcholine substrate specificity of lecithin: cholestrol acyltransferase-in high density lipoproteins and in lipids dispersions.

    PubMed

    Yokoyama, S; Murase, T; Akanuma, Y

    1977-09-01

    Lecithin: cholesterol acyltransferase (LCAT) was more highly activated by apolipoprotein A-I (apoA-I) with dimyristoyl phosphatidylcholine (DMPC) than with dilinoleoyl phosphatidylcholine (DLPC) when lipid dispersion of cholesterol and each phosphatidylcholine was used as a substrate. When the enzyme reactions were activated by whole apolipoproteins of high density lipoproteins (HDL), DLPC was more available to the LCAT reaction than DMPC with high concentrations of apoHDL in an incubation mixture. However, no detectable enzyme reaction was observed with dipalmitoyl phosphatidylcholine (DPPC) under both conditions. On the other hand, all of these phosphatidylcholines acted as substrates of LCAT when they were incorporated into HDL coupled to Sepharose. The order of their relative reactivities to cholesterol was DMPC, DPPC, AND DLPC under the conditions used. PMID:199582

  17. Malonyldialdehyde and glyoxal act differently on low-density lipoproteins and endotheliocytes.

    PubMed

    Kumskova, Elena M; Antonova, Olga A; Balashov, Sergey A; Tikhaze, Alla K; Melkumyants, Arthur M; Lankin, Vadim Z

    2014-11-01

    Under some pathological conditions, the natural dicarbonyl compounds can accumulate in the blood. The examples are malonyldialdehyde (MDA) formed as a secondary product of lipid peroxidation of unsaturated fatty acids during atherosclerosis, and glyoxal (GOX), a homolog of MDA, which accumulates during glucose autoxidation in patients with diabetes mellitus. This study compared the influence of both dicarbonyl compounds on low-density lipoproteins (LDL) and the membrane of endotheliocytes. In comparison with GOX, MDA induced more pronounced changes in physical and chemical properties of LDL particles. On the other hand, GOX-modified LDL particles were more prone to oxidation and aggregation than MDA-modified LDL. Incubation of endotheliocytes with MDA increased cell mechanical stiffness in contrast to incubation with GOX, which decreased it. PMID:25064448

  18. High density lipoprotein: it’s not just about lipid transport anymore

    PubMed Central

    Gordon, Scott M.; Hofmann, Susanna; Askew, David S.; Davidson, W. Sean

    2011-01-01

    Plasma levels of high density lipoprotein cholesterol (HDL-C) have long been associated with protection against cardiovascular disease (CVD) in large populations. However, HDL-C has been significantly less useful for predicting CVD risk in individual patients. This has ignited a new debate on the merits of measuring HDL quantity versus quality in terms of protective potential. In addition, numerous recent studies have begun to uncover HDL functions that vary surprisingly from traditional lipid transport roles. In this paper, we review recent findings that point to important functions for HDL that go well beyond lipid transport. These discoveries suggest that HDL might be a platform that mediates protection from a host of disease states ranging from CVD to diabetes to infectious disease. PMID:21067941

  19. Inhibition of copper-mediated low density lipoprotein peroxidation by quinoline and indolinone nitroxide radicals.

    PubMed

    Damiani, E; Paganga, G; Greci, L; Rice-Evans, C

    1994-09-15

    Quinoline and indolinone nitroxide radicals are known to be efficient scavengers of oxygen-centred (rate constants (k) between 10(3) and 10(5)/M/sec) and carbon-centred radicals (almost diffusion-controlled rate). In this study, the relative effects of these compounds in protecting low density lipoprotein (LDL) from oxidation induced by copper have been investigated. The extent of lipid peroxidation was assessed by monitoring the increased conjugated diene formation, the altered surface charge of the apolipoprotein B and the generation of aldehydic breakdown products of oxidized LDL. All the nitroxides inhibited LDL peroxidation in a concentration-dependent manner. The corresponding hydroxylamines of the nitroxides were also studied and were shown to inhibit lipid peroxidation to almost the same extent as the parent nitroxide. The data indicates that this class of nitroxide radicals (and their reduced hydroxylamine forms) are effective lipophilic antioxidants with the quinoline nitroxide being more efficient than the indolinone nitroxides. PMID:7945409

  20. High-density lipoproteins in the prevention of cardiovascular disease: changing the paradigm.

    PubMed

    Tuteja, S; Rader, D J

    2014-07-01

    High-density-lipoprotein cholesterol (HDL-C) has been identified in population studies as an independent inverse predictor of cardiovascular events. Although the causal nature of this association has been questioned, HDL and its major protein, apolipoprotein (apo)A1, have been shown to prevent and reverse atherosclerosis in animal models. In addition, HDL and apoA1 have several putatively atheroprotective functions, such as the ability to promote efflux of cholesterol from macrophages in the artery wall, inhibit vascular inflammation, and enhance endothelial function. Therefore, HDL-C and apoA1 have been investigated as therapeutic targets for coronary heart disease. However, recent clinical trials with drugs that raise HDL-C, such as niacin and inhibitors of cholesteryl ester transfer protein, have been disappointing. Here, we review the current state of the science regarding HDL as a therapeutic target. PMID:24713591

  1. A mathematical model for the blood plasma flow around two aggregated low-density lipoproteins.

    PubMed

    Hadjinicolaou, Maria

    2015-01-01

    The rheological behaviour of low-density lipoprotein (LDL) particles within the blood plasma and their role in atherogenesis, as well as their ability to aggregate under certain circumstances, is the subject of many clinical tests and theoretical studies aiming at the prevention of atherosclerosis. In the present study we develop a mathematical model that describes the flow of the blood plasma around two aggregated LDLs. We consider the flow as a creeping steady incompressible axisymmetric one, while the two aggregated LDLs are described by an inverted oblate spheroid. The mathematical methods of Kelvin inversion and the semi-separation of variables are employed and analytical expressions for the stream function are derived. These expressions are expected to be useful for further model developing and screening as well as the theoretical justification and validation of laboratory results. PMID:25417023

  2. Tailoring of Biomimetic High-Density Lipoprotein (HDL) Nanostructures Changes Cholesterol Binding and Efflux

    PubMed Central

    Luthi, Andrea J.; Zhang, Heng; Kim, Dongwoo; Giljohann, David A.; Mirkin, Chad A.; Thaxton, C. Shad

    2014-01-01

    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

  3. Content of low density lipoprotein receptors in breast cancer tissue related to survival of patients.

    PubMed Central

    Rudling, M J; Ståhle, L; Peterson, C O; Skoog, L

    1986-01-01

    The content of low density lipoprotein (LDL) receptors in tissue from primary breast cancers was determined and its prognostic information compared with that of variables of established prognostic importance. Frozen tumour specimens were selected, and tissue from 72 patients (32 of whom had died) were studied. The LDL receptor content showed an inverse correlation with the survival time. Analysis by a multivariate statistical method showed that the presence of axillary metastasis, content of receptors for oestrogen and LDL, diameter of the tumour, and DNA pattern were all of prognostic value with regard to patient survival. Improved methods of predicting survival time in patients with breast cancer may be of value in the choice of treatment for individual patients. PMID:3081176

  4. Inhibition of human low-density lipoprotein oxidation in vitro by ginger extracts.

    PubMed

    Gunathilake, K D Prasanna P; Rupasinghe, H P Vasantha

    2014-04-01

    Oxidative modification of low-density lipoprotein (LDL) is thought to play a key role in atherosclerotic plaque formation. Currently, there is a renewed interest in ginger because of its antioxidants and cardioprotective properties. The effects of ethanol, methanol, ethyl acetate, and hexane solvent extracts of ginger and pure major ginger constituents on Cu(2+)-induced oxidation of human LDL in vitro were examined. The LDL oxidation inhibition by ethanol, methanol, ethyl acetate, and hexane extracts of ginger was 71%, 76%, 67%, and 67%, respectively, at their optimum extraction conditions. Inhibition of LDL oxidation by water extracts of ginger, which was prepared by ultrasonic-assisted extraction conditions of 52°C for 15 min, was about 43%. Phenolic bioactives of ginger-6-gingerols, 8-gingerols, 10-gingerols, and 6-shogaol-seem to be strong inhibitors of Cu(+2)-induced LDL oxidation. Overall, ginger extracts, including the water extract possess the antioxidant activities to inhibit human LDL oxidation in vitro. PMID:24404979

  5. Oxidatively modified low-density lipoprotein in mononuclear cells detected by laser-induced fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Glenn, Tami N.; Oraevsky, Alexander A.; Tittel, Frank K.; Thomsen, Sharon L.; Jacques, Steven L.; Henry, Philip D.

    1995-05-01

    Hyperlipidemic states are associated with focal accumulations in arterial walls of oxidatively modified low density lipoprotein (LDL) and monocyte-derived liquid-laden macrophages, biochemical and cellular hallmarks of atheromatous lesions. Mechanisms underlying the generation and cellular uptake of oxidized LDL are still incompletely understood. We have used laser-induced fluorescence spectroscopy to monitor the formation, intracellular accumulation, and tissue distribution of oxidized LDL. Oxidatively modified LDL excited by a XeCl excimer laser (308 nm) exhibits unique spectral characteristics that distinguish it from native (non-oxidized) LDL. The same spectral characteristics were demonstrated in lipid-rich atheromatous lesions, macrophages after incubation with oxidized LDL, and peripheral blood monocytes from hyperlipidemic, but not normolipidemic subjects. Detection of oxidized LDL in peripheral blood monocytes and arterial tissue may provide information on the atherogenic activity of hyperlipidemic states and serve as a novel risk factor for the assessment of atherosclerosis.

  6. Anticipatory role of high density lipoprotein and endothelial dysfunction: an overview.

    PubMed

    Eren, Esin; Y?lmaz, Necat; Aydin, Ozgur; Ellida?, Hamit Y

    2014-01-01

    High Density Lipoprotein (HDL) has been witnessed to possess a range of different functions that contribute to its atheroprotective effects. These functions are: the promotion of macrophage cholesterol efflux, reverse cholesterol transport, anti-inflammatory, anti-thrombotic, anti-apoptotic, pro-fibrinolytic and anti-oxidative functions. Paraoxonase 1 (PON1) is an HDL associated enzyme esterase/homocysteinethiolactonase that contributes to the anti-oxidant and anti-atherosclerotic capabilities of HDL. PON1 is directly involved in the etiopathogenesis of atherosclerosis through the modulation of nitric oxide (NO) bioavailability. The aim of this review is to summarize the role of HDL on endothelial homeostasis, and also to describe the recently characterized molecular pathways involved. PMID:25598849

  7. Relationship between paraoxonase 1 activity and high density lipoprotein concentration during naturally occurring babesiosis in dogs.

    PubMed

    Rossi, G; Kuleš, J; Rafaj, R Bari?; Mrljak, V; Lauzi, S; Giordano, A; Paltrinieri, S

    2014-10-01

    Paraoxonase 1 (PON1) is a negative acute phase protein bound to high density lipoproteins (HDL) and during the acute phase response (APR) protects HDL from peroxidation. The aim of this study was to assess the relationship between PON1 and HDL in canine babesiosis, a disease characterized by oxidative damages and by an APR. PON1, HDL and C-reactive protein (CRP), were measured in blood collected from 15 controls and 29 dogs with babesiosis sampled at admission, and on days 1 and 7 after treatment. At admission, PON1 and HDL were significantly lower in affected dogs. HDL concentration increased at day 1 while PON1 increased and CRP decreased at day 7. This suggests that the decrease of PON1 at admission is in part due to an increased consumption, the decreased HDL may depend on lipid peroxidation and its rapid increase after treatment may depend on the antioxidant activity of PON1. PMID:25104322

  8. Pitavastatin reduces lectin-like oxidized low-density lipoprotein receptor-1 ligands in hypercholesterolemic humans.

    PubMed

    Matsumoto, Tetsuya; Fujita, Masatoshi; Sawamura, Tatsuya; Kakino, Akemi; Sato, Yuko; Fujita, Yoshiko; Matsuda, Haruo; Nakanishi, Mamoru; Uchida, Kagehiro; Nakae, Izuru; Kanda, Hiroshi; Yoshida, Akira; Miwa, Kunihisa; Hayashi, Hideki; Mitsunami, Kenichi; Horie, Minoru

    2010-04-01

    The aim of this study was to determine the impact of pitavastatin on low-density lipoprotein cholesterol (LDL-C) and lectin-like oxidized LDL receptor-1 (LOX-1) in patients with hypercholesterolemia. Twenty-five hypercholesterolemic patients (8 male, 17 female; age 66 +/- 13, 21-80 years) who had not received anti-dyslipidemic agents and had LDL-C levels of more than 160 mg/dL were examined. Biochemical factors were measured at baseline and after treatment with pitavastatin (2 mg/day) for 6 months. Serum levels of LOX-1 with apolipoprotein B-100 particle ligand and a soluble form of LOX-1 (sLOX-1) were measured by ELISA. All subjects completed the study with no adverse side effects. Total-C (268 +/- 26 vs. 176 +/- 17 mg/dL), LDL-C (182 +/- 21 vs. 96 +/- 14 mg/dL), and LOX-1 ligand (867 +/- 452 vs. 435 +/- 262 ng/mL) were reduced with pitavastatin treatment (P < 0.0001 for each). Significant decreases in triacylglycerols were noted (P < 0.0001), but there were no changes in high-density lipoprotein cholesterol. After 6 months, there were no significant changes in high-sensitivity CRP or soluble LOX-1. At baseline, there were no significant correlations between LOX-1 ligand and either LDL-C or sLOX-1. The decrease in LOX-1 ligand was not correlated with the decrease in LDL-C, but was correlated with the decrease in sLOX-1 (r = 0.47, P < 0.05). In conclusion, pitavastatin therapy had beneficial effects on markers of oxidative stress in hypercholesterolemic subjects. Serum levels of LOX-1 ligand may be a useful biomarker of the pleiotropic effects of statins. PMID:20229124

  9. Low high-density lipoprotein cholesterol: current status and future strategies for management

    PubMed Central

    Singh, Vibhuti; Sharma, Rakesh; Kumar, Ajoy; Deedwania, Prakash

    2010-01-01

    Atherosclerotic cardiovascular disease is the foremost cause of death and disability in the Western world, and it is rapidly becoming so in the developing nations. Even though the use of statin therapy aiming at the low-density lipoprotein cholesterol (LDL) has significantly reduced cardiovascular events and mortality, substantial residual cardiac events still occur in those being treated to the currently recommended targets. In fact, residual risk is also seen in those who are treated “aggressively” such as the “high risk” patients so defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III). Consequently, one must look for the predictors of risk beyond LDL reduction. High-density lipoprotein cholesterol (HDL) is the next frontier. The protectiveness of elevated HDL against atherosclerosis is well described in the literature. HDL subdues several atherogenic processes, such as oxidation, inflammation, cell proliferation and thrombosis. It also helps mobilize the excess LDL via reverse cholesterol transport. Low levels of HDL have been shown to be independent predictors of risk. Thus, therapies to raise the HDL hold promise for additional cardiac risk reduction. In this regard, several randomized trials have recently tested this hypothesis, especially in patients at high risk. In addition to the use of aggressive lifestyle modification, clinical outcomes have been measured following augmentation of HDL levels with various treatment modalities, including aggressive statin therapy, combination therapy with fibrates and niacin, and direct HDL-raising drug treatments. These data for low HDL as an independent risk factor and as the new treatment target are reviewed in this paper. PMID:21127701

  10. High-density lipoprotein levels and risk of cardiovascular events: a review.

    PubMed

    Mureddu, Gian Francesco; Brandimarte, Filippo; De Luca, Leonardo

    2012-09-01

    High-density lipoprotein cholesterol (HDL-C) is a strong and independent predictor of major cardiovascular events in a wide range of patients. The relationship between HDL-C cholesterol and cardiovascular risk appears to be linear, continuous, negative and independent of other risk factors such as blood pressure, smoking and BMI. In addition, the inverse relationship between HDL-C and cardiovascular events does not depend on low-density lipoprotein cholesterol (LDL-C) levels, so a substantial residual cardiovascular risk is maintained also in individuals with LDL-C levels below the target recommended by scientific guidelines. Furthermore, a strong relationship among HDL-C levels, progression of atherosclerosis and risk of cardiovascular diseases has been also demonstrated. Treatments that increase HDL-C levels have been shown to be effective in reducing incidence of cardiovascular diseases both in primary and secondary prevention settings. However, proof that increasing HDL-C levels by pharmacological treatment is able to confer a reduction in major cardiovascular outcomes independent of changes in LDL-C or triglycerides levels is not completely defined. Among currently available compounds, statins do not seems to have a sufficient effect on HDL-C profile. Studies on fibrates have shown inconclusive results. Although niacin has been demonstrated to reduce the incidence of major cardiovascular events paralleling the regression of atherosclerosis, significant side-effects still limit its use. The potential benefit of cholesterol ester transfer protein inhibition is still under investigation. The combination therapy of fibrates with statins is also controversial. Thus, despite the potentially favorable effect of raising HDL-C levels, the available guidelines still do not consider HDL-C levels as a specific target for therapy. Further studies are needed to assess the role of new compounds to raise HDL-C levels or modify HDL composition and functionality. PMID:21986488

  11. Treating high density lipoprotein cholesterol (HDL-C): quantity versus quality.

    PubMed

    Pirillo, Angela; Norata, Giuseppe Danilo; Catapano, Alberico Luigi

    2013-01-01

    Low density lipoproteins (LDL) and high density lipoproteins (HDL) are independent risk factors for coronary heart disease (CHD); decreasing LDL-cholesterol (LDL-C) levels with statin therapy represents the primary goal in the management of cardiovascular disease. However, despite the efficacy of statins in reducing cardiovascular morbidity and mortality, a significant residual risk has been observed even after reaching the LDL-C target, suggesting that other risk factors beyond LDL-C should be addressed, including low levels of HDL-cholesterol (HDL-C). Several clinical trials have shown an inverse relationship between HDL-C levels and cardiovascular risk, and 1 mg/dl increment in HDL-C is associated in epidemiological studies with a 2-3% decrease in cardiovascular risk, suggesting that raising HDL-C levels might have beneficial effects to reduce cardiovascular disease. However, several lines of evidence indicate that the functional properties of HDL may be relevant as well. In patient with CAD and normal HDL-C levels, HDL exhibit significantly reduced protective functions, and rather appear to be pro-atherogenic; on the other hand some genetic mutations causing low levels of HDL-C are not associated with increased atherosclerosis. Furthermore, although niacin significantly increased HDL-C levels, no further clinical benefit was observed from the addition of niacin to statin therapy, suggesting that increasing HDL-C levels is not sufficient and perhaps functional properties of HDL must be considered when choosing a therapeutic strategy to reduce the residual cardiovascular risk. PMID:23286430

  12. Effect of bicarbonate on iron-mediated oxidation of low-density lipoprotein

    NASA Astrophysics Data System (ADS)

    Arai, Hirofumi; Berlett, Barbara S.; Chock, P. Boon; Stadtman, Earl R.

    2005-07-01

    Oxidation of low-density lipoprotein (LDL) may play an important role in atherosclerosis. We studied the effects of bicarbonate/CO2 and phosphate buffer systems on metal ion-catalyzed oxidation of LDL to malondialdehyde (MDA) and to protein carbonyl and MetO derivatives. Our results revealed that LDL oxidation in mixtures containing free iron or heme derivatives was much greater in bicarbonate/CO2 compared with phosphate buffer. However, when copper was substituted for iron in these mixtures, the rate of LDL oxidation in both buffers was similar. Iron-catalyzed oxidation of LDL was highly sensitive to inhibition by phosphate. Presence of 0.3-0.5 mM phosphate, characteristic of human serum, led to 30-40% inhibition of LDL oxidation in bicarbonate/CO2 buffer. Iron-catalyzed oxidation of LDL to MDA in phosphate buffer was inhibited by increasing concentrations of albumin (10-200 ?M), whereas MDA formation in bicarbonate/CO2 buffer was stimulated by 10-50 ?M albumin but inhibited by higher concentrations. However, albumin stimulated the oxidation of LDL proteins to carbonyl derivatives at all concentrations examined in both buffers. Conversion of LDL to MDA in bicarbonate/CO2 buffer was greatly stimulated by ADP, ATP, and EDTA but only when EDTA was added at a concentration equal to that of iron. At higher than stoichiometric concentrations, EDTA prevented oxidation of LDL. Results of these studies suggest that interactions between bicarbonate and iron or heme derivatives leads to complexes with redox potentials that favor the generation of reactive oxygen species and/or to the generation of highly reactive CO2 anion or bicarbonate radical that facilitates LDL oxidation. Freely available online through the PNAS open access option.Abbreviations: LDL, low-density lipoprotein; MDA, malondialdehyde; MetO, methionine sulfoxide.

  13. Paradoxical Elevation of High Density Lipoprotein Cholesterol in Association with Lacunar-Type Cerebral Infarction

    PubMed Central

    Meng, Gui-Lin; Tan, Yan; Fang, Min; Yang, Hong-Yan; Liu, Xue-Yuan; Zhao, Yan-Xin

    2015-01-01

    Background The aim of this study was to evaluate the association between high-density lipoprotein cholesterol (HDLC) levels and the risk of lacunar infarction (LI) in a retrospective cohort study in China. Material/Methods We recruited 229 patients with obsolete brain infarctions single side (SOBI), 218 with obsolete brain infarctions bilateral sides (BOBI), 193 with both acute stroke and obsolete lacunar infarctions single side (AI&SOBI), 113 with both acute stroke and obsolete lacunar infarctions bilateral sides (AI&BOBI), and 203 without any infarctions (Control). Results 1) The plasma levels of HDLC in group BOBI, AI&SOBI, and AI&BOBI were higher than in the control group, and lower in group SOBI than in the control group (p<0.01). 2) The plasma levels of HDLC in group AI&SOBI were significantly higher than in group SOBI (p<0.01). 3) The plasma levels of HLDL were similar between group AI&SOBI and AI&BOBI. 4) There were significant relationships between HDLC and acute lacunar stroke, even after adjusting for these factors such as age, sex, triglyceride, total cholesterol, low-density lipoprotein cholesterol, and history of diabetes (p=0.001). 4) Compared with the controls, the calculation of odds ratios indicated relative risk estimates of higher HDLC for acute lacunar stroke with obsolete lacunar infarction. Conclusions Elevated HDLC may be an independent predictor of recurrent stroke with obsolete lacunar infarctions single side in Chinese people, justifying clinical trials for secondary prevention of stroke by generally increasing HLDL level. According to the difference between single and bilateral side multiple silent lacunar infarcts, it is inferred that HDLC may increase the risk of atherothrombotic infarction but reduce the risk of cardioembolic infarction in the general Chinese population. PMID:26120926

  14. Hyperimmunization of apo-E-deficient mice with homologous malondialdehyde low-density lipoprotein suppresses early atherogenesis

    Microsoft Academic Search

    Jacob George; Arnon Afek; Boris Gilburd; Hana Levkovitz; Aviv Shaish; Iris Goldberg; Yuri Kopolovic; Georg Wick; Yehuda Shoenfeld; Dror Harats

    1998-01-01

    The role of the immune system in modulating atherosclerosis has recently been the subject of intensive research. Several previous authors have put forward a paradigm of the autoimmune process occurring in the vicinity of the plaque. Two recent studies have shown that immunization of rabbits with homologous modified low-density lipoprotein (LDL) led to suppression of atherosclerosis. In the current study

  15. Rapid isolation of apolipoprotein E from human plasma very low density lipoproteins by molecular sieve high performance liquid chromatography

    Microsoft Academic Search

    Ditta Pfaffinger; Celina Edelstein; Angelo M. Scanu

    A rapid (less than 1 hour) and sensitive technique was developed for the isolation of apolipoprotein E from the other main components of human plasma very low density lipoproteins using molecular sieve high performance liquid chromatography with an approximate 80% recovery. The properties of the pure apoprotein were those reported in the literature for products isolated by conventional chromato- graphic

  16. Significance of the variant and full-length forms of the very low density lipoprotein receptor in brain

    Microsoft Academic Search

    Yasuhiro Nakamura; Munehiko Yamamoto; Eriko Kumamaru

    2001-01-01

    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

  17. The various effects of fractionated oxidized low density lipoproteins on the growth of smooth muscle cells in culture

    Microsoft Academic Search

    Ming T. Lin; Wen-Chi Su; Mei-Ling Cheng; Kwang-Shien Cheng; Wen-Chang Chang; Lih-Yuh C. Wing; Chauyin J. Jen; Hua-Lin Wu

    1999-01-01

    The effects of fractionated oxidized low density lipoproteins (oxidized LDL) on the growth of vascular smooth muscle cells (VSMC) and their relationship to the formation of lysophosphatidylcholine (lyso-PC) as well as the activation of protein kinase C (PKC) were studied. VSMC were isolated from porcine aorta by explant culture. LDL was isolated from porcine blood by sequential ultracentrifugation and oxidized

  18. Aminoguanidine Inhibits Oxidative Modification of Low Density Lipoprotein Protein and the Subsequent Increase in Uptake by Macrophage Scavenger Receptors

    Microsoft Academic Search

    Sylvie Picard; Sampath Parthasarathy; Joachim Fruebis; Joseph L. Witztum

    1992-01-01

    Aminoguanidine decreases the formation of advanced glycosylation end products that occurs during chronic hyperglycemia. Presumably this occurs because early glycosylation products preferentially bind to aminoguanidine rather than to lysine groups of adjacent proteins. Because oxidative modification of low density lipoprotein (LDL) also involves derivatization of lysine residues of apolipoprotein (apo) B by reactive aldehydes formed during the decomposition of oxidized

  19. High-Density Lipoprotein Promotes Endothelial Cell Migration and Reendothelialization via Scavenger Receptor-B Type I

    Microsoft Academic Search

    Divya Seetharam; Chieko Mineo; Andrew K. Gormley; Linda L. Gibson; Wanpen Vongpatanasin; Ken L. Chambliss; Lisa D. Hahner; Melissa L. Cummings; Richard L. Kitchens; Yves L. Marcel; Daniel J. Rader; Philip W. Shaul

    2010-01-01

    Vascular disease risk is inversely related to circulating levels of high-density lipoprotein (HDL) cholesterol. However, the mechanisms by which HDL provides vascular protection are unclear. The disruption of endothelial monolayer integrity is an important contributing factor in multiple vascular disorders, and vascular lesion severity is tempered by enhanced endothelial repair. Here, we show that HDL stimulates endothelial cell migration in

  20. Identification of Modified Tryptophan Residues in Apolipoprotein B100 Derived from Copper Ion-Oxidized Low-Density Lipoprotein †

    Microsoft Academic Search

    Chao-yuh Yang; Zi-Wei Gu; Manlan Yang; Shen-Nan Lin; Gary Siuzdak; Charles V. Smith

    1999-01-01

    Oxidative modifications of low-density lipoproteins (LDL) may contribute to the pathogenesis of atherosclerosis. Although the oxidation products of the lipid components of LDL have been studied extensively, less is known about the oxidation products of the apoprotein, apolipoprotein B-100. To identify the specific oxidative modifications, we oxidized LDL in the presence of Cu2+, treated with DNPH, precipitated and delipidated the

  1. Oxidation of low density lipoproteins by myeloperoxidase at the surface of endothelial cells: an additional mechanism to subendothelium oxidation

    Microsoft Academic Search

    K. Zouaoui Boudjeltia; N. Moguilevskyf; I. Legssyer; S. Babar; M. Guillaume; P. Delree; M. Vanhaeverbeek; D. Brohee; J. Ducobue; C. Remacle

    2004-01-01

    The present paradigm of atherogenesis proposes that low density lipoproteins (LDL) are trapped in subendothelial space of the vascular wall where they are oxidized. Myeloperoxidase (MPO) plays a key role in oxidative damage. We propose that LDL oxidation by myeloperoxidase (Mox-LDL) could occur at the surface of the endothelial cells and not restricted to the subendothelial space. The triad constituted

  2. Theoretical Prediction of Low-Density Lipoproteins Concentration at the Luminal Surface of an Artery with a Multiple Bend

    Microsoft Academic Search

    Shigeo Wada; Takeshi Karino

    2002-01-01

    To elucidate the mechanisms of localization of atherosclerotic lesions in man, the effects of various physical and hemodynamic factors on transport of atherogenic low-density lipoproteins (LDL) from flowing blood to the wall of an artery with a multiple bend were studied theoretically by means of a computer simulation under the conditions of a steady flow. It was found that due

  3. 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...

  4. High density lipoprotein cholesterol is not a major risk factor for ischaemic heart disease in British men

    Microsoft Academic Search

    S J Pocock; A G Shaper; A N Phillips; M Walker; T P Whitehead

    1986-01-01

    The concentration of high density lipoprotein cholesterol (HDL cholesterol) in serum was measured at initial examination in a large prospective study of men aged 40-59 drawn from general practices in 24 British towns. After an average follow up of 4.2 years 193 cases of major ischaemic heart disease had been registered in 7415 men in whom both HDL cholesterol and

  5. Identification of the low density lipoprotein receptor-related protein (LRP) as an endocytic receptor for thrombospondin-1

    Microsoft Academic Search

    Svetlana Godyna; Gene Liau; Ileana Popa; Steingrimur Stefansson; W. Scott Argraves

    1995-01-01

    Thrombospondin-1 (TSP1) has potent biolog- ical effects on vasculature smooth muscle cells (SMCs) and endothelial cells. The regulation of extracellular ac- cumulation of TSP1 is mediated by a previously ob- scure process of endocytosis which leads to its lyso- somal degradation. Since members of the low density lipoprotein receptor (LDLR) family have been found to mediate endocytosis which leads to

  6. efficiently activates its G protein A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle

    E-print Network

    Zare, Richard N.

    efficiently activates its G protein A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle Brian Kobilka, and Roger K. Sunahara Matthew R. Whorton, Michael P. Bokoch, Søren G. F, see: Reprints www.pnas.org/misc/reprints.shtml To order reprints, see: Notes: #12;A monomeric G

  7. Glucagon, cyclic AMP and adrenaline stimulate the degradation of low-density lipoprotein by cultured rat hepatocytes.

    PubMed Central

    Brown, N F; Salter, A M; Fears, R; Brindley, D N

    1989-01-01

    Rat hepatocytes were preincubated for 16 h with hormones or drugs and then for a further 8 h with 125I-human low-density lipoprotein (LDL). Glucagon (via cyclic AMP) and adrenaline (via cyclic AMP and alpha-effects) increased the binding of 125I-LDL to the LDL receptor, and the degradation of LDL to [125I]iodotyrosine. The effects on degradation were antagonized by dexamethasone, and the action of cyclic AMP on binding and degradation was inhibited by actinomycin D. The results are discussed in relation to the control of lipoprotein metabolism in diabetes. PMID:2552996

  8. Mass Spectrometry-Based Proteomic Study Makes High-Density Lipoprotein a Biomarker for Atherosclerotic Vascular Disease

    PubMed Central

    Yang, Chao-Yuh; Tsai, Fuu-Jen; Lin, Shih-Yi

    2015-01-01

    High-density lipoprotein (HDL) is a lipid and protein complex that consists of apolipoproteins and lower level HDL-associated enzymes. HDL dysfunction is a factor in atherosclerosis and decreases patient survival. Mass spectrometry- (MS-) based proteomics provides a high throughput approach for analyzing the composition and modifications of complex HDL proteins in diseases. HDL can be separated according to size, surface charge, electronegativity, or apoprotein composition. MS-based proteomics on subfractionated HDL then allows investigation of lipoprotein roles in diseases. Herein, we review recent developments in MS-based quantitative proteomic techniques, HDL proteomics and lipoprotein modifications in diseases, and HDL subfractionation studies. We also discuss future directions and perspectives in MS-based proteomics on HDL.

  9. PFOS induced lipid metabolism disturbances in BALB/c mice through inhibition of low density lipoproteins excretion

    NASA Astrophysics Data System (ADS)

    Wang, Ling; Wang, Yu; Liang, Yong; Li, Jia; Liu, Yuchen; Zhang, Jie; Zhang, Aiqian; Fu, Jianjie; Jiang, Guibin

    2014-04-01

    Male BALB/c mice fed with either a regular or high fat diet were exposed to 0, 5 or 20 mg/kg perfluorooctane sulfonate (PFOS) for 14 days. Increased body weight, serum glucose, cholesterol and lipoprotein levels were observed in mice given a high fat diet. However, all PFOS-treated mice got reduced levels of serum lipid and lipoprotein. Decreasing liver glycogen content was also observed, accompanied by reduced serum glucose levels. Histological and ultrastructural examination detected more lipid droplets accumulated in hepatocytes after PFOS exposure. Moreover, transcripitonal activity of lipid metabolism related genes suggests that PFOS toxicity is probably unrelevant to PPAR?'s transcription. The present study demonstrates a lipid disturbance caused by PFOS and thus point to its role in inhibiting the secretion and normal function of low density lipoproteins.

  10. Collagenase-3 binds to a specific receptor and requires the low density lipoprotein receptor-related protein for internalization

    NASA Technical Reports Server (NTRS)

    Barmina, O. Y.; Walling, H. W.; Fiacco, G. J.; Freije, J. M.; Lopez-Otin, C.; Jeffrey, J. J.; Partridge, N. C.

    1999-01-01

    We have previously identified a specific receptor for collagenase-3 that mediates the binding, internalization, and degradation of this ligand in UMR 106-01 rat osteoblastic osteosarcoma cells. In the present study, we show that collagenase-3 binding is calcium-dependent and occurs in a variety of cell types, including osteoblastic and fibroblastic cells. We also present evidence supporting a two-step mechanism of collagenase-3 binding and internalization involving both a specific collagenase-3 receptor and the low density lipoprotein receptor-related protein. Ligand blot analysis shows that (125)I-collagenase-3 binds specifically to two proteins ( approximately 170 kDa and approximately 600 kDa) present in UMR 106-01 cells. Western blotting identified the 600-kDa protein as the low density lipoprotein receptor-related protein. Our data suggest that the 170-kDa protein is a specific collagenase-3 receptor. Low density lipoprotein receptor-related protein-null mouse embryo fibroblasts bind but fail to internalize collagenase-3, whereas UMR 106-01 and wild-type mouse embryo fibroblasts bind and internalize collagenase-3. Internalization, but not binding, is inhibited by the 39-kDa receptor-associated protein. We conclude that the internalization of collagenase-3 requires the participation of the low density lipoprotein receptor-related protein and propose a model in which the cell surface interaction of this ligand requires a sequential contribution from two receptors, with the collagenase-3 receptor acting as a high affinity primary binding site and the low density lipoprotein receptor-related protein mediating internalization.

  11. High-density lipoprotein-cholesterol, daily estradiol and progesterone, and mammographic density phenotypes in premenopausal women.

    PubMed

    Flote, Vidar G; Frydenberg, Hanne; Ursin, Giske; Iversen, Anita; Fagerland, Morten W; Ellison, Peter T; Wist, Erik A; Egeland, Thore; Wilsgaard, Tom; McTiernan, Anne; Furberg, Anne-Sofie; Thune, Inger

    2015-06-01

    High-density lipoprotein-cholesterol (HDL-C) may influence the proliferation of breast tumor cells, but it is unclear whether low HDL-C levels, alone or in combination with cyclic estrogen and progesterone, are associated with mammographic density, a strong predictor of breast cancer development. Fasting morning serum concentrations of HDL-C were assessed in 202 premenopausal women, 25 to 35 years of age, participating in the Norwegian Energy Balance and Breast Cancer Aspects (EBBA) I study. Estrogen and progesterone were measured both in serum, and daily in saliva, throughout an entire menstrual cycle. Absolute and percent mammographic density was assessed by a computer-assisted method (Madena), from digitized mammograms (days 7-12). Multivariable models were used to study the associations between HDL-C, estrogen and progesterone, and mammographic density phenotypes. We observed a positive association between HDL-C and percent mammographic density after adjustments (P = 0.030). When combining HDL-C, estradiol, and progesterone, we observed among women with low HDL-C (<1.39 mmol/L), a linear association between salivary 17?-estradiol, progesterone, and percent and absolute mammographic density. Furthermore, in women with low HDL-C, each one SD increase of salivary mid-menstrual 17?-estradiol was associated with an OR of 4.12 (95% confidence intervals; CI, 1.30-13.0) of having above-median percent (28.5%), and an OR of 2.5 (95% CI, 1.13-5.50) of having above-median absolute mammographic density (32.4 cm(2)). On the basis of plausible biologic mechanisms linking HDL-C to breast cancer development, our findings suggest a role of HDL-C, alone or in combination with estrogen, in breast cancer development. However, our small hypothesis generating study requires confirmation in larger studies. Cancer Prev Res; 8(6); 535-44. ©2015 AACR. PMID:25804612

  12. Oxidized Low Density Lipoprotein (LDL) Affects Hyaluronan Synthesis in Human Aortic Smooth Muscle Cells*

    PubMed Central

    Viola, Manuela; Bartolini, Barbara; Vigetti, Davide; Karousou, Evgenia; Moretto, Paola; Deleonibus, Sara; Sawamura, Tatsuya; Wight, Thomas N.; Hascall, Vincent C.; De Luca, Giancarlo; Passi, Alberto

    2013-01-01

    Thickening of the vessel in response to high low density lipoprotein(s) (LDL) levels is a hallmark of atherosclerosis, characterized by increased hyaluronan (HA) deposition in the neointima. Human native LDL trapped within the arterial wall undergoes modifications such as oxidation (oxLDL). The aim of our study is to elucidate the link between internalization of oxLDL and HA production in vitro, using human aortic smooth muscle cells. LDL were used at an effective protein concentration of 20–50 ?g/ml, which allowed 80% cell viability. HA content in the medium of untreated cells was 28.9 ± 3.7 nmol HA-disaccharide/cell and increased after oxLDL treatment to 53.9 ± 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX-1 scavenger receptor with a specific antibody (10 ?g/ml). The cholesterol moiety of LDL has an important role in HA accumulation because cholesterol-free oxLDL failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and unmodified cholesterol (20 ?g/ml) induce only HAS3 transcription, whereas 22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78). Our data suggest that HA synthesis can be induced in response to specific oxidized sterol-related species delivered through oxLDL. PMID:23979132

  13. A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol.

    PubMed

    Kotowski, Ingrid K; Pertsemlidis, Alexander; Luke, Amy; Cooper, Richard S; Vega, Gloria L; Cohen, Jonathan C; Hobbs, Helen H

    2006-03-01

    Selected missense mutations in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) cause autosomal dominant hypercholesterolemia, whereas nonsense mutations in the same gene are associated with low plasma levels of low-density lipoprotein cholesterol (LDL-C). Here, DNA sequencing and chip-based oligonucleotide hybridization were used to determine whether other sequence variations in PCSK9 contribute to differences in LDL-C levels. The coding regions of PCSK9 were sequenced in the blacks and whites from the Dallas Heart Study (n=3,543) who had the lowest (<5th percentile) and highest (>95th percentile) plasma levels of LDL-C. Of the 17 missense variants identified, 3 (R46L, L253F, and A443T) were significantly and reproducibly associated with lower plasma levels of LDL-C (reductions ranging from 3.5% to 30%). None of the low-LDL-C variants were associated with increased hepatic triglyceride content, as measured by proton magnetic resonance spectroscopy. This finding is most consistent with the reduction in LDL-C being caused primarily by accelerating LDL clearance, rather than by reduced lipoprotein production. Association studies with 93 noncoding single-nucleotide polymorphisms (SNPs) at the PCSK9 locus identified 3 SNPs associated with modest differences in plasma LDL-C levels. Thus, a spectrum of sequence variations ranging in frequency (from 0.2% to 34%) and magnitude of effect (from a 3% increase to a 49% decrease) contribute to interindividual differences in LDL-C levels. These findings reveal that PCSK9 activity is a major determinant of plasma levels of LDL-C in humans and make it an attractive therapeutic target for LDL-C lowering. PMID:16465619

  14. High density lipoprotein conversion mediated by human plasma phospholipid transfer protein.

    PubMed

    Tu, A Y; Nishida, H I; Nishida, T

    1993-11-01

    Phospholipid transfer protein (PLTP) was purified from lipoprotein-free human plasma, obtained upon treatment of plasma with dextran sulfate and Ca2+, by employing a series of column chromatography. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified PLTP showed a single main band, corresponding to the molecular mass of 78 kDa. However, isoelectric focusing of the purified preparation gave multiple bands with pI ranging from 4.3 to 5.1, indicative of microheterogeneity. Purified PLTP was shown to possess not only phospholipid transfer activity, but also high density lipoprotein (HDL) conversion activity (Tu, A.-Y., Nishida, H. I., and Nishida, T. (1990), FASEB J. 4, A2148; Jauhiainen, M., Metso, J., Pahlman, R., Blomqvist, S., van Tol, A., and Ehnholm, C. (1993) J. Biol. Chem. 268, 4032-4036). Isolated HDL3 was enlarged to the size of HDL2b upon incubation with purified PLTP for 6 h at 37 degrees C at the PLTP/HDL3 molar ratio of approximately 1:45. Both the HDL conversion and the phosphatidylcholine transfer activities of purified PLTP were effectively inhibited by rabbit anti-PLTP immunoglobulin G. The primary importance of PLTP in the HDL enlargement that occurs in human plasma upon incubation at 37 degrees C was shown by the strong inhibitory effect of the anti-PLTP immunoglobulin G. The process of PLTP-mediated HDL enlargement was accompanied by the release of apoproteins, primarily apoA-I. HDL3 enlargement mediated by PLTP was effectively inhibited by the addition of free fatty acids. PMID:8226827

  15. Gestational diabetes mellitus modulates neonatal high-density lipoprotein composition and its functional heterogeneity.

    PubMed

    Sreckovic, Ivana; Birner-Gruenberger, Ruth; Besenboeck, Carolin; Miljkovic, Milica; Stojakovic, Tatjana; Scharnagl, Hubert; Marsche, Gunther; Lang, Uwe; Kotur-Stevuljevic, Jelena; Jelic-Ivanovic, Zorana; Desoye, Gernot; Wadsack, Christian

    2014-11-01

    Gestational diabetes mellitus (GDM) is related to neonatal macrosomia and an increased risk of vascular events. We hypothesized that GDM exerts qualitative effects on neonatal high-density lipoprotein (HDL). HDL was isolated from control (n=11) and GDM maternal/neonatal donors (n=9) and subjected to shotgun proteomics. Differences in HDL mobility were assessed by FPLC and native gel-electrophoresis. Paraoxonase (PON1) activity, cholesterol ester-transfer protein (CETP) mass and activity, phospholipid, triglyceride and cholesterol concentrations were quantified with commercial kits. Total anti-oxidative capacity and cholesterol efflux capability of HDLs were measured. Four proteins involved in lipid metabolism, inflammation and innate immunity were differentially expressed between controls and GDM neonates. ApoM (decreased, p<0.05) and SAA1 (increased, p<0.05) showed the same differences on both, maternal and neonatal GDM HDL. Lower PON1 protein expression was corroborated by lower activity (p<0.05) which in turn was associated with attenuated anti-oxidant capacity of GDM HDL. Protein changes were accompanied by increased levels of triglycerides and decreased levels of cholesterol esters, respectively. The observed differences in GDM HDL lipid moiety may be related to CETP mass and activity alterations. The rate of cholesterol efflux from term trophoblasts to maternal and from placental endothelial cells to neonatal GDM HDL was impaired (p<0.05). In conclusion, GDM causes changes in HDL composition and is intimately associated with impaired cholesterol efflux capability as well as diminished anti-oxidative particle properties. Remodeling of neonatal GDM HDL in utero supports the hypothesis that maternal conditions in pregnancy impact neonatal lipoprotein metabolism. PMID:25130684

  16. A piezoelectric-based immunosensor for high density lipoprotein particle measurement.

    PubMed

    Chunta, Suticha; Suk-Anake, Jamikorn; Chansiri, Kosum; Promptmas, Chamras

    2014-09-21

    A piezoelectric-based immunosensor was developed for high density lipoprotein particle (HDL-P) measurement. Monoclonal anti-human apolipoprotein A1 antibody was used as a specific binding molecule for the major apolipoprotein of HDL-P. This sensing element was fabricated by immobilizing the anti-human apolipoprotein A1 on a 12 MHz AT-cut quartz crystal via a 3-mercaptopropionic acid (MPA) self-assembled monolayer. The frequency shift from the mass change of the antigen-antibody binding refers to the amount of HDL-P. The optimal antibody immobilization was performed to achieve the maximum potential of the antibody. The appropriate quantity and immobilization time of the antibody were 0.1 mg ml(-1) and 90 minutes, respectively. The immobilized antibody in the HDL-P immunosensor accomplished perfect binding with HDL-P within 60 minutes. The dose-response curve for HDL-P showed a linear response from 0.21 to 2.50 mg protein per ml equivalent to 0.40 × 10(10) to 3.65 × 10(10) particles per ?l without significant interference from other lipoproteins. The intra- and inter-assay imprecision (CV) were 7.8 and 18.5%, respectively. The analytical accuracy of this measurement was 96.29-96.31%. The HDL-P concentration obtained from the sensor revealed a 2.05 mg protein per ml with 0.26 mg protein per ml of expanded uncertainty at the 95% confidence level. This immunosensor gave an assay result which correlated with the homogeneous enzymatic colorimetric assay (R(2) = 0.902). PMID:25030774

  17. Species differences in the proportion of plasma lipoprotein lipid carried by high-density lipoproteins influence the distribution of free and liposomal nystatin in human, dog, and rat plasma.

    PubMed

    Ramaswamy, M; Wallace, T L; Cossum, P A; Wasan, K M

    1999-06-01

    The objective of this study was an interspecies comparison of free nystatin (NYS) and liposomal NYS (Nyotran) distribution in plasma. NYS and liposomal NYS at concentrations of 5, 10, and 20 microg of NYS/ml were incubated in human, dog, and rat plasma for 5, 60, and 180 min at 37 degrees C. Following these incubations, plasma samples were separated into their high-density lipoprotein (HDL), triglyceride-rich lipoprotein, low-density lipoprotein, and lipoprotein-deficient plasma (LPDP) fractions by density-gradient ultracentrifugation, and each fraction was assayed for NYS by high-pressure liquid chromatography. Total plasma and lipoprotein cholesterol, triglyceride, and protein concentrations in each human, dog, or rat plasma sample were determined by enzymatic assays. When NYS and liposomal NYS were incubated in human, dog, or rat plasma, the majority of the NYS was recovered in the LPDP fraction. For the 5- and 60-min incubation times for all plasmas measured, a significantly greater percentage of NYS was recovered in the lipoprotein fraction (primarily HDL) following the incubation of liposomal NYS than following the incubation of NYS. There was a significant correlation between the lipoprotein lipid and protein profiles in human, dog, and rat plasmas and the distribution of NYS and liposomal NYS in plasma. In particular, differences in the proportion of plasma lipoprotein cholesterol, triglyceride, and apolar lipids (cholesteryl ester and triglycerides) carried by HDL influenced the distribution of NYS and liposomal NYS within plasmas of different species. These findings suggest that the distribution of NYS among plasma lipoproteins of different species is defined by the proportion of lipid carried by HDL, and this is possibly an important consideration when evaluating the pharmacokinetics, toxicities, and activities of these compounds following administration to different animal species. PMID:10348764

  18. Lipoprotein receptors in copper-deficient rats: in vitro binding of high-density lipoprotein subfractions to liver membranes

    SciTech Connect

    Hassel, C.A.

    1986-01-01

    Three studies were conducted to determine whether the elevated plasma and HDL cholesterol levels observed in copper-deficient rats could be explained by the interaction of /sup 125/I-HDL subfractions with liver membrane preparations in vitro. Rats from all studies were randomly divided into two dietary treatments, copper-deficient and adequate (0.7 mg and 8.0 mg Cukg diet, respectively). Total binding data and computer derived estimates (K/sub d/ and B/sub max/) were used to compare differences between treatments. Binding data from all experiments conformed to a one-site model. In all cases, binding was saturable and EDTA and pronase insensitive. Treatment differences were observed in Study I (/sup 125/I-apo E-free HDL binding to crude liver membranes). Significantly lower total binding and B/sub max/ were observed when lipoproteins and membranes from copper-deficient animals were used in the assay. Competition experiments from Studies II and III demonstrate that the different HDL subfractions competed effectively with one another for binding sites, indicating that apo E is not a determinant in binding of rat /sup 125/I-HDL subfractions to purified liver plasma membranes

  19. Macrophage plasma membrane chondroitin sulfate proteoglycan binds oxidized low-density lipoprotein

    Microsoft Academic Search

    Marielle Kaplan; Michael Aviram

    2000-01-01

    Lipoprotein interactions with macrophage proteoglycans (PGs) is believed to play an important role in the cellular uptake of lipoproteins and in macrophage cholesterol accumulation. Recently, we have shown the participation of macrophage plasma membrane glycosaminoglycans (GAGs) in the cellular uptake of oxidized LDL (Ox-LDL). The aim of the present study was to identify the specific cell surface proteoglycans involved in

  20. Depressed serum high density lipoprotein cholesterol levels in veterans with spinal cord injury

    Microsoft Academic Search

    W A Bauman; A M Spungen; You-Gong Zhong; J L Rothstein; C Petry; S K Gordon

    1992-01-01

    Cardiovascular diseases are the most frequent cause of death among persons with spinal cord injury (SCI), and these diseases are reported to occur prematurely in the disabled compared to the able bodied population. The mechanism of accelerated coronary heart disease (CHD) in persons with SCI may be partially explicable on the basis of the lipoprotein profile. We performed fasting lipoprotein

  1. ApoE and the role of very low density lipoproteins in adipose tissue inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our goal was too identify the role of triglyceride-rich lipoproteins and apoE, a major apolipoprotein in triglyceride-rich lipoproteins, in adipose tissue inflammation with high-fat diet induced obesity. Male apoE-/- and C57BL/6J wild-type mice fed high fat diets for 12 weeks were assessed for metab...

  2. Mechanisms responsible for hepatic very low density lipoprotein-apoB100 overproduction in Otsuka Long-Evans Tokushima fatty rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Overproduction of hepatic very low-density lipoprotein (VLDL)1 particles is a major abnormality of lipoprotein dysregulation in type 2 diabetes (T2D). We sought to examine the mechanisms linking systemic/hepatic inflammation associated with insulin resistance and apolipoprotein (apo) B100-containing...

  3. The Ser(447)-Stop polymorphism of lipoprotein lipase is associated with variation in longitudinal serum high-density lipoprotein-cholesterol profiles: the Bogalusa Heart Study.

    PubMed

    Hallman, D M; Srinivasan, S R; Elkasabany, A; Boerwinkle, E; Berenson, G S

    2001-08-01

    The Ser(447)-Stop polymorphism of lipoprotein lipase (LPL) has been associated with altered high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) levels at individual measurements, but nothing is known of its associations with lipid profiles derived from serial measurements. We used multilevel statistical models to study effects of this polymorphism on longitudinal lipid profiles in 1,006 Bogalusa Heart Study subjects examined 4 to 9 times between the ages of 4 and 38 years. Stop(447) allele frequencies in African Americans (0.053 +/- 0.011) and whites (0.091 +/- 0.009) differed significantly (chi(2) = 7.595, 1 df, P =.006; Stop(447) homozygotes and heterozygotes combined). Overall, TG levels were lower and HDL-C levels higher in blacks than in whites of the same age and sex. Longitudinal TG profiles were lower in Stop(447) carriers at all ages. However, longitudinal HDL-C profiles differed among genotype groups with age: the Stop(447) allele was associated with higher HDL-C only in subjects above approximately 10 years of age. Genotype-specific HDL-C profiles also differed significantly among race/sex groups. Thus, we found evidence of LPL genotype effects that vary within individuals with age. Possible mechanisms, which could account for age-related changes in the effects of LPL variants, are discussed. PMID:11474476

  4. Sex and time differences in the associations of non–high-density lipoprotein cholesterol versus other lipid and lipoprotein factors in the prediction of cardiovascular death (The Rancho Bernardo Study)

    Microsoft Academic Search

    Denise von Mühlen; Robert D. Langer; Elizabeth Barrett-Connor

    2003-01-01

    Non–high-density lipoprotein (HDL) cholesterol (total cholesterol [TC] minus HDL cholesterol) has been suggested as the preferred lipid fraction to predict cardiovascular disease. We compared the ability of lipids, lipoproteins, the ratio of total to HDL cholesterol (TC\\/HDL), and non-HDL cholesterol to predict fatal coronary heart disease (CHD) and cardiovascular disease in 1,386 women and 1,094 men (mean age 69 years).

  5. Lipid-free apolipoprotein (apo) AI is converted into alpha-migrating high density lipoproteins by lipoprotein-depleted plasma of normolipidemic donors and apo AI-deficient patients but not of Tangier disease patients

    Microsoft Academic Search

    Arnold von Eckardstein; Yadong Huang; John J. P Kastelein; Jürgen Geisel; José T Real; Jan-Albert Kuivenhoven; Roberto Miccoli; Giorgio Noseda; Gerd Assmann

    1998-01-01

    Plasma of patients with Tangier disease (TD) is devoid of ?-LpA-I (apolipoprotein A-I-containing lipoprotein), which in normolipidemic plasma constitutes the majority of high density lipoprotein (HDL). The residual amounts of apolipoprotein A-I (apo A-I) in TD plasma have electrophoretic pre?1-LpA-I mobility. We have previously demonstrated that TD plasma does not convert pre?1-LpA-I into ?-LpA-I. In this study we found that

  6. Increased expression of apolipoprotein E in transgenic rabbits results in reduced levels of very low density lipoproteins and an accumulation of low density lipoproteins in plasma.

    PubMed Central

    Fan, J; Ji, Z S; Huang, Y; de Silva, H; Sanan, D; Mahley, R W; Innerarity, T L; Taylor, J M

    1998-01-01

    Transgenic rabbits expressing human apo E3 were generated to investigate mechanisms by which apo E modulates plasma lipoprotein metabolism. Compared with nontransgenic littermates expressing approximately 3 mg/dl of endogenous rabbit apo E, male transgenic rabbits expressing approximately 13 mg/dl of human apo E had a 35% decrease in total plasma triglycerides that was due to a reduction in VLDL levels and an absence of large VLDL. With its greater content of apo E, transgenic VLDL had an increased binding affinity for the LDL receptor in vitro, and injected chylomicrons were cleared more rapidly by the liver in transgenic rabbits. In contrast to triglyceride changes, transgenic rabbits had a 70% increase in plasma cholesterol levels due to an accumulation of LDL and apo E-rich HDL. Transgenic and control LDL had the same binding affinity for the LDL receptor. Both transgenic and control rabbits had similar LDL receptor levels, but intravenously injected human LDL were cleared more slowly in transgenic rabbits than in controls. Changes in lipoprotein lipolysis did not contribute to the accumulation of LDL or the reduction in VLDL levels. These observations suggest that the increased content of apo E3 on triglyceride-rich remnant lipoproteins in transgenic rabbits confers a greater affinity for cell surface receptors, thereby increasing remnant clearance from plasma. The apo E-rich large remnants appear to compete more effectively than LDL for receptor-mediated binding and clearance, resulting in delayed clearance and the accumulation of LDL in plasma. PMID:9593771

  7. Adrenal imaging with technetium-99m-labelled low density lipoproteins

    SciTech Connect

    Isaacsohn, J.L.; Lees, A.M.; Lees, R.S.; Strauss, H.W.; Barlai-Kovach, M.; Moore, T.J.

    1986-04-01

    Evaluation of adrenal cortical function by external imaging is currently accomplished by injection of radiolabelled analogs of cholesterol. Although the adrenals do utilized exogenous cholesterol for steroid hormone synthesis, the cholesterol is delivered to the glands not as free cholesterol but through the uptake of low density lipoproteins (LDL), which are subsequently degraded within the adrenal cortical cells to provide cholesterol. Thus, we sought to assess the use of /sup 99m/Tc-labelled LDL injected into rabbits to obtain external images of the adrenal glands. Adrenal images of all nine rabbits tested were obtained within 18 to 21 hours after injection of /sup 99m/Tc-LDL. Seven of the rabbits were subjected to adrenal cortical suppression with dexamethasone and then all nine rabbits were imaged a second time. In the untreated animals, visualization of the adrenal glands was accompanied by normal serum cortisol concentrations and accumulation of radiolabel in the adrenals, whereas in the dexamethasone-treated animals, lack of visualization of the adrenal glands was correlated with low serum cortisols, and greatly decreased accumulation of the radionuclide in the adrenals. These findings demonstrate for the first time that LDL, when labelled with /sup 99m/Tc, can be used to evaluate adrenal cortical function by external imaging.

  8. Fluorescence correlation spectroscopy to measure the metabolism of high-density lipoprotein

    NASA Astrophysics Data System (ADS)

    Deitrick, Russell; Gibson, Emily; Razzaghi, Hamid

    2009-10-01

    High-density lipoprotein (HDL), referred to as the ``good cholesterol'', carries free cholesterol to the liver to be filtered from the bloodstream and is important to our understanding of atherosclerosis. HDL is metabolized in part by the enzyme Endothelial Lipase (EL). With this project we will use fluorescence correlation spectroscopy (FCS) to study the metabolism of HDL by EL comparing wild type with different genetic mutations. FCS is an advanced microscopy technique in which we record fluctuations in the fluorescence of dye-labeled molecules (in this case, HDL labeled with Nile Red) as they freely diffuse through a small focal volume. This data can be analyzed mathematically using the cross-correlation function, from which we can ultimately ascertain much information. In our case, we are interested in the diffusion coefficient which, via the Stokes-Einstein relation for a sphere, we can determine the size of HDL as it undergoes the process of metabolism. Preliminary results seem to indicate that the metabolic process occurs very quickly, that the final size of HDL depends primarily on the concentration of EL, and that the wild and mutant variants of EL have a similar effectiveness. In following experiments, we hope to investigate these relationships further.

  9. A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

    NASA Astrophysics Data System (ADS)

    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

  10. Ordering and stability in lipid droplets with applications to low-density lipoproteins

    NASA Astrophysics Data System (ADS)

    Lancaster, Jarrett L.; Antonijevic, Todor; Starobin, Joseph M.

    2014-06-01

    In this article, we present a framework for investigating the order-disorder transition in lipid droplets using the standard Ising model. While a single lipid droplet is itself a complex system whose constituent cholesteryl esters each possesses many degrees of freedom, we present justification for using this effective approach to isolate the underlying physics. It is argued that the behavior of the esters confined within lipid droplets is significantly different from that of a bulk system of similar esters, which is adequately described by continuum mean-field theory in the thermodynamic limit. When the droplet's shell is modeled as an elastic membrane, a simple picture emerges for a transition between two ordered phases within the core which is tuned by the strength of interactions between the esters. Triglyceride concentration is proposed as a variable which strongly influences the strength of interactions between cholesteryl esters within droplets. The possible relevance of this mechanism to the well known atherogenic nature of small low-density lipoprotein particles is discussed in detail.

  11. Oxidized low density lipoproteins stimulate phosphoinositide turnover in cultured vascular smooth muscle cells.

    PubMed

    Resink, T J; Tkachuk, V A; Bernhardt, J; Bühler, F R

    1992-03-01

    Atherogenesis is associated with alterations in the properties of different cell types, including monocytes/macrophages (foam cell formation), platelets (increased aggregation), endothelial cells (injury), and smooth muscle cells (SMCs) (lipid accumulation or foam cell formation). Oxidized low density lipoproteins (ox-LDL) play a key role in this vascular pathology. This study investigated the ability of ox-LDL to elicit chemical signaling events in cultured human vascular smooth muscle cells (VSMCs). Ox-LDL was found to stimulate phospholipase C-mediated phosphoinositide turnover in human VSMCs. This response occurred rapidly (within 1 minute) and at low concentrations of ox-LDL (half-maximal effective concentration, approximately 5 micrograms/ml). Ox-LDL-stimulated inositol phosphate accumulation in human VSMCs was inhibited by pretreatment of cells with phorbol 12-myristate 13-acetate and with compounds that elevate cyclic AMP or cyclic GMP. Ca2+ antagonists also blocked the effects of ox-LDL on phosphoinositide turnover. Inhibitors of receptor-endocytotic processes (including receptor clustering, cross-linking, and cytoskeleton-dependent internalization) effectively prevented ox-LDL-induced inositol phosphate generation. The data suggest that ox-LDL promotes phospholipase C-mediated phosphoinositide turnover in a manner analogous to that for other Ca(2+)-mobilizing hormones. The results also support an association between phosphoinositide turnover and receptor-mediated endocytosis. Prevention of the direct effects of ox-LDL on SMCs could prove an interesting therapeutic avenue for the prevention of atherosclerosis. PMID:1312338

  12. Interaction of peroxynitrite with carotenoids and tocopherols within low density lipoprotein.

    PubMed

    Pannala, A S; Rice-Evans, C; Sampson, J; Singh, S

    1998-02-27

    Peroxynitrite is a powerful oxidising and nitrating agent generated in vivo by the combination of nitric oxide and superoxide. Previous studies have shown that on exposure to peroxynitrite, low density lipoprotein (LDL) is modified resulting in both a time- and concentration-dependent change to lipid and protein components. The present investigation highlights the reaction between carotenoids and tocopherols, present within the lipophilic phase of LDL, and peroxynitrite at varying concentrations. It was observed that the carotenoids were consumed by a significantly greater proportion than that of the tocopherols with lycopene (87.2 +/- 11%) being more reactive than beta-carotene (68.2 +/- 5.8%) when exposed to peroxynitrite (50 microM) for 1 min. Among the tocopherols, alpha-tocopherol (54.9 +/- 20.2%) was more extensively depleted than gamma-tocopherol (14.7 +/- 1.09%) at peroxynitrite concentration of 500 microM. It was also observed that peroxynitrite, unlike copper ions, does not lead to significant peroxidation of LDL as determined by the formation of conjugated dienes and thiobarbituric acid-reactive substances. PMID:9515727

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

    PubMed

    Schroeter, H; Williams, R J; Matin, R; Iversen, L; Rice-Evans, C A

    2000-12-15

    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 the induction of oxidative injury, and the abilities of phenolic antioxidants, flavonoids and hydroxycinnamic acid derivatives, to attenuate this neuronal damage were examined. OxLDL was demonstrated to enter neuronal cells and to be capable of eliciting neurotoxicity in a dose- and time-dependent manner, inducing DNA fragmentation and cell lysis. Flavonoids exert protective effects, which appear to be related to specific structural characteristics, particularly relevant being those defining their reduction potentials and partition coefficients. In summary, these data suggest a possible role for flavonoids in reducing neurodegeneration associated with chronic disorders in which oxidative stress is implicated. PMID:11118812

  14. Nuclear imaging analysis of human low-density lipoprotein biodistribution in rabbits and monkeys

    SciTech Connect

    Hay, R.V.; Fleming, R.M.; Ryan, J.W.; Williams, K.A.; Stark, V.J.; Lathrop, K.A.; Harper, P.V. (Department of Pathology, University of Chicago, Illinois (USA))

    1991-06-01

    We have evaluated the biodistribution of human low-density lipoprotein (LDL) radiolabeled with 99mTc or with {sup 123}I-tyramine cellobiose in rabbits and in rhesus monkeys. Biodistribution was assessed after intravenous injection of radiolabeled LDL by quantitative analysis of scintigrams, counting of excreta, and counting of tissues at necropsy. Both rabbits and monkeys showed lower renal uptake ({sup 123}I:99mTc {approximately} 1:3, as regional percent injected activity corrected for physical decay) and excretion (1:2 to 1:4), but higher hepatic (1.5:1 to 2:1) and cardiac (1.7:1 to 4:1) uptake of {sup 123}I than of 99mTc. Adrenals were visualized in normolipemic animals with {sup 123}I-tyramine cellobiose-LDL but not with 99mTc-LDL. Hyperlipemic animals showed increased cardiac (up to six-fold) and decreased hepatic activity (by 50%-60%) of both radionuclides. We conclude that {sup 123}I-tyramine cellobiose-LDL is better suited than 99mTc-LDL for dynamic studies of LDL metabolism in vivo.

  15. Fast determination of virgin olive oil phenolic metabolites in human high-density lipoproteins.

    PubMed

    Fernández-Ávila, C; Montes, R; Castellote, A I; Chisaguano, A M; Fitó, M; Covas, M I; Muñoz-Aguallo, D; Nyyssönen, K; Zunft, H J; López-Sabater, M C

    2015-07-01

    In recent years it has been confirmed that the consumption of olive oil prevents the oxidation of biomolecules owing to its monounsaturated fatty acids (MUFA) and phenolic content. The main objective of the study was to develop an ultra-high-performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method for the determination of phenolic compounds in human high-density lipoprotein (HDL) samples. At the same time, the influence of olive oil consumption on the phenolic metabolite levels was evaluated in a European population. The participants were 51 healthy men, aged 20-60. They were randomized to two consecutive intervention periods with the administration of raw olive oil with low and high polyphenolic content. The UHPLC-MS/MS analytical method has been validated for hydroxytyrosol and homovanillic acid in terms of linearity (r(2) ?=?0.99 and 1.00), repeatability (5.7 and 6.5%) reproducibility (6.2 and 7%), recovery (98 to 97%), limits of detection (1.7 to 1.8?ppb) and quantification (5.8 and 6.3?ppb).The levels of the studied metabolites increased significantly after high polyphenolic content virgin olive oil ingestion (p <0.05) compared with lowpolyphenolic content olive oil. Virgin olive oil consumption increases the levels of phenolic metabolites in HDL and thus provides human HDL with more efficient antioxidant protection. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25425119

  16. Glucuronic Acid Epimerase Is Associated with Plasma Triglyceride and High Density Lipoprotein Cholesterol Levels in Turks

    PubMed Central

    Hodo?lugil, U?ur; Williamson, David W.; Yu, Yi; Farrer, Lindsay A.; Mahley, Robert W.

    2011-01-01

    Summary We narrowed chromosome 15q21-23 linkage to plasma high density lipoprotein cholesterol (HDL-C) levels in atherogenic dyslipidemic Turkish families by fine mapping, then focused on glucuronic acid epimerase (GLCE), a heparan sulfate proteoglycan (HSPG) biosynthesis enzyme. HSPGs participate in lipid metabolism along with apolipoprotein (apo) E. Of 31 SNPs in the GLCE locus, nine analyzed by haplotype were associated with plasma HDL-C and triglyceride levels (permuted p = 0.006 and 0.013, respectively) in families. Of five tagging GLCE SNPs in two cohorts of unrelated subjects, three (rs16952868, rs11631403, rs3865014) were associated with triglyceride and HDL-C levels in males (non-permuted p < 0.05). The association was stronger in APOE 2/3 subjects (apoE2 has reduced binding to HSPGs) and reached multiple-testing significance (p < 0.05) in both males and females (n = 2612). Similar results were obtained in the second cohort (n = 1164). Interestingly, at the GLCE locus, bounded by recombination hotspots, Turks had a minor allele frequency of SNPs resembling Chinese more than European ancestry; adjoining regions on chromosome 15 resembled the European pattern. Studies of glce+/–apoe–/– mice fed a chow or high-fat diet supported a role for GLCE in lipid metabolism. Thus, SNPs in GLCE are associated with triglyceride and HDL-C levels in Turks, and mouse studies support a role for glce in lipid metabolism. PMID:21488854

  17. A Statin-Loaded Reconstituted High-Density Lipoprotein Nanoparticle Inhibits Atherosclerotic Plaque Inflammation

    PubMed Central

    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S.G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J.M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show this effect is mediated through inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show they accumulate in atherosclerotic lesions where they directly affect plaque macrophages. Finally we demonstrate that a three-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a one-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation. PMID:24445279

  18. Intercorrelations among plasma high density lipoprotein, obesity and triglycerides in a normal population

    SciTech Connect

    Albrink, M.J. (West Virgina Unov., Morgantown); Krauss, R.M.; Lindgren, F.T.; von der Groeben, J.; Pan, S.; Wood, P.D.

    1980-01-01

    The interrelationships among fatness measures, plasma triglycerides and high density lipoproteins (HDL) were examined in 131 normal adult subjects: 38 men aged 27 to 46, 50 men aged 47 to 66, 29 women aged 27 to 46 and 24 women aged 47 to 66. None of the women were taking estrogens or oral contraceptive medication. The HDL concentration was subdivided into HDL/sub 2b/, HDL/sub 2a/ and HDL by a computerized fitting of the total schileren pattern to reference schlieren patterns. Anthropometric measures employed included skinfolds at 3 sites, 2 weight/height indices and 2 girth measurements. A high correlation was found among the various fatness measures. These measures were negatively correlated with total HDL, reflecting the negative correlation between fatness measures and HDL/sub 2/ (as the sum of HDL/sub 2a/ and /sub 2b/). Fatness measures showed no relationship to HDL/sub 3/. There was also an inverse correlation between triglyceride concentration and HDL/sub 2/. No particular fatness measure was better than any other for demonstrating the inverse correlation with HDL but multiple correlations using all of the measures of obesity improved the correlations. Partial correlations controlling for fatness did not reduce any of the significnt correlations between triglycerides and HDL/sub 2/ to insignificance. The weak correlation between fatness and triglycerides was reduced to insigifnicance when controlled for HDL/sub 2/.

  19. A rare polymorphism in the low density lipoprotein (LDL) gene that affects mRNA splicing.

    PubMed

    Bourbon, M; Sun, X-M; Soutar, A K

    2007-11-01

    Familial hypercholesterolaemia (FH) is usually caused by mutations in the low density lipoprotein (LDL) receptor gene (LDLR) that impair clearance of LDL from the circulation. The increased risk of premature coronary heart disease associated with FH can be reduced by dietary advice and treatment with lipid-lowering drug therapy, but it is important to identify affected individuals at an early stage. Several programmes for genetic diagnosis of FH that rely on identifying nucleotide substitutions in genomic DNA have been initiated, but the validity of these is dependent on distinguishing between a silent nucleotide variant and a mutation that affects LDL-receptor function. Here we describe a single nucleotide substitution in the coding region of exon 9 of LDLR that is an apparently silent polymorphism: CGG (Arg406) to AGG (Arg). Analysis of mRNA from the patient's cells showed that the mutation introduces a new splice site that is used to the exclusion of the natural splice site and causes a deletion of 31 bp from the mRNA, predicted to introduce premature termination four codons after R406. This finding emphasizes the caution needed in genetic diagnosis of FH based on genomic DNA sequence alone. PMID:17335829

  20. Antioxidant effects of 14 Chinese traditional medicinal herbs against human low-density lipoprotein oxidation.

    PubMed

    Lin, Hsin-Hung; Charles, Albert Linton; Hsieh, Chang-Wei; Lee, Ya-Chi; Ciou, Jhih-Ying

    2015-01-01

    The relationship between the antioxidant activities and inhibitory effect of 14 Chinese medicinal herbs against oxidized low-density lipoprotein (LDL) formation was evaluated. Prolongation of the lag phase of LDL oxidation depended on the concentration of the herbs. The concentration of each herb that was able to prolong the lag time by about two-fold was calculated and expressed as doubling-time concentration. The lower the doubling-time concentration, the stronger the inhibitory effect exhibited toward LDL oxidation. Among them, Chrysanthemi Flos (Chrysanthemum morifolium ramat; g?n jú hu?), Crataegi Fructus (Crataegus pinnatifida Bge. var. major N.E.Br.; sh?n zh?), and Roselle (Hibiscus sabdariffa Linn.; luò shén) showed significant inhibitory effects. Correlation coefficients between doubling-time concentration and radical-scavenging activities were high; the total phenolic content was also high. In conclusion, phenolic compounds contributed not only to antioxidant activities, but also to the inhibitory effect against LDL oxidation. Chrysanthemi Flos, Crataegi Fructus, and H. sabdariffa, with lower doubling-time concentrations, could be potent phytochemical agents to reduce LDL oxidation and prevent the progression of atherosclerosis. PMID:26151009

  1. Ordering and stability in lipid droplets with applications to low-density lipoproteins.

    PubMed

    Lancaster, Jarrett L; Antonijevic, Todor; Starobin, Joseph M

    2014-06-01

    In this article, we present a framework for investigating the order-disorder transition in lipid droplets using the standard Ising model. While a single lipid droplet is itself a complex system whose constituent cholesteryl esters each possesses many degrees of freedom, we present justification for using this effective approach to isolate the underlying physics. It is argued that the behavior of the esters confined within lipid droplets is significantly different from that of a bulk system of similar esters, which is adequately described by continuum mean-field theory in the thermodynamic limit. When the droplet's shell is modeled as an elastic membrane, a simple picture emerges for a transition between two ordered phases within the core which is tuned by the strength of interactions between the esters. Triglyceride concentration is proposed as a variable which strongly influences the strength of interactions between cholesteryl esters within droplets. The possible relevance of this mechanism to the well known atherogenic nature of small low-density lipoprotein particles is discussed in detail. PMID:25019815

  2. Targeting high-density lipoproteins: increasing de novo production versus decreasing clearance.

    PubMed

    Mooradian, Arshag D; Haas, Michael J

    2015-05-01

    Although cardiovascular mortality has been decreasing in industrialized countries, there continues to be a substantial residual risk; thus, novel therapeutic agents and new targets of therapy have been sought. One highly plausible therapeutic target is high-density lipoprotein (HDL). HDL is a key player in reverse cholesterol transport and possesses a slew of other cardioprotective properties; however, recent trials with agents known to increase HDL levels have generally not shown any reduction in cardiovascular events. Further analysis of these trials suggest that fibrates have consistently reduced some cardiovascular outcomes, at least in the subgroup of patients with high serum triglycerides and low HDL cholesterol (HDLc) levels. Since fibrates, unlike niacin or cholesterol ester transfer protein inhibitors, increase HDLc level mostly through the stimulation of apolipoprotein A-I production, it is suggested that the quality and functionality of HDL are enhanced when de novo synthesis rather than inhibition of turnover is the mechanism of increasing HDL level. In this communication, the evidence for and against the cardioprotective properties of HDL is reviewed and the contemporary clinical trials are discussed. PMID:25895465

  3. Ferritin protects endothelial cells from oxidized low density lipoprotein in vitro.

    PubMed Central

    Juckett, M. B.; Balla, J.; Balla, G.; Jessurun, J.; Jacob, H. S.; Vercellotti, G. M.

    1995-01-01

    Low density lipoprotein (LDL), if it becomes oxidized, develops several unique properties including the capacity to provoke endothelial cytotoxicity via metal-catalyzed free radical-mediated mechanisms. As were previously have shown that iron-catalyzed oxidant injury to endothelial cells can be attenuated by the addition of exogenous iron chelators such as the lazaroids and deferoxamine, we have examined whether the endogenous iron chelator, ferritin, might provide protection from oxidized LDL. LDL oxidized by iron-containing hemin and H2O2 is toxic to endothelial cells in a time- and dose-dependent fashion. Endothelial cell ferritin content is increased by pretreatment of cells with iron compounds or by the direct addition of exogenous apoferritin; ferritin-loaded cells are markedly resistant to the toxicity caused by oxidized LDL. Iron inactivation by ferritin depends on its ferroxidase activity. When a recombinant human ferritin heavy chain mutant, 222, which is devoid of ferroxidase activity, is added to endothelial cells, unlike the excellent protection afforded by the wild-type recombinant heavy chain, endothelial cells are not protected from oxidized LDL. To assess the in vivo relevance of our observation, we examined human coronary arteries of cardiac explants taken from patients with end-stage atherosclerosis. Large amounts of immunoreactive ferritin are focally detected in atherosclerotic lesions, specifically in the myofibroblasts, macrophages, and endothelium without a notable increase in Prussian blue-detectable iron. These findings suggest that ferritin may modulate vascular cell injury in vivo. Images Figure 3 Figure 4 PMID:7677189

  4. The binding of human aortic glycosaminoglycans and proteoglycans to plasma low density lipoproteins.

    PubMed

    Mourão, P A; Bracamonte, C A

    1984-02-01

    The interaction of glycosaminoglycans and proteoglycans with low density lipoproteins has been studied. Aortic and cartilaginous glycosaminoglycans are retained in LDL affinity columns and produce turbidity when added to LDL in presence of Ca2+. When extracted from whole aortic walls, dermatan sulfate is the glycosaminoglycan that shows greatest affinity for LDL. However, when using the glycosaminoglycans obtained by papain hydrolysis of the proteoglycans extracted from aorta, the binding affinity with LDL was similar for dermatan sulfate and chondroitin 4/6-sulfate. Removal of the protein core of the aortic or cartilaginous proteoglycans did not prevent interaction with LDL. However, treatment with testicular hyaluronidase abolished totally such interaction. When aortic glycosaminoglycans and proteoglycans were applied to LDL affinity columns in presence of Ca2+, a marked increase in the average molecular weight of the glycans found in the eluates of higher NaCl concentration was observed. This result suggests that the molecular weight of the glycosaminoglycans is a relevant factor for the binding of these compounds to LDL. PMID:6712767

  5. Proteoglycan form of macrophage colony-stimulating factor binds low density lipoprotein.

    PubMed Central

    Suzu, S; Inaba, T; Yanai, N; Kawashima, T; Yamada, N; Oka, T; Machinami, R; Ohtsuki, T; Kimura, F; Kondo, S

    1994-01-01

    We recently isolated a proteoglycan form of macrophage colony-stimulating factor (PG-M-CSF) that carries a chondroitin sulfate glycosaminoglycan chain. Here, we examined the interaction of PG-M-CSF with low density lipoprotein (LDL). When LDL preincubated with PG-M-CSF was fractionated by molecular size sieving chromatography, it was eluted earlier than untreated LDL. When LDL was preincubated with chondroitin sulfate-free 85-kD M-CSF instead of PG-M-CSF, the elution profile of LDL remained unchanged, indicating specific interaction between PG-M-CSF and LDL. The level of PG-M-CSF binding in the wells of a plastic microtitration plate precoated with LDL was significant, this binding being completely abolished by pretreatment of PG-M-CSF with chondroitinase AC, which degrades chondroitin sulfate. The addition of exogenous chondroitin sulfate or apolipoprotein B inhibited the binding of PG-M-CSF to LDL in a dose-dependent manner, indicating that the interaction between PG-M-CSF and LDL was mediated by the binding of the chondroitin sulfate chain of PG-M-CSF to LDL apolipoprotein B. PG-M-CSF was also demonstrated in the arterial wall, and there were increased amounts of PG-M-CSF in atherosclerotic lesions. The in vitro interaction between PG-M-CSF and LDL thus appears to have physiological significance. Images PMID:7929840

  6. Ethnicity and coronary artery disease: the role of high-density lipoprotein - a change in paradigm.

    PubMed

    Bravo, Katia; Velarde, Gladys P

    2015-08-01

    Cardiovascular disease (CVD) is the number one killer of men and women across ethnic groups in the USA. Health disparities in CVD, especially coronary artery disease (CAD), are well documented in the diverse American population. Despite efforts taken toward reducing cardiovascular health disparities, there are still gaps in its diagnosis and management. Current risk assessment guidelines consider high high-density lipoprotein (HDL) levels a protective factor against CAD, although its significance across races remains poorly understood. Recent clinical trials focused on increasing HDL levels have been disappointing. In this article, the authors have explored the role of HDL in CAD, have analyzed its significance across gender and ethnic groups and have challenged the broad application of widely used HDL level cutoffs in CAD risk assessment tools across these vulnerable groups. The current evidence suggests a paradigm change from HDL quantity to quality and function in future CVD risk research. This may better explain why some ethnic minority groups with a seemingly more benign lipid profile experience a higher CAD burden. PMID:26159553

  7. Chitosan-modified carbon nanotubes-based platform for low-density lipoprotein detection.

    PubMed

    Ali, Md Azahar; Singh, Nawab; Srivastava, Saurabh; Agrawal, Ved V; John, Renu; Onoda, M; Malhotra, Bansi D

    2014-10-01

    We have fabricated an immunosensor based on carbon nanotubes and chitosan (CNT-CH) composite for detection of low density lipoprotein (LDL) molecules via electrochemical impedance technique. The CNT-CH composite deposited on indium tin oxide (ITO)-coated glass electrode has been used to covalently interact with anti-apolipoprotein B (antibody: AAB) via a co-entrapment method. The biofunctionalization of AAB on carboxylated CNT-CH surface has been confirmed by Fourier transform infrared spectroscopic and electron microscopic studies. The covalent functionalization of antibody on transducer surface reveals higher stability and reproducibility of the fabricated immunosensor. Electrochemical properties of the AAB/CNT-CH/ITO electrode have been investigated using cyclic voltammetric and impedimetric techniques. The impedimetric response of the AAB/CNT-CH/ITO immunoelectrode shows a high sensitivity of 0.953??/(mg/dL)/cm(2) in a detection range of 0-120 mg/dL and low detection limit of 12.5 mg/dL with a regression coefficient of 0.996. The observed low value of association constant (0.34 M(-1)s(-1)) indicates high affinity of AAB/CNT-CH/ITO immunoelectrode towards LDL molecules. This fabricated immunosensor allows quantitative estimation of LDL concentration with distinguishable variation in the impedance signal. PMID:25201210

  8. Antioxidant effects of 14 Chinese traditional medicinal herbs against human low-density lipoprotein oxidation

    PubMed Central

    Lin, Hsin-Hung; Charles, Albert Linton; Hsieh, Chang-Wei; Lee, Ya-Chi; Ciou, Jhih-Ying

    2014-01-01

    The relationship between the antioxidant activities and inhibitory effect of 14 Chinese medicinal herbs against oxidized low-density lipoprotein (LDL) formation was evaluated. Prolongation of the lag phase of LDL oxidation depended on the concentration of the herbs. The concentration of each herb that was able to prolong the lag time by about two-fold was calculated and expressed as doubling-time concentration. The lower the doubling-time concentration, the stronger the inhibitory effect exhibited toward LDL oxidation. Among them, Chrysanthemi Flos (Chrysanthemum morifolium ramat; ??? g?n jú hu?), Crataegi Fructus (Crataegus pinnatifida Bge. var. major N.E.Br.; ?? sh?n zh?), and Roselle (Hibiscus sabdariffa Linn.; ?? luò shén) showed significant inhibitory effects. Correlation coefficients between doubling-time concentration and radical-scavenging activities were high; the total phenolic content was also high. In conclusion, phenolic compounds contributed not only to antioxidant activities, but also to the inhibitory effect against LDL oxidation. Chrysanthemi Flos, Crataegi Fructus, and H. sabdariffa, with lower doubling-time concentrations, could be potent phytochemical agents to reduce LDL oxidation and prevent the progression of atherosclerosis.

  9. Carvedilol, a new antihypertensive, prevents oxidation of human low density lipoprotein by macrophages and copper.

    PubMed

    Yue, T L; McKenna, P J; Lysko, P G; Ruffolo, R R; Feuerstein, G Z

    1992-12-01

    Growing evidence indicates that oxidized low-density lipoprotein (LDL) may promote atherogenesis. Therefore, inhibition of LDL oxidation may impede this process. Carvedilol is a vasodilating, beta-adrenoceptor blocking agent. As a new antihypertensive drug, carvedilol is unique by virtue of its potent antioxidant activity. Therefore, we tested the ability of carvedilol to inhibit the oxidation of LDL by either macrophages or Cu2+. Carvedilol inhibited LDL oxidation by macrophages in a dose-dependent manner, with an IC50 value of 3.8 microM, as assessed by a thiobarbituric acid reactive substance (TBARS) assay. Under the same conditions, propranolol showed only a mild inhibitory effect (IC50 > 100 microM), while pindolol, atenolol and labetalol had almost no effect. Carvedilol, at 10 microM, almost completely inhibited the macrophage-induced increase in electrophoretic mobility of LDL, while other beta-blockers at 50-300 microM had no significant effect. Carvedilol inhibited superoxide release from mouse macrophages, which correlated well with its inhibition of LDL oxidation. Carvedilol also inhibited Cu(2+)-induced LDL oxidation with an IC50 value of 17 microM, while all other beta-blockers were inactive up to 300 microM. These observations suggest that carvedilol might not only be an effective antihypertensive drug, but might also be effective in prevention of atherosclerosis. PMID:1361324

  10. Hemin: a possible physiological mediator of low density lipoprotein oxidation and endothelial injury.

    PubMed

    Balla, G; Jacob, H S; Eaton, J W; Belcher, J D; Vercellotti, G M

    1991-01-01

    Oxidized low density lipoprotein (LDL), formed in vivo from presently unknown reactions, may play a role in atherogenesis. In vitro, transition metals such as iron and copper will facilitate LDL oxidation, but these metals are unlikely to exist in free form in normal body fluids. We have explored the possibility that LDL oxidation may be promoted by heme, a physiologically ubiquitous, hydrophobic, iron-containing compound. Indeed, during several-hour incubation, heme caused extensive oxidative modification of LDL; however, such modification requires only minutes in the presence of small amounts of H2O2 or preformed lipid hydroperoxides within the LDL. Oxidative interactions between heme, LDL, and peroxides lead to degradation of the heme ring and consequent release of heme iron, which further accelerates heme degradation. Coupled (evidently iron-catalyzed) heme degradation and LDL oxidation are both effectively inhibited by hydrophobic antioxidants and iron chelators. That such hemin-induced LDL oxidation may be involved in atherogenesis is supported by the finding that LDL oxidized by hemin is extremely cytotoxic to cultured aortic endothelial cells. Overall, these investigations not only lend support to the idea that LDL oxidation by physiological substances such as heme may play a role in the process of atherogenesis but also may have broader implications, as similar oxidative reactions between heme and unsaturated fatty acids may occur consequent to hemorrhagic injury. PMID:1931871

  11. The role of oxidized low-density lipoproteins in atherosclerosis: the myths and the facts.

    PubMed

    Maiolino, Giuseppe; Rossitto, Giacomo; Caielli, Paola; Bisogni, Valeria; Rossi, Gian Paolo; Calò, Lorenzo A

    2013-01-01

    The oxidative modification hypothesis of atherosclerosis, which assigns to oxidized low-density lipoproteins (LDLs) a crucial role in atherosclerosis initiation and progression, is still debated. This review examines the role played by oxidized LDLs in atherogenesis taking into account data derived by studies based on molecular and clinical approaches. Experimental data carried out in cellular lines and animal models of atherosclerosis support the proatherogenic role of oxidized LDLs: (a) through chemotactic and proliferating actions on monocytes/macrophages, inciting their transformation into foam cells; (b) through stimulation of smooth muscle cells (SMCs) recruitment and proliferation in the tunica intima; (c) through eliciting endothelial cells, SMCs, and macrophages apoptosis with ensuing necrotic core development. Moreover, most of the experimental data on atherosclerosis-prone animals benefiting from antioxidant treatment points towards a link between oxidative stress and atherosclerosis. The evidence coming from cohort studies demonstrating an association between oxidized LDLs and cardiovascular events, notwithstanding some discrepancies, seems to point towards a role of oxidized LDLs in atherosclerotic plaque development and destabilization. Finally, the results of randomized clinical trials employing antioxidants completed up to date, despite demonstrating no benefits in healthy populations, suggest a benefit in high-risk patients. In conclusion, available data seem to validate the oxidative modification hypothesis of atherosclerosis, although additional proofs are still needed. PMID:24222937

  12. Low-density lipoprotein-mediated delivery of docosahexaenoic acid selectively kills murine liver cancer cells

    PubMed Central

    Reynolds, Lacy; Mulik, Rohit S.; Wen, Xiaodong; Dilip, Archana; Corbin, Ian R.

    2014-01-01

    Aim The natural omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), has recently been credited for possessing anticancer properties. Herein, we investigate the cytotoxic actions of DHA-loaded low-density lipoprotein (LDL) nanoparticles in normal and liver cancer cells. Materials & methods LDL-DHA nanoparticles were prepared and subjected to extensive biophysical characterization. The therapeutic utility of LDL-DHA nanoparticles was evaluated in normal and malignant murine hepatocyte cell lines, TIB-73 and TIB-75, respectively. Results & discussion The engineered LDL-DHA nanoparticles possessed enhanced physical and oxidative stabilities over native LDL and free DHA. Dose–response studies showed that therapeutic doses of LDL-DHA nanoparticles that completely killed TIB-75 were innocuous to TIB-73. The selective induction of lipid peroxidation and reactive oxygen species in the cancer cells was shown to play a central role in LDL-DHA nanoparticle-mediated cytotoxicity. Conclusion In summary, these findings indicate that LDL-DHA nanoparticles show great promise as a selective anticancer agent against hepatocellular carcinoma. PMID:24397600

  13. High Density Lipoprotein Nanoparticles Deliver RNAi to Endothelial Cells to Inhibit Angiogenesis

    PubMed Central

    Tripathy, Sushant; Vinokour, Elena; McMahon, Kaylin M.; Volpert, Olga V.; Thaxton, C. Shad

    2014-01-01

    Systemic delivery of therapeutic nucleic acids to target cells and tissues outside of the liver remains a major challenge. We synthesized a biomimetic high density lipoprotein nanoparticle (HDL NP) for delivery of a cholesteryl modified therapeutic nucleic acid (RNAi) to vascular endothelial cells, a cell type naturally targeted by HDL. HDL NPs adsorb cholesteryl modified oligonucleotides and protect them from nuclease degradation. As proof of principle, we delivered RNAi targeting vascular endothelial growth factor receptor 2 (VEGFR2) to endothelial cells to effectively silence target mRNA and protein expression in vitro. In addition, data show that treatment strongly attenuated in vivo neovascularization measured using a standard angiogenesis assay and in hypervascular tumor allografts where a striking reduction in tumor growth was observed. For effective delivery, HDL NPs required the expression of the cell surface protein scavenger receptor type-B1 (SR-B1). No toxicity of HDL NPs was measured in vitro or after in vivo administration. Thus, by using a biomimetic approach to nucleic acid delivery, data demonstrate that systemically administered RNAi-HDL NPs target SR-B1 expressing endothelial cells to deliver functional anti-angiogenic RNAi as a potential treatment of cancer and other neo-vascular diseases. PMID:25400330

  14. High Density Lipoproteins for the Systemic Delivery of short interfering RNA

    PubMed Central

    McMahon, Kaylin M.; Thaxton, C. Shad

    2014-01-01

    Introduction RNA interference (RNAi) is a powerful mechanism for gene silencing with the potential to greatly impact the development of new therapies for many human diseases. Short interfering RNAs (siRNAs) may be the ideal molecules for therapeutic RNAi. However, therapeutic siRNAs face significant challenges that must be overcome prior to widespread clinical use. Many efforts have been made to overcome the hurdles associated with systemic administration of siRNA; however, current approaches are still limited. As such, there is an urgent need to develop new strategies for siRNA delivery that have the potential to impact a broad spectrum of systemic diseases. Areas covered This review focuses on the promise of siRNA therapies and highlights current siRNA delivery methods. With an eye toward new strategies, this review first introduces high density lipoproteins (HDL) and their natural functions, and then transitions into how HDLs may provide significant opportunities as next generation siRNA delivery vehicles. Importantly, this review describes how synthetic HDLs leverage the natural ability of HDL to stabilize and deliver siRNAs. Expert Opinion HDLs are natural nanoparticles that are critical to understanding the systemic delivery of therapeutic nucleic acids, like siRNA. Methods to synthesize biomimetic HDLs are being explored and data demonstrate that this type of delivery vehicle may be highly beneficial for targeted and efficacious systemic delivery of siRNAs. PMID:24313310

  15. Novel fluorescently labeled peptide compounds for detection of oxidized low-density lipoprotein at high specificity.

    PubMed

    Sato, Akira; Yamanaka, Hikaru; Oe, Keitaro; Yamazaki, Yoji; Ebina, Keiichi

    2014-10-01

    The probes for specific detection of oxidized low-density lipoprotein (ox-LDL) in plasma and in atherosclerotic plaques are expected to be useful for the identification, diagnosis, prevention, and treatment for atherosclerosis. In this study, to develop a fluorescent peptide probe for specific detection of ox-LDL, we investigated the interaction of fluorescein isothiocyanate (FITC)-labeled peptides with ox-LDL using polyacrylamide gel electrophoresis. Two heptapeptides (KWYKDGD and KP6) coupled through the ?-amino group of K at the N-terminus to FITC in the presence/absence of 6-amino-n-caproic acid (AC) linker to FITC--(FITC-AC)KP6 and (FITC)KP6--both bound with high specificity to ox-LDL in a dose-dependent manner. In contrast, a tetrapeptide (YKDG) labeled with FITC at the N-terminus and a pentapeptide (YKDGK) coupled through the ?-amino group of K at the C-terminus to FITC did not bind selectively to ox-LDL. Furthermore, (FITC)KP6 and (FITC-AC)KP6 bound with high specificity to the protein in mouse plasma (probably ox-LDL fraction). These findings strongly suggest that (FITC)KP6 and (FITC-AC)KP6 may be effective novel fluorescent probes for specific detection of ox-LDL. PMID:24717143

  16. Sphingomyelin in High-Density Lipoproteins: Structural Role and Biological Function

    PubMed Central

    Martínez-Beamonte, Roberto; Lou-Bonafonte, Jose M.; Martínez-Gracia, María V.; Osada, Jesús

    2013-01-01

    High-density lipoprotein (HDL) levels are an inverse risk factor for cardiovascular diseases, and sphingomyelin (SM) is the second most abundant phospholipid component and the major sphingolipid in HDL. Considering the marked presence of SM, the present review has focused on the current knowledge about this phospholipid by addressing its variable distribution among HDL lipoparticles, how they acquire this phospholipid, and the important role that SM plays in regulating their fluidity and cholesterol efflux from different cells. In addition, plasma enzymes involved in HDL metabolism such as lecithin–cholesterol acyltransferase or phospholipid transfer protein are inhibited by HDL SM content. Likewise, HDL SM levels are influenced by dietary maneuvers (source of protein or fat), drugs (statins or diuretics) and modified in diseases such as diabetes, renal failure or Niemann–Pick disease. Furthermore, increased levels of HDL SM have been shown to be an inverse risk factor for coronary heart disease. The complexity of SM species, described using new lipidomic methodologies, and their distribution in different HDL particles under many experimental conditions are promising avenues for further research in the future. PMID:23571495

  17. A new class mutation of low density lipoprotein receptor with altered carbohydrate chains.

    PubMed

    Shite, S; Seguchi, T; Yoshida, T; Kohno, K; Ono, M; Kuwano, M

    1988-12-25

    In a monensin-resistant mutant (Monr-31) of Chinese hamster ovary cells, the O-linked sugar chains of the low density lipoprotein (LDL) receptor are altered, suggesting a mutation at a Golgi apparatus gene. In a compactin-resistant mutant (MF-2) of Chinese hamster V79 cells, the mature LDL receptor is apparently 5000 daltons smaller; the difference is due to altered glycosylation of O-linked sugar chains. Hybrids between MF-2 and Monr-31 still produced LDL receptor molecules with aberrant sugar chains; thus both mutants are in the same complementation group. Krieger and his colleagues (Krieger, M., Kingsley, D., Sege, R., Hobbie, L., and Kozarsky, K. (1985) Trends. Biochem. Sci. 10, 447-452) have classified Chinese hamster ovary cell mutants with altered LDL receptor structure into four groups: ldlA, ldlB, ldlC, and ldlD. Cell-cell hybrids between their ldl mutants and Monr-31 produced wild type mature LDL receptors with normal molecular sizes, suggesting that these compactin- and monensin-resistant mutants define a new class of LDL receptor mutant. Since both of our mutants are defective in internalization of LDL, we assign them as int mutants. This may imply a further etiology for hypercholesterolemia, and cases can now be examined for such a class. PMID:3198628

  18. Equilibrium and kinetic studies of the interactions of a porphyrin with low-density lipoproteins.

    PubMed Central

    Bonneau, Stéphanie; Vever-Bizet, Christine; Morlière, Patrice; Mazière, Jean-Claude; Brault, Daniel

    2002-01-01

    Low-density lipoproteins (LDL) play a key role in the delivery of photosensitizers to tumor cells in photodynamic therapy. The interaction of deuteroporphyrin, an amphiphilic porphyrin, with LDL is examined at equilibrium and the kinetics of association/dissociation are determined by stopped-flow. Changes in apoprotein and porphyrin fluorescence suggest two classes of bound porphyrins. The first class, characterized by tryptophan fluorescence quenching, involves four well-defined sites. The affinity constant per site is 8.75 x 10(7) M(-1) (cumulative affinity 3.5 x 10(8) M(-1)). The second class corresponds to the incorporation of up to 50 molecules into the outer lipidic layer of LDL with an affinity constant of 2 x 10(8) M(-1). Stopped-flow experiments involving direct LDL porphyrin mixing or porphyrin transfer from preloaded LDL to albumin provide kinetic characterization of the two classes. The rate constants for dissociation of the first and second classes are 5.8 and 15 s(-1); the association rate constants are 5 x 10(8) M(-1) s(-1) per site and 3 x 10(9) M(-1) s(-1), respectively. Both fluorescence and kinetic analysis indicate that the first class involves regions at the boundary between lipids and the apoprotein. The kinetics of porphyrin-LDL interactions indicates that changes in the distribution of photosensitizers among various carriers could be very sensitive to the specific tumor microenvironment. PMID:12496113

  19. Rosiglitazone attenuates atherosclerosis and increases high-density lipoprotein function in atherosclerotic rabbits.

    PubMed

    Li, Chen; Tu, Yan; Liu, Ting-Rong; Guo, Zhi-Gang; Xie, Di; Zhong, Jian-Kai; Fan, Yong-Zhen; Lai, Wen-Yan

    2015-03-01

    Rosiglitazone has been found to have anti-atherogenic effects and to increase serum high-density lipoprotein (HDL) cholesterol (HDL-C) levels. However, in vivo studies investigating the regulation of adenosine triphosphate-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) by rosiglitazone are limited. Moreover, the effects of rosiglitazone on the function and levels of HDL are unclear. In the present study, we investigated the effects of rosiglitazone on HDL function and its mechanisms of action in atherosclerotic rabbits. Our results revealed that rosiglitazone induced a significant increase in serum HDL-C levels, paraoxonase 1 (PON1) activity, [(3)H]cholesterol efflux rates, and the expression of ABCA1 and SR-BI in hepatocytes and peritoneal macrophages. The expression of ABCA1 was also increased in aortic lesions. Rosiglitazone markedly reduced serum myeloperoxidase (MPO) activity, aortic intima-media thickness (IMT) and the percentage of plaque area in the aorta. It can thus be concluded that in atherosclerotic rabbits, rosigitazone increases the levels of HDL-C and hinders atherosclerosis. Thus, it improves HDL quality and function, as well as the HDL-induced cholesterol efflux, exerting anti-inflammatory and antioxidant effects. PMID:25604880

  20. Acute Coronary Syndrome Remodels the Protein Cargo and Functions of High-Density Lipoprotein Subfractions

    PubMed Central

    Tan, Ying; Liu, Ting Rong; Hu, Shui Wang; Tian, Di; Li, Chen; Zhong, Jian Kai; Sun, Hai Ge; Luo, Tian Tian; Lai, Wen Yan; Guo, Zhi-Gang

    2014-01-01

    Objectives This study examined alterations in the functions and proteome of high-density lipoprotein (HDL) subfractions (HDL2 and HDL3) isolated from patients with acute coronary syndrome (ACS) compared with control subjects. Methods We measured HDL subfraction cholesterol efflux capacity, inflammatory index (HII), paraoxonase-1 (PON1) activity, and lipid hydroperoxide (LOOH) levels in both male age-matched controls and the ACS group (n?=?40/group). Additionally, proteomic analysis was used to monitor changes in the HDL subfraction proteome between controls and ACS subjects. Results Both HDL2 and HDL3 from ACS patients had greater HII and LOOH levels compared with controls (P<0.001); PON1 activity and cholesterol efflux capacity in both HDL2 and HDL3 from the ACS group were significantly less than those of controls (P<0.001). Using proteomic analysis, we demonstrated that, compared with the control group, nine proteins were selectively enriched in HDL3 from subjects with ACS, and ras-related protein Rab-7b was decreased in HDL3. Additionally, in the ACS subjects, 12 proteins were decreased in HDL2 and 4 proteins were increased in HDL2. Conclusions Functional HDL subfractions shifted to dysfunctional HDL subfractions during ACS, and the functional impairment was linked to remodeled protein cargo in HDL subfractions from ACS patients. PMID:24736723

  1. Rosiglitazone attenuates atherosclerosis and increases high-density lipoprotein function in atherosclerotic rabbits

    PubMed Central

    LI, CHEN; TU, YAN; LIU, TING-RONG; GUO, ZHI-GANG; XIE, DI; ZHONG, JIAN-KAI; FAN, YONG-ZHEN; LAI, WEN-YAN

    2015-01-01

    Rosiglitazone has been found to have anti-atherogenic effects and to increase serum high-density lipoprotein (HDL) cholesterol (HDL-C) levels. However, in vivo studies investigating the regulation of adenosine triphosphate-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) by rosiglitazone are limited. Moreover, the effects of rosiglitazone on the function and levels of HDL are unclear. In the present study, we investigated the effects of rosiglitazone on HDL function and its mechanisms of action in atherosclerotic rabbits. Our results revealed that rosiglitazone induced a significant increase in serum HDL-C levels, paraoxonase 1 (PON1) activity, [3H]cholesterol efflux rates, and the expression of ABCA1 and SR-BI in hepatocytes and peritoneal macrophages. The expression of ABCA1 was also increased in aortic lesions. Rosiglitazone markedly reduced serum myeloperoxidase (MPO) activity, aortic intima-media thickness (IMT) and the percentage of plaque area in the aorta. It can thus be concluded that in atherosclerotic rabbits, rosigitazone increases the levels of HDL-C and hinders atherosclerosis. Thus, it improves HDL quality and function, as well as the HDL-induced cholesterol efflux, exerting anti-inflammatory and antioxidant effects. PMID:25604880

  2. Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy

    PubMed Central

    Zabirnyk, Olga; Liu, Wei; Khalil, Shadi; Sharma, Anit; Phang, James M.

    2010-01-01

    Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy. PMID:19942609

  3. Revising the high-density lipoprotein targeting strategies - insights from human and preclinical studies.

    PubMed

    Nesan, Dinushan; Ng, Dominic S

    2014-12-01

    In recent years, the high-density lipoprotein (HDL) hypothesis has been challenged. Several completed randomized clinical trials continue to fall short in demonstrating HDL, or at least HDL-cholesterol (HDL-C) levels, as being a consistent target in the prevention of cardiovascular diseases. However, population studies and findings in lipid modifying trials continue to strongly support HDL-C as a superb risk predictor. It is increasingly evident that the complexity of HDL metabolism confounds the use of HDL-C concentration as a unified target. However, important insights continue to emerge from the post hoc analyses of recently completed (i) fibrate-based FIELD and ACCORD trials, including the unexpected beneficial effect of fibrates in microvascular diseases, (ii) the niacin-based AIM-HIGH and HPS2-THRIVE studies, (iii) recombinant HDL-based as well as (iv) the completed CETP inhibitor-based trials. These together with on-going mechanistic studies on novel pathways, which include the unique roles of microRNAs, post-translational remodeling of HDL and novel pathways related to HDL modulators will provide valuable insights to guide how best to refocus and redesign the conceptual framework for selecting HDL-based targets. PMID:25115413

  4. The myeloperoxidase product hypochlorous acid generates irreversible high-density lipoprotein receptor inhibitors

    PubMed Central

    Binder, Veronika; Ljubojevic, Senka; Haybaeck, Johannes; Holzer, Michael; El-Gamal, Dalia; Schicho, Rudolf; Pieske, Burkert; Heinemann, Akos; Marsche, Gunther

    2014-01-01

    Objective Elevated levels of advanced oxidation protein products (AOPPs) have been described in several chronic inflammatory diseases, like chronic renal insufficiency, rheumatoid arthritis and atherosclerosis. Recent findings revealed that AOPPs are inhibitors of the major high-density lipoprotein (HDL) receptor, scavenger receptor class B, type 1 (SR-BI). Here we investigated what oxidation induced structural alterations convert plasma albumin into an HDL-receptor inhibitor. Approach and Results Exposure of albumin to the physiological oxidant, hypochlorous acid, generated high affinity SR-BI ligands. Protection of albumin lysine-residues prior exposure to hypochlorous acid as well as regeneration of N-chloramines after oxidation of albumin completely prevented binding of oxidized albumin to SR-BI, indicating that modification of albumin lysine-residues is required to generate SR-BI ligands. Of particular interest, N-chloramines within oxidized albumin promoted irreversible binding to SR-BI, resulting in permanent receptor blockade. We observed that the SR-BI inhibitory activity of albumin isolated from chronic kidney disease patients correlated with the content of the myeloperoxidase-specific oxidation product 3-chlorotyrosine and was associated with alterations in the composition of HDL. Conclusion Given that several potential atheroprotective activities of HDL are mediated by SR-BI, the present results raise the possibility that oxidized plasma albumin, through permanent SR-BI blockade, contributes to the pathophysiology of cardiovascular disease. PMID:23493288

  5. Oxidized low-density lipoprotein as a biomarker of cardiovascular diseases.

    PubMed

    Trpkovic, Andreja; Resanovic, Ivana; Stanimirovic, Julijana; Radak, Djordje; Mousa, Shaker A; Cenic-Milosevic, Desanka; Jevremovic, Danimir; Isenovic, Esma R

    2015-04-01

    Atherosclerosis is a life-long illness that begins with risk factors, which in turn contribute to the development of subclinical disease, followed by the establishment of overt cardiovascular disease (CVD). Thrombotic-occlusive complications of atherosclerosis are among the most widespread and costly health problems. Oxidized low-density lipoprotein (OxLDL) plays an important role in atherogenesis by promoting an inflammatory environment and lipid deposition in the arterial wall. As cardiovascular events occur in individuals without common risk factors, there is a need for additional tools that may help in CVD risk assessment and management. The use of biomarkers has improved diagnostic, therapeutic and prognostic outcome in cardiovascular medicine. This review elaborates on the value of circulating OxLDL as a biomarker of CVD. Three enzyme-linked immunosorbent assays (4E6, DLH3 and E06) using murine monoclonal antibodies for determination of OxLDL blood levels have been developed. However, none of these assays are currently approved for routine clinical practice. We identified studies investigating OxLDL in CVD (measured by 4E6, DLH3 or E06 assay) by searching the PubMed database. Circulating OxLDL was found to be associated with all stages of atherosclerosis, from early atherogenesis to hypertension, coronary and peripheral arterial disease, acute coronary syndromes and ischemic cerebral infarction. The results of studies investigating the usefulness of OxLDL for CVD prediction were also summarized. Furthermore, OxLDL was found to be associated with pathologic conditions linked to CVD, including diabetes mellitus, obesity and metabolic syndrome (MetS). In addition, we have addressed the mechanisms by which OxLDL promotes atherogenesis, and the effects of antiatherogenic treatments on circulating OxLDL. Finally, we highlight the evidence suggesting that lipoprotein (a) [Lp(a)] is the preferential carrier of oxidized phospholipids (OxPL) in human plasma. A strong association between OxPL/apoB level (representing the content of OxPL on apolipoprotein B-100 particles, measured by E06 assay) and Lp(a) has been determined. PMID:25537066

  6. Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis

    PubMed Central

    Chen, Suet Nee; Cilingiroglu, Mehmet; Todd, Josh; Lombardi, Raffaella; Willerson, James T; Gotto, Antonio M; Ballantyne, Christie M; Marian, AJ

    2009-01-01

    Background Plasma level of high-density lipoprotein-cholesterol (HDL-C), a heritable trait, is an important determinant of susceptibility to atherosclerosis. Non-synonymous and regulatory single nucleotide polymorphisms (SNPs) in genes implicated in HDL-C synthesis and metabolism are likely to influence plasma HDL-C, apolipoprotein A-I (apo A-I) levels and severity of coronary atherosclerosis. Methods We genotyped 784 unrelated Caucasian individuals from two sets of populations (Lipoprotein and Coronary Atherosclerosis Study- LCAS, N = 333 and TexGen, N = 451) for 94 SNPs in 42 candidate genes by 5' nuclease assays. We tested the distribution of the phenotypes by the Shapiro-Wilk normality test. We used Box-Cox regression to analyze associations of the non-normally distributed phenotypes (plasma HDL-C and apo A-I levels) with the genotypes. We included sex, age, body mass index (BMI), diabetes mellitus (DM), and cigarette smoking as covariates. We calculated the q values as indicators of the false positive discovery rate (FDR). Results Plasma HDL-C levels were associated with sex (higher in females), BMI (inversely), smoking (lower in smokers), DM (lower in those with DM) and SNPs in APOA5, APOC2, CETP, LPL and LIPC (each q ?0.01). Likewise, plasma apo A-I levels, available in the LCAS subset, were associated with SNPs in CETP, APOA5, and APOC2 as well as with BMI, sex and age (all q values ?0.03). The APOA5 variant S19W was also associated with minimal lumen diameter (MLD) of coronary atherosclerotic lesions, a quantitative index of severity of coronary atherosclerosis (q = 0.018); mean number of coronary artery occlusions (p = 0.034) at the baseline and progression of coronary atherosclerosis, as indicated by the loss of MLD. Conclusion Putatively functional variants of APOA2, APOA5, APOC2, CETP, LPL, LIPC and SOAT2 are independent genetic determinants of plasma HDL-C levels. The non-synonymous S19W SNP in APOA5 is also an independent determinant of plasma apo A-I level, severity of coronary atherosclerosis and its progression. PMID:19878569

  7. Polar phospholipids from bovine endogenously oxidized low density lipoprotein interfere with follicular thecal function.

    PubMed

    Löhrke, B; Viergutz, T; Krüger, B

    2005-12-01

    The role of endogenously oxidized low density lipoprotein (oxLDL) in follicular steroidogenic regulation is unknown. Information may be important in order to elucidate ovulatory dysregulation in disordered lipid metabolism. To obtain specific data, we studied the effect of polar phospholipids (PL) isolated from oxLDL with different endogenous levels of lipohydroperoxides (LHP) on the thecal expression of mRNA encoding steroidogenic enzymes and cyclooxygenase 2 (COX-2), and on the thecal production of superoxide and progesterone. Large (preovulatory) bovine follicles were used and analyses of thecal fragments from single follicles were performed by radioimmunoassays, chemiluminescence assays and quantitative RT-PCR. Basal concentration of mRNA for several lipoprotein receptors exceeded by about 10-times the basal level of mRNA encoding steroidogenic enzymes, suggesting that preovulatory theca receptors may favour uptake of oxLDL. PL (5-11 pmol phosphorus/ml) decreased (up to 0.5-times the control) progesterone synthesis, production of superoxide and levels of P450 cholesterol side chain cleavage (P450 scc), 3beta-hydroxysteroid dehydrogenase and COX-2 mRNA. Abundance of COX-2 transcripts in thecal tissue incubated with forskolin depended on the progesterone/17beta-oestradiol ratio of the follicle fluid, i.e. the previous microenvironment in vivo. PL effects were mimicked by the platelet-activating factor (PAF). WEB 2086, a PAF receptor blocker, did not always abolish these responses, suggesting that the effects were not mediated solely by this receptor. PAF interfered dose-dependently with LH-induced responses, indicating interference with LH signalling. PL from mildly oxidized LDL (0.5 nmol/ml LHP) tended to exert greater effects than PL from oxLDL containing 1.5 nmol/ml LHP. In consideration of the known physiologic role of progesterone, COX-2 and possibly superoxide, these results provide evidence for a potential of PL from oxLDL to induce ovulatory dysregulation and suggest that the extent of the LDL oxidation seems to be important for interfering with thecal responses to the preovulatory LH surge. PMID:16326838

  8. In vitro evaluation of dextran sulfate cellulose beads for whole blood infusion low-density lipoprotein-hemoperfusion.

    PubMed

    Kobayashi, Akira; Nakatani, Masaru; Furuyoshi, Shigeo; Tani, Nobutaka

    2002-10-01

    We describe results from a feasibility study of a newly developed low-density lipoprotein (LDL) adsorbent designed for use in whole-blood infusion LDL-hemoperfusion. The adsorbent has almost the same chemical structure as the Liposorber adsorbent (dextran sulfate cellulose beads) but has a larger particle size. In whole-blood perfusion tests, the adsorbent adsorbed atherogenic LDL cholesterol directly from whole blood but left concentrations of high-density lipoprotein cholesterol largely unchanged. In whole-blood perfusion tests using fresh human donor blood or bovine blood anticoagulated with acid citrate dextrose solution or sodium citrate, the adsorbent showed minimal side effects in terms of blood cell activation, complement activation, and blood cell loss, suggesting that it has excellent blood compatibility. In addition, the adsorbent showed mechanical stability and absence of hemolysis. In conclusion, the new adsorbent showed the appropriate characteristics for an LDL adsorbent column for use in whole-blood infusion LDL-hemoperfusion. PMID:12423531

  9. Modified Low Density Lipoprotein and Lipoprotein-Containing Circulating Immune Complexes as Diagnostic and Prognostic Biomarkers of Atherosclerosis and Type 1 Diabetes Macrovascular Disease

    PubMed Central

    Orekhov, Alexander N.; Bobryshev, Yuri V.; Sobenin, Igor A.; Melnichenko, Alexandra A.; Chistiakov, Dimitry A.

    2014-01-01

    In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The immunogenicity of modified LDL results in induction of self-antibodies specific to a certain type of modified LDL. The antibodies react with modified LDL forming circulating immune complexes. Circulating immune complexes exhibit prominent immunomodulatory properties that influence atherosclerotic inflammation. Compared to freely circulating modified LDL; modified LDL associated with the immune complexes have a more robust atherogenic and proinflammatory potential. Various lipid components of the immune complexes may serve not only as diagnostic but also as essential predictive markers of cardiovascular events in atherosclerosis. Accumulating evidence indicates that LDL-containing immune complexes can also serve as biomarker for macrovascular disease in type 1 diabetes. PMID:25050779

  10. Members of the Low Density Lipoprotein Receptor Family Mediate Cell Entry of a Minor-Group Common Cold Virus

    Microsoft Academic Search

    Franz Hofer; Martin Gruenberger; Heinrich Kowalski; Herwig Machat; Manfred Huettinger; Ernst Kuechler; Dieter Blaas

    1994-01-01

    A protein binding to a minor-group human rhinovirus (HRV2) was purified from HeLa cell culture supernatant. The amino acid sequences of tryptic peptides showed identity with the human low density lipoprotein (LDL) receptor (LDLR). LDL and HRV2 mutually competed for binding sites on human fibroblasts. Cells down-regulated for LDLR expression yielded much less HRV2 upon infection than cells with up-regulated

  11. Cholesteryl ester transfer protein gene: Two common mutations and their effect on plasma high-density lipoprotein cholesterol content

    Microsoft Academic Search

    H. Akita; H. Chiba; K. Matsuno

    1994-01-01

    Cholesteryl ester transfer protein regulates high-density lipoprotein cholestrol (HDL-C) level, and genetic deficiency causes hyperalphalpoproteinemia (HALP). The G to A mutation in the intron 14 splice donor (I14A) has been known to be a common mutation in HALP. Recently, another mutant, D442G (Asp 442 to Gly), was ascertained. The allelic frequencies of I14A and D442G were investigated using 226 unrelated

  12. A single bout of brisk walking increases basal very low-density lipoprotein triacylglycerol clearance in young men

    Microsoft Academic Search

    Tsekouras E. Yiannis; Yanni E. Amalia; Bougatsas Dimitrios; Kavouras A. Stavros; Sidossis S. Labros

    2007-01-01

    Very low-density lipoprotein triacylglycerol (VLDL-TG) turnover rate was evaluated in the morning, 12 hours after a single bout of brisk walking (90 minutes at approximately 60% of V?o2max; EXE), compared to a resting control period (CON) in 10 recreationally active men. VLDL-TG fractional catabolic rate was calculated from the decay in isotopic enrichment after a bolus injection of [2H5]glycerol. Plasma

  13. Functional Role of the Low-Density Lipoprotein Receptor-Related Protein in Alzheimer’s Disease

    Microsoft Academic Search

    Elaine Waldron; Sebastian Jaeger; Claus U. Pietrzik

    2006-01-01

    Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder, characterized by neuronal loss, neurofibrillary tangle formation and the extracellular deposition of amyloid-? (A?) plaques. The amyloid precursor protein (APP) and the enzymes responsible for A? generation seem to be the base elements triggering the destructive processes. Initially, the low-density lipoprotein receptor-related protein (LRP) was genetically linked to AD and

  14. Heterogeneity of dog interstitial fluid (peripheral lymph) high density lipoproteins: implications for a role in reverse cholesterol transport

    Microsoft Academic Search

    L. Dory; L. M. Boquet; R. L. Hamilton; C. H. Sloop; P. S. Roheim

    The heterogeneity of dog interstitial fluid (peripheral lymph) high density lipoprotein (HDL) was investigated and compared to plasma HDL. Interstitial fluid and plasma HDL of normal and cholesterol-fed dogs was subfractionated by ultra- centrifugation and affinity and molecular weight sieving chro- matography. Both plasma (P) and interstitial fluid (L) HDL can be subfractionated into a larger fraction (P-I and L-I)

  15. Autoxidation of human low density lipoprotein: loss of polyunsaturated fatty acids and vitamin E and generation of aldehydes

    Microsoft Academic Search

    Hermann Esterbauer; Gunther Jurgens; Oswald Quehenberger; Ernst Koller

    The alteration of structural and biological properties of human plasma low density lipoprotein (LDL) exposed to ox- idative conditions is in part ascribed to lipid peroxidation. The objective of this investigation was to measure quantitatively several parameters in oxidizing LDL indicative for lipid perox- idation. Exposure of freshly prepared ElYLA-free LDL to an oxygen-saturated buffer led to a complete depletion

  16. Adenovirus-Mediated Transfer of Low Density Lipoprotein Receptor Gene Acutely Accelerates Cholesterol Clearance in Normal Mice

    Microsoft Academic Search

    Joachim Herz; Robert D. Gerard

    1993-01-01

    We have explored the use of adenovirus-mediated gene transfer to transiently elicit production of low density lipoprotein (LDL) receptors in mice. A recombinant adenovirus carrying the human LDL receptor cDNA restored LDL receptor function in receptor-deficient cultured cells. Intravenous injection of recombinant virus acutely lowered plasma cholesterol levels and increased the rate of 125I-labeled LDL clearance from the circulation in

  17. Catabolism of native and oxidized low density lipoproteins: in vivo insights from small animal positron emission tomography studies

    Microsoft Academic Search

    J. Pietzsch; R. Bergmann; F. Wuest; B. Pawelke; C. Hultsch; J. van den Hoff

    2005-01-01

    Summary.  The human organism is exposed to numerous processes that generate reactive oxygen species (ROS). ROS may directly or indirectly\\u000a cause oxidative modification and damage of proteins. Protein oxidation is regarded as a crucial event in the pathogenesis\\u000a of various diseases ranging from rheumatoid arthritis to Alzheimer’s disease and atherosclerosis. As a representative example,\\u000a oxidation of low density lipoprotein (LDL) is

  18. Persistent high levels of plasma oxidized low-density lipoprotein after acute myocardial infarction predict stent restenosis

    Microsoft Academic Search

    T. Naruko; M. Ueda; S. Ehara; A. Itoh; K. Haze; N. Shirai; Y. Ikura; M. Ohsawa; H. Itabe; Y. Kobayashi; H. Yamagishi; M. Yoshiyama; J. Yoshikawa; A. E. Becker

    2006-01-01

    Objective-Recently, elevated levels of plasma oxidized low-density lipoprotein (LDL) have been shown to relate to plaque instability in human atherosclerotic lesions. We investigated prospectively patients admitted with acute myocardial infarction (AMI) who underwent primary coronary stenting to evaluate whether the 6-month outcome could be predicted by measuring plasma oxidized LDL (ox-LDL) levels at the time of hospital discharge. Methods and

  19. Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers

    Microsoft Academic Search

    Giovanni B Vigna; Fabrizio Costantini; Giancarlo Aldini; Marina Carini; Alberico Catapano; Fabio Schena; Arianna Tangerini; Rosanna Zanca; Egidio Bombardelli; Paolo Morazzoni; Andrea Mezzetti; Renato Fellin; Roberto Maffei Facino

    2003-01-01

    The aim of our study was to evaluate the effect of a standardized formulation of a polyphenolic extract of grapes (Leucoselect-Phytosome [LP]) on low-density lipoprotein (LDL) susceptibility to oxidation in a group of heavy smokers. A randomized, double-blind, crossover study was undertaken in 24 healthy male heavy smokers, aged ? 50 years. Enrolled subjects were given 2 capsules twice daily

  20. Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells

    Microsoft Academic Search

    S. D. Cushing; J. A. Berliner; A. J. Valente; M. C. Territo; M. Navab; F. Parhami; R. Gerrity; C. J. Schwartz; A. M. Fogelman

    1990-01-01

    After exposure to low density lipoprotein (LDL) that had been minimally modified by oxidation (MM-LDL), human endothelial cells (EC) and smooth muscle cells (SMC) cultured separately or together produced 2- to 3-fold more monocyte chemotactic activity than did control cells or cells exposed to freshly isolated LDL. This increase in monocyte chemotactic activity was paralleled by increases in mRNA levels

  1. Increased hepatic secretion of very-low-density-lipoprotein apolipoprotein B100 in heterozygous familial hypercholesterolaemia: a stable isotope study

    Microsoft Academic Search

    Michael H. Cummings; Gerald F. Watts; Margot Umpleby; Thomas R. Hennessy; Jeremy R. Quiney; Peter H. Sönksen

    1995-01-01

    We have measured the hepatic secretion of very-low-density-lipoprotein apolipoprotein B-100 (VLDL apo B) in 6 patients with heterozygous familial hypercholesterolaemia (FH) (4 males, 2 females, age 47.0 ± 2.7 years (mean ± S.E.M.), weight 71.0 ± 5.3 kg) and 6 normocholesterolaemic subjects matched for age, weight and sex (4 males, 2 females, age 47.5 ± 3.1 years, weight 70.0 ±

  2. Low-density lipoprotein receptor gene (LDLR) world-wide website in familial hypercholesterolaemia: update, new features and mutation analysis

    Microsoft Academic Search

    Karen E. Heath; Mike Gahan; Ros A. Whittall; Steve E. Humphries

    2001-01-01

    Mutations in the low density lipoprotein receptor gene (LDLR) cause familial hypercholesterolaemia (FH). The FH website (http:\\/\\/www.ucl.ac.uk\\/fh) has been updated to provide various functions enabling the analysis of the large number of LDLR mutations. To date, 683 LDLR mutations have been reported; of these 58.9% are missense mutations, 21.1% minor rearrangements, 13.5% major rearrangements and 6.6% splice site mutations. Of

  3. Oxidized Low-Density Lipoprotein Induces Macrophage Respiratory Burst via Its Protein Moiety: A Novel Pathway in Atherogenesis?

    Microsoft Academic Search

    Thao Nguyen-Khoa; Ziad A. Massy; Véronique Witko-Sarsat; Sandrine Canteloup; Messeret Kebede; Bernard Lacour; Tilman Drüeke; Béatrice Descamps-Latscha

    1999-01-01

    Oxidized low-density lipoproteins (oxLDL) play a crucial role in atherogenesis mainly via their capacity to bind and to activate macrophages. However, the role of the protein LDL moiety in this process is not yet established. In this study, human LDL were exposed to hypochlorous acid (HOCl), a selective protein oxidant, or copper sulfate (CuSO4), a major lipid oxidant, and tested

  4. Comparison between copper-mediated and hypochlorite-mediated modifications of human low density lipoproteins evaluated by protein carbonyl formation

    Microsoft Academic Search

    Liang-Jun Yan; John K. Lodge; Maret G. Traber; Seiichi Matsugo; Lester Packer

    The purpose of this study was to evaluate the mech- anisms of apolipoprotein B (apoB) modification during oxi- dation of human low density lipoproteins (LDL) mediated ei- ther by copper or by hypochlorite (HOCl). The kinetics of protein carbonyl formation, the relationship of apoB carbonyl formation to lipid peroxidation, and the loss of apoB lysine residues were determined. During copper-mediated

  5. Anti-oxidized low density lipoprotein antibody determination as a predictor of restenosis following percutaneous transluminal coronary angioplasty

    Microsoft Academic Search

    Jacob George; Dror Harats; Erez Bakshi; Yehuda Adler; Yair Levy; Boris Gilburd; Yehuda Shoenfeld

    1999-01-01

    Recent data suggests that autoimmune factors play an important role in the pathogenesis of atherosclerosis. In this context several autoantigens have been shown to elicit an immune response that results in accelerated atherosclerotic plaque formation. In the present study, we investigated whether elevated titers of anti-oxidized low density lipoprotein (oxLDL), anticardiolipin and antibodies to ?2-glycoprotein I (?2GPI) can predict subsequent

  6. Inhibition of Mammalian 15-Lipoxygenase-Dependent Lipid Peroxidation in Low-Density Lipoprotein by Quercetin and Quercetin Monoglucosides

    Microsoft Academic Search

    Edson Luiz da Silva; Tojiro Tsushida; Junji Terao

    1998-01-01

    Lipoxygenase is suggested to be involved in the early event of atherosclerosis by inducing plasma low-density lipoprotein (LDL) oxidation in the subendothelial space of the arterial wall. Since flavonoids such as quercetin are recognized as lipoxygenase inhibitors and they occur mainly in the glycoside form, we assessed the effect of quercetin and its glycosides (quercetin 3-O-?-glucopyranoside, Q3G; quercetin 4?-O-?-glucopyranoside, Q4?G;

  7. Impact of Vitamin A on High-Density Lipoprotein-Cholesterol and Scavenger Receptor Class BI in the Obese Rat

    Microsoft Academic Search

    Shanmugam M. Jeyakumar; Ayyalasomayajula Vajreswari; Nappan V. Giridharan

    2007-01-01

    Objective:Scavenger receptor class BI (SR-BI), authentic high-density lipoprotein (HDL) receptors expressed in liver, are known to play an important role in HDL-cholesterol (C) metabolism and reverse cholesterol transport. Interestingly, obese rats of WNIN\\/Ob strain have abnormally elevated levels of serum HDL-C compared with their lean counterparts. Based on the well-established role of SR-B1 in HDL-C metabolism, it was hypothesized that

  8. Hepatic perfusate very low density lipoproteins obtained from fat-fed nonhuman primates stimulate cholesterol esterification in macrophages

    Microsoft Academic Search

    Patricia A. Soltys; Holly Gump; Lori Hennessy; Theodore Mazzone; K. D. Carey; Henry C. McGill; Godfrey S. Getz; Sandra R. Bates

    The livers of both baboons and rhesus monkeys fed a high fat, high cholesterol diet secreted very low density lipoproteins (VLDL) that were enriched in cholesteryl ester and apoE as compared to VLDL secreted by the livers of chow-fed animals. Stimulation of macrophage cholesterol esterification by the experimental VLDL was compared to that produced by the standard B-VLDL obtained from

  9. 3.P.121 Accumulation and metabolism of low density lipoprotein-derived cholesteryl linoleate hydroperoxide and hydroxide by macrophages

    Microsoft Academic Search

    L. Kritharides; J. Upston; W. Jessup; R. T. Dean

    1997-01-01

    Cholesteryl linoleate hydroperoxide (CLOOH) and hydroxide (CLOH) are present in human atheroma. The intracellular metabolism of low density lipoprotein (LDL)-derived CLOOH and CLOH remain undefined be- cause extensive free radical-mediated LDL oxidation, which modifies LDL apolipoprotein B sufficiently to allow endocy- tosis by the scavenger receptor (ScR), also degrades CLOOH and CLOH. This problem was approached by first acetylat- ing

  10. A moderate reduction in extracellular pH protects macrophages against apoptosis induced by oxidized low density lipoprotein

    Microsoft Academic Search

    Andrew B. Gerry; David S. Leake

    2008-01-01

    We investigated the effect of pH on macrophage apoptosis induced by oxidized low density lipoprotein (OxLDL), as human atherosclerotic lesions have regions of low pH. Hydroperoxide-rich and oxysterol-rich LDL caused 38% and 74% apoptosis of J774 macrophages, respectively, at 24 h, as measured by the externalization of phosphatidylserine. Native LDL, however, did not cause apoptosis. Reducing the pH of the

  11. Oxidative modification of low-density lipoproteins and the outcome of renal allografts at 11\\/2 years

    Microsoft Academic Search

    Jean-Louis Bosmans; Paul Holvoet; Simonne E. H. Dauwe; Dirk K. Ysebaert; Thierry Chapelle; Angelika Jürgens; Vera Kovacic; Eric A. Van Marck; Marc E. De Broe; Gert A. Verpooten

    2001-01-01

    Oxidative modification of low-density lipoproteins and the outcome of renal allografts at 11\\/2 years.BackgroundPrevious studies reported a significant association between hyperlipidemia of the recipient and chronic allograft nephropathy (CAN). However, the nature and the pathogenic mechanism of circulating lipid abnormalities in CAN remain unclear.MethodsIn a prospective study of 50 consecutive adult recipients of a cadaveric renal allograft, we investigated the

  12. Hyperhomocysteinemia Decreases Circulating High-Density Lipoprotein by Inhibiting Apolipoprotein AI Protein Synthesis and Enhancing HDL Cholesterol Clearance

    Microsoft Academic Search

    Dan Liao; Hongmei Tan; Rutai Hui; Zhaohui Li; Xiaohua Jiang; John Gaubatz; Fan Yang; William Durante; Lawrence Chan; Andrew I. Schafer; Henry J. Pownall; Xiaofeng Yang; Hong Wang

    2010-01-01

    We previously reported that hyperhomocysteinemia (HHcy), an independent risk factor of coronary artery disease (CAD), is associated with increased atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) in cystathionine -synthase-\\/apolipoprotein E-deficient (CBS\\/\\/apoE\\/) mice. We observed that plasma homocysteine (Hcy) concentrations are negatively correlated with HDL-C and apolipoprotein A1 (apoA-I) in patients with CAD. We found the loss of large HDL

  13. Visualization of the binding, endocytosis, and transcytosis of low- density lipoprotein in the arterial endothelium in situ

    Microsoft Academic Search

    ELIZA VASILE; MAYA SIMIONESCU; NICOLAE SIMIONESCU

    1983-01-01

    We investigated the interaction and transport of low-density lipoprotein (LDL) through the arterial endothelium in rat aorta and coronary artery, by perfusing in situ native, untagged human, and rat LDL. The latter was rendered electron-opaque after it interacted with the endothelial cell and was subsequently fixed within tissue. We achieved LDL electron- opacity by an improved fixation procedure using 3,3'-diaminobenzidine,

  14. Role of reactive oxygen species and Bax in oxidized low density lipoprotein-induced apoptosis of human monocytes

    Microsoft Academic Search

    Natalia Ermak; Bernard Lacour; Tilman B. Drüeke; Stéphanie Vicca

    2008-01-01

    This study investigated the proapoptotic effects of oxidized low density lipoprotein (oxLDL), which plays a key role in atherogenesis, on normal fresh human monocytes isolated from peripheral blood (PBMs), on human monocyte-derived macrophages, and on U937 monocytic cell line. OxLDL were generated by hypochlorous acid (HOCl) treatment of native LDL. We demonstrated that HOCl–oxLDL (200?g\\/ml) induced apoptosis in PBMs and

  15. Cost-effectiveness of Gemfibrozil for Coronary Heart Disease Patients With Low Levels of High-Density Lipoprotein Cholesterol

    Microsoft Academic Search

    John A. Nyman; Melissa S. Martinson; David Nelson; Sean Nugent; Dorothea Collins

    Background: Although numerous clinical trials and eco- nomic analyses have established the efficacy and cost- effectiveness of lowering cholesterol for the prevention of coronary heart disease, there are few data on the role of raising high-density lipoprotein cholesterol (HDL-C) levels and lowering triglyceride levels. The US Depart- ment of Veterans Affairs (VA) Cooperative Studies Pro- gram HDL-C Intervention Trial (VA-HIT)

  16. Isolated low high density lipoprotein-cholesterol (HDLC): implications of global risk reduction. Case report and systematic scientific review

    Microsoft Academic Search

    Melvin R Hayden; Suresh C Tyagi

    2005-01-01

    BACKGROUND: The importance of low high-density lipoprotein cholesterol (HDL-C), elevated non HDL-C (as part of the metabolic syndrome, prediabetes, and type 2 diabetes mellitus), and an isolated low HDL-C is rapidly emerging. The antiatherosclerotic roles of reverse cholesterol transport and the pleiotropic antioxidant – anti-inflammatory mechanistic effects of HDL-C are undergoing rapid exponential growth. CASE PRESENTATION: In 1997 a 53-year-old

  17. A comparison of plasma cholesterol, triglycerides. and high density lipoprotein-cholesterol in speed skaters, weightlifters and non-athletes

    Microsoft Academic Search

    Peter A. Farrell; Michael G. Maksud; Michael L. Pollock; Carl Foster; James Anholm; John Hare; Arthur S. Leon

    1982-01-01

    Summary  Venous plasma cholesterol, triglycerides and high-density lipoprotein cholesterol (HDL-C) were measured after a 12–16 h overnight fast in three groups of men with different physical training histories. The groups consisted of 11 untrained men (aged 19–25 years), 11 well-trained weightlifters (20–32 years), who had not trained aerobically for at least 6 months, and 11 candidates for an Olympic speed skating

  18. Low density lipoprotein cholesterol is inversely correlated with abdominal visceral fat area: a magnetic resonance imaging study

    Microsoft Academic Search

    Michel R Hoenig; Gary Cowin; Raymond Buckley; Christine McHenery; Allan Coulthard

    2011-01-01

    BACKGROUND: Visceral Fat Area (VFA) is an independent predictor of coronary disease. While low density lipoprotein cholesterol (LDL-C) is used to determine risk and guide therapy, its accuracy fails in obese patients who may have low LDL-C despite high VFA. OBJECTIVE: We sought to describe the relationship between VFA, LDL-C and to describe shifting cholesterol metabolism with increasing VFA. METHODS:

  19. Genetic variations in the cholesteryl ester transfer protein gene and high density lipoprotein cholesterol levels in Taiwanese Chinese

    Microsoft Academic Search

    Lung-An Hsu; Yu-Lin Ko; Kuang-Hung Hsu; Yu-Hsien Ko; Ying-Shiung Lee

    2002-01-01

    This study analyzed the association of the I14A mutation, the D442G mutation, and the TaqIB polymorphism of the cholesteryl ester transfer protein (CETP) gene in 718 Chinese individuals with high-density lipoprotein cholesterol levels (HDL-C) living in Taiwan. The analysis revealed that the I14A mutation was not present in any of the 110 subjects with HDL-C levels above 60 mg\\/dl. By

  20. High-density lipoprotein cholesterol and triglycerides as therapeutic targets for preventing and treating coronary artery disease

    Microsoft Academic Search

    Antonio M. Gotto

    2002-01-01

    Epidemiologic and clinical trials show that elevated triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C) are independent risk factors for coronary heart disease (CHD). However, adjustment for covariates frequently weakens or abolishes the predictive significance of triglycerides, whereas the evidence for HDL-C is more consistently strong. Data indicate that there is a 2% to 3% decrease in coronary risk

  1. Decreased hepatic production of very low density lipoproteins following activation of fatty acid oxidation by Ro 22-0654

    Microsoft Academic Search

    Munehiko Yamamoto; Nobuhim Fukuda; Joseph Triscari; Ann C. Sullivan; Joseph A. Ontko

    In fed rat livers perfused with (l-'*C)oleic acid, Ro 22-0654 (4-amino-5-ethyl-3-thiophenecarboxylic acid methyl ester hydrochloride), an inhibitor of fatty acid synthesis, acti- vated ketogenesis and decreased the secretion of triglyceride in very low density lipoproteins (VLDL). Ro 22-0654 was without effect on total oleic acid uptake and utilization by the liver. The liver triglyceride content, urea synthesis, and bile production

  2. Unusual forms of low density lipoprotein receptors in hamster cell mutants with defects in the receptor structural gene

    Microsoft Academic Search

    Karen F. Kozarsky; Hilarie A. Brush; Monty Krieger

    1986-01-01

    The structure and processing of low density lipoprotein (LDL) receptors in wild-type and LDL re- ceptor-deficient mutant Chinese hamster ovary cells was examined using polyclonal anti-receptor antibod- ies. As previously reported for human LDL receptors, the LDL receptors in wild-type Chinese hamster ovary cells were synthesized as precursors which were exten- sively processed by glycosylation to a mature form. In

  3. Plasma Kinetics and Biodistribution of a Lipid Emulsion Resembling Low-Density Lipoprotein in Patients with Acute Leukemia

    Microsoft Academic Search

    Raul C. Maranhao; Bernardo Garicochea; Edson L. Silva; Pedro Dorlhiac-Llacer; Silvia M. S. Cadena; Iris J. C. Coelho; Claudio Meneghetti; Fulvio J. C. Fileggi; Dalton A. F. Chamone

    1994-01-01

    Low-density lipoprotein (LDL) could be used as a carrier of chemo- therapeutic agents to neoplastic cells that overexpress LDL receptors n-I.DI.i, but LDL is difficult to obtain and handle. Recently, it was observed that a protein-free emulsion resembling the lipid portion of LDL (LDE) behave like native LDL when injected into the bloodstream. In this study, the evidence that LDE

  4. Plasma kinetic behavior in hyperlipidemic subjects of a lipidic microemulsion that binds to low density lipoprotein receptors

    Microsoft Academic Search

    Raul C. Maranhão; Ivete A. Roland; Odaly Toffoletto; José Antonio Ramires; Romélia P. Gonçalves; Carlos H. Mesquita; Fulvio Pileggi

    1997-01-01

    It was previously reported that a protein-free microemulsion (LDE) with structure roughly resembling that of the lipid portion\\u000a of low density lipoprotein (LDL) was presumably taken up by LDL receptors when injected into the bloodstream. In contact with\\u000a plasma, LDE acquires apolipoproteins (apo) including apo E that would be the ligand for receptor binding. Currently, apo were\\u000a associated to LDE

  5. Tangier Disease: Defective Recombination of a Specific Tangier Apolipoprotein AI Isoform (Pro-apo AI) with High Density Lipoproteins

    Microsoft Academic Search

    Gerd Schmitz; Gerd Assmann; Stanley C. Rall; Robert W. Mahley

    1983-01-01

    Isoforms of apolipoprotein A-I (apo A-I) from subjects with Tangier disease were characterized, and their ability to recombine with normal high density lipoproteins (HDL) was studied. In contrast to normal serum, in which isoprotein 4 is the dominant species [7.9± 1.8% (mean ± SD)], the Tangier serum contained much less total apo A-I (≈ 1% of that in normal serum),

  6. Decreased Cholesterol Efflux from Fibroblasts of a Patient without Tangier Disease, but with Markedly Reduced High Density Lipoprotein Cholesterol Levels

    Microsoft Academic Search

    GRETCHEN P. EBERHART; ARMANDO J. MENDEZ; MASON W. FREEMAN

    2010-01-01

    A 51-yr-old woman without clinical evidence of Tangier disease, but with an extremely low high density lipoprotein (HDL) cholesterol level, was studied. No defect in the major structural protein of HDL, apolipoprotein AI (apo AI), was detected. A preponderance of small HDL particles in the patient's plasma suggested defective uptake of cellular cholesterol. Efflux of (3H)cholesterol from patient fibroblasts to

  7. Cholesterol efflux from cells to immunopurified subfractions of human high density lipoprotein: LP-AI and LP-AI\\/AII

    Microsoft Academic Search

    William J. Johnson; Elisabeth P. C. Kilsdonk; Arie van Tol; Michael C. Phillips; George H. Rothblat

    Using immunoaffinity chromatography, we sepa- cells, there is little or no oxidative degradation of rated human high density lipoprotein (HDL) into two subfrac- cholesterol, and sterol homeostasis requires that excess tions: LP-AI, in which all particles contain apolipoprotein A-I cholestero~ be removed and transported to the liver. These (apoA-I) but no apoA-11, and LP-AI\\/AII, in which all particles removal and

  8. Factors regulating the metabolism of low-density lipoprotein-proteoglycan complex in macrophages.

    PubMed

    Vijayagopal, P; Srinivasan, S R; Radhakrishnamurthy, B; Berenson, G S

    1990-02-01

    We studied the factors regulating the metabolism of low-density lipoprotein (LDL)-proteoglycan complex, LDL and acetyl-LDL in mouse peritoneal macrophages. Macrophage conditioned medium stimulated the degradation of LDL-proteoglycan complex and acetyl-LDL in a dose-dependent manner and enhanced cholesteryl ester synthesis mediated by these ligands. The conditioned medium had no such effect in a cell-free system. The conditioned medium enhanced the degradation of both the LDL and proteoglycan components of the complex. The degradation of LDL was not affected by the conditioned medium. The active factor in the conditioned medium was labile to boiling, suggesting that it may be protein in nature. The conditioned medium also lost its stimulatory activity after dialysis through a membrane with an exclusion limit of 25,000 daltons, suggesting the involvement of cytokines and/or other growth factors. Macrophage activation was accompanied by a 2-3-fold increase in the degradation of LDL-proteoglycan complex and acetyl-LDL as compared to the degradation of these ligands in resident macrophages; however, this had no effect on LDL degradation. The degradation of all three ligands increased markedly with decreasing cell density. Preincubation of macrophages for 48 h with increasing concentrations of fetal bovine serum produced a substantial increase in the subsequent degradation of LDL-proteoglycan complex and acetyl-LDL, while it had very little effect on the degradation of LDL. The active factor in serum was destroyed by boiling, suggesting that it may be a protein. These results show that the scavenger receptor, mediating the uptake and degradation of LDL-proteoglycan complex and acetyl-LDL and LDL receptor are regulated differently in mouse peritoneal macrophages. PMID:2302422

  9. Serum amyloid A stimulates macrophage foam cell formation via lectin-like oxidized low-density lipoprotein receptor 1 upregulation

    SciTech Connect

    Lee, Ha Young, E-mail: hayoung@skku.edu [Department of Biological Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 (Korea, Republic of); Kim, Sang Doo [Department of Biological Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)] [Department of Biological Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Baek, Suk-Hwan [Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)] [Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Joon Hyuk [Department of Pathology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)] [Department of Pathology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Cho, Kyung-Hyun [School of Biotechnology, Yeungnam University, Gyeongsan 712-749 (Korea, Republic of)] [School of Biotechnology, Yeungnam University, Gyeongsan 712-749 (Korea, Republic of); Zabel, Brian A. [Palo Alto Institute for Research and Education, Veterans Affairs Hospital, Palo Alto, CA 94304 (United States)] [Palo Alto Institute for Research and Education, Veterans Affairs Hospital, Palo Alto, CA 94304 (United States); Bae, Yoe-Sik, E-mail: yoesik@skku.edu [Department of Biological Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of) [Department of Biological Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 (Korea, Republic of); Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710 (Korea, Republic of)

    2013-03-29

    Highlights: ? SAA induced macrophage foam cell formation. ? SAA stimulated upregulation of lectin-like oxidized low-density lipoprotein receptor 1 (LOX1). ? SAA-induced LOX1 expression and foam cell formation is mediated by JNK/NF-?B signaling. ? HDL-conjugated SAA also stimulates foam cell formation via LOX1 upregulation. ? The finding reveals a novel mechanism of action of SAA in the pathogenesis of atherosclerosis. -- Abstract: Elevated levels of serum amyloid A (SAA) is a risk factor for cardiovascular diseases, however, the role of SAA in the pathophysiology of atherosclerosis remains unclear. Here we show that SAA induced macrophage foam cell formation. SAA-stimulated foam cell formation was mediated by c-jun N-terminal kinase (JNK) signaling. Moreover, both SAA and SAA-conjugated high density lipoprotein stimulated the expression of the important scavenger receptor lectin-like oxidized low-density lipoprotein receptor 1 (LOX1) via nuclear factor-?B (NF-?B). A LOX1 antagonist carrageenan significantly blocked SAA-induced foam cell formation, indicating that SAA promotes foam cell formation via LOX1 expression. Our findings therefore suggest that SAA stimulates foam cell formation via LOX1 induction, and thus likely contributes to atherogenesis.

  10. Tissue specific regulation of the high density lipoprotein (HDL) receptor, scavenger receptor Class B, Type I (SR-BI) by the scaffold protein PDZK1

    E-print Network

    Fenske, Sara Anne

    2008-01-01

    PDZK1 is a four PDZ-domain containing cytoplasmic adaptor protein that binds the Cterminus of the high-density lipoprotein (HDL) receptor SR-BI. Abolishing PDZK1 expression in PDZK1 knockout (KO) mice leads to a ...

  11. Abnormalities in very low, low and high density lipoproteins in hypertriglyceridemia. Reversal toward normal with bezafibrate treatment.

    PubMed Central

    Eisenberg, S; Gavish, D; Oschry, Y; Fainaru, M; Deckelbaum, R J

    1984-01-01

    The effects of triglyceridemia on plasma lipoproteins were investigated in 16 hypertriglyceridemic (HTG) subjects (222-2,500 mg/dl) before and after the initiation of bezafibrate therapy. Bezafibrate caused a mean reduction of 56% in plasma triglyceride and increased the levels of lipoprotein and hepatic triglyceride lipases by 260 and 213%, respectively. The natures of very low density lipoprotein (VLDL), isolated at plasma density and of low and high density lipoprotein (LDL and HDL), separated by zonal ultracentrifugation, were determined. HTG-LDL appears as multiple fractions whereas HTG-HDL is seen predominantly as HDL3. HTG-VLDL is relatively poor in apoproteins and triglycerides but enriched in free and esterified cholesterol. HTG-LDL (main fraction) is depleted of free and esterified cholesterol but enriched in apoprotein and triglyceride. It is also denser and smaller than normal. HTG-HDL3 is denser than N-HDL3 and demonstrates compositional abnormalities similar to those of HTG-LDL. With the reduction of the VLDL mass, all abnormalities revert towards normal. This is accompanied by an increase in LDL-apoprotein B and cholesterol levels, which indicates an increased conversion of VLDL to LDL. Significant correlations between plasma triglyceride and the degree of all abnormalities are shown. The data obtained during treatment corroborate these relationships. The observations support the concept that most abnormalities reflect the degree of triglyceridemia. We suggest that plasma core-lipid transfer protein(s) is an effector of the abnormal cholesteryl ester distribution. Its prolonged action on increasingly large and slowly metabolized VLDL populations would entail a correspondingly excessive transfer of cholesteryl ester to VLDL and of triglyceride to LDL and HDL. It is calculated that, in moderate HTG, LDL and HDL contain only 50% of the normal cholesterol load. It is suggested that cholesteryl ester redistribution in HTG might be important in regulating metabolic events. Images PMID:6378975

  12. Structural and metabolic heterogeneity of @-very low density lipoproteins from cholesterol-fed dogs and f rom humans with Type 111 hyperlipoproteinemia

    Microsoft Academic Search

    Menahem Fainaru; Robert W. Mahley; Robert L. Hamilton; Thomas L. Innerarity

    Cholesteryl ester-rich @-very low density lipoproteins (@-VLDL) are @-migrating lipoproteins that accumulate in the d < 1.006 g\\/ml fraction of plasma from cholesterol-fed animals and from patients with Type 111 hyperlipoproteinemia. They can be separated from pre-@-migrating very low density lipo- proteins in the d 1.006 g\\/ml fraction by Geon-Pevikon block electrophoresis. The @-VLDL have a general property of stim-

  13. Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis

    Microsoft Academic Search

    Matthias Briel; Ignacio Ferreira-Gonzalez; John J You; Paul J Karanicolas; Elie A Akl; Ping Wu; Boris Blechacz; Dirk Bassler; Xinge Wei; Asheer Sharman; Irene Whitt; Suzana Alves da Silva; Zahira Khalid; Alain J Nordmann; Qi Zhou; Stephen D Walter; Noah Vale; Neera Bhatnagar; Christopher O’Regan; Edward J Mills; Heiner C Bucher; Victor M Montori; Gordon H Guyatt

    2009-01-01

    Objective To investigate the association between treatment induced change in high density lipoprotein cholesterol and total death, coronary heart disease death, and coronary heart disease events (coronary heart disease death and non-fatal myocardial infarction) adjusted for changes in low density lipoprotein cholesterol and drug class in randomised trials of lipid modifying interventions.Design Systematic review and meta-regression analysis of randomised controlled

  14. Non–high-density lipoprotein cholesterol (non-HDL-C) as a predictor of cardiovascular mortality in patients with end-stage renal disease

    Microsoft Academic Search

    Yoshiki Nishizawa; Tetsuo Shoji; Ryusuke Kakiya; Yoshihiro Tsujimoto; Tsutomu Tabata; Eiji Ishimura; Tatsuya Nakatani; Takami Miki; Masaaki Inaba

    2003-01-01

    Non–high-density lipoprotein cholesterol (non-HDL-C) as a predictor of cardiovascular mortality in patients with end-stage renal disease.BackgroundPatients with end-stage renal disease (ESRD) often show lipid abnormalities that may promote atherosclerosis. Although the standard lipid marker is low-density lipoprotein cholesterol (LDL-C) in official recommendations, the need of fasting blood sampling has prevented routine screening for plasma lipids in hemodialysis patients.MethodsWe therefore evaluated

  15. Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study

    Microsoft Academic Search

    Ernst J. Schaefer; Stefania Lamon-Fava; Susan D. Cohn; Mary M. Schaefer; Jose M. Ordovas; William P. Castelli; Peter W. F. Wilson

    Plasma low density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B, the major protein constituent of LDL, were measured in 1,533 men (mean age 49 f 10 years) and 1,597 women (mean age 49 f 10 years) participating in the 3rd exami- nation cycle of the Framingham Offspring Study. Mean plasma levels of LDL cholesterol and

  16. The analysis of triglyceride-rich lipoproteins in human serum for clinical studies

    E-print Network

    Chandra, Richa

    2009-06-02

    Intermediate density lipoprotein(s) LCAT Lecithin-cholesterol acyltransferase LDL Low density lipoprotein(s) LDLr LDL receptor LDS Lauryl alcohol sulfate, lithium salt LP Lipoprotein(s) Lp(a) Lipoprotein a LpL Lipoprotein lipase LRP LDL receptor...

  17. Reduced high density lipoprotein cholesterol in severe hypertriglyceridemic ApoCIII transgenic mice via lowered hepatic ApoAI synthesis.

    PubMed

    Han, Yingchun; Qi, Rong; Liu, George

    2015-07-10

    Clinical and epidemiological investigations confirm that patients with loss-of-function mutations (R19X, etc.) in Apolipoprotein CIII (ApoCIII) showed beneficial lipid profile including decreased plasma triglyceride and increased high density lipoprotein (HDL) levels. However, whether HDL level would be reduced in hypertriglyceridemia (HTG) induced by high ApoCIII expression has not been demonstrated yet. Here we showed, ApoCIII transgenic mice (ApoCIIItg) displayed severe HTG and had significantly lower HDL level. Analysis of apolipoproteins in lipoprotein fractions by SDS-PAGE revealed marked decrease of apolipoprotein AI (ApoAI) in HDL in transgenic mice compared with the wild type mice (WT) as controls. Further examination demonstrated that hepatic but not intestinal ApoAI mRNA was significantly reduced. Therefore, the decreased ApoAI synthesis might be accounted for the lower plasma HDL level in ApoCIII transgenic mice. PMID:25969427

  18. l-Ficolin binding and lectin pathway activation by acetylated low-density lipoprotein

    PubMed Central

    Faro, J; Chen, Y; Jhaveri, P; Oza, P; Spear, G T; Lint, T F; Gewurz, H

    2008-01-01

    l-Ficolin, like mannan-binding lectin (MBL), is a lectin pathway activator present in normal human plasma. Upon binding ligand, l-ficolin similarly initiates C4 cleavage via the serine protease MBL-associated serine protease-2 (MASP-2). We sought further insight into l-ficolin binding reactions and MASP-2 activation by passing plasma through GlcNAc-derivatized Sepharose. l-Ficolin bound in 1·0 M NaCl-ethylenediamine tetraacetic acid (EDTA), and remained bound in NaCl-free EDTA, while MASP-2 eluted in proenzyme form (?20% yield, > 40 000-fold purification). l-Ficolin was eluted with GlcNAc in 1·0 M NaCl (?10% yield, > 3000-fold purification), with trace amounts of C3, ?2-macroglobulin and both native and activated MASP-2. These preparations were utilized to investigate l-ficolin reactivities with acetylated low-density lipoprotein (A-LDL) as a model ligand in albumin-free systems. l-Ficolin bound strongly to A-LDL in the absence as well as presence of calcium, including saline-EDTA, and was optimal in 1·0 M NaCl-EDTA, but binding failed to occur in EDTA in the absence of NaCl. The addition of l-ficolin to immobilized A-LDL resulted in activation of MASP-2 in unmodified but not ficolin-depleted plasma unless l-ficolin was restored. We conclude that A-LDL is a useful ligand for investigation of l-ficolin function; both binding and activation are optimally examined in systems free of albumin; and ligand binding in 1·0 M NaCl in EDTA can be useful in the isolation of l-ficolin and native MASP-2. PMID:18031558

  19. Adrenal imaging with technetium-99m-labelled low density lipoproteins

    SciTech Connect

    Isaacsohn, J.L.; Lees, A.M.; Lees, R.S.; Kovach, M.B.; Strauss, H.W.

    1984-01-01

    Plasma low density lipoproteins (LDL) are a major source of cholesterol for adrenal cortical steroid hormones synthesis. To test whether LDL labelled with Tc-99m could be used to assess adrenal cortical function, the authors prepared Tc-99m-LDL by dithionite reduction of Tc0/sub 4//sup -/ in the presence of LDL. About 80% of the Tc-LDL bonds were covalent. Purified Tc-99m-LDL was injected intravenously into 16 rabbits (4 t 8mCi/rabbit). External imaging was carried out 16 to 18 hrs later, at which time the adrenals were visualized clearly; the animals were sacrificed, the organs dissected out, weighed, and counted. The biodistribution demonstrated that 0.8l +- 0.19% of the injected radioactivity was taken up per gm of whole adrenal gland. This compared with an uptake of 0.19 +- 0.02% per gm by liver, 0.22 +- 0.04% per gm by spleen, and 0.11 +- 0.02% per gm by kidney. To verify that they were indeed imaging the adrenals, additional rabbits were tested with dexamethasone. First they were injected with Tc-99m-LDL; 28 hrs later the adrenals were again well visualized. Then the rabbits were given dexamethasone for 5 days to suppress adrenal cortical function. The adequacy of suppression was monitored by serum cortisol measurements. When Tc-99m-LDL was injected again, the adrenals could not be seen 18 hrs later. Counts of the adrenals from the suppressed rabbits were at background levels. These data indicate that Tc-99m-LDL is a useful radiopharmaceutical for evaluating adrenal cortical function.

  20. The Oxidized Low-Density Lipoprotein Receptor Mediates Vascular Effects of Inhaled Vehicle Emissions

    PubMed Central

    Lucero, JoAnn; Harman, Melissa; Madden, Michael C.; McDonald, Jacob D.; Seagrave, Jean Clare; Campen, Matthew J.

    2011-01-01

    Rationale: To determine vascular signaling pathways involved in inhaled air pollution (vehicular engine emission) exposure–induced exacerbation of atherosclerosis that are associated with onset of clinical cardiovascular events. Objectives: To elucidate the role of oxidized low-density lipoprotein (oxLDL) and its primary receptor on endothelial cells, the lectin-like oxLDL receptor (LOX-1), in regulation of endothelin-1 expression and matrix metalloproteinase activity associated with inhalational exposure to vehicular engine emissions. Methods: Atherosclerotic apolipoprotein E knockout mice were exposed by inhalation to filtered air or mixed whole engine emissions (250 ?g particulate matter [PM]/m3 diesel + 50 ?g PM/m3 gasoline exhausts) 6 h/d for 7 days. Concurrently, mice were treated with either mouse IgG or neutralizing antibodies to LOX-1 every other day. Vascular and plasma markers of oxidative stress and expression proatherogenic factors were assessed. In a parallel study, healthy human subjects were exposed to either 100 ?g PM/m3 diesel whole exhaust or high-efficiency particulate air and charcoal-filtered “clean” air (control subjects) for 2 hours, on separate occasions. Measurements and Main Results: Mixed emissions exposure increased oxLDL and vascular reactive oxygen species, as well as LOX-1, matrix metalloproteinase-9, and endothelin-1 mRNA expression and also monocyte/macrophage infiltration, each of which was attenuated with LOX-1 antibody treatment. In a parallel study, diesel exhaust exposure in volunteer human subjects induced significant increases in plasma-soluble LOX-1. Conclusions: These findings demonstrate that acute exposure to vehicular source pollutants results in up-regulation of vascular factors associated with progression of atherosclerosis, endothelin-1, and matrix metalloproteinase-9, mediated through oxLDL–LOX-1 receptor signaling, which may serve as a novel target for future therapy. PMID:21493736

  1. Soluble lectin-like oxidized low density lipoprotein receptor-1 in type 2 diabetes mellitus.

    PubMed

    Tan, Kathryn C B; Shiu, Sammy W M; Wong, Ying; Leng, Lin; Bucala, Richard

    2008-07-01

    The lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) can be proteolytically cleaved and released as soluble forms (sLOX-1). We have determined serums LOX-1 in type 2 diabetes and evaluated the effect of glucose and advanced glycation end products (AGEs) on sLOX-1 in vitro and in vivo. Endothelial cells were incubated with glucose or AGEs, and sLOX-1 in cell medium was measured. Serum sLOX-1 was measured in 219 diabetic patients and 187 controls by ELISA. The effect of lowering glucose and AGEs on sLOX-1 was determined in 38 poorly controlled diabetic patients after improvement in glycemic control. Incubation of endothelial cells with AGE-BSA led to a dose-dependent increase in sLOX-1, whereas the effect of glucose on sLOX-1 was less marked. Serum sLOX-1 was 9% higher in diabetic patients compared with controls (P<0.01). In the poorly controlled patients, serum sLOX-1 decreased by 12.5% after improvement in glycemic control (P<0.05). The magnitude of reduction in sLOX-1 correlated with the improvement in hemoglobin A1c and AGEs but not with the reduction in oxidized LDL. sLOX-1 level is increased in type 2 diabetes. Both glucose and AGEs are important determinants of LOX-1 expression, and lowering glucose and AGEs leads to a reduction in sLOX-1. PMID:18408244

  2. Revealing binding sites for myeloperoxidase on the surface of human low density lipoproteins.

    PubMed

    Sokolov, Alexej V; Chekanov, Andrej V; Kostevich, Valeria A; Aksenov, Denis V; Vasilyev, Vadim B; Panasenko, Oleg M

    2011-01-01

    Low density lipoproteins (LDL) of human blood, once oxidized, provoke cholesterol accumulation in cells of arterial wall, which favors the development of atherosclerosis. Oxidative modification of LDL can result from their interaction with hypochlorous acid produced in the halogenation cycle of myeloperoxidase (MPO). On account that MPO is able to form complexes with LDL it seems important to learn the forces promoting such contacts and to spot the likely binding sites for the enzyme on the surface of LDL particles. In this study affinity chromatography on MPO-Sepharose showed that MPO-LDL complexes are uncoupled at ionic strength above 0.3M NaCl or when pH of solution goes below 3.6. This is an evidence of ionic interaction between MPO and LDL. We used spin probes of lipid nature embedded in phospholipid monolayer so that a variety of distances between the surface of an LDL particle and the paramagnetic center of a spin probes was provided. Since MPO interaction with labeled LDL caused no alteration of EPR spectra it was concluded that lipid components of LDL are not involved in MPO binding. Analysis of Mn(2+) distribution between LDL surface and the aqueous milieu showed that the surface negative charge of LDL is not considerably changed upon interaction with MPO. It can be suggested that interaction of LDL with MPO does not involve phospholipids that are the principal carriers of the surface charge. Among synthetic oligopeptides with amino acid sequences mimicking those of apoB-100 fragments -(1)EEEMLEN(7), (53)VELEVPQ(59) and (445)EQIQDDCTGDED(456) - only the latter could replace MPO in the complex with LDL. It is concluded that the likely site of interaction with MPO is the amino acid stretch 445-456 of apoB-100 in LDL. PMID:21055395

  3. Oxidized low density lipoprotein exposure alters the transcriptional response of macrophages to inflammatory stimulus.

    PubMed

    Mikita, T; Porter, G; Lawn, R M; Shiffman, D

    2001-12-01

    Macrophage-derived foam cells in atherosclerotic lesions are generally thought to play a major role in the pathology of the disease. Because macrophages play a central role in the inflammatory response, and the atherosclerotic lesion has features associated with chronic inflammatory settings, we investigated foam cell inflammatory potential. THP-1-derived macrophages were treated with oxidized low density lipoprotein (OxLDL) for 3 days to lipid load the macrophages and establish a foam cell-like phenotype. The cells were then activated by treatment with lipopolysaccharide (LPS), and RNA was harvested at 0, 1, and 6 h after LPS addition. RNA from treated and control cells was hybridized to microarrays containing approximately 16,000 human cDNAs. Genes that exhibited a 4-fold or greater increase or decrease at either 1 or 6 h after LPS treatment were counted as LPS-responsive genes. Employing these criteria, 127 LPS-responsive genes were identified. Prior treatment of THP-1 macrophages with OxLDL affected the expression of 57 of these 127 genes. Among these 57 genes was a group of chemokine, cytokine, and signal transduction genes with pronounced expression changes. OxLDL pretreatment resulted in a significant perturbation of LPS-induced NF kappa B activation. Furthermore, some of the OxLDL effects appear to be mediated by the nuclear receptors retinoid X receptor and peroxisomal proliferator-activated receptor gamma because pretreatment of THP-1 macrophages with ligands for these receptors, followed by LPS treatment, recapitulates the OxLDL plus LPS results for several of the most significantly modulated genes. PMID:11577090

  4. Low Density Lipoprotein Receptor Class A Repeats Are O-Glycosylated in Linker Regions*

    PubMed Central

    Pedersen, Nis Borbye; Wang, Shengjun; Narimatsu, Yoshiki; Yang, Zhang; Halim, Adnan; Schjoldager, Katrine Ter-Borch Gram; Madsen, Thomas Daugbjerg; Seidah, Nabil G.; Bennett, Eric Paul; Levery, Steven B.; Clausen, Henrik

    2014-01-01

    The low density lipoprotein receptor (LDLR) is crucial for cholesterol homeostasis and deficiency in LDLR functions cause hypercholesterolemia. LDLR is a type I transmembrane protein that requires O-glycosylation for stable expression at the cell surface. It has previously been suggested that LDLR O-glycosylation is found N-terminal to the juxtamembrane region. Recently we identified O-glycosylation sites in the linker regions between the characteristic LDLR class A repeats in several LDLR-related receptors using the “SimpleCell” O-glycoproteome shotgun strategy. Herein, we have systematically characterized O-glycosylation sites on recombinant LDLR shed from HEK293 SimpleCells and CHO wild-type cells. We find that the short linker regions between LDLR class A repeats contain an evolutionarily conserved O-glycosylation site at position ?1 of the first cysteine residue of most repeats, which in wild-type CHO cells is glycosylated with the typical sialylated core 1 structure. The glycosites in linker regions of LDLR class A repeats are conserved in LDLR from man to Xenopus and found in other homologous receptors. O-Glycosylation is controlled by a large family of polypeptide GalNAc transferases. Probing into which isoform(s) contributed to glycosylation of the linker regions of the LDLR class A repeats by in vitro enzyme assays suggested a major role of GalNAc-T11. This was supported by expression of LDLR in HEK293 cells, where knock-out of the GalNAc-T11 isoform resulted in the loss of glycosylation of three of four linker regions. PMID:24798328

  5. Systemic Free Fatty Acid Disposal Into Very Low-Density Lipoprotein Triglycerides

    PubMed Central

    Koutsari, Christina; Mundi, Manpreet S.; Ali, Asem H.; Patterson, Bruce W.; Jensen, Michael D.

    2013-01-01

    We measured the incorporation of systemic free fatty acids (FFA) into circulating very low-density lipoprotein triglycerides (VLDL-TGs) under postabsorptive, postprandial, and walking conditions in humans. Fifty-five men and 85 premenopausal women with BMI 18–24 (lean) and 27–36 kg/m2 (overweight/obese) received an intravenous bolus injection of [1,1,2,3,3-2H5]glycerol (to measure VLDL-TG kinetics) and either [1-14C]palmitate or [9,10-3H]palmitate to determine the proportion of systemic FFA that is converted to VLDL-TG. Experiments started at 0630 h after a 12-h overnight fast. In the postabsorptive protocol, participants rested and remained fasted until 1330 h. In the postprandial protocol, volunteers ingested frequent portions of a fat-free smoothie. In the walking protocol, participants walked on a treadmill for 5.5 h at ?3× resting energy expenditure. Approximately 7% of circulating FFA was converted into VLDL-TG. VLDL-TG secretion rates (SRs) were not statistically different among protocols. Visceral fat mass was the only independent predictor of VLDL-TG secretion, explaining 33–57% of the variance. The small proportion of systemic FFA that is converted to VLDL-TG can confound the expected relationship between plasma FFA concentration and VLDL-TG SRs. Regulation of VLDL-TG secretion is complex in that, despite a broad spectrum of physiological FFA concentrations, VLDL-TG SRs did not vary based on different acute substrate availability. PMID:23434937

  6. Automated detection and tracking of individual and clustered cell surface low density lipoprotein receptor molecules.

    PubMed Central

    Ghosh, R N; Webb, W W

    1994-01-01

    We have developed a technique to detect, recognize, and track each individual low density lipoprotein receptor (LDL-R) molecule and small receptor clusters on the surface of human skin fibroblasts. Molecular recognition and high precision (30 nm) simultaneous automatic tracking of all of the individual receptors in the cell surface population utilize quantitative time-lapse low light level digital video fluorescence microscopy analyzed by purpose-designed algorithms executed on an image processing work station. The LDL-Rs are labeled with the biologically active, fluorescent LDL derivative dil-LDL. Individual LDL-Rs and unresolved small clusters are identified by measuring the fluorescence power radiated by the sub-resolution fluorescent spots in the image; identification of single particles is ascertained by four independent techniques. An automated tracking routine was developed to track simultaneously, and without user intervention, a multitude of fluorescent particles through a sequence of hundreds of time-lapse image frames. The limitations on tracking precision were found to depend on the signal-to-noise ratio of the tracked particle image and mechanical drift of the microscope system. We describe the methods involved in (i) time-lapse acquisition of the low-light level images, (ii) simultaneous automated tracking of the fluorescent diffraction limited punctate images, (iii) localizing particles with high precision and limitations, and (iv) detecting and identifying single and clustered LDL-Rs. These methods are generally applicable and provide a powerful tool to visualize and measure dynamics and interactions of individual integral membrane proteins on living cell surfaces. Images FIGURE 1 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 PMID:8061186

  7. High-Density Lipoprotein Function Measurement in Human Studies: Focus on Cholesterol Efflux Capacity.

    PubMed

    Rohatgi, Anand

    2015-01-01

    A low plasma level of high-density lipoprotein (HDL) cholesterol (HDL-C) is a major risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). However, several observations have highlighted the shortcomings of using cholesterol content as the sole reflection of HDL metabolism. In particular, several large randomized controlled trials of extended release niacin and cholesteryl-ester transfer protein (CETP) inhibitors on background statin therapy have failed to show improvement in ASCVD outcomes despite significant increases in HDL-C. Reverse cholesterol transport (RCT) is the principal HDL function that impacts macrophage foam cell formation and other functions such as endothelial activation of endothelial nitric oxide synthase, monocyte adhesion, and platelet aggregation. Cholesterol efflux from macrophages to plasma/serum reflects the first critical step of RCT and is considered a key anti-atherosclerotic function of HDL. Whether this function is operative in humans remains to be seen, but recent studies assessing cholesterol efflux in humans suggest that the cholesterol efflux capacity (CEC) of human plasma or serum is a potent marker of ASCVD risk. This review describes the methodology of measuring CEC ex vivo from human samples and the findings to date linking CEC to human disease. Studies to date confirm that CEC can be reliably measured using stored human blood samples as cholesterol acceptors and suggest that CEC may be a promising new biomarker for atherosclerotic and metabolic diseases. Further studies are needed to standardize measurements and clarify the role CEC may play in predicting risk of developing disease and response to therapies. PMID:25968932

  8. High-density lipoprotein-cholesterol: determining hygienic factors for intervention.

    PubMed

    Anzalone, D A; Anzalone, F L; Fos, P J

    1995-07-01

    Current guidelines of the Adult Treatment Panel on High-Density Lipoprotein-Cholesterol (HDL-C) emphasize the protective effect of HDL-C in reducing one's risk for coronary heart disease and recommend that individuals with serum HDL-C levels below 35 mg/dL utilize hygienic means to raise them. A cross-sectional study was performed to examine the relationship of the hygienic factors obesity (measured by percent body fat and body mass index), smoking, and aerobic exercise to HDL-C. The sample, consisting of 1701 male employees of a large aerospace hardware assembly plant, were evaluated by health risk appraisal and anthropometric measurement. Regression analysis revealed a significant negative relationship between body mass index, percent body fat, age, smoking and the level of HDL-C in the blood. Alcohol consumption was directly related to HDL-C, and Whites had a lower HDL-C than all other races combined. Aerobic exercise was not found to be significantly related to HDL-C. A model (multiple R2 = .1136) consisting of age, race, alcohol consumption, smoking, and body mass index fit the data well. These findings justify weight management and smoking cessation interventions for raising HDL-C. However, the role of aerobic exercise was not supported in this study as a means of raising HDL-C. Future studies should use maximum oxygen consumption as a measure of aerobic capacity, which may be a better indicator of aerobic exercise level. The role of medication and genetic and dietary factors in HDL-C management should also be explored. Although findings from this study support smoking cessation and weight management interventions, longitudinal research is needed to determine the most effective strategy for HDL-C management. PMID:7552471

  9. Accurate Quantification of High Density Lipoprotein Particle Concentration by Calibrated Ion Mobility Analysis

    PubMed Central

    Hutchins, Patrick M.; Ronsein, Graziella E.; Monette, Jeffrey S.; Pamir, Nathalie; Wimberger, Jake; He, Yi; Anantharamaiah, G.M.; Kim, Daniel Seung; Ranchalis, Jane E.; Jarvik, Gail P.; Vaisar, Tomas; Heinecke, Jay W.

    2015-01-01

    Background It is critical to develop new metrics to determine whether high density lipoprotein (HDL) is cardioprotective in humans. One promising approach is HDL particle concentration (HDL-P) – the size and concentration of HDL in plasma or serum. However, the two methods currently used to determine HDL-P yield concentrations that differ more than 5-fold. We therefore developed and validated an improved approach to quantify HDL-P, termed calibrated ion mobility analysis (calibrated IMA). Methods HDL was isolated from plasma by ultracentrifugation, introduced into the gas phase with electrospray ionization, separated by size, and quantified by particle counting. A calibration curve constructed with purified proteins was used to correct for the ionization efficiency of HDL particles. Results The concentrations of gold nanoparticles and reconstituted HDLs measured by calibrated IMA were indistinguishable from concentrations determined by orthogonal methods. In plasma of control (n=40) and cerebrovascular disease (n=40) subjects, three subspecies of HDL were reproducibility measured, with an estimated total HDL-P of 13.4±2.4 µM (mean±SD). HDL-C accounted for 48% of the variance in HDL-P. HDL-P was significantly lower in subjects with cerebrovascular disease, and this difference remained significant after adjustment for HDL cholesterol levels. Conclusions Calibrated IMA accurately and reproducibly determined the concentration of gold nanoparticles and synthetic HDL, strongly suggesting the method could accurately quantify HDL particle concentration. Importantly, the estimated stoichiometry of apoA-I determined by calibrated IMA was 3–4 per HDL particle, in excellent agreement with current structural models. Furthermore, HDL-P associated with cardiovascular disease status in a clinical population independently of HDL cholesterol. PMID:25225166

  10. Oxidative modification of low-density lipoprotein and immune regulation of atherosclerosis.

    PubMed

    Matsuura, Eiji; Kobayashi, Kazuko; Tabuchi, Masako; Lopez, Luis R

    2006-11-01

    Oxidized low-density lipoprotein (oxLDL) is thought to promote atherosclerosis through complex inflammatory and immunologic mechanisms that lead to lipid dysregulation and foam cell formation. Recent findings suggested that oxLDL forms complexes with beta2-glycoprotein I (beta2GPI) and/or C-reactive protein (CRP) in the intima of atherosclerotic lesions. Autoantibodies against oxLDL/beta2GPI complexes occur in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) and significantly correlate with arterial thrombosis. IgG autoantibodies having similar specificity emerged spontaneously in non-immunized NZWxBXSB F1 mice, an animal model of APS, and a monoclonal autoantibody (WB-CAL-1; IgG2a) against complexed beta2GPI (oxLDL/beta2GPI complexes) was derived from the same mice. WB-CAL-1 significantly increased the in vitro uptake of oxLDL/beta(2)GPI complexes by macrophages. This observation strongly suggests that such IgG autoantibodies are pro-atherogenic. In contrast, IgM anti-oxLDL natural antibodies found in the atherosclerosis-prone mice (ApoE(-/-) and LDL-R(-/-) mice) have been proposed to be anti-atherogenic (protective). The presence of IgG anti-oxLDL antibodies in humans has been documented in many publications but their exact clinical significance remains unclear. In this article, we review recent progress in our understanding of the mechanisms involved in oxidation of LDL, formation of oxLDL complexes, and antibody mediated-immune regulation of atherogenesis. PMID:16790279

  11. Low-Density-Lipoprotein Particle Size Predicts a Poor Outcome in Patients with Atherothrombotic Stroke

    PubMed Central

    Song, Tae-Jin; Cho, Hyun-Ji; Chang, Yoonkyung; Youn, Minjung; Shin, Min-Jeong; Jo, Inho; Heo, Ji Hoe

    2015-01-01

    Background and Purpose Low-density lipoprotein (LDL) particle size is considered to be one of the more important cardiovascular risk factors, and small LDL particles are known to have atherogenic potential. The aim of this study was to determine whether LDL particle size is associated with stroke severity and functional outcome in patients with atherothrombotic stroke. Methods Between January 2009 and May 2011, 248 patients with first-episode cerebral infarction who were admitted to our hospital within 7 days after symptom onset were prospectively enrolled. LDL particle size was measured using the nondenaturing polyacrylamide gradient gel electrophoresis assay. Stroke severity was assessed by applying the National Institutes of Health Stroke Scale (NIHSS) at admission. Functional outcome was investigated at 3 months after the index stroke using the modified Rankin Scale (mRS), and poor functional outcome was defined as an mRS score of ?3. Results The LDL particle size in the 248 patients was 25.9±0.9 nm (mean±SD). LDL particle size was inversely correlated with the degree of cerebral artery stenosis (p=0.010). Multinomial multivariate logistic analysis revealed that after adjustment for age, sex, and variables with p<0.1 in univariate analysis, LDL particle size was independently and inversely associated with stroke severity (NIHSS score ?5; reference, NIHSS score 0-2; odds ratio=0.38, p=0.028) and poor functional outcome (odds ratio=0.44, p=0.038). Conclusions The results of this study demonstrate that small LDL particles are independently correlated with stroke outcomes. LDL particle size is thus a potential biomarker for the prognosis of atherothrombotic stroke. PMID:25628741

  12. Modulation of adipose tissue lipolysis and body weight by high-density lipoproteins in mice

    PubMed Central

    Wei, H; Averill, M M; McMillen, T S; Dastvan, F; Mitra, P; Subramanian, S; Tang, C; Chait, A; LeBoeuf, R C

    2014-01-01

    Background: Obesity is associated with reduced levels of circulating high-density lipoproteins (HDLs) and its major protein, apolipoprotein (apo) A-I. As a result of the role of HDL and apoA-I in cellular lipid transport, low HDL and apoA-I may contribute directly to establishing or maintaining the obese condition. Methods: To test this, male C57BL/6 wild-type (WT), apoA-I deficient (apoA-I?/?) and apoA-I transgenic (apoA-Itg/tg) mice were fed obesogenic diets (ODs) and monitored for several clinical parameters. We also performed cell culture studies. Results: ApoA-I?/? mice gained significantly more body weight and body fat than WT mice over 20 weeks despite their reduced food intake. During a caloric restriction regime imposed on OD-fed mice, apoA-I deficiency significantly inhibited the loss of body fat as compared with WT mice. Reduced body fat loss with caloric restriction in apoA-I?/? mice was associated with blunted stimulated adipose tissue lipolysis as verified by decreased levels of phosphorylated hormone-sensitive lipase (p-HSL) and lipolytic enzyme mRNA. In contrast to apoA-I?/? mice, apoA-Itg/tg mice gained relatively less weight than WT mice, consistent with other reports. ApoA-Itg/tg mice showed increased adipose tissue lipolysis, verified by increased levels of p-HSL and lipolytic enzyme mRNA. In cell culture studies, HDL and apoA-I specifically increased catecholamine-induced lipolysis possibly through modulating the adipocyte plasma membrane cholesterol content. Conclusions: Thus, apoA-I and HDL contribute to modulating body fat content by controlling the extent of lipolysis. ApoA-I and HDL are key components of lipid metabolism in adipose tissue and constitute new therapeutic targets in obesity. PMID:24567123

  13. High-Density Lipoprotein Maintains Skeletal Muscle Function by Modulating Cellular Respiration in Mice

    PubMed Central

    Lehti, Maarit; Donelan, Elizabeth; Abplanalp, William; Al-Massadi, Omar; Habegger, Kirk; Weber, Jon; Ress, Chandler; Mansfeld, Johannes; Somvanshi, Sonal; Trivedi, Chitrang; Keuper, Michaela; Ograjsek, Teja; Striese, Cynthia; Cucuruz, Sebastian; Pfluger, Paul T.; Krishna, Radhakrishna; Gordon, Scott M.; Silva, R. A. Gangani D.; Luquet, Serge; Castel, Julien; Martinez, Sarah; D'Alessio, David; Davidson, W. Sean; Hofmann, Susanna M.

    2014-01-01

    Background Abnormal glucose metabolism is a central feature of disorders with increased rates of cardio-vascular disease (CVD). Low levels of high density lipoprotein (HDL) are a key predictor for CVD. We used genetic mouse models with increased HDL levels (apoA-I tg) and reduced HDL levels (apoA-I ko) to investigate whether HDL modulates mitochondrial bioenergetics in skeletal muscle. Methods and Results ApoA-I ko mice exhibited fasting hyperglycemia and impaired glucose tolerance test (GTT) compared to wild type (wt) mice. Mitochondria isolated from gastrocnemius muscle of apoA-I ko mice displayed markedly blunted ATP synthesis. Endurance capacity (EC) during exercise exhaustion test was impaired in apoA-I ko mice. HDL directly enhanced glucose oxidation by increasing glycolysis and mitochondrial respiration rate (OCR) in C2C12 muscle cells. ApoA-I tg mice exhibited lower fasting glucose levels, improved GTT, increased lactate levels, reduced fat mass, associated with protection against age-induced decline of EC compared to wt mice. Circulating levels of fibroblast growth factor 21 (FGF21), a novel biomarker for mitochondrial respiratory chain deficiencies and inhibitor of white adipose lipolysis, were significantly reduced in apoA-I tg mice. Consistent with an increase in glucose utilization of skeletal muscle, genetically increased HDL and apoA-I levels in mice prevented high fat diet-induced impairment of glucose homeostasis. Conclusions In view of impaired mitochondrial function and decreased HDL levels in T2D, our findings indicate that HDL-raising therapies may preserve muscle mitochondrial function and address key aspects of T2D beyond CVD. PMID:24170386

  14. Three-dimensional structure of a cysteine-rich repeat from the low-density lipoprotein receptor.

    PubMed Central

    Daly, N L; Scanlon, M J; Djordjevic, J T; Kroon, P A; Smith, R

    1995-01-01

    The low-density lipoprotein (LDL) receptor plays a central role in mammalian cholesterol metabolism, clearing lipoproteins which bear apolipoproteins E and B-100 from plasma. Mutations in this molecule are associated with familial hypercholesterolemia, a condition which leads to an elevated plasma cholesterol concentration and accelerated atherosclerosis. The N-terminal segment of the LDL receptor contains a heptad of cysteine-rich repeats that bind the lipoproteins. Similar repeats are present in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. The first repeat of the human LDL receptor has been expressed in Escherichia coli as a glutathione S-transferase fusion protein, and the cleaved and purified receptor module has been shown to fold to a single, fully oxidized form that is recognized by the monoclonal antibody IgG-C7 in the presence of calcium ions. The three-dimensional structure of this module has been determined by two-dimensional NMR spectroscopy and shown to consist of a beta-hairpin structure, followed by a series of beta turns. Many of the side chains of the acidic residues, including the highly conserved Ser-Asp-Glu triad, are clustered on one face of the module. To our knowledge, this structure has not previously been described in any other protein and may represent a structural paradigm both for the other modules in the LDL receptor and for the homologous domains of several other proteins. Calcium ions had only minor effects on the CD spectrum and no effect on the 1H NMR spectrum of the repeat, suggesting that they induce no significant conformational change. Images Fig. 1 Fig. 2 Fig. 6 PMID:7603991

  15. Role of high density lipoproteins in the biodistribution of two radioiodinated probes in the rat

    Microsoft Academic Search

    R. C. Pohland; R. E. Counsell

    1985-01-01

    Two radioiodinated probes, ¹²⁵I-cholesteryl oleate (¹²⁵I-CO), a derivative of a natural constituent of lipoproteins, and 1-(2-chlorophenyl)-1-(4(¹²⁵I)iodophenyl)-2,2-dichlorethane (¹²⁵I-DDD), an analog of the adrenolytic drug o,p'-DDD (mitotane), were selected to study the role of lipoproteins in drug disposition and to examine the ability of these vehicles to direct foreign molecules to specific tissues. In vivo and in vitro techniques were utilized to

  16. The Structure of Human High Density Lipoprotein and the Levels of Apolipoprotein A-I in Plasma as Determined by Radioimmunoassay

    PubMed Central

    Schonfeld, Gustav; Pfleger, Barbara

    1974-01-01

    The major apoprotein of high density lipoprotein is apolipoprotein A-I (ApoA-I). In addition to being a structural component of this class of lipoproteins, ApoA-I also has a physiologic role as an activator of lecithin-cholesterol acyl transferase, an enzyme important in the metabolism of all lipoproteins. To measure ApoA-I content in human plasma, to assess its immunologic activity in hyperlipoproteinemia, and to carry out certain structural studies of high density lipoproteins, we have developed a double antibody radioimmunoassay. ApoA-I, isolated by gel filtration, was used to produce monospecific antisera. ApoA-I was iodinated by chloramine-T and the resulting [125I]-ApoA-I was purified by gel filtration. > 85% of [125I]-ApoA-I was precipitated by antibody, and 90% of bound [125I]ApoA-I was displaced by “cold” ApoA-I. Other lipoproteins and apoproteins did not react. Plasma and high density lipoprotein from normals and subjects with hyperlipoproteinemia displaced counts in parallel with ApoA-I, suggesting that the same antigenic determinants were reacting with antibody on lipid-free and lipid-associated ApoA-I. However, less than 5% of ApoA-I of high density lipoprotein reacted in the assay. Removal of the lipid by extraction increased the reactivity of ApoA-I in high density lipoprotein 15-20-fold; thus more than 95% of the ApoA-I molecules in “intact” high density lipoprotein are unreactive with antibody. Normal and hyperlipoproteinemic plasma and high density lipoproteins isolated from the same subjects continued to display parallelism with ApoA-I standard after lipid extraction, suggesting that ApoA-I of normal and hyperliproteinemic subjects are immunologically identical. About 90% of ApoA-I was in the d 1.063-1.21 fractions of normal plasma, trace quantities were found in the lipoproteins of d < 1.063, and the rest (about 10%) was in the d > 1.21 fraction. Normal plasma levels, assessed in extracted plasmas with a precision of 8%, were 100±35 mg/dl. Levels were normal in small groups of subjects with types II and IV hyperlipoproteinemia and high in pregnancy. However, larger population studies need to be performed to determine the distribution of ApoA-I levels in the various hyperlipoproteinemias. Images PMID:4136225

  17. Structure, Immunology, and Cell Reactivity of Low Density Lipoprotein from Umbilical Vein of a Newborn Type II Homozygote

    PubMed Central

    Patsch, Wolfgang; Witztum, Joseph L.; Ostlund, Richard; Schonfeld, Gustav

    1980-01-01

    In this report we compare the cord blood lipoproteins of a newborn boy homozygote who has low density lipoprotein (LDL) receptor-defective familial hypercholesterolemia (FH) with the lipoproteins from cord blood of normal newborns. Plasma LDL-cholesterol and apoprotein (Apo)B were 612 and 233 mg/dl (vs. 31±16 and 24±12 mg/dl, respectively, for normals, n = 21). LDL-cholesterol/ApoB ratio was 2.6 vs. 1.4±0.5. Levels of ApoA-I, ApoA-II, and HDL-cholesterol were similar to normal cord plasma. Thus, the lipoprotein abnormality is apparent at birth and is definitely present in LDL. Abnormalities in other lipoprotein, lipid, and in plasma apoprotein levels were not detected. On zonal ultracentrifugation, FH LDL was comprised of two populations (LDLa and LDLb), both faster floating than normal cord LDL (LDLc). This difference was due to the larger diameters of the particles on electron microscopy (LDLa = 276ű32 and LDLb = 260ű38 vs. LDLc = 237ű26, n = 200 each, mean±1 SD), and their higher contents of lipids relative to protein (86 and 82% vs. 74%, LDLa, LDLb, and LDLc, respectively). More than 94% of the protein in both the FH and the normal preparations consisted of ApoB. FH LDL were more effective than control LDL in competing with 125I-LDL (adult) for limiting amounts of anti-LDL antibodies in radioimmunoassay. FH LDL also competed more effectively for binding to LDL receptors on cultured fibroblasts at 4°C, and FH LDL also delivered more cholesterol into the cells. Cells grown in lipoprotein-deficient serum contained 44±2 ?g cholesterol/mg cell protein, incubation of cells for 18 h at 37°C in 5 ?g/ml FH LDL (protein) or in normal LDL raised cellular cholesterol levels to 75±2 and 60±2 ?g/mg, respectively. LDL isolated from the FH patient's plasma at 6 mo of age and from his brother's plasma (a 5-yr-old boy FH homozygote) were similar to LDL isolated from normolipemic subjects in flotation properties, chemical composition, and immunochemical and cell reactivity. The fact that differences between normal cord LDL and FH cord LDL were present at birth, but that the differences between control and FH LDL were no longer present postnatally suggests that the altered immunologic and cell interactive properties of FH cord LDL were probably related to its unusually high contents of core lipids. PMID:7400306

  18. Predictive value of lipoprotein indices for residual risk of acute myocardial infarction and sudden death in men with low-density lipoprotein cholesterol levels <120 mg/dl.

    PubMed

    Tanaka, Fumitaka; Makita, Shinji; Onoda, Toshiyuki; Tanno, Kozo; Ohsawa, Masaki; Itai, Kazuyoshi; Sakata, Kiyomi; Omama, Shin-Ichi; Yoshida, Yuki; Ogasawara, Kuniaki; Ogawa, Akira; Ishibashi, Yasuhiro; Kuribayashi, Toru; Okayama, Akira; Nakamura, Motoyuki

    2013-10-15

    Several epidemiologic studies have demonstrated that plasma low-density lipoprotein cholesterol (LDL-C) profile is a key risk indicator for coronary heart disease (CHD). However, almost half of all patients with CHD have normal LDL-C levels. A total of 7,931 male subjects aged ?40 years from the general population with no cardiovascular history and no use of lipid-lowering agents were followed for incidence of acute myocardial infarction (AMI) and sudden death. Of the 4,827 participants with LDL-C levels <120 mg/dl, 55 subjects had a first AMI/sudden death during an average of 5.5 years of follow-up. After adjustment for confounding factors, multiadjusted hazard ratios (HRs) were increased by 1 SD for non-high-density lipoprotein cholesterol (non-HDL-C; HR = 1.36, 95% confidence interval [CI], 1.02 to 1.81), total cholesterol (TC)/HDL-C ratio (HR = 1.40, 95% CI: 1.11 to 1.78) and LDL-C/HDL-C ratio (HR = 1.32, 95% CI: 1.02 to 1.73) but not for LDL-C (HR = 1.09, 95% CI: 0.82 to 1.44) and HDL-C (HR = 0.84, 95% CI: 0.68 to 1.04). When stratified as categorical variables on the basis of points with highest accuracy on receiver operating characteristic analysis, non-HDL-C levels >126 mg/dl (HR = 1.25, 95% CI: 1.03 to 1.51), TC/HDL-C ratio above 3.5 (HR = 1.22, 95% CI: 1.01 to 1.48) and LDL-C/HDL-C ratio >1.9 (HR = 1.25, 95% CI: 1.04 to 1.51) had increased multiadjusted HRs for AMI/sudden death. In conclusion, in men with LDL-C levels <120 mg/dl, non HDL-C, TC/HDL-C, and LDL-C/HDL-C ratios have predictive value for residual risk of AMI/sudden death. PMID:23831165

  19. Oxidative tyrosylation of high density lipoprotein by peroxidase enhances cholesterol removal from cultured fibroblasts and macrophage foam cells.

    PubMed Central

    Francis, G A; Mendez, A J; Bierman, E L; Heinecke, J W

    1993-01-01

    Lipoprotein oxidation is thought to play a pivotal role in atherogenesis, yet the underlying reaction mechanisms remain poorly understood. We have explored the possibility that high density lipoprotein (HDL) might be oxidized by peroxidase-generated tyrosyl radical. Exposure of HDL to L-tyrosine, H2O2, and horseradish peroxidase crosslinked its apolipoproteins and strikingly increased protein-associated fluorescence. The reaction required L-tyrosine but was independent of free metal ions; it was blocked by either catalase or the heme poison aminotriazole. Dityrosine and other tyrosine oxidation products were detected in the apolipoproteins of HDL modified by the peroxidase/L-tyrosine/H2O2 system, implicating tyrosyl radical in the reaction pathway. Further evidence suggests that tyrosylated HDL removes cholesterol from cultured cells more effectively than does HDL. Tyrosylated HDL was more potent than HDL at inhibiting cholesterol esterification by the acyl-CoA:cholesterol acyltransferase reaction, stimulating the incorporation of [14C]acetate into [14C]cholesterol, and depleting cholesteryl ester stores in human skin fibroblasts. Moreover, exposure of mouse macrophage foam cells to tyrosylated HDL markedly diminished cholesteryl ester and free cholesterol mass. We have recently found that myeloperoxidase, a heme protein secreted by activated phagocytes, can also convert L-tyrosine to o,o'-dityrosine. This raises the possibility that myeloperoxidase-generated tyrosyl radical may modify HDL, enabling the lipoprotein to protect the artery wall against pathological cholesterol accumulation. Images Fig. 1 PMID:8341680

  20. Inhibitory effects of in vivo oxidized high-density lipoproteins on platelet aggregation: evidence from patients with abetalipoproteinemia.

    PubMed

    Calzada, Catherine; Véricel, Evelyne; Colas, Romain; Guillot, Nicolas; El Khoury, Graziella; Drai, Jocelyne; Sassolas, Agnès; Peretti, Noël; Ponsin, Gabriel; Lagarde, Michel; Moulin, Philippe

    2013-07-01

    There is evidence that high-density lipoproteins (HDLs) may regulate platelet function, but disparate results exist regarding the effects of oxidized HDLs on platelets. The objective of our study was to determine the role of in vivo oxidized HDLs on platelet aggregation. Platelet aggregation and redox status were investigated in 5 patients with abetalipoproteinemia (ABLP) or homozygous hypobetalipoproteinemia, two rare metabolic diseases characterized by the absence of apolipoprotein B-containing lipoproteins, compared to 5 control subjects. Platelets isolated from plasma of patients with ABLP aggregated 4 to 10 times more than control platelets, depending on the agonist. By contrast, no differences in the extent of platelet aggregation were observed between ABLP platelet-rich plasma (PRP) and control PRP, suggesting the presence of a protective factor in ABLP plasma. ABLP HDLs inhibited agonist-induced platelet aggregation by binding to SR-BI, while control HDLs had no effect. On the other hand, lipoprotein-deficient plasma from patients with ABLP did not inhibit platelet aggregation. Severe oxidative stress was evidenced in patients with ABLP. Compared to control HDLs, ABLP HDLs showed a 40% decrease of ?-tocopherol and an 11-fold increased malondialdehyde concentration. These results demonstrate that in vivo oxidized HDLs do not lose their antiaggregatory properties despite oxidation. PMID:23507868

  1. Different methods for particle diameter determination of low density and high density lipoproteins-Comparison and evaluation

    E-print Network

    Vaidyanathan, Vidya

    2009-05-15

    that particles of a small diameter may directly promote atherosclerosis (6). Differential precipitation (11, 12)and particle diameter analysis using nondenaturing polyacrylamide gradient gel electrophoresis (NDGGE) have been used to identify subclasses... inflammation that underlies atherosclerosis (36). Epidemiological studies linking LDL diameter and CAD Predominance of small dense LDL is associated with a two to threefold increase in risk for CHD (8). Case-control study of myocardial infarction supports...

  2. Low-density lipoprotein apheresis decreases ferritin, transferrin and vitamin B12, which may cause anemia in serially treated patients.

    PubMed

    Bramlage, Carsten P; Armstrong, Victor W; Zapf, Antonia; Bramlage, Peter; Mueller, Gerhard A; Koziolek, Michael J

    2010-04-01

    Clinical observations revealed an increased prevalence of iron deficiency anemia without chronic bleeding in patients treated with serial low-density lipoprotein (LDL) apheresis. Since several different proteins are adsorbed by LDL apheresis beside pro-atherogenic lipoproteins, we examined the modification of the full blood count, plasma iron, vitamin B12, folic acid, and hemolysis by LDL apheresis. Nineteen patients (55 (50-59) years, 4 female, 15 male) undergoing chronic LDL apheresis due to mixed dyslipidemia (N = 17), homozygous familiar hypercholesterolemia (N = 1) or isolated elevated lipoprotein(a) (N = 1) were included in this study. They were treated with direct adsorption of lipoproteins (DALI; N = 6), heparin-induced LDL-precipitation (HELP; N = 7) or double filtration plasmapheresis (DFPP; N = 6). The patients' full blood count, iron metabolism (plasma iron, ferritin, transferrin, transferrin saturation), vitamins involved in erythropoiesis (vitamin B12 and folic acid), and markers of hemolysis (haptoglobin and free hemoglobin) were analyzed directly before and after LDL apheresis. A single LDL apheresis session significantly decreased the levels (reduction in the median [25(th)-75(th) percentiles] of: ferritin 9.8 [1.3-18] %; P = 0.004), transferrin (12.1 [10.0-15.96] %; P = 0.0005), and vitamin B12 (17.8 [16.2-20.8] %; P = 0.0005). Thereby, transferrin and vitamin B12 were decreased in all (N = 19) and ferritin in 74% (N = 14) of the patients. Twelve out of 19 patients (63.2%) had mild anemia despite iron administration in 14 out of 19 patients (73.7%). LDL apheresis had no significant influence on full blood count, plasma iron, transferrin saturation, folic acid, or hemolysis. Similar changes were observed in all LDL apheresis methods used. LDL apheresis significantly decreases ferritin, transferrin, and vitamin B12, suggesting an influence of serial LDL apheresis on erythropoiesis. PMID:20438534

  3. Biochemical and Functional Characterization of Charge-defined Subfractions of High-density Lipoprotein From Normal Adults

    PubMed Central

    Huang, Max T.; Chang, Chia-Ming; Chen, Chia-Ying; Shen, Ming-Yi; Liao, Hsin-Yi; Wang, Guei-Jane; Chen, Chu-Huang; Chen, Chao-Jung; Yang, Chao-Yuh

    2013-01-01

    High-density lipoprotein (HDL) is regarded as atheroprotective because it provides antioxidant and anti-inflammatory benefits and plays an important role in reverse cholesterol transport. In this paper, we outline a novel methodology for studying the heterogeneity of HDL. Using anion-exchange chromatography, we separated HDL from 6 healthy individuals into 5 subfractions (H1 through H5) with increasing charge and evaluated the composition and biologic activities of each subfraction. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that apolipoprotein (apo) AI and apoAII were present in all 5 subfractions; apoCI was present only in H1; and apoCIII and apoE were most abundantly present in H4 and H5. HDL-associated antioxidant enzymes such as lecithin-cholesterol acyltransferase, lipoprotein-associated phospholipase A2, and paraoxonase 1 were most abundant in H4 and H5. Lipoprotein isoforms were analyzed in each subfraction by using matrix-assisted laser desorption–time of flight mass spectrometry. To quantify other proteins in the HDL subfractions, we used the isobaric tags for relative and absolute quantitation approach followed by nanoflow liquid chromatography–tandem mass spectrometry analysis. Most antioxidant proteins detected were found in H4 and H5. The ability of each subfraction to induce cholesterol efflux from macrophages increased with increasing HDL electronegativity, with the exception of H5, which promoted the least efflux activity. In conclusion, anion-exchange chromatography is an attractive method for separating HDL into subfractions with distinct lipoprotein compositions and biologic activities. By comparing the properties of these subfractions, it may be possible to uncover HDL-specific proteins that play a role in disease. PMID:24171625

  4. Dietary Squalene Increases High Density Lipoprotein-Cholesterol and Paraoxonase 1 and Decreases Oxidative Stress in Mice

    PubMed Central

    Gabás-Rivera, Clara; Barranquero, Cristina; Martínez-Beamonte, Roberto; Navarro, María A.; Surra, Joaquín C.; Osada, Jesús

    2014-01-01

    Background and Purpose Squalene, the main hydrocarbon in the unsaponifiable fraction of virgin olive oil, is involved in cholesterol synthesis and it has been reported to own antiatherosclerotic and antiesteatosic effects. However, the squalene's role on lipid plasma parameters and the influence of genotype on this effect need to be addressed. Experimental Approaches Three male mouse models (wild-type, Apoa1- and Apoe- deficient) were fed chow semisynthetic diets enriched in squalene to provide a dose of 1 g/kg during 11 weeks. After this period, their plasma parameters and lipoprotein profiles were analyzed. Key Results Squalene administration at a dose of 1 g/kg showed decreased reactive oxygen species in lipoprotein fractions independently of the animal background and caused an specific increase in high density lipoprotein (HDL)-cholesterol levels, accompanied by an increase in phosphatidylcholine and paraoxonase 1 and no changes in apolipoproteins A1 and A4 in wild-type mice. In these mice, the cholesterol increase was due to its esterified form and associated with an increased hepatic expression of Lcat. These effects were not observed in absence of apolipoprotein A1. The increases in HDL- paraoxonase 1 were translated into decreased plasma malondialdehyde levels depending on the presence of Apolipoprotein A1. Conclusions and Implications Dietary squalene promotes changes in HDL- cholesterol and paraoxonase 1 and decreases reactive oxygen species in lipoproteins and plasma malondialdehyde levels, providing new benefits of its intake that might contribute to explain the properties of virgin olive oil, although the phenotype related to apolipoproteins A1 and E may be particularly relevant. PMID:25117703

  5. Dietary fat saturation distinctly affects apolipoprotein gene expression and high density lipoprotein size distribution in two strains of Golden Syrian hamsters

    Microsoft Academic Search

    Donald Smith; Young-Shin Ahn; Juan Pedro-Botet; Jesus Osada; Pedro Mata; Ernst J Schaefer; Jose M Ordovas

    2001-01-01

    Plasma lipoprotein levels, high density lipoprotein (HDL) particle size distribution and tissue mRNA levels for several apolipoproteins were determined in two strains of Golden Syrian hamsters characterized as high (F1B) or low (LVG) responders to atherogenic diets. Twenty-four male hamsters per strain were fed semipurified diets containing 0.2 g\\/100 g diet cholesterol and 15 g\\/100 g diet fat enriched (13

  6. Decreased postprandial high density lipoprotein cholesterol and apolipoproteins AI and E in normolipidemic smoking men: relations with lipid transfer proteins and LCAT activities

    Microsoft Academic Search

    N. Mero; A. Van Tol; L. M. Scheek; T. Van Gent; C. Labeur; M. Rosseneu; M. R. Taskinen

    We have previously reported that normolipidemic smokers are lipid intolerant due to increased responses of triglyceride-rich lipoproteins (TRL) apolipoprotein B-48, triglyceride (TG), and retinyl esters to a mixed meal com- pared to non-smokers. To investigate whether postprandial high density lipoprotein (HDL), apolipoprotein A-I (apoA- I), apolipoprotein A-II (apoA-II), and apolipoprotein E (apoE) concentrations or lipid transfer protein activities are affected

  7. Effects of triton WR 1339 and heparin on the transfer of surface lipids from triglyceride-rich emulsions to high density lipoproteins in rats

    Microsoft Academic Search

    Raul C. Maranhão; Ivete A. Roland; Mário H. Hirata

    1990-01-01

    The influence of lipolytic mechanisms on the transfer of phospholipids and unesterified cholesterol from artificial emulsions,\\u000a serving as chylomicron models to other plasma lipoproteins, mainly high density lipoproteins (HDL) were testedin vivo. The emulsions labeled with radioactive lipids were injected into the bloodstream of rats (controls) and the results were\\u000a compared with those obtained from rats that had previously been

  8. Molecular requirements in the recognition of low-density lipoproteins (LDL) by specific platelet membrane receptors.

    PubMed

    Pedreño, J; Sánchez-Quesada, J L; Cabré, A; Masana, L

    2000-07-01

    We have demonstrated that platelet low-density lipoprotein (LDL) receptors differ from classic LDL receptors of nucleated cells. Although positively charged Arg and Lys residues of apoprotein B-100 are known to play a key role in LDL recognition by classic LDL receptors, there are no conclusive data on platelet LDL receptors. This study investigated the molecular requirements of LDL particle recognition by platelet LDL receptors. The involvement of lipid and protein fractions was determined by displacement studies of the binding of 125I-LDL to platelets and fibroblasts (used as a classical LDL receptor model). The role of the protein moiety was evaluated by chemically modifying positively charged apoB residues (Lys, Arg, and Tyr) via copper-induced oxidation, cyclohexanedione, and tetranitromethane, respectively. The involvement of the lipid fraction was determined by ligand binding assays using 125I-LDL particles that had previously been delipidated and subjected to apoB solubilization. The degree of particle modification was analyzed by agarose/acrylamide gel electrophoresis and anion exchange chromatography. Modifying the amino acid residues increased particle electronegativity in the following order of potency: CHD-LDL>TNM-LDL>ox-LDL>native LDL. The results obtained by displacement studies in fibroblasts suggested that the gain in the LDL negative charge was the most important factor in the loss of receptor affinity. The chemical models of protein modification used in our study greatly affected LDL binding to the classical fibroblast receptor. In contrast, there was very slight difference in the displacement capacity on platelet 125I-LDL binding, which suggests that the protein fraction does not play a major role in the interaction of LDL with its platelet receptor. On the other hand, whereas modifying the lipid moiety did not alter the ability of solubilized 125I-apoB to interact with the classical fibroblast LDL receptor, platelet LDL receptors were unable to recognize these particles. In conclusion, our results confirm that the protein fraction plays a key role in the fibroblast LDL-receptor recognition process, whereas the lipid fraction appears to have a more relevant role in platelet LDL-receptor recognition. PMID:10904103

  9. Proteins derived from platelet alpha granules modulate the uptake of oxidized low density lipoprotein by macrophages.

    PubMed

    Fuhrman, B; Brook, G J; Aviram, M

    1992-07-01

    Activated platelets secrete from their alpha granules a protein-like factor which stimulates the uptake of oxidized low-density lipoprotein (Ox-LDL) by macrophages. The aim of the present study was to evaluate the effect of three purified proteins obtained from platelet alpha granules: platelet-derived growth factor (PDGF), platelet factor-4 (PF-4), and beta-thromboglobulin (B-TG), on the uptake of Ox-LDL by macrophages. Cellular degradation of Ox-LDL by the J-774 A.1 macrophage-like cell line, that was preincubated for 18 h at 37 degrees C, with increasing concentrations of partially purified PDGF, (designated PDGF-CMS-III) was increased by up to 36% in comparison to control cells preincubated without PDGF. This effect was due to PDGF-mediated increase in the number of macrophage receptors for Ox-LDL. The enhanced uptake of Ox-LDL by PDGF resulted in an increase in cellular cholesterol content. Preincubation of macrophages with two types of recombinant PDGF dimers (10 ng/ml), revealed that PDGF-BB stimulated Ox-LDL cellular degradation by 64%, whereas PDGF-AB demonstrated only 34% stimulation, in comparison to control cells that were not treated with PDGF. The stimulatory effect of PDGF-CMS-III and PDGF-AB were reduced by 20% and 28%, respectively, when incubated in the presence of H-7, a specific protein kinase C inhibitor. When macrophages were preincubated with B-TG, cellular uptake of Ox-LDL was reduced by up to 30% at 100 ng B-TG/ml. This effect, however, was obtained only when B-TG was present in the incubation medium. Cellular degradation of Ox-LDL was not affected by preincubation of the cells with PF-4. Pretreatment of PCM with anti-PDGF or anti-B-TG antibodies abolished the effects of PCM on Ox-LDL degradation by macrophages. PDGF, thus, may represent the protein-like factor present in PCM which stimulates Ox-LDL degradation by macrophages, whereas B-TG may have a role in the recognition of PCM particles by the macrophage scavenger receptor. Modulation of macrophage cholesterol content by proteins secreted from activated platelets may have an important role in foam cell formation and atherosclerosis. PMID:1385728

  10. Effects of oxidized low density lipoprotein on transformation of valvular myofibroblasts to osteoblast-like phenotype.

    PubMed

    Chen, Di; Shen, Ying-Lian; Hu, Wei-Lin; Chen, Zheng-Ping; Li, Yong-Sheng

    2015-06-01

    In order to investigate the roles of Wnt signal pathway in transformation of cardiac valvular myofibroblasts to the osteoblast-like phenotype, the primary cultured porcine aortic valve myofibroblasts were incubated with oxidized low density lipoprotein (ox-LDL, 50 mg/L), and divided into four groups according to the ox-LDL treatment time: control group, ox-LDL 24-h group, ox-LDL 48-h group, and ox-LDL 72-h group. Wnt signal pathway blocker Dickkopf-1 (DDK-1, 100 ?g/L) was added in ox-LDL 72-h group. The expression of a-smooth muscle actin (?-SMA), bone morphogenetic protein 2 (BMP2), alkaline phosphatase (ALP), and osteogenic transcription factor Cbfa-1 was detected by Western blotting, and that of ?-catenin, a key mediator of Wnt signal pathway by immunocytochemical staining method. The Wnt/?-catenin was observed and the transformation of myofibroblasts to the osteoblast-like phenotype was examined. The expression of ?-SMA, BMP2, ALP and Cbfa-1 proteins in the control group was weaker than in the ox-LDL-treated groups. In ox-LDL-treated groups, the protein expression of a-SMA, BMP2, ALP, and Cbfa-1 was significantly increased in a time-dependent manner as compared with the control group, and there was significant difference among the three ox-LDL-treated groups (P<0.05 for all); ?-catenin protein was also up-regulated in the ox-LDL-treated groups in a time-dependent manner as compared with the control group (P<0.05), and its transfer from cytoplasm to nucleus and accumulation in the nucleus were increased in the same fashion (P<0.05). After addition of DKK-1, the expression of ?-SMA, bone-related proteins and ?-catenin protein was significantly reduced as compared with ox-LDL 72-h group (P<0.05). The Wnt/ ?-catenin signaling pathway may play an important role in transformation of valvular myofibroblasts to the osteoblast-like phenotype. PMID:26072074

  11. Relationship between oxidized low-density lipoprotein antibodies and obesity in different glycemic situations

    PubMed Central

    Babakr, Abdullatif Taha; Elsheikh, Osman Mohamed; Almarzouki, Abdullah A; Assiri, Adel Mohamed; Abdalla, Badr Eldin Elsonni; Zaki, Hani Yousif; Fatani, Samir H; NourEldin, EssamEldin Mohamed

    2014-01-01

    Background Autoantibodies to oxidized low-density lipoprotein (oxLDL) are a heterogeneous group of antibodies that are controversially discussed to be either pathogenic or protective. Biochemical and anthropometric measurements correlated with increased levels of these antibodies are also controversial, especially in conditions of impaired glucose tolerance and type 2 diabetes mellitus. The present study was conducted to evaluate levels of oxLDL antibodies and their correlation with obesity in different glycemic situations. Methods Two hundred and seventy-four adult males were classified into three subgroups: group 1 (n=125), comprising a control group of nondiabetic subjects; group 2 (n=77), comprising subjects with impaired glucose tolerance; and group 3 (n=72), comprising patients with type 2 diabetes mellitus. Body mass index was calculated, and measurement of oxLDL and oxLDL antibodies was performed. Results Higher mean concentrations of oxLDL were found in the type 2 diabetes mellitus and impaired glucose tolerance groups (143.5±21.9 U/L and 108.7±23.7 U/L, respectively). The mean value for the control group was 73.5±27.5 U/L (P<0.001). Higher mean concentrations of anti-oxLDL antibodies were observed in the type 2 diabetes mellitus and impaired glucose tolerance groups (55.7±17.8 U/L and 40.4±17.6 U/L, respectively). The mean value for the control group was 20.4±10 U/L (P<0.001). Levels of anti-oxLDL antibodies were found to be positively and significantly correlated with body mass index in the control group (r=0.46), impaired glucose tolerance (r=0.51), type 2 diabetes mellitus group (r=0.46), and in the whole study population (r=0.44; P<0.001). Conclusion Anti-oxLDL antibody levels were increased in subjects with type 2 diabetes mellitus and impaired glucose tolerance and were positively correlated with obesity and body mass index. PMID:25368528

  12. Synthesis and Characterization of Biomimetic High Density Lipoprotein Nanoparticles To Treat Lymphoma

    NASA Astrophysics Data System (ADS)

    Damiano, Marina Giacoma

    High density lipoproteins (HDLs), natural nanoparticles that function as vehicles for cholesterol transport, have enhanced uptake by several human cancers. This uptake is mediated, in part, by the high affinity HDL receptor, scavenger receptor B-1 (SR-B1). More specifically, studies show that the rate of cellular proliferation of lymphoma, a cancer of the lymphocytes, is directly proportional to the amount of HDL-cholesterol available. Thus, targeting of HDL-cholesterol uptake by these cells could be an effective therapeutic approach that may have lower toxicity to healthy cells compared to conventional therapies. Biomimetic HDL can be synthesized using a gold nanoparticle template (HDL-AuNPs), which provides control over size, shape, and surface chemistry. Like their natural counterparts, HDL-AuNPs sequester cholesterol. However, since the gold nanoparticle replaces the cholesterol core of natural HDL, HDL-AuNPs inherently deliver less cholesterol. We show that HDL-AuNPs are able to induce dose dependent apoptosis in B cell lymphoma cell lines and reduce tumor volume following systemic administration to mice bearing B cell lymphoma tumors. Furthermore, HDL-AuNPs are neither toxic to healthy human lymphocytes (SR-B1-), nor to hepatocytes and macrophages (SR-B1+), which are cells naturally encountered by HDLs. Manipulation of cholesterol flux and targeting of SR-B1 are responsible for the efficacy of HDL-AuNPs against B cell lymphoma. HDL-AuNPs could be used to treat B cell lymphomas and other diseases that involve pathologic accumulation of cholesterol. Titanium dioxide nanoparticle (TiO2 NP) core HDLs (HDL-TiO 2 NPs) have been synthesized for high resolution cellular localization studies and for future use as a therapeutic and imaging agent. In initial studies, HDL-TiO(2 NPs display maximum uptake in B cell lymphoma cell lines. X-ray fluorescence microscopy studies show interaction between HDL-TiO2 NPs and cells 10 minutes after treatment and internalization after 1 hour. HDL-TiO2 NPs induce apoptosis in B cell lymphoma cell lines. These results suggest that HDL-TiO2 NPs may be used as therapeutics for lymphoma and other cancers by inducing apoptosis through manipulation of cellular cholesterol flux.

  13. Low density lipoprotein for delivery of a water-insoluble alkylating agent to malignant cells. In vitro and in vivo studies of a drug-lipoprotein complex.

    PubMed Central

    Vitols, S.; Söderberg-Reid, K.; Masquelier, M.; Sjöström, B.; Peterson, C.

    1990-01-01

    Previous studies have shown that human leukaemic cells and certain tumour tissues have a higher receptor-mediated uptake of low density lipoprotein (LDL) than the corresponding normal cells or tissues. LDL has therefore been proposed as a carrier for anti-cancer agents. In the current study, a water-insoluble mitoclomine derivative (WB 4291) was incorporated into LDL. The WB 4291-LDL complex contained about 1,500 drug molecules per LDL particle and showed receptor-mediated toxicity in vitro as judged from the difference in growth inhibitory effect on normal and mutant (LDL-receptor-negative) cultured Chinese hamster ovary cells. However, cellular drug uptake did not exclusively occur by the receptor pathway since mutant cells were also affected to some extent. The LDL part of the complex had the same plasma clearance and organ distribution as native LDL after i.v. injection in mice and rabbits. Therapeutic effects were observed when Balb-C mice with experimental leukaemia were treated with the complex. After i.p. administration to mice with i.p. leukaemia median survival time was prolonged 2.5-fold and 40% became long time survivors. The effect was weaker (42% increase in life span) after i.v. injections of the complex to mice with i.v. leukaemia. Images Figure 3 PMID:2245164

  14. Niacin administration significantly reduces oxidative stress in patients with hypercholesterolemia and low levels of high-density lipoprotein cholesterol.

    PubMed

    Hamoud, Shadi; Kaplan, Marielle; Meilin, Edna; Hassan, Ahmad; Torgovicky, Rafael; Cohen, Raanan; Hayek, Tony

    2013-03-01

    Oxidative stress has been implicated in the pathogenesis of cardiovascular disorders, including atherosclerosis. In pharmacological doses, niacin (vitamin B3) was proven to reduce total cholesterol, triglyceride, very-low-density lipoprotein, and low-density lipoprotein levels, and to increase high-density lipoprotein (HDL) levels. The aim of this study was to evaluate the effect of niacin treatment in patients with low levels of HDL cholesterol (HDL-C; <40 mg%) on their lipid profile and oxidative stress status. Seventeen patients with hypercholesterolemia and low HDL-C and 8 healthy control subjects were enrolled in the study. The patients were treated with niacin for 12 weeks. Lipid profile, oxidative stress and C-reactive protein (CRP) levels were determined at the time of enrollment, and 2 and 12 weeks after initiation of niacin treatment. Subjects with lower HDL-C levels exhibited higher oxidative stress compared with subjects with normal HDL-C levels. Niacin treatment in hypercholesterolemic patients caused a significant increase in HDL-C and apolipoprotein A1 levels, and a decrease in triglyceride levels. Niacin also significantly reduced oxidative stress, as measured by a significant decrease in the serum content of thiobarbituric acid reactive substances, lipid peroxides and paraoxonase activity, compared with the levels before treatment. Although serum CRP levels were not affected by niacin treatment, a correlation between CRP and HDL levels was obtained when computing the results. Niacin treatment in hypercholesterolemic patients with low HDL levels caused a significant decrease in their oxidative stress status. These results indicate an additional beneficial effect of niacin beyond its ability to affect the lipid profile. PMID:22990043

  15. Exercise attenuates the increase in plasma monounsaturated fatty acids and high-density lipoprotein cholesterol but not high-density lipoprotein 2b cholesterol caused by high-oleic ground beef in women.

    PubMed

    Gilmore, L Anne; Crouse, Stephen F; Carbuhn, Aaron; Klooster, Jennifer; Calles, José Antonio Elias; Meade, Thomas; Smith, Stephen B

    2013-12-01

    We hypothesized that dietary monounsaturated fatty acids (MUFA) and exercise increase high-density lipoprotein cholesterol (HDL-C) by independent mechanisms, so there would be additive effects between a single, intensive session of exercise and high-MUFA ground beef on HDL-C and blood risk factors for cardiovascular disease. Seventeen postmenopausal women completed a 2-way crossover design in which they consumed five 114-g ground beef patties per week for two 6-week periods separated by a 4-week washout (habitual diet) period. The ground beef patties contained 21% total fat with either 9.97 (low-MUFA) or 12.72 (high-MUFA) g total MUFA. Blood was taken at entry, at the end of each 6-week diet period, after the 4-week washout period, and 24 hours after aerobic exercise sessions (75% VO?peak, 2.07 MJ). After the ground beef intervention, the high-MUFA ground beef increased plasma palmitoleic acid and oleic acid, low-density lipoprotein (LDL) particle density, HDL-C, and HDL2b-C (all P < .05), whereas the low-MUFA ground beef increased LDL density. After the washout (habitual diet) period, the single exercise session increased serum LDL cholesterol, HDL-C, and HDL2a and decreased TAG and oleic acid. After the low-MUFA ground beef diet, exercise increased LDL size and HDL density and decreased LDL density and very low-density lipoprotein cholesterol, but had no effect on HDL-C fractions. After the high-MUFA ground beef intervention, exercise decreased palmitioleic acid, oleic acid, HDL-C, and HDL2a-C, but not HDL2b-C. Contrary to our hypothesis, the effects of exercise and a high-MUFA diet were not additive; instead, exercise attenuated the effects of the high-MUFA ground beef on HDL-C and plasma MUFAs. The differential effects of high-MUFA ground beef and exercise on HDL2a-C and HDL2b-C indicate that diet and exercise affect HDL-C by different mechanisms. PMID:24267039

  16. Acetoacetyl-CoA ligase activity in the isolated rat hepatocyte: Effects of 25-hydroxycholesterol and high density lipoprotein

    Microsoft Academic Search

    Gail A. Wong; James D. Bergstrom; John Edmond

    1987-01-01

    The activity of acetoacetyl-CoA (AcAc-CoA) ligase (E.C.6.2.1.16) in hepatocytes from rats was shown to be the same as the activity in homogenates of their livers. In hepatocytes treated with 25-hydroxycholesterol, AcAc-CoA ligase, 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and rates of sterol synthesis were substantially decreased. Hepatocytes treated with high density lipoprotein (HDL) exhibited a 2 to 4 fold induction of HMG-CoA reductase

  17. The modulation of ferryl myoglobin formation and its oxidative effects on low density lipoproteins by nitric oxide.

    PubMed

    Dee, G; Rice-Evans, C; Obeyesekera, S; Meraji, S; Jacobs, M; Bruckdorfer, K R

    1991-12-01

    This study has investigated the interactions between nitric oxide and haem protein radicals. The results demonstrate that nitric oxide interacts with activated ferryl myoglobin species with reduction to metmyoglobin, but the extent and duration of the reduction depends on the relative concentrations of nitric oxide and hydrogen peroxide. Ferryl myoglobin has a much greater relative potential for oxidising polyunsaturated fatty acid side chains in low density lipoproteins than in cell membranes. The peroxidative response can be modulated by nitric oxide: ferryl myoglobin-mediated peroxidation of LDL may be enhanced or suppressed by nitric oxide depending on the relative concentrations of NO and hydrogen peroxide. PMID:1743289

  18. The T705I mutation of the low density lipoprotein receptor gene (FH Paris9) does not cause familial hypercholesterolemia

    Microsoft Academic Search

    Paola Lombardi; Eric J. G. Sijbrands; Sylvia Kamerling; Jan A. Gevers Leuven; Louis M. Havekes

    1996-01-01

    Familial hypercholesterolemia (FH) is a genetic disease caused by mutations in the low-density lipoprotein receptor gene.\\u000a Among the more than 200 mutations so far identified, the T705I substitution in exon 15, designated FH-Paris 9, has been previously\\u000a described as an FH-causing mutation. During the course of denaturing gradient gel electrophoretic screening of exon 15 we\\u000a have identified the T705I single-base

  19. Levels of high-density lipoprotein cholesterol (HDL-C) among children with steady-state sickle cell disease

    PubMed Central

    2010-01-01

    Background The search for sickle cell disease (SCD) prognosis biomarkers is a challenge. These markers identification can help to establish further therapy, later severe clinical complications and with patients follow-up. We attempted to study a possible involvement of levels of high-density lipoprotein cholesterol (HDL-C) in steady-state children with SCD, once that this lipid marker has been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities, important aspects to be considered in sickle cell disease pathogenesis. Methods We prospectively analyzed biochemical, inflammatory and hematological biomarkers of 152 steady-state infants with SCD and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records. Results Of the 152 infants investigated had a significant positive association of high-density lipoprotein cholesterol with hemoglobin (P < 0.001), hematocrit (P < 0.001) and total cholesterol (P < 0.001) and a negative significant association with reticulocytes (P = 0.046), leukocytes (P = 0.015), monocytes (P = 0.004) and platelets (P = 0.005), bilirubins [total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and indirect bilirubin (P < 0.001], iron (P < 0.001), aminotransferases [aspartate aminotransferase (P = 0.004), alanine aminotransferase (P = 0.035)], lactate dehydrogenase (P < 0.001), urea (P = 0.030), alpha 1-antitrypsin (P < 0.001), very low-density lipoprotein cholesterol (P = 0.003), triglycerides (P = 0.005) and hemoglobin S (P = 0.002). Low high-density lipoprotein cholesterol concentration was associated with the history of cardiac abnormalities (P = 0.025), pneumonia (P = 0.033) and blood transfusion use (P = 0.025). Lipids and inflammatory markers were associated with the presence of cholelithiasis. Conclusions We hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by low HDL-C with hypertriglyceridemia and high VLDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. Additional studies are warranted to test this hypothesis and the probably mechanisms involved in this complex network of markers and their role in SCD pathogenesis. PMID:20799970

  20. Interaction of high-density and low-density lipoproteins to solid surfaces coated with cholesterol as determined by an optical fiber-based biosensor

    NASA Astrophysics Data System (ADS)

    Singh, Bal R.; Poirier, Michelle A.

    1993-05-01

    In recent years, the use of fiber optics has become an important tool in biomedicine and biotechnology. We are involved in developing and employing a new system which, through the use of fiber optics, may be capable of measuring the content of cholesterol and lipoproteins in blood samples in real time. In the optical fiber-based biosensor, a laser beam having a wavelength of 512 nm (green light) is launched into an optical fiber, which transmits the light to its distal end. An evanescent wave (travelling just outside the fiber core) is used to excite rhodamine-labelled HDL or LDL which become bound to the fiber or to fiber-bound molecules. The fluorescence (red light) is coupled back into the fiber and detected with a photodiode. Preliminary work has involved testing of high density lipoprotein (HDL) binding to a cholesterol-coated fiber and to a bare fiber and low density lipoprotein (LDL) binding to a cholesterol-coated fiber. A significant difference was observed in the binding rate of HDL (5 (mu) g/mL and lower) to a bare fiber as opposed to a cholesterol-coated fiber. The binding rate of HDL (5 (mu) g/mL) to a bare fiber was 7.5 (mu) V/sec and to a cholesterol-coated fiber was 3.5 (mu) V/sec. We have calculated the binding affinity of LDL to a cholesterol- coated fiber as 1.4 (mu) M-1. These preliminary results suggest that the optical fiber-based biosensor can provide a unique and promising approach to the analysis of lipoprotein interaction with solid surfaces and with cholesterol. More importantly, the results suggest that this technique may be used to assess the binding of blood proteins to artificial organs/tissues, and to measure the amount of cholesterol, HDL and LDL in less than a minute.

  1. High-density lipoprotein acts as an opsonin to enhance phagocytosis of group A streptococcus by U937 cells.

    PubMed

    Liu, Ling; Zhou, Lulei; Li, Yuxin; Bai, Wencheng; Liu, Na; Li, Wenlong; Gao, Yumin; Liu, Zhi; Han, Runlin

    2015-07-01

    We have previously demonstrated that high-density lipoprotein (HDL) can specifically bind to streptococcal collagen-like protein 1 (Scl1) of M41-type group A Streptococcus (GAS). However, the pathological or physiological significance of Scl1-HDL interaction is unknown. Here, the hypothesis that HDL acts as an opsonin to enhance phagocytosis of HDL-bound GAS by monocytes given that some scavenger receptors can mediate the endocytosis of HDL was tested by using FITC-labeled bacteria, human U937 monocytes and HDL for phagocytic assays. HDL (10?µg/mL) was found to significantly enhance internalization of M41-type (ATCC 12373) GAS by U937 cells after 60?min incubation, compared with an HDL-free group. The internalized GAS were dead after 60?min incubation with U937 cells regardless of presence and absence of HDL. Although very-low-density lipoprotein (VLDL) could specifically bind to ATCC 12373 strain, it did not promote phagocytosis of GAS. Additionally, LDL, HDL and VLDL did not enhance phagocytosis of CMCC 32198 strain because this strain did not bind to these lipoproteins. A physiological concentration of HDL (1000?µg/mL) had a similar effect. Anti-CD36 antibody completely abolished opsonic phagocytosis whereas anti-CD4 antibody did not, indicating that CD36 is the major scavenger receptor mediating the uptake of HDL-opsonized GAS by U937 cells. Furthermore, because rScl1 competitively blocked the interaction of ATCC 12373 strain with HDL recombinant Scl1 (rScl1) derived from M41-type GAS, it significantly decreased opsonophagocytosis of ATCC 12373 strain but not of CMCC 32198 strain. Therefore, our findings suggest that HDL may be an opsonin that enhances CD36-dependent opsonophagocytosis of GAS by U937 cells. PMID:26094502

  2. A 52Week, Randomized, Open-Label, Parallel-Group Comparison of the Tolerability and Effects of Pitavastatin and Atorvastatin on High-Density Lipoprotein Cholesterol Levels and Glucose Metabolism in Japanese Patients with Elevated Levels of Low-Density Lipoprotein Cholesterol and Glucose Intolerance

    Microsoft Academic Search

    Jun Sasaki; Yoshihiko Ikeda; Tadanobu Kuribayashi; Keizou Kajiwara; Sadatoshi Biro; Kyosuke Yamamoto; Masato Ageta; Syozou Kobori; Tetsunori Saikawa; Takatoshi Otonari; Suminori Kono

    2008-01-01

    Background: Statin therapy has been found to produce substantial reductions in low-density lipoprotein cholesterol (LDL-C) levels, resulting in a reduced risk for cardiovascular events. Recently, research interest has focused on modification of high-density lipoprotein cholesterol (HDL-C) levels for the potential prevention of cardiovascular events. The effects of pitavastatin and atorvastatin on HDL-C have not been directly compared.Objectives: This study compared

  3. Anthocyanins increase low-density lipoprotein and plasma cholesterol and do not reduce atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits.

    PubMed

    Finné Nielsen, Inge L; Elbøl Rasmussen, Salka; Mortensen, Alicja; Ravn-Haren, Gitte; Ma, Hai Ping; Knuthsen, Pia; Hansen, Birgit Fischer; McPhail, Donald; Freese, Riitta; Breinholt, Vibeke; Frandsen, Henrik; Dragsted, Lars O

    2005-04-01

    Anthocyanin-rich beverages have shown beneficial effects on coronary heart disease in epidemiological and intervention studies. In the present study, we investigated the effect of black currant anthocyanins on atherosclerosis. Watanabe Heritable Hyperlipidemic rabbits (n = 61) were fed either a purified anthocyanin fraction from black currants, a black currant juice, probucol or control diet for 16 weeks. Purified anthocyanins significantly increased plasma cholesterol and low-density lipoprotein (LDL) cholesterol. Intake of black currant juice had no effect on total plasma cholesterol, but lowered very-low-density lipoprotein (VLDL) cholesterol significantly. There were no significant effects of either purified anthocyanins or black currant juice on aortic cholesterol or development of atherosclerosis after 16 weeks. Probucol had no effect on plasma cholesterol but significantly lowered VLDL-cholesterol and decreased aortic cholesterol accumulation. The erythrocyte antioxidant enzyme glutathione peroxidase was significantly increased by purified anthocyanins and superoxide dismutase was increased by both anthocyanin-containing treatments. Other markers of plasma antioxidant capacity, antioxidant enzymes, protein and lipid oxidation were not affected by any of the anthocyanin treatments. Adverse effects of purified anthocyanins were observed on plasma- and LDL-cholesterol. These effects were not observed with black currant juice, suggesting that black currants may contain components reducing the adverse effects of anthocyanins. PMID:15759306

  4. The lectin-like oxidized low-density lipoprotein receptor-1 and its soluble form: cardiovascular implications.

    PubMed

    Navarra, Teresa; Del Turco, Serena; Berti, Sergio; Basta, Giuseppina

    2010-04-30

    The lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is a multiligand receptor, whose repertoire of ligands includes oxidized low-density lipoprotein, advanced glycation endproducts, platelets, neutrophils, apoptotic/aged cells and bacteria. Sustained expression of LOX-1 by critical target cells, including endothelial cells, smooth muscle cells and macrophages in proximity to these ligands, sets the stage for chronic cellular activation and tissue damage suggesting the interaction of cellular LOX-1 with its ligands to contribute to the formation and development of atherosclerotic plaques. Studies with transgenic and knockout mouse models have elucidated in part the role of LOX-1 in the pathogenesis of atherosclerosis and cardiac remodeling. Recently, a circulating soluble form of LOX-1 (sLOX-1), corresponding solely to its extracellular domain, has been identified in human serum. Circulating levels of sLOX-1 are increased in inflammatory and atherosclerotic conditions and are associated with acute coronary syndrome, with the severity of coronary artery disease, and with serum biomarkers for oxidative stress and inflammation, suggesting that they could be a useful marker for vascular injury. However, many interesting questions have not yet been answered and in this review, we provide an updated overview of the literature on this receptor and on likely future directions. PMID:20009416

  5. Soluble lectin-like oxidized low density lipoprotein receptor-1 as a biochemical marker for atherosclerosis-related diseases.

    PubMed

    Pirillo, Angela; Catapano, Alberico Luigi

    2013-01-01

    Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), the main oxidized low-density lipoprotein (OxLDL) in endothelial cells, is upregulated in atherosclerotic lesions and is involved in several cellular processes that regulate the pathogenesis of atherosclerosis. The LOX-1 expressed on the cell surface can be proteolytically cleaved and released in a soluble form (sLOX-1) in the circulation under pathological conditions. Serum levels of sLOX-1, in fact, are elevated at the early stages of acute coronary syndrome and are associated with coronary plaque vulnerability and with the presence of multiple complex coronary lesions. Moreover, in subjects with stable CAD, levels of serum sLOX-1 are associated with the presence of lesions in the proximal and mid-segments of the left anterior descending artery that are the most prone to rupture; in subjects undergoing percutaneous coronary intervention, baseline preprocedural serum sLOX-1 levels are associated with the incidence of periprocedural myocardial infarction. Altogether, these findings suggest that circulating levels of sLOX-1 might be a diagnostic and prognostic marker for atherosclerotic-related events. PMID:24198442

  6. Association of Pro-Inflammatory High Density Lipoprotein Cholesterol with Clinical and Laboratory Variables in Sickle Cell Disease

    PubMed Central

    Ataga, Kenneth I.; Hinderliter, Alan; Brittain, Julia E.; Jones, Susan; Xu, Hao; Cai, Jianwen; Kim, Soyoung; Pritchard, Kirkwood A.; Hillery, Cheryl A.

    2014-01-01

    Background Although cholesterol levels are known to be decreased in sickle cell disease (SCD), the level of pro-inflammatory high density lipoprotein cholesterol (proHDL) and its association with clinical complications and laboratory variables has not been evaluated. Design and Methods Plasma levels of total cholesterol, high density lipoprotein cholesterol (HDL), proHDL and selected clinical and laboratory variables were ascertained in a cohort of SCD patients and healthy African American control subjects in this single center, cross-sectional study. Results Although total cholesterol was significantly lower in SCD patients compared with control subjects, HDL and proHDL levels were similar in both SCD and control groups. In univariate analyses, proHDL was correlated with echocardiography-derived tricuspid regurgitant jet velocity. ProHDL was higher in SCD patients with suspected pulmonary hypertension (PHT) compared to patients without suspected PHT. ProHDL was positively correlated with lactate dehydrogenase, total bilirubin, direct bilirubin, indirect bilirubin, prothrombin fragment 1+2, D-dimer and thrombin-antithrombin complexes (TAT). In multivariable analyses, only higher lactate dehydrogenase and direct bilirubin levels were associated with higher levels of proHDL. Conclusions SCD is characterized by hypocholesterolemia. Although proHDL is not increased in SCD patients compared with healthy controls, it is significantly associated with markers of liver disease. In addition, proHDL is associated with tricuspid regurgitant jet velocity and markers of coagulation, although these associations are not significant in multivariable analyses. PMID:24801127

  7. Association of pro-inflammatory high-density lipoprotein cholesterol with clinical and laboratory variables in sickle cell disease.

    PubMed

    Ataga, Kenneth I; Hinderliter, Alan; Brittain, Julia E; Jones, Susan; Xu, Hao; Cai, Jianwen; Kim, Soyoung; Pritchard, Kirkwood A; Hillery, Cheryl A

    2015-06-01

    Background Although cholesterol levels are known to be decreased in sickle cell disease (SCD), the level of pro-inflammatory high-density lipoprotein cholesterol (proHDL) and its association with clinical complications and laboratory variables has not been evaluated. Design and methods Plasma levels of total cholesterol, high-density lipoprotein cholesterol (HDL), proHDL, and selected clinical and laboratory variables were ascertained in a cohort of SCD patients and healthy African American control subjects in this single-center, cross-sectional study. Results Although total cholesterol was significantly lower in SCD patients compared with control subjects, HDL and proHDL levels were similar in both the SCD and control groups. In univariate analyses, proHDL was correlated with echocardiography-derived tricuspid regurgitant jet velocity. ProHDL was higher in SCD patients with suspected pulmonary hypertension (PHT) compared to patients without suspected PHT. ProHDL was positively correlated with lactate dehydrogenase, total bilirubin, direct bilirubin, indirect bilirubin, prothrombin fragment 1+2, D-dimer, and thrombin-antithrombin complexes. In multivariable analyses, only higher lactate dehydrogenase and direct bilirubin levels were associated with higher levels of proHDL. Conclusions SCD is characterized by hypocholesterolemia. Although proHDL is not increased in SCD patients compared with healthy controls, it is significantly associated with markers of liver disease. In addition, proHDL is associated with tricuspid regurgitant jet velocity and markers of coagulation, although these associations are not significant in multivariable analyses. PMID:24801127

  8. Endothelial NOS-dependent activation of c-Jun NH(2)- terminal kinase by oxidized low-density lipoprotein

    NASA Technical Reports Server (NTRS)

    Go, Y. M.; Levonen, A. L.; Moellering, D.; Ramachandran, A.; Patel, R. P.; Jo, H.; Darley-Usmar, V. M.

    2001-01-01

    Oxidized low-density lipoprotein (oxLDL) is known to activate a number of signal transduction pathways in endothelial cells. Among these are the c-Jun NH(2)-terminal kinase (JNK), also known as stress-activated protein kinase, and extracellular signal-regulated kinase (ERK). These mitogen-activated protein kinases (MAP kinase) determine cell survival in response to environmental stress. Interestingly, JNK signaling involves redox-sensitive mechanisms and is activated by reactive oxygen and nitrogen species derived from both NADPH oxidases, nitric oxide synthases (NOS), peroxides, and oxidized low-density lipoprotein (oxLDL). The role of endothelial NOS (eNOS) in the activation of JNK in response to oxLDL has not been examined. Herein, we show that on exposure of endothelial cells to oxLDL, both ERK and JNK are activated through independent signal transduction pathways. A key role of eNOS activation through a phosphatidylinositol-3-kinase-dependent mechanism leading to phosphorylation of eNOS is demonstrated for oxLDL-dependent activation of JNK. Moreover, we show that activation of ERK by oxLDL is critical in protection against the cytotoxicity of oxLDL.

  9. Uptake of low density lipoproteins by human leukemic cells in vivo: relation to plasma lipoprotein levels and possible relevance for selective chemotherapy.

    PubMed Central

    Vitols, S; Angelin, B; Ericsson, S; Gahrton, G; Juliusson, G; Masquelier, M; Paul, C; Peterson, C; Rudling, M; Söderberg-Reid, K

    1990-01-01

    The success of cancer chemotherapy is dependent on the possibility to utilize biological differences between malignant and normal cells to selectively destroy the tumor cells. One such difference may be that of receptor-mediated cellular uptake of low density lipoproteins (LDLs). Previous studies have shown that leukemic cells from patients with acute myelogenous leukemia have elevated receptor-mediated uptake and degradation rates of plasma LDL in vitro compared to normal white blood and bone marrow cells, and that plasma cholesterol levels at diagnosis are inversely correlated with the LDL receptor activity of the malignant cells. An important question is whether the uptake of LDL by the leukemic cells is also increased in vivo. To evaluate the in vivo uptake of LDL, 11 adult patients with newly diagnosed acute myelogenous leukemia received an i.v. injection of [14C]-sucrose-labeled LDL. On degradation of [14C]sucrose-LDL, the radiolabeled sucrose moiety is known to remain trapped in the lysosomal compartment of the cells. After injection, radioactivity accumulated progressively for at least 12 hr in the leukemic cells. The uptake of radioactivity in vivo correlated with the rate of receptor-mediated degradation of 125I-labeled LDL by the leukemic cells assayed in vitro (r = +0.88, P less than 0.001). An inverse correlation between plasma LDL cholesterol concentrations and the in vivo cellular uptake of [14C]sucrose-LDL in whole blood (r = -0.76, P less than 0.01) indicates that the hypocholesterolemia is due to elevated LDL uptake by the leukemic cells. Postmortem biopsies from virtually all tissues were obtained from one patient, and the distribution of radioactivity revealed that the liver and bone marrow had accumulated most radioactivity; the adrenals had the highest uptake of label per gram of tissue weight. The results indicate that LDL may be used as a carrier targeting lipophilic cytotoxic drugs to leukemic cells. PMID:2320578

  10. Fenofibrate Increases Very Low Density Lipoprotein Triglyceride Production Despite Reducing Plasma Triglyceride Levels in APOE*3-Leiden.CETP Mice*

    PubMed Central

    Bijland, Silvia; Pieterman, Elsbet J.; Maas, Annemarie C. E.; van der Hoorn, José W. A.; van Erk, Marjan J.; van Klinken, Jan B.; Havekes, Louis M.; van Dijk, Ko Willems; Princen, Hans M. G.; Rensen, Patrick C. N.

    2010-01-01

    The peroxisome proliferator-activated receptor alpha (PPAR?) activator fenofibrate efficiently decreases plasma triglycerides (TG), which is generally attributed to enhanced very low density lipoprotein (VLDL)-TG clearance and decreased VLDL-TG production. However, because data on the effect of fenofibrate on VLDL production are controversial, we aimed to investigate in (more) detail the mechanism underlying the TG-lowering effect by studying VLDL-TG production and clearance using APOE*3-Leiden.CETP mice, a unique mouse model for human-like lipoprotein metabolism. Male mice were fed a Western-type diet for 4 weeks, followed by the same diet without or with fenofibrate (30 mg/kg bodyweight/day) for 4 weeks. Fenofibrate strongly lowered plasma cholesterol (?38%) and TG (?60%) caused by reduction of VLDL. Fenofibrate markedly accelerated VLDL-TG clearance, as judged from a reduced plasma half-life of glycerol tri[3H]oleate-labeled VLDL-like emulsion particles (?68%). This was associated with an increased post-heparin lipoprotein lipase (LPL) activity (+110%) and an increased uptake of VLDL-derived fatty acids by skeletal muscle, white adipose tissue, and liver. Concomitantly, fenofibrate markedly increased the VLDL-TG production rate (+73%) but not the VLDL-apolipoprotein B (apoB) production rate. Kinetic studies using [3H]palmitic acid showed that fenofibrate increased VLDL-TG production by equally increasing incorporation of re-esterified plasma fatty acids and liver TG into VLDL, which was supported by hepatic gene expression profiling data. We conclude that fenofibrate decreases plasma TG by enhancing LPL-mediated VLDL-TG clearance, which results in a compensatory increase in VLDL-TG production by the liver. PMID:20501652

  11. Beta-blocker induced changes in the cholesterol: High-density lipoprotein cholesterol ratio and risk of coronary heart disease

    Microsoft Academic Search

    B. G. Woodcock; N. Rietbrock

    1984-01-01

    Summary The lowering of blood pressure with beta-blocking drugs has had a low impact on coronary heart disease (CHD) mortality and the question has been raised whether adverse changes in plasma lipoproteins offset the benefits of blood pressure reduction. Comparison of plasma lipoprotein concentrations in hypertensive patients treated with commonly used beta-blockers with lipoprotein concentrations in patients with coronary heart

  12. Effects of efonidipine hydrochloride on cholesterol esterification mediated by beta-very low density lipoprotein in J774 macrophages.

    PubMed

    Kitahara, M; Toyoda, K; Yamashita, T; Sakashita, M; Tanaka, S; Saito, Y

    1995-10-01

    The effects of efonidipine hydrochloride (efonidipine), a dihydropyridine calcium antagonist, on the cholesterol ester metabolism induced by beta-migrating very low density lipoprotein (beta-VLDL) in J774 macrophages were studied. The cholesteryl ester content in the macrophages was increased by incubation with beta-VLDL, and the increase was inhibited by efonidipine. Oleic acid incorporation into cellular cholesteryl ester was increased by beta-VLDL in J774 macrophages. The incorporation at an early phase of beta-VLDL induction (0-3 hr) was inhibited by efonidipine. This inhibitory effect of efonidipine was greater at an early phase of beta-VLDL induction (0-3 hr) than at a late phase of the induction (8-11 hr). Pretreatment of the cells with efonidipine enhanced the inhibitory effect. Efonidipine also inhibited beta-VLDL degradation but not the binding and association in macrophages without pretreatment. beta-VLDL binding and association to macrophages were decreased by pretreatment of the cells with efonidipine. beta-VLDL metabolism was also decreased by dibutyryl cyclic AMP pretreatment. The decrease of beta-VLDL metabolism by efonidipine was prevented by co-treatment with efonidipine and HA1004, a protein kinase A inhibitor. Furthermore, efonidipine increased the intracellular cyclic AMP content in J774 macrophages. These findings suggest that efonidipine suppresses cholesterol ester deposition in atherosclerotic foam cells by inhibiting the modified lipoprotein metabolism and cholesterol esterification mainly through elevation of the cellular cyclic AMP level. PMID:8569046

  13. Low Density Lipoprotein Receptor-related Protein 1 Promotes Anti-apoptotic Signaling in Neurons by Activating Akt Survival Pathway*

    PubMed Central

    Fuentealba, Rodrigo A.; Liu, Qiang; Kanekiyo, Takahisa; Zhang, Juan; Bu, Guojun

    2009-01-01

    The low density lipoprotein receptor-related protein 1 (LRP1) is a multi-ligand receptor abundantly expressed in neurons. Previous work has shown that brain LRP1 levels are decreased during aging and in Alzheimer disease. Although mounting evidence has demonstrated a role for LRP1 in the metabolism of apolipoprotein E/lipoprotein and amyloid-? peptide, whether LRP1 also plays a direct role in neuronal survival is not clear. Here, we show that LRP1 expression is critical for the survival of primary neurons under stress conditions including trophic withdrawal, the presence of apoptosis inducers, or amyloid-?-induced neurotoxicity. Using lentiviral short hairpin RNA to knock down endogenous LRP1 expression, we showed that a depletion of LRP1 leads to an activation of caspase-3 and increased neuronal apoptosis, an effect that was rescued by a caspase-3 inhibitor. A correlation between decreased Akt phosphorylation and the activation of caspase-3 was demonstrated in LRP1 knocked down neurons. Notably, LRP1 knockdown decreased insulin receptor levels in primary neurons, suggesting that decreased neuronal survival might be a consequence of an impaired insulin receptor signaling pathway. Correspondingly, both insulin receptor and phospho-Akt levels were decreased in LRP1 forebrain knock-out mice. These results demonstrate that LRP1 mediates anti-apoptotic function in neurons by regulating insulin receptor and the Akt survival pathway and suggest that restoring LRP1 expression in Alzheimer disease brain might be beneficial to inhibiting neurodegeneration. PMID:19815552

  14. An Immunohistochemical Analysis to Validate the Rationale behind the Enhanced Immunogenicity of D-Ribosylated Low Density Lipo-Protein

    PubMed Central

    Akhter, Firoz; Khan, M. Salman; Singh, Sarika; Ahmad, Saheem

    2014-01-01

    Advanced glycation end products (AGEs) are thought to contribute to the abnormal lipoprotein profiles and increased risk of cardiovascular disease in patients with diabetes and renal failure. D-ribose is one of the naturally occurring pentose monosaccharide present in all living cells and is a key component of numerous biomolecules involved in many important metabolic pathways. Formation of D-ribose derived glycated low density lipoprotein (LDL) has been previously demonstrated but no studies have been performed to assess the immune complex deposition in the kidney of rabbits immunized with glycated LDL. In this study, LDL was glycated with D-ribose, and it was further used as an immunogen for immunizing NZW female rabbits. The results showed that female rabbits immunized with D-ribose modified LDL induced antibodies as detected by direct binding and competitive ELISA. The modified LDL was found to be highly immunogenic eliciting high titer immunogen-specific antibodies, while the native forms were moderately immunogenic. The induced antibodies from modified LDL exhibited wide range of heterogeneity in recognizing various proteins and amino acids conformers. Furthermore, our histopathological results illustrated the deposits of immune complex in glomerular basement membrane in rabbits immunized with D-ribose-LDL. PMID:25393017

  15. Effect of atorvastatin on low-density lipoprotein subpopulations and comparison between indicators of plasma atherogenicity: a pilot study.

    PubMed

    Kucera, Marek; Oravec, Stanislav; Hirnerova, Eva; Huckova, Nada; Celecova, Zuzana; Gaspar, Ludovit; Banach, Maciej

    2014-10-01

    Treatment with statins to achieve target low-density lipoprotein cholesterol (LDL-C) levels is still associated with residual risk. Lipoprotein subfraction evaluation can provide additional information regarding atherogenicity in these individuals. Patients (n = 40) with hypercholesterolemia (29 females, mean age 63 years), without previous hypolipemic treatment, were treated with atorvastatin 40 mg/d for 3 months. Atorvastatin significantly reduced total cholesterol (6.7 ± 1.0 vs 4.6 ± 1.3 mmol/L, P < .001), LDL-C (4.3 ± 1.0 vs 2.6 ± 0.9 mmol/L, P < .001), triglycerides (1.8 ± 0.9 vs 1.5 ± 1.00 mmol/L, P < .05), small-dense LDL (sdLDL) fraction 3 to 7 (0.22 ± 0.37 vs 0.09 ± 0.16 mmol/L, P < .001), and apolipoprotein B (apoB; 1.0 ± 0.2 vs 0.74 ± 0.2 g/L, P < .001). There was a negative correlation of atherogenic index of plasma (AIP) with buoyant LDL-1 and LDL-2 (r = -.35; P < .05) and positive with sdLDL-3 to sdLDL-7 (r = .52, P < .001). Administration of atorvastatin 40 mg/d in patients with hypercholesterolemia caused a shift in sdLDL subfractions to large, buoyant subfractions. The AIP better correlated with sdLDL than apoB levels. PMID:24163116

  16. Heparin induces an accumulation of atherogenic lipoproteins during hemodialysis in normolipidemic end-stage renal disease patients.

    PubMed

    Barbagallo, Carlo M; Noto, Davide; Cefalù, Angelo B; Ganci, Antonia; Giammarresi, Carlo; Panno, Donata; Cusumano, Gaspare; Greco, Massimiliano; Di Gaudio, Francesca; Averna, Maurizio R

    2015-07-01

    Dyslipidemias may account for the excess of cardiovascular mortality in end-stage renal disease (ESRD). Lipoprotein studies in ESRD patients are usually relative to prehemodialysis samples even if significative changes may occur after dialysis. In this study, we aimed to investigate the effects of ESRD on triglyceride-rich lipoproteins (TRL) subpopulations distribution and acute change following hemodialytic procedures, including the relative contribution of heparin administration. We selected a group of normolipidemic male middle-aged ESRD patients free of any concomitant disease affecting lipoprotein remnant metabolism compared with controls. We separated TRL subfractions according to density and apoE content and evaluated the changes of these particles after hemodialytic procedures with or without heparin. ESRD subjects had higher TRL subfractions, with the exception of apoE-rich particles, lower high-density lipoprotein (HDL) largest subclasses, and a smaller low-density lipoprotein peak particle size than controls. After a hemodialytic standard procedure with heparin, we demonstrated a significant reduction of triglyceride, an increase of HDL-cholesterol levels, and a raise of small very-low-density lipoprotein, intermediate-density lipoproteins (IDL), apoE-rich particles, and non-HDL-cholesterol levels. When hemodialysis was performed without heparin, no significant changes were observed. In the absence of concomitant hyperlipidemic triggers, ESRD patients show significant lipoprotein abnormalities before dialysis, but without any increased remnant particles concentrations. We speculate that hemodialysis, in particular heparin administration during this procedure, leads to a massive atherogenic TRLs production because of the acute stimulation of the dysfunctional lipolytic system not followed by an efficient removal, determining a recurrent lipoprotein remnant accumulation. PMID:25495659

  17. Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT)

    Microsoft Academic Search

    Giacomo Ruotolo; Carl-Göran Ericsson; Cristina Tettamanti; Fredrik Karpe; Lars Grip; Bertil Svane; Jan Nilsson; Ulf de Faire; Anders Hamsten

    1998-01-01

    Objectives. To investigate the mechanisms by which bezafibrate retarded the progression of coronary lesions in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), we examined the relationships of on-trial lipoproteins and lipoprotein subfractions to the angiographic outcome measurements.Background. BECAIT, the first double-blind, placebo-controlled, randomized serial angiographic trial of a fibrate compound, showed that progression of focal coronary atherosclerosis in young survivors

  18. Tannerella forsythia is associated with increased levels of atherogenic low density lipoprotein and total cholesterol in chronic periodontitis

    PubMed Central

    Perez-Valencia, Aide-Yancelly; Rendon-Osorio, Willer-Leandro

    2015-01-01

    Background Accumulating evidence suggests that acute and chronic infections with periodontopathogens are associated with an increased risk of cardiovascular disease. The objective of this study was to assess whether Tanerella forsythia and Porphyromonas gingivalis are associated with increased levels of atherogenic low-density lipoprotein (LDL), high-density lipoprotein, total cholesterol (TC), triglycerides and body mass index (BMI) in chronic periodontitis patients. Material and Methods Medical history and clinical and radiographic examination were conducted in 80 chronic periodontitis patients and 28 healthy individuals. Fasting blood samples were drawn for the measurement of the parameters of dyslipidemia. Anthropometric measurements such as height in meters and weight in kilograms were recorded. Both periodontitis and control subjects were asked to answer a questionnaire with regard to their socio-demographic and smoking status. The presence of T. forsythia, and P. gingivalis was detected using primers designed to target the respective 16S rRNA gene sequences. Results The occurrence of T. forsythia and P. gingivalis was higher in the group of subjects with periodontitis. Superior levels of triglycerides were observed in chronic periodontitis patients compared to healthy individuals. High levels of TC in periodontitis persons were significantly associated with increased bleeding on probing. Greater mean levels of TC and LDL were shown in the presence of T. forsythia (P<0.05). Likewise, higher proportions of patients with BMI ?25 kg/m2 related with T. forsythia (P<0.05). T. forsythia was a significant discriminating factor in the multivariate linear regression model emerging as significant explanatory of increased levels of TC (?=17,879, 95% CI = 4,357-31,401; p=0.01) and LDL (?=17,162, 95% CI= 4,009-30,316; p=0.01). Conclusions Higher levels of serum total cholesterol and LDL were observed in the occurrence of T. forsythia and the presence of this periodontopathogen may increase the atherogenic potency of low-density lipoprotein that may augment the risk for atherosclerosis in periodontal disease patients. Key words:Periodontitis, dyslipidemia, Tannerella forsythia, cardiovascular disease.

  19. Role of lysophosphatidylcholine in the inhibition of endothelial cell motility by oxidized low density lipoprotein.

    PubMed Central

    Murugesan, G; Fox, P L

    1996-01-01

    Endothelial cell (EC) movement is required for the development and repair of blood vessels. We have previously shown that LDL oxidized by transition metals almost completely suppressed the wound-healing migratory response of vascular EC in vitro. We now report that lysophosphatidylcholine (lysoPC), a lipid component of oxidized LDL, has an important role in the antimigratory activity of the lipoprotein. Purified 1-palmitoyl lysoPC inhibited movement with a half-maximal activity at 12-15 micrometers, and near complete inhibition at 20 micrometers; the inhibitory concentration of lysoPC was consistent with its abundance in oxidized LDL. The inhibition was not due to cytotoxicity since protein synthesis was unaffected and since EC movement was restored after removal of lysoPC. Lysophospholipid activity was dependent on lipid structure. LysoPC's containing 1-position C16 or C18 saturated fatty acids were antimigratory, but those containing C < or = 14 saturated fatty acids or polyunsaturated fatty acids were not. The activity of 1-palmitoyl lysolipids with various head groups was examined. Lysophosphatidylinositol was more antimigratory than lysophosphatidylglycerol and lysophosphatidylcholine, which were more potent than lysophosphatidylserine and lysophosphatidylethanolamine. Monoglyceride was inactive while lysophosphatidate had promigratory activity. These results are consistent with head group size rather than charge as a critical determinant of activity. To show that lysophospholipids within an intact lipoprotein were active, LDL was treated with bee venom phospholipase A2 (PLA2). The modified lipoprotein inhibited EC movement to the same extent as iron-oxidized LDL and antimigratory activity correlated with the amount of lysoPC formed. To determine antimigratory activity of lysoPC present in oxidized LDL, lipid extracts from oxidized LDL were fractionated by normal phase HPLC. The fraction comigrating with lysoPC had nearly the same activity as the total extract confirming that lysoPC (or a co-eluting lipid) was a major antimigratory molecule in oxidized LDL. These studies demonstrate that lysoPC in oxidized LDL limit EC wound healing responses in vitro, and suggest a possible role for lysolipids in limiting endothelial regeneration after a denuding injury in vivo. PMID:8675684

  20. High density lipoprotein mediates anti-inflammatory transcriptional reprogramming of macrophages via the transcriptional repressor ATF3

    PubMed Central

    De Nardo, Dominic; Labzin, Larisa I.; Kono, Hajime; Seki, Reiko; Schmidt, Susanne V.; Beyer, Marc; Xu, Dakang; Zimmer, Sebastian; Lahrmann, Catharina; Schildberg, Frank A.; Vogelhuber, Johanna; Kraut, Michael; Ulas, Thomas; Kerksiek, Anja; Krebs, Wolfgang; Bode, Niklas; Grebe, Alena; Fitzgerald, Michael L.; Hernandez, Nicholas J.; Williams, Bryan; Knolle, Percy; Kneilling, Manfred; Röcken, Martin; Lütjohann, Dieter; Wright, Samuel D.; Schultze, Joachim L.; Latz, Eicke

    2014-01-01

    High Density Lipoprotein (HDL) mediates reverse cholesterol transport and it is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional repressor ATF3, as an HDL-inducible target gene in macrophages that down-regulates the expression of Toll-like receptor (TLR)-induced pro-inflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of novel HDL-based therapies. PMID:24317040

  1. A biosensor of high-density lipoprotein of human serum on a liquid crystal and polymer composite film

    NASA Astrophysics Data System (ADS)

    Lin, Yi-Hsin; Chang, Kai-Han; Chu, Wei-Lin; Tsou, Yu-Shih; Wu, Li-Ching; Li, Chien-Feng

    2013-10-01

    A biosensor for the concentration of high-density lipoprotein (HDL) in human serum on a liquid crystal and polymer composite film (LCPCF) is demonstrated. The sensing mechanism is based on a polar-polar interaction between orientation of LC directors and HDL in human serum. The concentration of polar HDL in human serum affects the orientations of LC directors at the interface between LCPCF and the human serum. In addition, the surface free energy of LCPCF changes with the applied voltage due to the electrically tunable orientations of LC directors anchored among the polymer grains of LCPCF. As a result, the droplet motion of human serum on LCPCF under applied voltages can sense the concentration of HDL in human serum.

  2. The effects of pH on the oxidation of low-density lipoprotein by copper and metmyoglobin are different.

    PubMed

    Rodríguez-Malaver, A J; Leake, D S; Rice-Evans, C A

    1997-04-01

    The amplification of low-density lipoprotein (LDL) peroxidation in vitro by copper and myoglobin are well-studied biochemical approaches for investigating the oxidative modification of LDL and its role in the pathogenesis of atherosclerosis. Since the acidity of the environment is increased in inflammatory sites, the aim of this study was to investigate the effects of acidic pH on the oxidisability of LDL mediated by the haem protein myoglobin in comparison with that of copper-mediated LDL oxidation. The results show that acidic pH enhances myoglobin-mediated LDL oxidation as measured by conjugated dienes, lipid hydroperoxides and electrophoretic mobility, whilst a retardation is observed with copper as pro-oxidant; the mechanism probably relates to the effects of pH on the decomposition and formation of lipid hydroperoxides and the relative influences of copper ions and of myoglobin under these conditions. PMID:9109382

  3. Recyclable heparin and chitosan conjugated magnetic nanocomposites for selective removal of low-density lipoprotein from plasma.

    PubMed

    Li, Jinghua; Hou, Yanhua; Chen, Xiuyong; Ding, Xingwei; Liu, Yun; Shen, Xinkun; Cai, Kaiyong

    2014-04-01

    A new fabrication protocol is described to obtain heparin and chitosan conjugated magnetic nanocomposite as a blood purification material for removal of low-density lipoprotein (LDL) from blood plasma. The adsorbent could be easily separated with an external magnet for recyclable use since it had a magnetic core. The LDL level of plasma decreased by 67.3 % after hemoperfusion for 2 h. Moreover, the adsorbent could be recycled simply washing with NaCl solution. After eight cycles, the removal efficiency of the adsorbent was still above 50 %. The recyclable magnetic adsorbent had good blood compatibility due to the conjugation of heparin to the chitosan-coated magnetic nanocomposites. The fabricated magnetic adsorbent could be applied for LDL apheresis without side effects. PMID:24394982

  4. Complementary response of In2O3 nanowires and carbon nanotubes to low-density lipoprotein chemical gating

    NASA Astrophysics Data System (ADS)

    Tang, Tao; Liu, Xiaolei; Li, Chao; Lei, Bo; Zhang, Daihua; Rouhanizadeh, Mahsa; Hsiai, Tzung; Zhou, Chongwu

    2005-03-01

    In2O3 nanowire and carbon nanotube transistors were used to study the chemical gating effect of low-density lipoproteins (LDL). The adsorption of LDL on these two different surfaces was investigated, which revealed a tenfold more LDL particle adsorption on carbon nanotubes than on In2O3 nanowires because of hydrophobic/hydrophilic interactions. The conductance of field-effect transistors based on nanowires and nanotubes showed complementary response after the adsorption of LDL: while In2O3 nanowire transistors exhibited higher conductance accompanied by a negative shift of the threshold voltage, the nanotube transistors showed lower conductance after the exposure. This is attributed to the complementary doping type of In2O3 nanowires (n type) and carbon nanotubes (p type).

  5. Circulating levels of lectin-like oxidized low-density lipoprotein receptor-1 are associated with inflammatory markers.

    PubMed

    Lubrano, Valter; Del Turco, Serena; Nicolini, Giuseppina; Di Cecco, Pietro; Basta, Giuseppina

    2008-10-01

    Lectin-like oxidized-low-density lipoprotein receptor-1 (LOX-1) is increasingly linked to atherosclerotic plaque formation and the soluble form of this receptor may reflect activities of disease. We investigated the associations among levels of sLOX-1, oxidized-low-density lipoprotein (ox-LDL), cytokines and the extension of atherosclerosis in patients with coronary artery disease (CAD). Lipid, TNF-alpha, IL-6, C reactive protein (CRP), ox-LDL, peroxy radical and sLOX-1 levels were measured in 29 controls and 60 patients with CAD, 30 of which with one or two vessels involved (group 1), and 30 patients with three or four vessels involved (group 2). The serum levels of sLOX-1 were significantly and progressively higher in group 1 [611 (346-1,313) pg/ml, median (interquartile range)] and in group 2 [2,143 (824-3,201) pg/ml] than in control subjects [268 (111-767) pg/ml]. LOX-1 levels positively correlated with IL-6 (r = 0.38, P = 0.0042), TNF-alpha (r = 0.38, P = 0.0037), CRP levels (r = 0.32, P = 0.027) and age (r = 0.25, P = 0.048). In the multivariate analysis TNF-alpha resulted the only independent determinant of LOX-1 serum levels (beta-value = 0.304, P = 0.017). These findings suggest that sLOX-1 levels are up-regulated during CAD progression and are associated with inflammatory markers. The measurement of the circulating soluble form of this receptor may be potentially useful in predicting CAD progression in humans. PMID:18781352

  6. Characterization of the role of EGF-A of low density lipoprotein receptor in PCSK9 binding

    PubMed Central

    Gu, Hong-mei; Adijiang, Ayinuer; Mah, Matthew; Zhang, Da-wei

    2013-01-01

    Proprotein convertase subtilisin kexin-like 9 (PCSK9) promotes the degradation of low density lipoprotein receptor (LDLR) and plays an important role in regulating plasma LDL-cholesterol levels. We have shown that the epidermal growth factor precursor homology domain A (EGF-A) of the LDLR is critical for PCSK9 binding at the cell surface (pH 7.4). Here, we further characterized the role of EGF-A in binding of PCSK9 to the LDLR. We found that PCSK9 efficiently bound to the LDLR but not to other LDLR family members. Replacement of EGF-A in the very low density lipoprotein receptor (VLDLR) with EGF-A of the LDLR promoted the degradation of the mutant VLDLR induced by PCSK9. Furthermore, we found that PCSK9 bound to recombinant EGF-A in a pH-dependent manner with stronger binding at pH 6.0. We also identified amino acid residues in EGF-A of the LDLR important for PCSK9 binding. Mutations G293H, D299V, L318D, and L318H reduced PCSK9 binding to the LDLR at neutral pH without effect at pH 6.0, while mutations R329P and E332G reduced PCSK9 binding at both pH values. Thus, our findings reveal that EGF-A of the LDLR is critical for PCSK9 binding at the cell surface (neutral pH) and at the acidic endosomal environment (pH 6.0), but different determinants contribute to efficient PCSK9 binding in different pH environments. PMID:24103783

  7. Both inherited susceptibility and environmental exposure determine the low-density lipoprotein-subfraction pattern distribution in healthy Dutch families

    SciTech Connect

    Graaf, J. de; Swinkels, D.W.; Haan, A.F.J. de; Demacker, P.N.M.; Stalenhoef, A.F.H. (University Hospital, Nijmegen (Netherlands))

    1992-12-01

    A lipoprotein profile characterized by a predominance of small, dense, low-density lipoprotein (LDL) particles has been associated with an increased risk of atherosclerosis. To investigate whether genetic factors are involved in determining this heavy LDL subfraction pattern, this study was undertaken with the aim of resolving the effects that major genes, multifactorial heritability, and environmental exposures have on the LDL subfraction pattern. In a random sample of 19 healthy Dutch families including 162 individuals, the distribution of the LDL subfraction pattern was determined by density gradient ultracentrifugation. For each subject a specific LDL subfraction profile was observed, characterized by the relative contribution of the three major LDL subfractions - LDL1 (d = 1.030-1.033 g/ml), LDL2 (d = 1.033-1.040 g/ml), and LDL3 (d = 1.040-1.045 g/ml) - to total LDL. A continuous variable, parameter K, was defined to characterize each individual LDL subfraction pattern. Complex segregation analysis of this quantitative trait, under a model which includes a major locus, polygenes, and both common and random environment, was applied to analyze the distribution of the LDL subfraction pattern in these families. The results indicate that the LDL subfraction pattern, described by parameter K, is controlled by a major autosomal, highly penetrant, recessive allele with a population frequency of .19 and an additional multifactorial inheritance component. The results indicate that genetic influences as well as environmental exposure, sex, age and hormonal status in women are important in determining the distribution of the LDL subfraction patterns in this population and that these influences may contribute to the explanation of familial clustering of coronary heart disease. 40 refs., 3 figs., 8 tabs.

  8. Impact of red blood cells count and high density lipoproteins with the prevalence and extent of coronary artery disease.

    PubMed

    Schaffer, Alon; Verdoia, Monica; Cassetti, Ettore; Barbieri, Lucia; Perrone-Filardi, Pasquale; Marino, Paolo; De Luca, Giuseppe

    2015-07-01

    We have hypothesized that high red blood cells (RBC) count can potentially play an atheroprotective role in patients with coronary atherosclerosis. We, therefore, have investigated the relationship between high density lipoproteins cholesterol (HDL-C) and RBC levels in patients undergoing coronary angiography. Coronary artery disease (CAD) is a major cause of mortality. Impaired lipid profile represents a major risk factor for atherosclerosis. High density lipoprotein (HDL) is a key factor in atherosclerosis disease development. RBC can mimic HDL's reverse cholesterol transportation with a potential atheroprotective role. Coronary angiography has been evaluated in 3,534 patients. Fasting samples were collected for haematology and lipids levels assessment. Coronary disease was defined for at least 1 vessel stenosis >50 %. Patients were divided according to HDL-C and RBC tertiles. Lower HDL-C was significantly associated to the prevalence of CAD (84.8 vs 78.5 vs 67.3 %, p ? 0.001; adjusted OR [95 % CI] = 1.55 [1.3-1.8], p < 0.001) and severe CAD (30 % vs 30 % vs 24.4 %, p = 0.002; adjusted OR [95 % CI] = 1.08 [1.01-1.16], p = 0.02), this relationship was maintained even dividing our population according to RBC tertiles (p < 0.001).In conclusion, HDL-C levels are directly related to RBC count and inversely to the prevalence and extent of coronary disease. Higher RBC levels can reduce the risk of CAD in patients with lower HDL-C levels, suggesting an important atheroprotective role. PMID:25680891

  9. Tissue-type plasminogen activator-binding RNA aptamers inhibiting low-density lipoprotein receptor family-mediated internalisation.

    PubMed

    Bjerregaard, N; Bøtkjær, K A; Helsen, N; Andreasen, P A; Dupont, D M

    2015-06-30

    Recombinant tissue-type plasminogen activator (tPA, trade name Alteplase), currently the only drug approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of cerebral ischaemic stroke, has been implicated in a number of adverse effects reportedly mediated by interactions with the low-density lipoprotein (LDL) family receptors, including neuronal cell death and an increased risk of cerebral haemorrhage. The tissue-type plasminogen activator is the principal initiator of thrombolysis in human physiology, an effect that is mediated directly via localised activation of the plasmin zymogen plasminogen at the surface of fibrin clots in the vascular lumen. Here, we sought to identify a ligand to tPA capable of inhibiting the relevant LDL family receptors without interfering with the fibrinolytic activity of tPA. Systematic evolution of ligands by exponential enrichment (SELEX) was employed to isolate tPA-binding RNA aptamers, which were characterised in biochemical assays of tPA association to low density lipoprotein receptor-related protein-1 (LRP-1, an LDL receptor family member); tPA-mediated in vitro and ex vivo clot lysis; and tPA-mediated plasminogen activation in the absence and presence of a stimulating soluble fibrin fragment. Two aptamers, K18 and K32, had minimal effects on clot lysis, but were able to efficiently inhibit tPA-LRP-1 association and LDL receptor family-mediated endocytosis in human vascular endothelial cells and astrocytes. These observations suggest that coadministration alongside tPA may be a viable strategy to improve the safety of thrombolytic treatment of cerebral ischaemic stroke by restricting tPA activity to the vascular lumen. PMID:25855589

  10. The association of alanine aminotransferase within the normal and mildly elevated range with lipoproteins and apolipoproteins: the Insulin Resistance Atherosclerosis Study

    PubMed Central

    Lorenzo, C.; Hanley, A. J.; Rewers, M. J.; Haffner, S. M.

    2013-01-01

    Aims/hypothesis Markers of liver injury, such as alanine aminotransferase (ALT), have been associated with atherogenic lipoprotein changes. We examined the extent to which this association was explained by insulin resistance, adiposity, glucose tolerance and chronic inflammation. Methods In this analysis we included 824 non-diabetic participants (age 40–69 years) in the Insulin Resistance Atherosclerosis Study. No participants reported excessive alcohol intake or treatment with lipid-lowering medications. Lipoproteins and apolipoproteins were measured by conventional methods and lipoprotein heterogeneity by nuclear magnetic resonance (NMR) spectroscopy. Results ALT had a positive relationship with triacylglycerols, LDL-to-HDL-cholesterol ratio and apolipoprotein B (ApoB) after adjusting for demographic variables (p <0.001 for all three relationships). ALT was also associated with the following NMR lipoproteins: positively with large VLDL (p <0.001), intermediate-density lipoprotein (IDL) (p <0.001) and small LDL subclass particles (p <0.001), and VLDL particle size (p <0.001); and negatively with large LDL subclass particles (p <0.05) and LDL (p <0.001) and HDL particle sizes (p <0.01). ALT remained associated with IDL and small LDL subclass particles and ApoB after adjusting for glucose tolerance, adiposity, directly measured insulin sensitivity and C-reactive protein. Conclusions/interpretation ALT is associated with a wide range of atherogenic lipoprotein changes, which are partially explained by insulin resistance, adiposity, glucose tolerance and chronic inflammation. Because of the significant variability in the relationship between ALT and liver fat, further studies are needed to assess the extent of the lipoprotein changes using a direct measure of liver fat. PMID:23344727

  11. Effects of an acute bout of exercise on high density lipoprotein cholesterol following consumption of a high or low fat diet

    Microsoft Academic Search

    Mark Kern; Danny R. Harris; Heidi Broder; Jennifer Imgrund Edmondson

    2000-01-01

    Research suggests that a low fat diet may decrease high density lipoprotein cholesterol (HDL?C) concentration and that exercise may increase HDL?C. The purpose of this randomized, crossover study was to determine the influence of acute exercise on blood lipid concentration of 8 minimally active young women after consuming a high fat diet or low fat diet for 5 days. At

  12. Simultaneous Production of Superoxide Radical and Singlet Oxygen by Sulphonated Chloroaluminum Phthalocyanine Incorporated in Human Low-density Lipoproteins: Implications for Photodynamic Therapy¶

    Microsoft Academic Search

    Joana Martins; Leonor Almeida; João Laranjinha

    2004-01-01

    Sulfonated chloroaluminum phthalocyanines have been studied for their use in the photodynamic therapy (PDT) of tumors. Plasma low-density lipoproteins (LDL) are important carriers of phthalocyanines in the blood, but on exposure to visible light, phthalocyanine-loaded LDL undergo an oxida- tion process that propagates to erythrocytes. We attempted to identify the reactive species involved in LDL and erythrocyte oxidation by means

  13. Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis

    Microsoft Academic Search

    GABRIEL PERLEMUTER; ABDELMAJID SABILE; PHILIPPE LETTERON; GIOVANNA VONA; YVES CHRETIEN; KAZUHIKO KOIKE; DOMINIQUE PESSAYRE; JOHN CHAPMAN; GIOVANNA BARBA; CHRISTIAN BRECHOT

    2002-01-01

    Liver steatosis, which involves accumula- tion of intracytoplasmic lipid droplets, is characteristic of hepatitis C virus (HCV) infection. By use of an in vivo transgenic murine model, we demonstrate that hepatic overexpression of HCV core protein interferes with the hepatic assembly and secretion of triglyceride- rich very low density lipoproteins (VLDL). Core expres- sion led to reduction in microsomal triglyceride

  14. Correction of Apolipoprotein A-I-mediated Lipid Efflux and High Density Lipoprotein Particle Formation in Human Niemann-Pick Type C Disease Fibroblasts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Impaired cell cholesterol trafficking in Niemann-Pick type C (NPC) disease results in the first known instance of impaired regulation of the ATP-binding cassette transporter A1 (ABCA1), a lipid transporter mediating the rate-limiting step in high density lipoprotein (HDL) formation, as a cause of lo...

  15. Association of Coronary Atherosclerosis with Hyper Apo Betalipoproteinemia [Increased Protein but Normal Cholesterol Levels in Human Plasma Low Density (beta) Lipoproteins

    Microsoft Academic Search

    Allan Sniderman; Stanley Shapiro; Derek Marpole; Bernard Skinner; Babie Teng; Peter O. Kwiterovich

    1980-01-01

    Most patients with coronary artery disease do not have elevated plasma or low density lipoprotein (LDL) cholesterol. To test whether the protein moiety of LDL, LDL B, might be a parameter to identify ischemic heart disease, the plasma cholesterol, triglyceride, LDL cholesterol, and LDL B were measured in 100 consecutive patients undergoing cardiac catheterization. On the basis of coronary angiography,

  16. Effects of a 12-week healthy-life exercise program on oxidized low-density lipoprotein cholesterol and carotid intima-media thickness in obese elderly women

    PubMed Central

    Park, Jong-Hwan; Park, Hyuntae; Lim, Seung-Taek; Park, Jin-Kee

    2015-01-01

    [Purpose] This study examined the effects of a 12-week exercise program on plasma level of oxidized low-density lipoprotein cholesterol in obese elderly women, who are at increased risk of heart disease morbidity. [Subjects and Methods] Twenty participants were assigned into either a control (n = 10) or a supervised exercise program (n = 10) group. The 12-week exercise intervention was performed 3 days per week and involved combined aerobic exercise, resistance exercise, and traditional Korean dance. [Results] Two-factor analysis of variance revealed significant group × time interactions for body mass, diastolic blood pressure, appendicular muscle mass. For high-density lipoprotein cholesterol, oxidized low-density lipoprotein cholesterol, and the ratio of oxidized low-/high-density lipoprotein cholesterol, two-factor analysis of variance revealed significant interactions (group × time), indicating responses differed significantly between the control and exercise groups after 12 weeks. [Conclusion] A 12-week low- to moderate-intensity exercise program appears to be beneficial for obese elderly women by improving risk factors for cardiovascular disease.

  17. Colocalization of 15Lipoxygenase mRNA and Protein with Epitopes of Oxidized Low Density Lipoprotein in Macrophage-Rich Areas of Atherosclerotic Lesions

    Microsoft Academic Search

    Seppo Yla-Herttuala; Michael E. Rosenfeld; Sampath Parthasarathy; Christopher K. Glass; Elliott Sigal; Joseph L. Witztum; Daniel Steinberg

    1990-01-01

    Oxidation of low density lipoprotein (LDL) enhances its atherogenicity, and inhibition of such oxidation decreases the rate of progression of atherosclerotic lesions. The mechanism of LDL oxidation in vivo remains uncertain, but in vitro studies have suggested that cellular lipoxygenases may play a role by initiating lipid peroxidation in LDL. In situ hybridization studies using a 15-lipoxygenase riboprobe and immunostaining

  18. Molina et al., LDLR and HCV infection of normal hepatocyte 1 The Low Density Lipoprotein Receptor plays a role in the

    E-print Network

    Paris-Sud XI, Université de

    plays a role in the infection of primary human hepatocytes by hepatitis C virus Sonia Molina1 *, Valérie implication of low density lipoprotein receptor (LDLR) in hepatitis C virus (HCV) infection of human antibodies against r-shLDLR4-292, squalestatin or 25- hydroxycholesterol. Intracellular amounts

  19. Development of divergent lines of lean and fat broilers using plasma very low density lipoprotein concentration as selection criterion: The first three generations

    Microsoft Academic Search

    C. C. Whitehead; H. D. Griffin

    1984-01-01

    1. Male and female broilers of a pure line were selected over three generations on the basis of high or low plasma very low density lipoprotein (VLDL) concentration at 7 weeks of age.2. Heritability of plasma VLDL was high (h = 0·50 ± 0·08) and by the third generation mean values in the two lines differed by a factor of

  20. Small dense low density lipoprotein has increased affinity for LDL receptor-independent cell surface binding sites: a potential mechanism for increased atherogenicity 1

    Microsoft Academic Search

    Narmer F. Galeano; Maysoon Al-Haideri; Fannie Keyserman; Steven C. Rumsey; Richard J. Deckelbaum

    Small dense low density lipoprotein (LDL) parti- cles have altered apolipoprotein (apo) B conformation and lowered affinity for the LDL receptor ( J. Biol. Chem. 1994. 269: 511-519). Herein, we examine the interaction of small dense LDL with cell LDL receptor-independent binding sites. Compared to normal LDL, at low LDL cell media con- centrations ( , 10 m g\\/ml), small

  1. Up-regulated expression of type II very low density lipoprotein receptor correlates with cancer metastasis and has a potential link to ?-catenin in different cancers

    Microsoft Academic Search

    Lei He; Yanjun Lu; Peng Wang; Jun Zhang; Chuanchang Yin; Shen Qu

    2010-01-01

    BACKGROUND: Very low density lipoprotein receptor (VLDLR) has been considered as a multiple function receptor due to binding numerous ligands, causing endocytosis and regulating cellular signaling. Our group previously reported that enhanced activity of type II VLDLR (VLDLR II), one subtype of VLDLR, promotes adenocarcinoma SGC7901 cells proliferation and migration. The aim of this study is to explore the expression

  2. NPXY, a Sequence Often Found in Cytoplasmic Tails, Is Required for Coated Pit-mediated Internalization of the Low Density Lipoprotein Receptor

    Microsoft Academic Search

    Wen-Ji Chen; Joseph L. Goldstein; Michael S. Brown

    1990-01-01

    Rapid internalization of the cell surface low density lipoprotein (LDL) receptor requires the first 22 amino acids of the cytoplasmic domain (residues 790-811), which must include an aromatic residue at position 807. In the human LDL receptor, this position is part of a tetrameric sequence, NPVY. A similar tetramer, NPXY (where X stands for any amino acid), is con- served

  3. Oxidized low density lipoproteins induce apoptosis in PHA-activated peripheral blood mononuclear cells and in the Jurkat T-cell line

    Microsoft Academic Search

    Julie Alcouffe; Sylvie Caspar-Bauguil; Virginie Garcia; Robert Salvayre; Mogens Thomsen; Hervé Benoist

    Oxidized low density lipoproteins (oxLDLs) and activated T lymphocytes are present in early atherosclerotic plaques. It has been shown that oxLDLs are cytotoxic to cul- tured vascular cells but their possible toxic action on T lym- phocytes has not been described. Peripheral blood lympho- cytes from healthy individuals were stimulated in vitro with the polyclonal activator phytohemagglutinin and treated with

  4. Deficiency of Low Density Lipoprotein Receptors in Liver and Adrenal Gland of the WHHL Rabbit, an Animal Model of Familial Hypercholesterolemia

    Microsoft Academic Search

    Toru Kita; Michael S. Brown; Yoshio Watanabe; Joseph L. Goldstein

    1981-01-01

    The WHHL (Watanabe heritable hyperlipidemic) rabbit has been proposed as an animal model for human familial hypercholesterolemia. Homozygous WHHL rabbits have marked increases in the plasma level of low density lipoprotein (LDL), removal of LDL from their plasma is delayed, and LDL receptors are absent from their cultured fibroblasts [Tanzawa, K., Shimada, Y., Kuroda, M., Tsujita, Y., Arai, M. &

  5. Genetic variation at the SLCO1B1 gene locus and low density lipoprotein cholesterol lowering response to pravastatin in the elderly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our goal was to determine whether genetic variation at genes affecting statin metabolism or targets of statin therapy would influence low density lipoprotein (LDL) cholesterol lowering with pravastatin, baseline heart disease, or cardiac endpoints on trial. We examined associations of single nucleot...

  6. The Effect of Aerobic Exercise on Total Cholesterol, High-Density Lipoprotein, Apolipoprotein B, Apolipoprotein A-I, and Percent Body Fat in Adolescent Females.

    ERIC Educational Resources Information Center

    Lungo, Diane; And Others

    The effect of aerobic exercise on total cholesterol (TC), high-density lipoprotein (HDL), apolipoprotein B (Apo B), apolioprotein A-I (Apo A-I), and percent body fat in adolescent females was studied. The control subjects (n=86) were volunteers who had completed a physical education class at least six months prior to the commencement of the study,…

  7. Tumor necrosis factor-alpha impairs hepatic insulin signaling and stimulates the overproduction of hepatic apolipoprotein B100-containing very low density lipoproteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mechanisms underlying hepatic overproduction of apolipoprotein B (apoB) 100-containing very low density lipoproteins (VLDL) in insulin resistance induced by tumor necrosis factor (TNF)-a were investigated. In the present study, we examined the potential role of TNF-a in insulin signaling and lipopro...

  8. DNA-mediated transfer of a human gene required for low-density lipoprotein receptor expression and for multiple Golgi processing pathways.

    PubMed Central

    Kingsley, D M; Sege, R D; Kozarsky, K F; Krieger, M

    1986-01-01

    Transfection of a hamster cell mutant with human DNA corrected both the low-density lipoprotein receptor-deficient phenotype and the multiple glycosylation defects of the cells. Independently transfected colonies contained a small set of common human DNA fragments. These fragments may correspond to the human analog of a single gene required for several different Golgi processing pathways. Images PMID:3785210

  9. Hepatic metabolism of colloidal gold-low-density lipoprotein complexes in the rat: evidence for bulk excretion of lysosomal contents into bile

    SciTech Connect

    Renaud, G.; Hamilton, R.L.; Havel, R.J.

    1989-03-01

    Rats were treated with 17 alpha-ethinyl estradiol to induce high levels of low-density lipoprotein receptors in hepatocytes. When these rats were given intravenous injections of low-density lipoprotein-colloidal gold complexes, most of the gold (labeled with /sup 195/Au) appeared to be taken up by Kupffer cells, as were complexes of colloidal gold with albumin or polyvinylpyrrolidone. However, when these rats were also administered gadolinium chloride, which blocks Kupffer cell activity, most of the low-density lipoprotein-gold (but not gold complexed with albumin or polyvinylpyrrolidone) was taken up into hepatocytes by receptor-mediated endocytosis and concentrated in peribiliary lysosomes, as determined by electron microscopy. Colloidal gold taken up as a complex with low-density lipoprotein was excreted into the feces via the common bile duct at a maximal rate of about 5% daily, 4 to 12 days after injection. Thereafter, the rate of gold excretion fell off until reaching a plateau after 3 weeks. At this late time, most of the colloidal gold was shown by electron microscopy to be in Kupffer cells, whereas earlier (6 days after injection) it was contained mainly in older hepatocytic lysosomes, identified by lipofuscin granules. It is concluded that, in rats, hepatocytic lysosomes empty most of their contents into bile every week or two, apparently by exocytosis.

  10. Human absorption of a supplement containing purified hydroxytyrosol, a natural antioxidant from olive oil, and evidence for its transient association with low-density lipoproteins

    Microsoft Academic Search

    Maria González-Santiago; Juristo Fonollá; Eduardo Lopez-Huertas

    2010-01-01

    There is growing interest in the health effects of olive oil polyphenols, particularly hydroxytyrosol (HT), for their potential application in the treatment of inflammatory conditions such as cardiovascular disease (CVD). As oxidative modification of low-density lipoproteins (LDL) plays a central role in the development of CVD, natural antioxidants are a main target for the nutraceutical industry. In this study we

  11. Novel mutations in ABCA1 gene in Japanese patients with Tangier disease and familial high density lipoprotein deficiency with coronary heart disease

    Microsoft Academic Search

    Wei Huang; Kengo Moriyama; Takafumi Koga; Han Hua; Masato Ageta; Seiro Kawabata; Koji Mawatari; Takuro Imamura; Tanenao Eto; Mitsunobu Kawamura; Tamio Teramoto; Jun Sasaki

    2001-01-01

    Mutations in the ATP-binding cassette transporter 1 (ABCA1) gene have been recently identified as the molecular defect in Tangier disease (TD) and familial high density lipoprotein deficiency (FHA). We here report novel mutations in the ABCA1 gene in two sisters from a Japanese family with TD who have been described previously (S. Ohtaki, H. Nakagawa, N. Kida, H. Nakamura, K.

  12. The Degradation of Platelet-Activating Factor in the Plasma of a Patient with Familial High Density Lipoprotein Deficiency (Tangier Disease)

    Microsoft Academic Search

    P. Haydn Pritchard; Arcadio Chonn; Chuck C. H. Yeung

    1985-01-01

    T ANGlER DISEASE is a rare autosomal recessive disor- der characterized by the virtual absence of high density lipoprotein (HDL) in the patients plasma and an accumula- tion of cholesteryl esters in a number of peripheral tissues.' The exact genetic defect in this disorder has not yet been fully elucidated. However, it has been proposed that a defect in the

  13. Macrophage plasma membrane chondroitin sulfate proteoglycan binds oxidized low-density lipoprotein.

    PubMed

    Kaplan, M; Aviram, M

    2000-03-01

    Lipoprotein interactions with macrophage proteoglycans (PGs) is believed to play an important role in the cellular uptake of lipoproteins and in macrophage cholesterol accumulation. Recently, we have shown the participation of macrophage plasma membrane glycosaminoglycans (GAGs) in the cellular uptake of oxidized LDL (Ox-LDL). The aim of the present study was to identify the specific cell surface proteoglycans involved in this interaction. J-774 A.1 macrophage-like cell line plasma membrane proteoglycans were isolated by anion exchange chromatography from cells that were prelabeled with [35S]sodium sulfate. Using Sepharose 6B chromatography, cell surface major proteoglycans were identified as chondroitin sulfate (CS) proteoglycans (77%) and heparan sulfate (HS) proteoglycans (23%). Binding rates of these 35S-labeled proteoglycans to Ox-LDL and to native LDL were analyzed by their ability to bind lipoproteins coupled to a CnBr-activated Sepharose CL-4B chromatography. Of the total labeled cell surface proteoglycans added to the column, 57% were bound to the Sepharose-coupled Ox-LDL, whereas 73% of the cell surface proteoglycans were bound to the Sepharose-coupled native LDL. Binding of the plasma membrane macrophage 35S-labeled proteoglycans to Ox-LDL was inhibited by adding increasing concentrations of non-labeled chondroitin sulfate, or by pretreatment of the 35S-labeled proteoglycans fraction with chondroitinase ABC. In contrast, neither the addition of non-labeled heparan sulfate, nor pretreatment of the labeled proteoglycans fraction with heparinase III, had any significant effect on proteoglycan binding to Ox-LDL. These findings were further supported by using mutant cells characterized by specific glycosaminoglycan deficiencies. Ox-LDL binding and degradation by mutant 745 CHO cells which are characterized by a deficiency in both heparan sulfate and chondroitin sulfate, was decreased by 28 and 27% respectively, compared to the binding of Ox-LDL to the wild-type CHO cells. Ox-LDL binding and degradation by mutant 677 CHO cells, which lack heparan sulfate but have increased levels of chondroitin sulfate, however, was found to be increased by 29 and 19%, respectively, compared to Ox-LDL binding to the wild-type CHO cells. Finally, analysis of the cell surface proteoglycans in macrophages that were subjected to oxidative stress, by their preincubation with angiotensin II, exhibited a 51-59% increase in their cell surface proteoglycan content, with a major effect on chondroitin sulfate proteoglycans. The present study thus demonstrated that Ox-LDL can specifically bind to macrophage surface chondroitin sulfate proteoglycans, and the macrophage content of this proteoglycan is increased under oxidative stress. The interaction between macrophage chondroitin sulfate proteoglycans and Ox-LDL can contribute to enhanced uptake of Ox-LDL with the formation of cholesterol-loaded foam cells, and accelerated atherosclerosis. PMID:10704609

  14. Uptake of zinc(II)-phthalocyanine by HepG2 cells expressing the low-density lipoprotein receptor: studies with the liposomal formulation CGP55847

    NASA Astrophysics Data System (ADS)

    Love, William G.; Havenaar, Ellen C.; Lowe, Philip J.; Taylor, Peter W.

    1994-03-01

    Hydrophobic photosensitizers readily intercalate into plasma lipoproteins. Some tumors acquire cholesterol from the circulation as a result of increased low density lipoprotein (LDL) receptor activity. Thus, circulating LDL may function as a vehicle for the delivery of bound Zn-Pc to cells within a tumor. Zn-Pc:LDL complexes, resulting from the interaction of LDL with the liposomal Zn-Pc formulation CGP55847, bind to the LDL receptor expressed on HepG2 cells but with reduced affinity in comparison to LDL. Confocal fluorescence microscopy facilitated the subcellular localization of Zn-Pc in microcolonies of HepG2 cells; the photosensitizer was distributed throughout the cellular membrane systems but was absent from the cell nucleus. Uptake of Zn-Pc in the presence of LDL was twofold greater than in the absence of the lipoprotein. These data suggest that the LDL uptake pathway may contribute to the localization of Zn-Pc in hyperproliferative tissue.

  15. Reduction in cholesterol and low density lipoprotein synthesis after portacaval shunt surgery in a patient with homozygous familial hypercholesterolemia.

    PubMed

    Bilheimer, D W; Goldstein, J L; Grundy, S M; Brown, M S

    1975-12-01

    The turnover of 125I-labeled low density lipoprotein (LDL) and the total body balance of cholestrol were studied in a 6-yr-old girl with the homozygous form of familial hypercholesterolemia (FH) before and after the surgical creation of an end-to-side portacaval shunt. The results were compared with those of similar studies simultaneously performed in untreated patients with the heterozygous form of FH and with the results of earlier studies performed on normolipidemic subjects. Before shunt surgery, the rate of synthesis of LDL in the FH homozygote (mg/kg per day) was fourfold higher than in normolipidemic subjects and twofold higher than in her heterozygous mother. The fractional catabolic rate for LDL in the homozygote was decreased to 33% of normal control values. The rate of cholesterol synthesis, estimated by chemical sterol balance, was higher in the FH homozygote than in two FH heterozygotes of similar age studied simultaneously. When considered in relation to the markedly elevated level of plasma cholesterol, the observed rate of cholesterol synthesis in the FH homozygote was inappropriately elevated. Bile acid production was normal in all three children. 5 mo after shunt surgery, the rate of LDL synthesis in the homozygote had declined by 48% as compared with the preoperative value, and this caused a 39% drop in the plasma LDL cholesterol level despite a 17% reduction in the fractional catabolic rate of the lipoprotein. The rate of cholesterol synthesis fell by 62% as compared with the preoperative value. The findings of an inappropriately elevated rate of production of both cholesterol and LDL as well as a reduced fractional catabolic rate for the lipoprotein in the untreated FH homozygote are consistent with results of studies in cultured fibroblasts indicating that the primary genetic defect in FH involves a deficiency in a cell-surface receptor for LDL that regulates both cholesterol synthesis and LDL degradation. Although the mechanism for the decline in production of cholesterol and LDL after portacaval shunt surgery is unknown, it was observed that these changes were associated with marked increases in the plasma concentrations of bile acids and glucagon. PMID:172531

  16. The effects of apolipoprotein F deficiency on high density lipoprotein cholesterol metabolism in mice.

    PubMed

    Lagor, William R; Fields, David W; Khetarpal, Sumeet A; Kumaravel, Arthi; Lin, Wen; Weintraub, Nathaniel; Wu, Kaijin; Hamm-Alvarez, Sarah F; Drazul-Schrader, Denise; de la Llera-Moya, Margarita; Rothblat, George H; Rader, Daniel J

    2012-01-01

    Apolipoprotein F (apoF) is 29 kilodalton secreted sialoglycoprotein that resides on the HDL and LDL fractions of human plasma. Human ApoF is also known as Lipid Transfer Inhibitor protein (LTIP) based on its ability to inhibit cholesteryl ester transfer protein (CETP)-mediated transfer events between lipoproteins. In contrast to other apolipoproteins, ApoF is predicted to lack strong amphipathic alpha helices and its true physiological function remains unknown. We previously showed that overexpression of Apolipoprotein F in mice reduced HDL cholesterol levels by 20-25% by accelerating clearance from the circulation. In order to investigate the effect of physiological levels of ApoF expression on HDL cholesterol metabolism, we generated ApoF deficient mice. Unexpectedly, deletion of ApoF had no substantial impact on plasma lipid concentrations, HDL size, lipid or protein composition. Sex-specific differences were observed in hepatic cholesterol content as well as serum cholesterol efflux capacity. Female ApoF KO mice had increased liver cholesteryl ester content relative to wild type controls on a chow diet (KO: 3.4+/-0.9 mg/dl vs. WT: 1.2+/-0.3 mg/dl, p<0.05). No differences were observed in ABCG1-mediated cholesterol efflux capacity in either sex. Interestingly, ApoB-depleted serum from male KO mice was less effective at promoting ABCA1-mediated cholesterol efflux from J774 macrophages relative to WT controls. PMID:22363685

  17. The Effects of Apolipoprotein F Deficiency on High Density Lipoprotein Cholesterol Metabolism in Mice

    PubMed Central

    Lagor, William R.; Fields, David W.; Khetarpal, Sumeet A.; Kumaravel, Arthi; Lin, Wen; Weintraub, Nathaniel; Wu, Kaijin; Hamm-Alvarez, Sarah F.; Drazul-Schrader, Denise; de la Llera-Moya, Margarita; Rothblat, George H.; Rader, Daniel J.

    2012-01-01

    Apolipoprotein F (apoF) is 29 kilodalton secreted sialoglycoprotein that resides on the HDL and LDL fractions of human plasma. Human ApoF is also known as Lipid Transfer Inhibitor protein (LTIP) based on its ability to inhibit cholesteryl ester transfer protein (CETP)-mediated transfer events between lipoproteins. In contrast to other apolipoproteins, ApoF is predicted to lack strong amphipathic alpha helices and its true physiological function remains unknown. We previously showed that overexpression of Apolipoprotein F in mice reduced HDL cholesterol levels by 20–25% by accelerating clearance from the circulation. In order to investigate the effect of physiological levels of ApoF expression on HDL cholesterol metabolism, we generated ApoF deficient mice. Unexpectedly, deletion of ApoF had no substantial impact on plasma lipid concentrations, HDL size, lipid or protein composition. Sex-specific differences were observed in hepatic cholesterol content as well as serum cholesterol efflux capacity. Female ApoF KO mice had increased liver cholesteryl ester content relative to wild type controls on a chow diet (KO: 3.4+/?0.9 mg/dl vs. WT: 1.2+/?0.3 mg/dl, p<0.05). No differences were observed in ABCG1-mediated cholesterol efflux capacity in either sex. Interestingly, ApoB-depleted serum from male KO mice was less effective at promoting ABCA1-mediated cholesterol efflux from J774 macrophages relative to WT controls. PMID:22363685

  18. Effect of low density lipoprotein receptor deficiency on the metabolism of apolipoprotein B-100 in blood plasma. Kinetic studies in normal and Watanabe heritable hyperlipidemic rabbits.

    PubMed Central

    Yamada, N; Shames, D M; Havel, R J

    1987-01-01

    The kinetics of apolipoprotein (apo) B-100 in particles containing apo E (B,E particles) or lacking apo E (B particles) were studied in Watanabe heritable hyperlipidemic (WHHL) rabbits deficient in low density lipoprotein (LDL) receptors, and compared with those of normal rabbits after injection of radioiodinated very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and LDL. In both groups results of kinetic modeling were consistent with the hypothesis that all apo B enters the plasma in VLDL, mainly as B,E particles, followed by delipidation and partial conversion to IDL and LDL, with concomitant conversion of some B,E particles to B particles. In WHHL rabbits, production of VLDL apo B was reduced by 40%, but LDL production was increased threefold. Defective removal of B,E and B particles in all three lipoprotein classes, coupled with preserved processes of delipidation, can account for the observed increases in the concentration of apo B (threefold in VLDL, fivefold in IDL, and twenty-twofold in LDL) in WHHL rabbits. PMID:3611356

  19. Human low density lipoprotein receptor fragment. Successful refolding of a functionally active ligand-binding domain produced in Escherichia coli.

    PubMed

    Simmons, T; Newhouse, Y M; Arnold, K S; Innerarity, T L; Weisgraber, K H

    1997-10-10

    The low density lipoprotein (LDL) receptor plays a key role in cholesterol homeostasis, mediating cellular uptake of lipoprotein particles by high affinity binding to its ligands, apolipoprotein (apo) B-100 and apoE. The ligand-binding domain of the LDL receptor contains 7 cysteine-rich repeats of approximately 40 amino acids; each repeat contains 6 cysteines, which form 3 intra-repeat disulfide bonds. As a first step toward determining the structure of the LDL receptor, both free and bound to its ligands, we produced in Escherichia coli a soluble fragment containing the ligand-binding domain (residues 1-292) as a thrombin-cleavable, heat-stable thioredoxin fusion. Modest amounts (5 mg/liter) of partially purified but inactive fragment were obtained after cell lysis, heat treatment, thrombin cleavage, and gel filtration under denaturing conditions. We were able to refold the receptor fragment to an active conformation with approximately 10% efficiency. The active fragment was isolated and purified with an LDL affinity column. The refolded receptor fragment was homogeneous, as determined by sodium dodecyl sulfate or non-denaturing polyacrylamide gel electrophoresis and isoelectric focusing. The purified fragment did not react with fluorescein-5-maleimide, indicating that all 42 cysteines were disulfide linked. In addition, the refolded fragment exhibited properties identical to those of the intact native receptor: Ca2+-dependent binding and isoform-dependent apoE binding (apoE2 binding <5% of apoE3). Furthermore, antibodies to the fragment recognized native receptors and inhibited the binding of 125I-LDL to fibroblast LDL receptors. We conclude that we have produced a properly folded and fully active receptor fragment that can be used for further structural studies. PMID:9325268

  20. Hepatic perfusate very low density lipoproteins obtained from fat-fed nonhuman primates stimulate cholesterol esterification in macrophages.

    PubMed

    Soltys, P A; Gump, H; Hennessy, L; Mazzone, T; Carey, K D; McGill, H C; Getz, G S; Bates, S R

    1988-02-01

    The livers of both baboons and rhesus monkeys fed a high fat, high cholesterol diet secreted very low density lipoproteins (VLDL) that were enriched in cholesteryl ester and apoe as compared to VLDL secreted by the livers of chow-fed animals. Stimulation of macrophage cholesterol esterification by the experimental VLDL was compared to that produced by the standard beta-VLDL obtained from the plasma of a rhesus monkey fed 25% coconut oil plus 2% cholesterol. This standard beta-VLDL stimulated 7- to 10-fold more esterification than did the bovine albumin control. Hepatic VLDL from fat-fed animals stimulated esterification in J774 macrophages 50 to 150% as well as did the standard beta-VLDL, even though hepatic VLDL did not display beta electrophoretic mobility on agarose gel electrophoresis. Plasma VLDL from lard-fed baboons did not exhibit beta electrophoretic mobility but did stimulate esterification in macrophages. Baboons were divided into high and low responders based on the change in plasma cholesterol levels in response to a high fat, high cholesterol diet. Both plasma and hepatic VLDL from high responders stimulated cholesterol esterification, whereas hepatic VLDL obtained from low responders or chow-fed baboons did not stimulate cholesterol esterification in macrophages. There was a strong positive correlation (r = 0.866) between the number of apoE molecules per VLDL particle in VLDL obtained from chow-fed, lard-fed, or coconut oil-fed primates and the rate of cholesterol esterification in macrophages. Our results show that hepatic perfusate VLDL obtained from fat- and cholesterol-fed primates have compositional and functional properties usually ascribed to circulating beta-VLDL, without displaying beta mobility, and indicate that the liver may be an important source of atherogenic lipoproteins. PMID:3367088