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Sample records for lipoprotein explain increased

  1. [Lipoproteins].

    PubMed

    Manso, C

    1991-02-01

    The problem of plasma lipid transport between several organs is reviewed. The constitution of plasma lipoproteins is described as well as the importance of enzymes related to them. The problem of lipid transfer proteins is discussed. The origin of atherosclerosis is analyzed in relation to abnormalities of cholesterol metabolism, of its transport and of free radicals generation. PMID:2059473

  2. Fine Mapping of Five Loci Associated with Low-Density Lipoprotein Cholesterol Detects Variants That Double the Explained Heritability

    PubMed Central

    Sidore, Carlo; Kang, Hyun M.; Jackson, Anne U.; Piras, Maria Grazia; Usala, Gianluca; Maninchedda, Giuseppe; Sassu, Alessandro; Serra, Fabrizio; Palmas, Maria Antonietta; Wood, William H.; Njølstad, Inger; Laakso, Markku; Hveem, Kristian; Tuomilehto, Jaakko; Lakka, Timo A.; Rauramaa, Rainer; Boehnke, Michael; Cucca, Francesco; Uda, Manuela; Schlessinger, David; Nagaraja, Ramaiah; Abecasis, Gonçalo R.

    2011-01-01

    Complex trait genome-wide association studies (GWAS) provide an efficient strategy for evaluating large numbers of common variants in large numbers of individuals and for identifying trait-associated variants. Nevertheless, GWAS often leave much of the trait heritability unexplained. We hypothesized that some of this unexplained heritability might be due to common and rare variants that reside in GWAS identified loci but lack appropriate proxies in modern genotyping arrays. To assess this hypothesis, we re-examined 7 genes (APOE, APOC1, APOC2, SORT1, LDLR, APOB, and PCSK9) in 5 loci associated with low-density lipoprotein cholesterol (LDL-C) in multiple GWAS. For each gene, we first catalogued genetic variation by re-sequencing 256 Sardinian individuals with extreme LDL-C values. Next, we genotyped variants identified by us and by the 1000 Genomes Project (totaling 3,277 SNPs) in 5,524 volunteers. We found that in one locus (PCSK9) the GWAS signal could be explained by a previously described low-frequency variant and that in three loci (PCSK9, APOE, and LDLR) there were additional variants independently associated with LDL-C, including a novel and rare LDLR variant that seems specific to Sardinians. Overall, this more detailed assessment of SNP variation in these loci increased estimates of the heritability of LDL-C accounted for by these genes from 3.1% to 6.5%. All association signals and the heritability estimates were successfully confirmed in a sample of ∼10,000 Finnish and Norwegian individuals. Our results thus suggest that focusing on variants accessible via GWAS can lead to clear underestimates of the trait heritability explained by a set of loci. Further, our results suggest that, as prelude to large-scale sequencing efforts, targeted re-sequencing efforts paired with large-scale genotyping will increase estimates of complex trait heritability explained by known loci. PMID:21829380

  3. High Density Lipoprotein Cholesterol Increasing Therapy: The Unmet Cardiovascular Need

    PubMed Central

    Cimmino, Giovanni; Ciccarelli, Giovanni; Morello, Alberto; Ciccarelli, Michele; Golino, Paolo

    2015-01-01

    Despite aggressive strategies are now available to reduce LDL-cholesterol, the risk of cardiovascular events in patients with coronary artery disease remains substantial. Several preclinical and clinical studies have shown that drug therapy ultimately leads to a regression of the angiographic lesions but also results in a reduction in cardiovascular events. The dramatic failure of clinical trials evaluating the cholesterol ester transfer protein (CEPT) inhibitors, torcetrapib and dalcetrapib, has led to considerable doubt about the value of the current strategy to raise high-density lipoprotein cholesterol (HDL-C) as a treatment for cardiovascular disease. These clinical results, as well as animal studies, have revealed the complexity of HDL metabolism, assessing a more important role of functional quality compared to circulating quantity of HDL. As a result, HDL-based therapeutic interventions that maintain or enhance HDL functionality, such as improving its main property, the reverse cholesterol transport, require closer investigation. In this review, we will discuss HDL metabolism and function, clinical-trial data available for HDL-raising agents, and potential strategies for future HDL-based therapies. PMID:26535185

  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. A rapid increase in lipoprotein (a) levels after ethanol withdrawal in alcoholic men

    SciTech Connect

    Kervinen, K.; Savolainen, J.J.; Kesaeniemi, Y.A. )

    1991-01-01

    Plasma concentrations of lipoprotein (a) (Lp(a)) were studied in 11 male alcoholics at the end of a drinking period and monitored during subsequent abstinence. Lp(a) levels showed a daily increase for four consecutive days after the beginning of abstinence, the values for the third and the fourth day being significantly higher than those of the first day. The changes in Lp(a) showed no association with the changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels. In one alcoholic subject with a heterozygous form of familial hypercholesterolemia who was monitored for 11 days, the Lp(a) levels rose up to the fourth day and remained at a high level thereafter. These results suggest that ethanol ingestion may be associated with a lower of Lp(a) levels, which may contribute to the delayed progression of atherosclerosis observed in alcohol drinkers.

  6. Multiple associated variants increase the heritability explained for plasma lipids and coronary artery disease

    PubMed Central

    Tada, Hayato; Won, Hong-Hee; Melander, Olle; Yang, Jian; Peloso, Gina M; Kathiresan, Sekar

    2015-01-01

    Background Plasma lipid levels as well as coronary artery disease (CAD) have been shown to be highly heritable with estimates ranging from 40%–60%. However, top variants detected by large-scale genome-wide association studies (GWAS) explain only a fraction of the total variance in plasma lipid phenotypes and CAD. Methods and Results We performed a conditional and joint association analysis using summary-level statistics from two large GWAS meta-analyses: (1) the Global Lipids Genetics Consortium (GLGC) study, and (2) the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAM) study. There were 100,184 individuals from 46 GLGC studies for plasma lipids, and 22,233 cases and 64,762 controls from 14 studies for CAD. We detected a number of loci where multiple independent SNPs were associated with lipid traits within a locus (12 out of 33 loci for high-density lipoprotein cholesterol [HDL-C], 10 of 35 loci for low-density lipoprotein cholesterol [LDL-C], 13 of 44 loci for total cholesterol [TC], and 8 of 28 loci for triglycerides [TG]), reaching genome-wide significance (P<5×10−8), nearly doubling the heritability explained by GWAS (3.6% to 7.6% for HDL-C, 5.0% to 8.8% for LDL-C, 5.5% to 8.8% for TC, and 5.7% to 8.5% for TG). Multiple SNPs were also associated with CAD (3 of 15 loci, 9.6% to 11.4% of increased heritability). Conclusion These results demonstrate that a portion of the missing heritability for lipid traits and CAD can be explained by multiple variants at each locus. PMID:25170055

  7. Increases in plasma pool size of lipoprotein components in copper-deficient hamsters

    SciTech Connect

    Al-Othman, A.A.; Rosenstein, F.; Lei, K.Y. )

    1991-03-15

    Twenty-four male Golden Syrian hamsters, were randomly assigned to 2 dietary copper (Cu) treatments; deficient and adequate. Reductions in weight gain, hematocrit and liver Cu as well as increases in heart weight and plasma volume were observed in CD hamsters after 7 weeks of treatment. Plasma very low (VLDL), low (LDL) and high (HDL) density lipoproteins were isolated by ultracentrifugation and Sepharose column chromatography. The percentage of total plasma cholesterol carried by LDL was increased from 20 to 24% but was reduced from 71 to 68% for HDL as a result of Cu deficiency. In LDL the % composition of triglycerides (TG) and phospholipids (PL) was increased by 25% but that of cholesterol was reduced by 13%. The % composition of protein was reduced 24% but that of TG was increased 18% in VLDL by Cu deficiency. Since plasma volume was increased 50% in CD hamsters, the data were expressed as the amount present in the plasma pool corrected for body weight. With the exceptions of smaller increased in VLDL protein and PL as well as the more than threefold increases in LDL TG and PL plasma pool size, the pool size for the rest of the lipoprotein components were increased about twofold in CD hamsters. The lipoprotein data further indicate that Cu deficiency increased the particle number of VLDL, LDL and HDL but enlarged the size of only VLDL and LDL.

  8. Increased production of apolipoprotein B and its lipoproteins by oleic acid in Caco-2 cells.

    PubMed

    Dashti, N; Smith, E A; Alaupovic, P

    1990-01-01

    The production of lipids, apolipoproteins (apo), and lipoproteins induced by oleic acid has been examined in Caco-2 cells. The rates of accumulation in the control medium of 15-day-old Caco-2 cells of triglycerides, unesterified cholesterol, and cholesteryl esters were 102 +/- 8, 73 +/- 5, and 11 +/- 1 ng/mg cell protein/h, respectively; the accumulation rates for apolipoproteins A-I, B, C-III, and E were 111 +/- 9, 53 +/- 4, 13 +/- 1, and 63 +/- 4 ng/mg cell protein/h, respectively. Whereas apolipoproteins A-IV and C-II were detected by immunoblotting, apoA-II was absent in most culture media. In contrast to an early production of apolipoproteins A-I and E occurring 2 days after plating, the apoB expression appeared to be differentiation-dependent and was not measurable in the medium until the sixth day post-confluency. In the control medium, very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL), and lipid-poor very high density lipoproteins (VHDL) accounted for 12%, 46%, 18%, and 24% of the total lipid and apolipoprotein contents, respectively. The triglyceride-rich VLDL contained mainly apoE (75%) and apoB (23%), while the protein moiety of LDL was composed of apoB (59%), apoE (20%), apoA-I (15%), and apoC-III (6%). The cholesterol-rich HDL contained mainly apoA-I (69%) and apoE (27%). In the control medium, major portions of apolipoproteins B and C-III (93-97%) were present in LDL, whereas the main parts of apoA-I (92%) and apoE (76%) were associated with HDL and VHDL. Oleate increased the production of triglycerides 10-fold, cholesteryl esters 7-fold, and apoB 2- to 4-fold. There was also a moderate increase (39%) in the production of apoC-III but no significant changes in those of apolipoproteins A-I and E. These increases were reflected mainly in a 55-fold elevation in the concentration of VLDL, and a 2-fold increase in the level of LDL; there were no significant changes in HDL and VHDL. VLDL contained the

  9. Inhibitors of cholesterol biosynthesis increase hepatic low-density lipoprotein receptor protein degradation.

    PubMed

    Ness, G C; Zhao, Z; Lopez, D

    1996-01-15

    Inhibitors of cholesterol biosynthesis are believed to lower serum cholesterol levels by enhancing the removal of serum low-density lipoprotein (LDL) by increasing hepatic LDL receptor function. Thus, the effects of several different inhibitors of cholesterol biosynthesis were examined for their effects on the expression of the hepatic LDL receptor in rats. We found that administration of inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase such as lovastatin, pravastatin, fluvastatin, and rivastatin resulted in increased hepatic LDL receptor mRNA levels. Surprisingly, these agents failed to increase levels of immunoreactive LDL receptor protein in rat liver even when the dose and length of treatment were increased. Treatment of rats with zaragozic acid A, an inhibitor of squalene synthase, caused even greater increases in hepatic LDL receptor mRNA levels, but did not increase levels of immunoreactive protein. Further investigation revealed that the rate of degradation of the hepatic LDL receptor was increased in rats given inhibitors of cholesterol biosynthesis. The greatest increase in the rate of degradation was seen in animals treated with zaragozic acid A which caused the largest increase in hepatic LDL receptor mRNA levels. In contrast, hepatic LDL receptor protein was stabilized in cholesterol-fed rats. It appears that increased potential for LDL receptor protein synthesis, reflected in increased mRNA levels, is offset by a corresponding increase in the rate of receptor protein degradation resulting in constant steady-state levels of hepatic LDL receptor protein. These findings are suggestive of increased cycling of the hepatic LDL receptor. This postulated mechanism can provide for enhanced hepatic uptake of lipoproteins without increasing steady-state levels of LDL receptor protein. PMID:8561503

  10. Down-regulation of lipoprotein lipase increases glucose uptake in L6 muscle cells

    SciTech Connect

    Lopez, Veronica; Saraff, Kumuda; Medh, Jheem D.

    2009-11-06

    Thiazolidinediones (TZDs) are synthetic hypoglycemic agents used to treat type 2 diabetes. TZDs target the peroxisome proliferator activated receptor-gamma (PPAR-{gamma}) and improve systemic insulin sensitivity. The contributions of specific tissues to TZD action, or the downstream effects of PPAR-{gamma} activation, are not very clear. We have used a rat skeletal muscle cell line (L6 cells) to demonstrate that TZDs directly target PPAR-{gamma} in muscle cells. TZD treatment resulted in a significant repression of lipoprotein lipase (LPL) expression in L6 cells. This repression correlated with an increase in glucose uptake. Down-regulation of LPL message and protein levels using siRNA resulted in a similar increase in insulin-dependent glucose uptake. Thus, LPL down-regulation improved insulin sensitivity independent of TZDs. This finding provides a novel method for the management of insulin resistance.

  11. Angiotensin II Reduces Lipoprotein Lipase Expression in Visceral Adipose Tissue via Phospholipase C β4 Depending on Feeding but Increases Lipoprotein Lipase Expression in Subcutaneous Adipose Tissue via c-Src.

    PubMed

    Uchiyama, Tsuyoshi; Tomono, Shoichi; Sato, Koichi; Nakamura, Tetsuya; Kurabayashi, Masahiko; Okajima, Fumikazu

    2015-01-01

    Metabolic syndrome is characterized by visceral adiposity, insulin resistance, high triglyceride (TG)- and low high-density lipoprotein cholesterol-levels, hypertension, and diabetes-all of which often cause cardiovascular and cerebrovascular diseases. It remains unclear, however, why visceral adiposity but not subcutaneous adiposity causes insulin resistance and other pathological situations. Lipoprotein lipase (LPL) catalyzes hydrolysis of TG in plasma lipoproteins. In the present study, we investigated whether the effects of angiotensin II (AngII) on TG metabolism are mediated through an effect on LPL expression. Adipose tissues were divided into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) for comparison. AngII accelerated LPL expression in SAT but, on the contrary, suppressed its expression in VAT. In both SAT and VAT, AngII signaled through the same type 1 receptor. In SAT, AngII increased LPL expression via c-Src and p38 MAPK signaling. In VAT, however, AngII reduced LPL expression via the Gq class of G proteins and the subsequent phospholipase C β4 (PLCβ4), protein kinase C β1, nuclear factor κB, and inducible nitric oxide synthase signaling pathways. PLCβ4 small interfering RNA experiments showed that PLCβ4 expression is important for the AngII-induced LPL reduction in VAT, in which PLCβ4 expression increases in the evening and falls at night. Interestingly, PLCβ4 expression in VAT decreased with fasting, while AngII did not decrease LPL expression in VAT in a fasting state. In conclusion, AngII reduces LPL expression through PLCβ4, the expression of which is regulated by feeding in VAT, whereas AngII increases LPL expression in SAT. The different effects of AngII on LPL expression and, hence, TG metabolism in VAT and SAT may partly explain their different contributions to the development of metabolic syndrome. PMID:26447765

  12. Angiotensin II Reduces Lipoprotein Lipase Expression in Visceral Adipose Tissue via Phospholipase C β4 Depending on Feeding but Increases Lipoprotein Lipase Expression in Subcutaneous Adipose Tissue via c-Src

    PubMed Central

    Uchiyama, Tsuyoshi; Tomono, Shoichi; Sato, Koichi; Nakamura, Tetsuya; Kurabayashi, Masahiko; Okajima, Fumikazu

    2015-01-01

    Metabolic syndrome is characterized by visceral adiposity, insulin resistance, high triglyceride (TG)- and low high-density lipoprotein cholesterol-levels, hypertension, and diabetes—all of which often cause cardiovascular and cerebrovascular diseases. It remains unclear, however, why visceral adiposity but not subcutaneous adiposity causes insulin resistance and other pathological situations. Lipoprotein lipase (LPL) catalyzes hydrolysis of TG in plasma lipoproteins. In the present study, we investigated whether the effects of angiotensin II (AngII) on TG metabolism are mediated through an effect on LPL expression. Adipose tissues were divided into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) for comparison. AngII accelerated LPL expression in SAT but, on the contrary, suppressed its expression in VAT. In both SAT and VAT, AngII signaled through the same type 1 receptor. In SAT, AngII increased LPL expression via c-Src and p38 MAPK signaling. In VAT, however, AngII reduced LPL expression via the Gq class of G proteins and the subsequent phospholipase C β4 (PLCβ4), protein kinase C β1, nuclear factor κB, and inducible nitric oxide synthase signaling pathways. PLCβ4 small interfering RNA experiments showed that PLCβ4 expression is important for the AngII-induced LPL reduction in VAT, in which PLCβ4 expression increases in the evening and falls at night. Interestingly, PLCβ4 expression in VAT decreased with fasting, while AngII did not decrease LPL expression in VAT in a fasting state. In conclusion, AngII reduces LPL expression through PLCβ4, the expression of which is regulated by feeding in VAT, whereas AngII increases LPL expression in SAT. The different effects of AngII on LPL expression and, hence, TG metabolism in VAT and SAT may partly explain their different contributions to the development of metabolic syndrome. PMID:26447765

  13. Increased Small Dense LDL and Intermediate-Density Lipoprotein With Albuminuria in Type 1 Diabetes

    PubMed Central

    Sibley, Shalamar D.; Hokanson, John E.; Steffes, Michael W.; Purnell, Jonathan Q; Marcovina, Santica M.; Cleary, Patricia A.; Brunzell, John D.

    2009-01-01

    OBJECTIVE This population study examines the relationship between LDL density and persistent albuminuria in subjects with type 1 diabetes at the end of the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS Subjects were classified as persistently normoalbuminuric (albumin excretion rate [AER] <30 mg/d, n = 1,056), microalbuminuric (AER ≥30–299 mg/day, n = 80), and macroalbuminuric (AER = 300 mg/day, n = 24) based on the last two AER measures. RESULTS Triglyceride (P <0.01) and LDL cholesterol (P <0.01) levels were higher in macroalbuminuric subjects compared with normoalbuminuric subjects. Cholesterol distribution by density-gradient ultracentrifugation showed an increase in intermediate-density lipoprotein (IDL) and a shift in peak LDL from buoyant toward more dense particles with progressive albuminuria. In the entire group, there was a significant negative correlation between the peak buoyancy of LDL particles and albuminuria (r = −0.238, P <0.001, n = 1,160). This correlation persisted in the normoalbuminuric DCCT group (r = −0.138, P<0.001, n = 1,056). CONCLUSIONS As albuminuria increases in subjects with type 1 diabetes, dyslipidemia occurs with an increase in IDL and dense LDL that may lead to increased cardiovascular disease. PMID:10388983

  14. Down-regulation of lipoprotein lipase increases ABCA1-mediated cholesterol efflux in THP-1 macrophages.

    PubMed

    Kawashima, Ryoko L; Medh, Jheem D

    2014-08-01

    The ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of excess cholesterol from foam cells to lipid-poor apolipoprotein A-I, in a process called reverse cholesterol transport. Lipoprotein lipase (LPL) is a lipolytic enzyme expressed by macrophages within atherosclerotic lesions. Lentivirus-mediated RNA interference was used to genetically knock-down (KD) the expression of LPL in THP-1 macrophages. Silencing of the LPL gene was confirmed by end-point PCR, real time PCR, and protein analysis. Suppression of LPL expression correlated with a 1.6-fold up-regulation of ABCA1 mRNA levels, and resulted in a 4.5-fold increase in ABCA1-dependent cholesterol efflux. Replenishing LPL by addition of purified bovine LPL to the cell culture media resulted in down-regulation of ABCA1-mediated cholesterol efflux in both wild-type and LPL knockdown cells. These findings suggest an inverse correlation between macrophage LPL levels and ABCA1 cholesterol transport activity. PMID:25017912

  15. Electronegative Low-density Lipoprotein Increases Coronary Artery Disease Risk in Uremia Patients on Maintenance Hemodialysis.

    PubMed

    Chang, Chiz-Tzung; Wang, Guei-Jane; Kuo, Chin-Chi; Hsieh, Ju-Yi; Lee, An-Sean; Chang, Chia-Ming; Wang, Chun-Cheng; Shen, Ming-Yi; Huang, Chiu-Ching; Sawamura, Tatsuya; Yang, Chao-Yuh; Stancel, Nicole; Chen, Chu-Huang

    2016-01-01

    Electronegative low-density lipoprotein (LDL) is a recognized factor in the pathogenesis of coronary artery disease (CAD) in the general population, but its role in the development of CAD in uremia patients is unknown. L5 is the most electronegative subfraction of LDL isolated from human plasma. In this study, we examined the distribution of L5 (L5%) and its association with CAD risk in uremia patients.The LDL of 39 uremia patients on maintenance hemodialysis and 21 healthy controls was separated into 5 subfractions, L1-L5, with increasing electronegativity. We compared the distribution and composition of plasma L5 between uremia patients and controls, examined the association between plasma L5% and CAD risk in uremia patients, and studied the effects of L5 from uremia patients on endothelial function.Compared to controls, uremia patients had significantly increased L5% (P < 0.001) and L5 that was rich in apolipoprotein C3 and triglycerides. L5% was significantly higher in uremia patients with CAD (n = 10) than in those without CAD (n = 29) (P < 0.05). Independent of other major CAD risk factors, the adjusted odds ratio for CAD was 1.88 per percent increase in plasma L5% (95% CI, 1.01-3.53), with a near-linear dose-response relationship. Compared with controls, uremia patients had decreased flow-mediated vascular dilatation. In ex vivo studies with preconstricted rat thoracic aortic rings, L5 from uremia patients inhibited acetylcholine-induced relaxation. In cultured human endothelial cells, L5 inhibited endothelial nitric oxide synthase activation and induced endothelial dysfunction.Our findings suggest that elevated plasma L5% may induce endothelial dysfunction and play an important role in the increased risk of CAD in uremia patients. PMID:26765403

  16. Electronegative Low-density Lipoprotein Increases Coronary Artery Disease Risk in Uremia Patients on Maintenance Hemodialysis

    PubMed Central

    Chang, Chiz-Tzung; Wang, Guei-Jane; Kuo, Chin-Chi; Hsieh, Ju-Yi; Lee, An-Sean; Chang, Chia-Ming; Wang, Chun-Cheng; Shen, Ming-Yi; Huang, Chiu-Ching; Sawamura, Tatsuya; Yang, Chao-Yuh; Stancel, Nicole; Chen, Chu-Huang

    2016-01-01

    Abstract Electronegative low-density lipoprotein (LDL) is a recognized factor in the pathogenesis of coronary artery disease (CAD) in the general population, but its role in the development of CAD in uremia patients is unknown. L5 is the most electronegative subfraction of LDL isolated from human plasma. In this study, we examined the distribution of L5 (L5%) and its association with CAD risk in uremia patients. The LDL of 39 uremia patients on maintenance hemodialysis and 21 healthy controls was separated into 5 subfractions, L1–L5, with increasing electronegativity. We compared the distribution and composition of plasma L5 between uremia patients and controls, examined the association between plasma L5% and CAD risk in uremia patients, and studied the effects of L5 from uremia patients on endothelial function. Compared to controls, uremia patients had significantly increased L5% (P < 0.001) and L5 that was rich in apolipoprotein C3 and triglycerides. L5% was significantly higher in uremia patients with CAD (n = 10) than in those without CAD (n = 29) (P < 0.05). Independent of other major CAD risk factors, the adjusted odds ratio for CAD was 1.88 per percent increase in plasma L5% (95% CI, 1.01–3.53), with a near-linear dose–response relationship. Compared with controls, uremia patients had decreased flow-mediated vascular dilatation. In ex vivo studies with preconstricted rat thoracic aortic rings, L5 from uremia patients inhibited acetylcholine-induced relaxation. In cultured human endothelial cells, L5 inhibited endothelial nitric oxide synthase activation and induced endothelial dysfunction. Our findings suggest that elevated plasma L5% may induce endothelial dysfunction and play an important role in the increased risk of CAD in uremia patients. PMID:26765403

  17. [THE EFFECT OF SATINS: ACTIVATION OF LIPOLYSIS AND ABSORPTION BY INSULIN-DEPENDED CELLS LIPOPROTEINS OF VERY LOW DENSITY, INCREASING OF BIO-AVAILABILITY OF POLYENOIC FATTY ACIDS AND DECREASING OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY].

    PubMed

    Titov, V N; Malyshev, P P; Amelyushkina, V A; Aripovsky, A V; Smirnov, G P; Polevaya, T Yu; Kabo, S I; Kukhartchuk, V V

    2015-10-01

    The Russian cardiologic R&D production complex of Minzdrav of Russia, 121552 Moscow, Russia The statins are synthetic xenobiotics alien to animal cells. They are unlikely capable to manifest pleiotropic effect. It is feasible to evaluate effect of statins by stages: a) initially a specific inhibition of synthesis of cholesterol alcohol; b) further indirect activation of hydrolysis of triglycerides in lipoproteins of very low density; c) nonspecific activation of cells' receptor absorption of palmitic and oleic lipoproteins of very low density and then d) linoleic and linolenic lipoproteins of low density with all polyenoic fatty acids. On balance, statins activate absorption ofpolyenoic fatty acids by cells. Just they manifest physiological, specific pleiotropic effect. The statins inhibit synthesis of pool of cholesterol alcohol-lipoproteins of very low density condensed between phosphatidylcholines in polar mono-layer phosphatidylcholines+cholesterol alcohol on surface oftriglycerides. The low permeability of mono-layer separates substrate-triglycerides in lipoproteins of very low density and post-heparin lipoprotein lipase in hydrophilic blood plasma. The higher is ratio cholesterol alcohol/phosphatidylcholines in mono-layer of lipoproteins of very low density the slower is lipolysis, formation of ligand lipoproteins of very low density and their absorption by cells under apoB-100-endocytosis. The statins normalize hyperlipemia by force of a) activation of absorption oflipoproteins of very low density by insulin-depended cells and b) activation of absorption of lipoproteins of low density by all cells, increasing of bio-availability of polyenoic fatty acids, activation of apoB-100-endocytosis. The limitation in food of content of palmitic saturated fatty acid and increasing of content of ω-3 polyenoic fatty acids improve "bio-availability" of polyenoic fatty acids and their absorption by cells and also decreases cholesterol alcohol/phosphatidylcholines and

  18. Increased Free Cholesterol in Plasma Low and Very Low Density Lipoproteins in Non-Insulin-Dependent Diabetes Mellitus: Its Role in the Inhibition of Cholesteryl Ester Transfer

    NASA Astrophysics Data System (ADS)

    Fielding, Christopher J.; Reaven, Gerald M.; Liu, George; Fielding, Phoebe E.

    1984-04-01

    Recombination of low and very low density lipoproteins (VLDL and LDL) from normal subjects with plasma from patients with non-insulin-dependent diabetes mellitus significantly increased the reduced rate of transfer of cholesteryl ester to these lipoproteins, which is characteristic of diabetic plasma, whereas diabetic VLDL and LDL reduced cholesteryl ester transfer rates in normal plasma. VLDL and LDL from diabetic plasma had an increased ratio of free cholesterol to phospholipid compared to normal, and unlike normal VLDL and LDL spontaneously lost free cholesterol to high density lipoprotein. These data suggest that the block to cholesteryl ester transfer to these lipoproteins in non-insulin-dependent diabetes is mediated by their increased free cholesterol content and may be related to the increased risk of these patients for developing atherosclerosis.

  19. Streptococcal serum opacity factor increases the rate of hepatocyte uptake of human plasma high-density lipoprotein cholesterol.

    PubMed

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

    2010-11-16

    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 ∼400000 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. The uptake of [(3)H]CE by HepG2 and Huh7 cells from HDL after SOF treatment, which transfers >90% of HDL-CE to CERM, was 2.4 and 4.5 times faster, respectively, than from control HDL. CERM-[(3)H]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-[(3)H]CE uptake by both receptors. RAP and heparin inhibit CERM-[(3)H]CE but not HDL-[(3)H]CE uptake, thereby implicating LRP-1 and cell surface proteoglycans in this process. These data demonstrate that SOF treatment of HDL increases the rate of CE uptake via multiple hepatic apo E receptors. In so doing, SOF might increase the level of hepatic disposal of plasma cholesterol in a way that is therapeutically useful. PMID:20879789

  20. Antagonism of Secreted PCSK9 Increases Low Density Lipoprotein Receptor Expression in HepG2 Cells

    SciTech Connect

    McNutt, Markey C.; Kwon, Hyock Joo; Chen, Chiyuan; Chen, Justin R.; Horton, Jay D.; Lagace, Thomas A.

    2009-07-10

    PCSK9 is a secreted protein that degrades low density lipoprotein receptors (LDLRs) in liver by binding to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR. It is not known whether PCSK9 causes degradation of LDLRs within the secretory pathway or following secretion and reuptake via endocytosis. Here we show that a mutation in the LDLR EGF-A domain associated with familial hypercholesterolemia, H306Y, results in increased sensitivity to exogenous PCSK9-mediated cellular degradation because of enhanced PCSK9 binding affinity. The crystal structure of the PCSK9-EGF-A(H306Y) complex shows that Tyr-306 forms a hydrogen bond with Asp-374 in PCSK9 at neutral pH, which strengthens the interaction with PCSK9. To block secreted PCSK9 activity, LDLR (H306Y) subfragments were added to the medium of HepG2 cells stably overexpressing wild-type PCSK9 or gain-of-function PCSK9 mutants associated with hypercholesterolemia (D374Y or S127R). These subfragments blocked secreted PCSK9 binding to cell surface LDLRs and resulted in the recovery of LDLR levels to those of control cells. We conclude that PCSK9 acts primarily as a secreted factor to cause LDLR degradation. These studies support the concept that pharmacological inhibition of the PCSK9-LDLR interaction extracellularly will increase hepatic LDLR expression and lower plasma low density lipoprotein levels.

  1. Increased J774 macrophage cytotoxicity of late postprandial triglyceride-rich lipoproteins from normolipidemic young men expressing an apolipoprotein epsilon 4 allele.

    PubMed

    Ragogna, F; Angeli, A; Corazza, S; Tettamanti, C; Faggiotto, A; Grassi, A; Ruotolo, G

    1997-07-25

    It has been demonstrated that normolipidemic young men with apolipoprotein E4/3 phenotype have a prolonged postprandial clearance of triglyceride-rich lipoproteins following a high-fat diet. In the present study, we isolated fasting and postprandial (3 and 8 h) lipoprotein fraction from normolipidemic young men with E3/3 and E4/3 phenotypes and examined the in vitro cytotoxicity of these lipoproteins towards J774 macrophages. 8 h E4/3 very low density lipoprotein (VLDL) were significantly more cytotoxic than either 8 h E3/3 VLDL or fasting and 3 h E4/3 VLDL (lactate dehydrogenase (LDH) released: 161 +/- 21, 107 +/- 9, 88 +/- 16 and 101 +/- 12 I.U./l, respectively). Fasting E4/3 intermediate density lipoprotein (IDL) were also significantly more cytotoxic than either fasting E3/3 IDL or 3 h and 8 h E4/3 IDL (LDH released: 105 +/- 23, 60 +/- 9, 37 +/- 5 and 53 +/- 16 I.U./l, respectively), whereas either fasting or postprandial low density lipoprotein (LDL) and high density lipoprotein (HDL) samples did not show any difference in cytotoxicity between the two groups studied. 8 h E4/3 VLDL samples incubated with J774 macrophages had a lower esterified cholesterol (40 +/- 3 versus 52 +/- 3 micrograms), and higher triglyceride (783 +/- 133 versus 418 +/- 64 micrograms) and free fatty acid (FFA) (2.0 +/- 0.4 versus 0.9 +/- 0.1 microgram) content than fasting E4/3 VLDL. The increased macrophage cytotoxicity of late postprandial triglyceride-rich lipoproteins seems to be related to the FFA content of E4/3 VLDL. PMID:9242961

  2. Uptake and Trafficking of Mildly Oxidized LDL and Acetylated LDL in THP-1 Cells Does Not Explain the Differences in Lysosomal Metabolism of These Two Lipoproteins

    NASA Astrophysics Data System (ADS)

    Yancey, Patricia G.; Miles, Stacia; Schwegel, Jennifer; Gray Jerome, W.

    2002-04-01

    Foam cells in the atherosclerotic lesion have substantial cholesterol stores within large, swollen lysosomes. This feature is mimicked by incubating THP-1 macrophages with mildly oxidized low density lipoprotein (LDL). Incubation of THP-1 cells with acetylated LDL produces cytoplasmic cholesteryl ester accumulation rather than lysosomal storage. The differences could be due to differences in uptake and delivery of lipoprotein to lysosomes or to lysosomal and post-lysosomal processing events. We compared uptake and lysosomal trafficking of acetylated and oxidized LDL using colloidal gold-labeled lipoproteins. Labeling did not alter cellular cholesterol accumulation. We found that uptake and delivery to lysosomes are not different for acetylated and oxidized LDL. In fact, both oxidized and acetylated LDL can be delivered to the same lysosomes. Sequential incubation with oxidized LDL followed by acetylated LDL showed that the lipid-engorged lysosomes are long-lived structures, continuously accepting newly ingested lipoprotein. Comparison of acetylated and oxidized LDL in mouse peritoneal macrophages, a cell which does not accumulate substantial lysosomal lipid, also revealed no differences in uptake. This indicates that in THP-1 cells, the differences in metabolism of oxidized and acetylated LDL are due to cell-specific lysosomal or post-lysosomal events not present in B6C3F1 mouse macrophages.

  3. Lipoprotein metabolism indicators improve cardiovascular risk prediction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Cardiovascular disease risk increases when lipoprotein metabolism is dysfunctional. We have developed a computational model able to derive indicators of lipoprotein production, lipolysis, and uptake processes from a single lipoprotein profile measurement. This is the first study to inves...

  4. Lipoproteins and lipoprotein metabolism in periodontal disease

    PubMed Central

    Griffiths, Rachel; Barbour, Suzanne

    2010-01-01

    A growing body of evidence indicates that the incidence of atherosclerosis is increased in subjects with periodontitis – a chronic infection of the oral cavity. This article summarizes the evidence that suggests periodontitis shifts the lipoprotein profile to be more proatherogenic. LDL-C is elevated in periodontitis and most studies indicate that triglyceride levels are also increased. By contrast, antiatherogenic HDL tends to be low in periodontitis. Periodontal therapy tends to shift lipoprotein levels to a healthier profile and also reduces subclinical indices of atherosclerosis. In summary, periodontal disease alters lipoprotein metabolism in ways that could promote atherosclerosis and cardiovascular disease. PMID:20835400

  5. Explaining the Increase in Publication Productivity among Academic Staff: A Generational Perspective

    ERIC Educational Resources Information Center

    Kyvik, Svein; Aksnes, Dag W.

    2015-01-01

    In Norwegian research universities, a large individual increase has taken place in scientific and scholarly publishing over the last 30 years. The purpose of this article is to explain the reasons for this growth in a generational perspective. We put forward six hypotheses that can be illuminated by cross-sectional data drawn from five surveys to…

  6. Maternal High-Fat Feeding Increases Placental Lipoprotein Lipase Activity by Reducing SIRT1 Expression in Mice.

    PubMed

    Qiao, Liping; Guo, Zhuyu; Bosco, Chris; Guidotti, Stefano; Wang, Yunfeng; Wang, Mingyong; Parast, Mana; Schaack, Jerome; Hay, William W; Moore, Thomas R; Shao, Jianhua

    2015-09-01

    This study investigated how maternal overnutrition and obesity regulate expression and activation of proteins that facilitate lipid transport in the placenta. To create a maternal overnutrition and obesity model, primiparous C57BL/6 mice were fed a high-fat (HF) diet throughout gestation. Fetuses from HF-fed dams had significantly increased serum levels of free fatty acid and body fat. Despite no significant difference in placental weight, lipoprotein lipase (LPL) protein levels and activity were remarkably elevated in placentas from HF-fed dams. Increased triglyceride content and mRNA levels of CD36, VLDLr, FABP3, FABPpm, and GPAT2 and -3 were also found in placentas from HF-fed dams. Although both peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α protein levels were significantly increased in placentas of the HF group, only PPARγ exhibited a stimulative effect on LPL expression in cultured JEG-3 human trophoblasts. Maternal HF feeding remarkably decreased SIRT1 expression in placentas. Through use of an SIRT1 activator and inhibitor and cultured trophoblasts, an inhibitory effect of SIRT1 on LPL expression was demonstrated. We also found that SIRT1 suppresses PPARγ expression in trophoblasts. Most importantly, inhibition of PPARγ abolished the SIRT1-mediated regulatory effect on LPL expression. Together, these results indicate that maternal overnutrition induces LPL expression in trophoblasts by reducing the inhibitory effect of SIRT1 on PPARγ. PMID:25948680

  7. Activation of intestinal peroxisome proliferator-activated receptor-α increases high-density lipoprotein production

    PubMed Central

    Colin, Sophie; Briand, Olivier; Touche, Véronique; Wouters, Kristiaan; Baron, Morgane; Pattou, François; Hanf, Rémy; Tailleux, Anne; Chinetti, Giulia; Staels, Bart; Lestavel, Sophie

    2013-01-01

    Aims Peroxisome Proliferator-Activated Receptor (PPAR) α is a transcription factor controlling lipid metabolism in liver, heart, muscle and macrophages. PPARα-activation increases plasma HDL-cholesterol and exerts hypotriglyceridemic actions via the liver. However, the intestine expresses PPARα, produces HDL and chylomicrons and is exposed to diet-derived PPARα ligands. Therefore, we examined the effects of PPARα-activation on intestinal lipid and lipoprotein metabolism. Methods and Results The impact of PPARα-activation was evaluated in term of HDL-related gene expression in mice, ex-vivo in human jejunal biopsies and in Caco-2/TC7 cells. ApoAI/HDL secretion, cholesterol esterification and trafficking were also studied in-vitro. In parallel to improving plasma lipid profiles and increasing liver and intestinal expression of fatty-acid-oxidation genes, treatment with the dual PPARα/δ-ligand GFT505 resulted in a more pronounced increase of plasma HDL compared to fenofibrate in mice. GFT505, but not fenofibrate, increased the expression of HDL-production genes such as apolipoprotein-AI and ATP-Binding-Cassette-A1 transporter in murine intestines. A similar increase was observed upon PPARα-activation of human biopsies and Caco-2/TC7 cells. Additionally, HDL secretion by Caco-2/TC7 cells increased. Moreover, PPARα-activation decreased the cholesterol-esterification capacity of Caco-2/TC7 cells, modified cholesterol trafficking and reduced apolipoprotein-B secretion. Conclusions PPARα-activation reduces cholesterol esterification, suppresses chylomicron- and increases HDL-secretion by enterocytes. These results identify the intestine as a target organ of PPARα-ligands with entero-hepatic tropism to reduce atherogenic dyslipidemia. PMID:22843443

  8. Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress

    SciTech Connect

    Mazière, Cécile; Salle, Valéry; Gomila, Cathy; Mazière, Jean-Claude

    2013-10-18

    Highlights: •Oxidized LDL enhances RANKL level in human smooth muscle cells. •The effect of OxLDL is mediated by the transcription factor NFAT. •UVA, H{sub 2}O{sub 2} and buthionine sulfoximine also increase RANKL level. •All these effects are observed in human fibroblasts and endothelial cells. -- Abstract: Receptor Activator of NFκB Ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) have been shown to play a role not only in bone remodeling but also in inflammation, arterial calcification and atherosclerotic plaque rupture. In human smooth muscle cells, Cu{sup 2+}-oxidized LDL (CuLDL) 10–50 μg/ml increased reactive oxygen species (ROS) and RANKL level in a dose-dependent manner, whereas OPG level was not affected. The lipid extract of CuLDL reproduced the effects of the whole particle. Vivit, an inhibitor of the transcription factor NFAT, reduced the CuLDL-induced increase in RANKL, whereas PKA and NFκB inhibitors were ineffective. LDL oxidized by myeloperoxidase (MPO-LDL), or other pro-oxidant conditions such as ultraviolet A (UVA) irradiation, incubation with H{sub 2}O{sub 2} or with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis{sub ,} also induced an oxidative stress and enhanced RANKL level. The increase in RANKL in pro-oxidant conditions was also observed in fibroblasts and endothelial cells. Since RANKL is involved in myocardial inflammation, vascular calcification and plaque rupture, this study highlights a new mechanism whereby OxLDL might, by generation of an oxidative stress, exert a deleterious effect on different cell types of the arterial wall.

  9. Telmisartan increases lipoprotein lipase expression via peroxisome proliferator-activated receptor-alpha in HepG2 cells.

    PubMed

    Yin, Shi Nan; Liu, Min; Jing, Dan Qing; Mu, Yi Ming; Lu, Ju Ming; Pan, Chang Yu

    2014-01-01

    In addition to their hypotensive properties, angiotensin receptor blockers (ARBs) have been shown to exert clinical antidyslipidemic effects. The mechanism underlying these ARB lipid metabolic effects remains unclear. Some ARBs, for example, telmisartan, activate peroxisome proliferator-activated activated receptor-gamma (PPAR-gamma). We hypothesized that PPAR-gamma-activating ARBs might exert antidyslipidemic effects via PPAR-alpha. In this study, we assessed the effect of telmisartan on the expression of PPAR-alpha and lipoprotein lipase (LPL). PPAR-alpha expression was detected by reverse-transcription polymerase chain reaction and Western blot in HepG2 hepatocytes as well as differentiated C2C12 myocytes treated with increasing concentrations of telmisartan (0.1-10 μmol/L) for 48 h. Results showed that 1 μmol/L and 10 μmol/L telmisartan significantly increased the expression of PPAR-alpha mRNA and protein in HepG2 cells (p < 0.01). No effect was shown in differentiated C2C12 cells. Similarly, 1 µmol/L and 10 μmol/L telmisartan significantly increased the expression of LPL mRNA and protein in HepG2 cells (p < 0.01), and this increase was significantly (p < 0.01) inhibited by the PPAR-alpha-specific antagonist MK886. These results indicate that certain of the antidyslipidemic effects of telmisartan might be mediated via increased PPAR-alpha-dependent induction of LPL expression. PMID:24067162

  10. A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase

    PubMed Central

    Fu, Zhiyao; Abou-Samra, Abdul B.; Zhang, Ren

    2015-01-01

    Lipasin/Angptl8 is a feeding-induced hepatokine that regulates triglyceride (TAG) metabolism; its therapeutical potential, mechanism of action, and relation to the lipoprotein lipase (LPL), however, remain elusive. We generated five monoclonal lipasin antibodies, among which one lowered the serum TAG level when injected into mice, and the epitope was determined to be EIQVEE. Lipasin-deficient mice exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white adipose tissue (WAT), suggesting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles. Consistently, mice injected with the effective antibody or with lipasin deficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state. These results suggest that lipasin acts, at least in part, in an endocrine manner. We propose the following model: feeding induces lipasin, activating the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulating TAG to WAT for storage; conversely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skeletal muscles for oxidation. This model suggests a general mechanism by which TAG trafficking is coordinated by lipasin, Angptl3 and Angptl4 at different nutritional statuses. PMID:26687026

  11. Adiponectin inhibits oxidized low density lipoprotein-induced increase in matrix metalloproteinase 9 expression in vascular smooth muscle cells

    PubMed Central

    Saneipour, Maryam; Ghatreh-Samani, Keihan; Heydarian, Esfandiar; Farrokhi, Effat; Abdian, Narges

    2015-01-01

    BACKGROUND High expression of matrix metalloproteinase 9 (MMP9) during vascular injury and inflammation plays an important role in atherosclerotic plaque formation and rupture. In the process of atherosclerosis, oxidized low-density lipoprotein (oxLDL) upregulates MMP9 in human aortic vascular smooth muscle cells (HA/VSMCs). Adiponectin is an adipose tissue-derived hormone that has been shown to exert anti-atherogenic and anti-inflammatory effects. The aim of this study was to investigate the effect of adiponectin on MMP9 expression under pathogenic condition created by oxLDL in HA/VSMCs. METHODS In this experimental study, HA/VSMC were stimulated with oxLDL alone and in the presence of adiponectin for 24 and 48 h. The expression of MMP9 gene was determined by real-time polymerase chain reaction method. The protein level of this gene was investigated by western blotting technique. RESULTS An oxLDL increased MMP9 expression 2.16 ± 0.24- and 3.32 ± 0.25-fold after 24 and 48 h, respectively and adiponectin decreased oxLDL-induced MMP9 expression in a time-dependent manner. CONCLUSION These results show that adiponectin changes extracellular matrix by reducing MMP9 mRNA and protein, therefore, may stabilize lesions and reduce atheroma rupture. PMID:26405452

  12. Can we explain increases in young people’s psychological distress over time?

    PubMed Central

    Sweeting, Helen; West, Patrick; Young, Robert; Der, Geoff

    2010-01-01

    This paper aims to explain previously described increases in self-reported psychological distress between 1987 and 2006 among samples identical in respect of age (15 years), school year and geographical location (West of Scotland). Such increases might be explained by changes in exposure (changes in levels of risk or protective factors) and/or by changes in vulnerability (changes in the relationship between risk/protective factors and psychological distress). Key areas of social change over this time period allow identification of potential explanatory factors, categorised as economic, family, educational, values and lifestyle and represented by variables common to each study. Psychological distress was measured via the 12-item General Health Questionnaire, Likert scored. Analyses were conducted on those with complete data on all variables (N = 3276 of 3929), and separately for males and females. Between 1987 and 2006, levels of almost every potential explanatory factor changed in line with general societal trends. Associations between explanatory factors and GHQ tended to be stronger among females, and at the later date. The strongest associations were with worries, arguments with parents, and, at the later date, school disengagement. The factors which best accounted for the increase in mean GHQ between 1987 and 2006 were arguments with parents, school disengagement, worry about school and, for females, worry about family relationships, reflecting both increasing exposure and vulnerability to these risk factors. A number of limitations to our analysis can be identified. However, our results reinforce the conclusions of others in highlighting the role of family and educational factors as plausible explanations for increases in young people’s psychological distress. PMID:20870334

  13. Testosterone increases the muscle protein synthesis rate but does not affect very-low-density lipoprotein metabolism in obese premenopausal women

    PubMed Central

    Wang, Xuewen; Smith, Gordon I.; Patterson, Bruce W.; Reeds, Dominic N.; Kampelman, Janine; Magkos, Faidon

    2012-01-01

    Men and women with hyperandrogenemia have a more proatherogenic plasma lipid profile [e.g., greater triglyceride (TG) and total and low-density lipoprotein-cholesterol and lower high-density lipoprotein-cholesterol concentrations] than healthy premenopausal women. Furthermore, castration of male rats markedly reduces testosterone availability below normal and decreases plasma TG concentration, and testosterone replacement reverses this effect. Testosterone is, therefore, thought to be an important regulator of plasma lipid homeostasis. However, little is known about the effect of testosterone on plasma TG concentration and kinetics. Furthermore, testosterone is a potent skeletal muscle protein anabolic agent in men, but its effect on muscle protein turnover in women is unknown. We measured plasma lipid concentrations, hepatic very low density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 secretion rates, and the muscle protein fractional synthesis rate in 10 obese women before and after trandermal testosterone (1.25 g of 1% AndroGel daily) treatment for 3 wk. Serum total and free testosterone concentrations increased (P < 0.05) by approximately sevenfold in response to testosterone treatment, reaching concentrations that are comparable to those in women with hyperandrogenemia, but lower than the normal range for eugonadal men. Except for a small (∼10%) decrease in plasma high-density lipoprotein particle and cholesterol concentrations (P < 0.04), testosterone therapy had no effect on plasma lipid concentrations, lipoprotein particle sizes, and hepatic VLDL-TG and VLDL-apolipoprotein B-100 secretion rates (all P > 0.05); the muscle protein fractional synthesis rate, however, increased by ∼45% (P < 0.001). We conclude that testosterone is a potent skeletal muscle protein anabolic agent, but not an important regulator of plasma lipid homeostasis in obese women. PMID:22252942

  14. Lack of nitric oxide synthases increases lipoprotein immune complex deposition in the aorta and elevates plasma sphingolipid levels in lupus

    PubMed Central

    Al Gadban, Mohammed M.; German, Jashalynn; Truman, Jean-Philip; Soodavar, Farzan; Riemer, Ellen C; Twal, Waleed O; Smith, Kent J; Heller, Demarcus; Hofbauer, Ann F; Oates, Jim C.; Hammad, Samar M.

    2012-01-01

    Systemic lupus erythematosus (SLE) patients display impaired endothelial nitric oxide synthase (eNOS) function required for normal vasodilatation. SLE patients express increased compensatory activity of inducible nitric oxide synthase (iNOS) generating excess nitric oxide that may result in inflammation. We examined the effects of genetic deletion of NOS2 and NOS3, encoding iNOS and eNOS respectively, on accelerated vascular disease in MRL/lpr lupus mouse model. NOS2 and NOS3 knockout (KO) MRL/lpr mice had higher plasma levels of triglycerides (23% and 35%, respectively), ceramide (45% and 21%, respectively), and sphingosine 1-phosphate (S1P) (21%) compared to counterpart MRL/lpr controls. Plasma levels of the anti-inflammatory cytokine interleukin 10 (IL-10) in NOS2 and NOS3 KO MRL/lpr mice were lower (53% and 80%, respectively) than counterpart controls. Nodule-like lesions in the adventitia were detected in aortas from both NOS2 and NOS3 KO MRL/lpr mice. Immunohistochemical evaluation of the lesions revealed activated endothelial cells and lipid-laden macrophages (foam cells), elevated sphingosine kinase 1 expression, and oxidized low-density lipoprotein immune complexes (oxLDL-IC). The findings suggest that advanced vascular disease in NOS2 and NOS3 KO MRL/lpr mice maybe mediated by increased plasma triglycerides, ceramide and S1P; decreased plasma IL-10; and accumulation of oxLDL-IC in the vessel wall. The results expose possible new targets to mitigate lupus-associated complications. PMID:22560558

  15. Low-density Lipoprotein Receptor Deficiency Causes Impaired Osteoclastogenesis and Increased Bone Mass in Mice because of Defect in Osteoclastic Cell-Cell Fusion*

    PubMed Central

    Okayasu, Mari; Nakayachi, Mai; Hayashida, Chiyomi; Ito, Junta; Kaneda, Toshio; Masuhara, Masaaki; Suda, Naoto; Sato, Takuya; Hakeda, Yoshiyuki

    2012-01-01

    Osteoporosis is associated with both atherosclerosis and vascular calcification attributed to hyperlipidemia. However, the cellular and molecular mechanisms explaining the parallel progression of these diseases remain unclear. Here, we used low-density lipoprotein receptor knockout (LDLR−/−) mice to elucidate the role of LDLR in regulating the differentiation of osteoclasts, which are responsible for bone resorption. Culturing wild-type osteoclast precursors in medium containing LDL-depleted serum decreased receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation, and this defect was additively rescued by simultaneous treatment with native and oxidized LDLs. Osteoclast precursors constitutively expressed LDLR in a RANKL-independent manner. Osteoclast formation from LDLR−/− osteoclast precursors was delayed, and the multinucleated cells formed in culture were smaller and contained fewer nuclei than wild-type cells, implying impaired cell-cell fusion. Despite these findings, RANK signaling, including the activation of Erk and Akt, was normal in LDLR−/− preosteoclasts, and RANKL-induced expression of NFATc1 (a master regulator of osteoclastogenesis), cathepsin K, and tartrate-resistant acid phosphatase was equivalent in LDLR-null and wild-type cells. In contrast, the amounts of the osteoclast fusion-related proteins v-ATPase V0 subunit d2 and dendritic cell-specific transmembrane protein in LDLR−/− plasma membranes were reduced when compared with the wild type, suggesting a correlation with impaired cell-cell fusion, which occurs on the plasma membrane. LDLR−/− mice consistently exhibited increased bone mass in vivo. This change was accompanied by decreases in bone resorption parameters, with no changes in bone formation parameters. These findings provide a novel mechanism for osteoclast differentiation and improve the understanding of the correlation between osteoclast formation and lipids. PMID:22500026

  16. Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans.

    PubMed

    Lähdesmäki, Katariina; Öörni, Katariina; Alanne-Kinnunen, Mervi; Jauhiainen, Matti; Hurt-Camejo, Eva; Kovanen, Petri T

    2012-02-01

    Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte-derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB-100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V-modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan-binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions. PMID:22041135

  17. Increased serum triglyceride clearance and elevated high-density lipoprotein 2 and 3 cholesterol during treatment of primary hypertriglyceridemia with bezafibrate☆

    PubMed Central

    Sakuma, Nagahiko; Ikeuchi, Reiko; Hibino, Takeshi; Yoshida, Takayuki; Mukai, Seiji; Akita, Sachie; Yajima, Kazuhiro; Miyabe, Hiromichi; Goto, Toshihiko; Takada, Norio; Ohte, Nobuyuki; Kunimatu, Mitoshi; Kimura, Genjiro

    2003-01-01

    Background Hypertriglyceridemia accompanied by low levels of high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. High-density lipoprotein 2 (HDL2) and 3 (HDL3) are believed to suppress the progress of atherosclerosis through reverse cholesterol transport. As a result, peripheral tissues can be protected against excessive accumulation of cholesterol. Although bezafibrate is known to accelerate the increase of HDL-C, results are not standardized regarding increases of HDL3 and HDL2 subfractions. Objective This study assessed the effects of bezafibrate on serum triglyceride (TG) fractional clearance rate (K2) and HDL2 and HDL3 cholesterol (HDL2-C and HDL3-C, respectively) levels in patients with primary hypertriglyceridemia (serum TG ≥150 mg/dL). Methods Outpatients with primary hypertriglyceridemia were enrolled in this 8-week study conducted at the Third Department of Internal Medicine, Nagoya City University Hospital (Nagoya, Japan). Oral bezafibrate was administered at a dose of 400 mg/d (200-mg tablet BID, morning and evening) for 8 weeks. After 8 weeks, serum levels of total cholesterol (TC), TG, HDL-C, HDL2-C, and HDL3-C were measured. A fat emulsion tolerance test to assess K2 and measurements of plasma lipoprotein lipase (LPL) mass, LPL activity, and hepatic triglyceride lipase (HTGL) activity in postheparin plasma were performed before bezafibrate administration and after the course of treatment. Results Sixteen patients (10 men, 6 women; mean [SD] age, 54 [12] years [range, 30–69 years]; mean [SD] body mass index, 23 [2] kg/m2) entered the study. The following findings were observed in male and female patients after 8 weeks of treatment. A statistically significant reduction was observed in mean serum TG level (P<0.01). Significant increases were seen in HDL-C, HDL2-C, and HDL3-C (all P<0.01), K2 (P<0.01), and in plasma LPL mass (P<0.01) and LPL activity (P<0.05). TC level and HTGL activity did not change

  18. Brazil nut ingestion increased plasma selenium but had minimal effects on lipids, apolipoproteins, and high-density lipoprotein function in human subjects.

    PubMed

    Strunz, Célia C; Oliveira, Tatiane V; Vinagre, Juliana C M; Lima, Adriana; Cozzolino, Silvia; Maranhão, Raul C

    2008-03-01

    The Brazil nut (Bertholletia excelsa) of the Amazon region is consumed worldwide. It is rich in both monounsaturated fatty acids and polyunsaturated fatty acids and is known for its high selenium content. This study tested the hypothesis whether the consumption of this nut could affect the plasma lipids and apolipoproteins and some functional properties of the antiatherogenic high-density lipoprotein (HDL). Fifteen normolipidemic subjects aged 27.3 +/- 3.9 years and with body mass index of 23.8 +/- 2.8 kg/m(2) consumed 45 g of Brazil nuts per day during a 15-day period. On days 0 and 15, blood was collected for biochemical analysis, determination of HDL particle size, paraoxonase 1 activity, and lipid transfer from a lipoprotein-like nanoparticle to the HDL fraction. Brazil nut ingestion did not alter HDL, low-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A-I, or apolipoprotein B concentrations. HDL particle diameter and the activity of antioxidative paraoxonase 1, mostly found in the HDL fraction, were also unaffected. Supplementation increased the reception of cholesteryl esters (P < .05) by the HDL yet did not alter the reception of phospholipids, free cholesterol, or triacylglycerols. As expected, plasma selenium was significantly increased. However, the consumption of Brazil nuts for short duration by normolipidemic subjects in comparable amounts to those tested for other nuts did not alter serum lipid profile. The only alteration in HDL function was the increase in cholesteryl ester transfer. This latter finding may be beneficial because it would improve the nonatherogenic reverse cholesterol transport pathway. PMID:19083402

  19. [Low density lipoprotein apheresis].

    PubMed

    Zaliūnas, Remigijus; Slapikas, Rimvydas; Gustiene, Olivija; Siurkus, Jonas; Vaitkus, Eduardas

    2003-01-01

    Increased blood cholesterol concentration is one of the main factors in ischemic heart disease, development of which is determined by atherosclerotic changes in coronary vessels. Diet and treatment with 3-hydroxi-3-metilglutaril coenzyme A (HMG-CoA) reductase inhibitors helps to reduce low density lipoprotein cholesterol (LDL-Ch) blood concentration up to recommended level of 3.0 mmol/l in most patients but in some patients particularly with familial dyslipidemias cholesterol concentration remains increased even after treatment with maximal doses of lipid-regulating agents or their combinations. The most frequently used mechanical methods of cholesterol removal from blood include the procedures of extracorporeal apheresis. Low density lipoprotein (LDL) apheresis not only significantly reduces the blood concentrations of total cholesterol (TCh), and LDL-Ch, lipoprotein (a) (Lp(a) and fibrinogen but also stops the progression of atherosclerosis in coronary vessels. PMID:14704503

  20. Can Developmental Changes in Inhibition and Peer Relationships Explain Why Depressive Symptoms Increase in Early Adolescence?

    ERIC Educational Resources Information Center

    Buck, Katharine Ann; Dix, Theodore

    2012-01-01

    Why do depressive symptoms increase during adolescence? Because inhibition and poor peer relationships predict adolescents' depressive symptoms concurrently, we hypothesized that adolescents who cope with the stresses of this period by becoming increasingly inhibited may experience increasing depressive symptoms both directly and due to increased…

  1. Factors explaining the increase in cost for physician care in Quebec's elderly population.

    PubMed Central

    Demers, M

    1996-01-01

    OBJECTIVE: To examine what role demographic factors and increases in physician fees and utilization played in the rise in costs of physician services provided for elderly people in Quebec between 1982 and 1992, and to investigate changes in patterns of care (type and amount of services) related to utilization. DESIGN: Retrospective study of population-based data. SETTING: Province of Quebec. SUBJECTS: Elderly people (65 years of age and over) in Quebec in 1982 (n = 589,800) and in 1992 (n = 803,600). OUTCOME MEASURES: Proportion of the increase in physician care costs attributable to (a) aging (defined as a shift in the age distribution) of the elderly population, (b) the increase in the size of the elderly population, (c) the increase in physician fees and (d) the increase in utilization of physician services; proportion of care provided by general practitioners (GPs) and by specialists; proportion of minor and complete examinations provided by GPs; and rates of hospital admissions and surgery. RESULTS: Aging was responsible for 0.5% of the increase in physician care costs between 1982 and 1992, population growth for 27.0% and the increase in physician fees for 25.5%. The increased utilization accounted for 47.0% of the total cost increase. Analyses of the utilization data revealed a shift toward more costly services, more visits to specialists and higher rates of hospital admissions and surgery in 1992 than in 1982. CONCLUSIONS: Aging and population growth had minor effects on the increase in physician care costs between 1982 and 1992. Increased utilization was the most important factor. The appropriateness of this trend needs to be verified. PMID:8956832

  2. Higher Levels of Lipoprotein Associated Phospholipase A2 is associated with Increased Prevalence of Cognitive Impairment: the APAC Study

    PubMed Central

    Jiang, Ruixuan; Chen, Shengyun; Shen, Yuan; Wu, Jianwei; Chen, Shuohua; Wang, Anxin; Wu, Shouling; Zhao, Xingquan

    2016-01-01

    Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a unique circulating phospholipase with inflammatory and oxidative activities and the limited data regarding the relationship between Lp-PLA2 and cognitive impairment are conflicted. We conducted a cross-sectional study including 1,374 Chinese adults recruited from 2010 to 2011, aiming to evaluate the relationship between Lp-PLA2 levels and the prevalence of cognitive impairment in a Chinese community-based population. Participants underwent standardized evaluation. Serum Lp-PLA2 mass was measured by ELISA. Cognition status was evaluated via the Mini-Mental Status Exam (MMSE) and cognitive impairment was identified as MMSE <24. Multivariable logistic regression models were used to assess the associations of Lp-PLA2 mass with cognitive impairment. Lp-PLA2 mass was significantly associated with the prevalence of cognitive impairment after adjusting for other potential confounding factors (compared with the first quartile, adjusted ORs of the second, third, and fourth quartile were 2.058 (95% CI, 0.876–4.835), 2.834 (95% CI, 1.255–6.398), and 4.882 (95% CI, 2.212–10.777), p < 0.0001). In conclusion, elevated level of Lp-PLA2 mass was independently associated with the prevalence of cognitive impairment in Chinese adults. PMID:27609335

  3. Higher Levels of Lipoprotein Associated Phospholipase A2 is associated with Increased Prevalence of Cognitive Impairment: the APAC Study.

    PubMed

    Jiang, Ruixuan; Chen, Shengyun; Shen, Yuan; Wu, Jianwei; Chen, Shuohua; Wang, Anxin; Wu, Shouling; Zhao, Xingquan

    2016-01-01

    Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a unique circulating phospholipase with inflammatory and oxidative activities and the limited data regarding the relationship between Lp-PLA2 and cognitive impairment are conflicted. We conducted a cross-sectional study including 1,374 Chinese adults recruited from 2010 to 2011, aiming to evaluate the relationship between Lp-PLA2 levels and the prevalence of cognitive impairment in a Chinese community-based population. Participants underwent standardized evaluation. Serum Lp-PLA2 mass was measured by ELISA. Cognition status was evaluated via the Mini-Mental Status Exam (MMSE) and cognitive impairment was identified as MMSE <24. Multivariable logistic regression models were used to assess the associations of Lp-PLA2 mass with cognitive impairment. Lp-PLA2 mass was significantly associated with the prevalence of cognitive impairment after adjusting for other potential confounding factors (compared with the first quartile, adjusted ORs of the second, third, and fourth quartile were 2.058 (95% CI, 0.876-4.835), 2.834 (95% CI, 1.255-6.398), and 4.882 (95% CI, 2.212-10.777), p < 0.0001). In conclusion, elevated level of Lp-PLA2 mass was independently associated with the prevalence of cognitive impairment in Chinese adults. PMID:27609335

  4. Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout mice.

    PubMed

    Forrest, Lolita M; Lough, Christopher M; Chung, Soonkyu; Boudyguina, Elena Y; Gebre, Abraham K; Smith, Thomas L; Colvin, Perry L; Parks, John S

    2013-07-01

    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model. PMID:23857172

  5. Echium Oil Reduces Plasma Triglycerides by Increasing Intravascular Lipolysis in apoB100-Only Low Density Lipoprotein (LDL) Receptor Knockout Mice

    PubMed Central

    Forrest, Lolita M.; Lough, Christopher M.; Chung, Soonkyu; Boudyguina, Elena Y.; Gebre, Abraham K.; Smith, Thomas L.; Colvin, Perry L.; Parks, John S.

    2013-01-01

    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model. PMID:23857172

  6. What explains the increased utilization of Powder River Basin coal in electric power generation?

    SciTech Connect

    Gerking, S.; Hamilton, S.F.

    2008-11-15

    This article examines possible explanations for increased utilization of Powder River Basin (PRB) coal in electric power generation that occurred over the last two decades. Did more stringent environmental policy motivate electric power plants to switch to less polluting fuels? Or, did greater use of PRB coal occur because relative price changes altered input markets in favor of this fuel. A key finding is that factors other than environmental policy such as the decline in railroad freight rates together with elastic demand by power plants were major contributors to the increased utilization of this fuel.

  7. Cryo-Hydrologic Warming Explains Increased Ice Velocities on Sermeq Avannarleq, West Greenland

    NASA Astrophysics Data System (ADS)

    Rajaram, H.; Phillips, T. P.; Colgan, W.; Steffen, K.

    2011-12-01

    The area of West Greenland experiencing surface melt is increasing at a rate of ~3.9%/year, in response to a > 200m increase in equilibrium line altitude (ELA) between 1990 and 2000. Recent observations indicate that meltwater is retained in the englacial and subglacial cryo-hydrologic systems (CHS) through multiple years in this region. Latent heat transfer from this retained meltwater has the potential to warm ice relatively rapidly (decadal time scales) by cryo-hydrologic warming (CHW). Warmer ice temperature leads to reduced ice viscosity and higher ice velocity. We incorporated CHW into a flowline thermo-mechanical model of Sermeq Avannarleq (SA), west Greenland, to quantify the influence of CHW on ice velocities. Our model also considers the influence of softer Wisconsin ice at greater depths in the ice, and basal sliding. The dependence of the flow law parameter on depth and the local temperature was explicitly represented. We calculate mutually consistent temperature and velocity fields accounting for subtle thermo-mechanical feedbacks such as the enhancement of horizontal advection of cold ice by basal sliding. Our model uses measured ice surface and bedrock elevations, thus avoiding potential errors from calculating ice thickness based on mass balance (MB). We demonstrate that InSAR derived ice surface velocities on SA in winter 2005 cannot be reproduced unless the influence of CHW is invoked; conventional thermo-mechanical models that neglect CHW predict surface velocities that are up to 70 m/year smaller. The only available ice temperature measurements in this region (from 1990) are also not matched unless the influence of CHW is incorporated. Thus, our results provide the first quantitative demonstration of the impact of cryo-hydrologic warming on ice velocities, based on comparisons with real data. The influence of CHW on ice velocities is most significant in the region where melt inputs were initiated relatively recently (after ~ 1990) due to the

  8. Symptoms of notalgia paresthetica may be explained by increased dermal innervation.

    PubMed

    Springall, D R; Karanth, S S; Kirkham, N; Darley, C R; Polak, J M

    1991-09-01

    Notalgia paresthetica is a sensory neuropathy characterized by infrascapular pruritus, burning pain, hyperalgesia, or tenderness. To assess whether the symptoms may be caused by alterations in the cutaneous innervation, skin from the affected area of patients (n = 5) was compared with controls (n = 10) comprising the contralateral unaffected area from the same patients and site-matched biopsies of normals, using immunohistochemistry. Frozen sections were immunostained with antisera to the neuropeptides substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, and neuropeptide with tyrosine, and to the general neural marker PGP 9.5 and the glial marker S-100 to show the overall innervation and glial cells, respectively. No discernible change in the distribution of neuropeptide-immunoreactive axons was found, but all of the specimens from the affected areas had a significant increase in the number of intradermal PGP 9.5-immunoreactive nerve fibers compared with unaffected areas from the same patients and normal controls. Epidermal dendritic cells immunoreactive for S-100, possibly Langerhans cells, were substantially increased. It is concluded that there is an increase in the sensory epidermal innervation in the affected skin areas in notalgia paresthetica, which could contribute to the symptoms, and that neural immunohistochemistry of skin biopsies could be helpful in the diagnosis of the disease. PMID:1831466

  9. A Minimalistic Resource Allocation Model to Explain Ubiquitous Increase in Protein Expression with Growth Rate

    PubMed Central

    Keren, Leeat; Segal, Eran; Milo, Ron

    2016-01-01

    Most proteins show changes in level across growth conditions. Many of these changes seem to be coordinated with the specific growth rate rather than the growth environment or the protein function. Although cellular growth rates, gene expression levels and gene regulation have been at the center of biological research for decades, there are only a few models giving a base line prediction of the dependence of the proteome fraction occupied by a gene with the specific growth rate. We present a simple model that predicts a widely coordinated increase in the fraction of many proteins out of the proteome, proportionally with the growth rate. The model reveals how passive redistribution of resources, due to active regulation of only a few proteins, can have proteome wide effects that are quantitatively predictable. Our model provides a potential explanation for why and how such a coordinated response of a large fraction of the proteome to the specific growth rate arises under different environmental conditions. The simplicity of our model can also be useful by serving as a baseline null hypothesis in the search for active regulation. We exemplify the usage of the model by analyzing the relationship between growth rate and proteome composition for the model microorganism E.coli as reflected in recent proteomics data sets spanning various growth conditions. We find that the fraction out of the proteome of a large number of proteins, and from different cellular processes, increases proportionally with the growth rate. Notably, ribosomal proteins, which have been previously reported to increase in fraction with growth rate, are only a small part of this group of proteins. We suggest that, although the fractions of many proteins change with the growth rate, such changes may be partially driven by a global effect, not necessarily requiring specific cellular control mechanisms. PMID:27073913

  10. Liquid films on shake flask walls explain increasing maximum oxygen transfer capacities with elevating viscosity.

    PubMed

    Giese, Heiner; Azizan, Amizon; Kümmel, Anne; Liao, Anping; Peter, Cyril P; Fonseca, João A; Hermann, Robert; Duarte, Tiago M; Büchs, Jochen

    2014-02-01

    In biotechnological screening and production, oxygen supply is a crucial parameter. Even though oxygen transfer is well documented for viscous cultivations in stirred tanks, little is known about the gas/liquid oxygen transfer in shake flask cultures that become increasingly viscous during cultivation. Especially the oxygen transfer into the liquid film, adhering on the shake flask wall, has not yet been described for such cultivations. In this study, the oxygen transfer of chemical and microbial model experiments was measured and the suitability of the widely applied film theory of Higbie was studied. With numerical simulations of Fick's law of diffusion, it was demonstrated that Higbie's film theory does not apply for cultivations which occur at viscosities up to 10 mPa s. For the first time, it was experimentally shown that the maximum oxygen transfer capacity OTRmax increases in shake flasks when viscosity is increased from 1 to 10 mPa s, leading to an improved oxygen supply for microorganisms. Additionally, the OTRmax does not significantly undermatch the OTRmax at waterlike viscosities, even at elevated viscosities of up to 80 mPa s. In this range, a shake flask is a somehow self-regulating system with respect to oxygen supply. This is in contrary to stirred tanks, where the oxygen supply is steadily reduced to only 5% at 80 mPa s. Since, the liquid film formation at shake flask walls inherently promotes the oxygen supply at moderate and at elevated viscosities, these results have significant implications for scale-up. PMID:23904288

  11. A Minimalistic Resource Allocation Model to Explain Ubiquitous Increase in Protein Expression with Growth Rate.

    PubMed

    Barenholz, Uri; Keren, Leeat; Segal, Eran; Milo, Ron

    2016-01-01

    Most proteins show changes in level across growth conditions. Many of these changes seem to be coordinated with the specific growth rate rather than the growth environment or the protein function. Although cellular growth rates, gene expression levels and gene regulation have been at the center of biological research for decades, there are only a few models giving a base line prediction of the dependence of the proteome fraction occupied by a gene with the specific growth rate. We present a simple model that predicts a widely coordinated increase in the fraction of many proteins out of the proteome, proportionally with the growth rate. The model reveals how passive redistribution of resources, due to active regulation of only a few proteins, can have proteome wide effects that are quantitatively predictable. Our model provides a potential explanation for why and how such a coordinated response of a large fraction of the proteome to the specific growth rate arises under different environmental conditions. The simplicity of our model can also be useful by serving as a baseline null hypothesis in the search for active regulation. We exemplify the usage of the model by analyzing the relationship between growth rate and proteome composition for the model microorganism E.coli as reflected in recent proteomics data sets spanning various growth conditions. We find that the fraction out of the proteome of a large number of proteins, and from different cellular processes, increases proportionally with the growth rate. Notably, ribosomal proteins, which have been previously reported to increase in fraction with growth rate, are only a small part of this group of proteins. We suggest that, although the fractions of many proteins change with the growth rate, such changes may be partially driven by a global effect, not necessarily requiring specific cellular control mechanisms. PMID:27073913

  12. Overweight explains the increased red blood cell aggregation in patients with obstructive sleep apnea.

    PubMed

    Sinnapah, Stéphane; Cadelis, Gilbert; Waltz, Xavier; Lamarre, Yann; Connes, Philippe

    2015-01-01

    Sleep apnea patients and obese subjects are overexposed to cardiovascular diseases. These two health conditions may be associated with hemorheological alterations which could increase the cardiovascular risk. The present study investigated the hemorheological characteristics in patients with overweight and/or sleep apnea to identify the main predictor of red blood cell (RBC) abnormalities in sleep apnea patients. Ninety-seven patients were subjected to one night sleep polygraphy to determine their sleep apnea status. Body mass index (BMI) and the apnea/hypopnea index (AHI) were determined for categorization of obesity and sleep apnea status. Blood was sampled for hematocrit, blood viscosity, RBC deformability, aggregation and disaggregation threshold measurements. BMI and AHI were positively associated and were both positively associated with RBC aggregation. Analyses of covariance and multiple regression analyses revealed that BMI was more predictive of RBC aggregation than AHI. No association of BMI classes and AHI classes with RBC deformability or blood viscosity was observed. This study shows that increased RBC aggregation in sleep apnea patients is caused by overweight. Therapies to improve blood rheology in sleep apnea patients, and therefore reduce the risk for cardiovascular disorders, should focus on weight-loss. PMID:23271197

  13. Increased inflammation in sanctuary sites may explain viral blips in HIV infection

    DOE PAGESBeta

    Piovoso, Michael J.; Cardozo, E. Fabian; Zurakowski, Ryan

    2016-05-18

    Here, combined antiretroviral therapy (cART) suppress HIV-1 viral replication, such that viral load in plasma remains below the limit of detection in standard assays. However, intermittent episodes of transient viremia (blips) occur in a set of HIV-patients. Given that follicular hyperplasia occurs during lymphoid inflammation as a normal response to infection, it is hypothesised that when the diameter of the lymph node follicle (LNF) increases and crosses a critical size, a viral blip occurs due to cryptic viremia. To study this hypothesis, a theoretical analysis of a mathematical model is performed to find the conditions for virus suppression in allmore » compartments and different scenarios of LNF size changes are simulated. According to the analysis, blips with duration of around 30 days arise when the diameter rise rate is between 0.02 and 0.03 days–1. Moreover, the final diameter of the site is directly related to the steady states of the virus load after the occurrence of a blip. When the value of R0 is around 2.1, to have a steady-state below the limit of detection after the viral blip, the maximum final diameters should be greater than 0.7 mm so that there is a relative loss of connection between compartments.« less

  14. Increased inflammation in sanctuary sites may explain viral blips in HIV infection.

    PubMed

    Cardozo, E Fabian; Piovoso, Michael J; Zurakowski, Ryan

    2016-08-01

    Combined antiretroviral therapy (cART) suppress HIV-1 viral replication, such that viral load in plasma remains below the limit of detection in standard assays. However, intermittent episodes of transient viremia (blips) occur in a set of HIV-patients. Given that follicular hyperplasia occurs during lymphoid inflammation as a normal response to infection, it is hypothesised that when the diameter of the lymph node follicle (LNF) increases and crosses a critical size, a viral blip occurs due to cryptic viremia. To study this hypothesis, a theoretical analysis of a mathematical model is performed to find the conditions for virus suppression in all compartments and different scenarios of LNF size changes are simulated. According to the analysis, blips with duration of around 30 days arise when the diameter rise rate is between 0.02 and 0.03 days(-1). Moreover, the final diameter of the site is directly related to the steady states of the virus load after the occurrence of a blip. When the value of R0 is around 2.1, to have a steady-state below the limit of detection after the viral blip, the maximum final diameters should be greater than 0.7 mm so that there is a relative loss of connection between compartments. PMID:27444025

  15. Explaining the Rapid Increase in Nigeria's Sex Ratio at Birth: Factors and Implications.

    PubMed

    Kaba, Amadu J

    2015-06-01

    This paper examines the rapid increase in Nigeria's sex ratio at birth from 1.03 boys born for every 1 girl born in each year from 1996-2008 to 1.06 in each year from 2009-2014, second only to Tunisia in Africa at 1.07. The average sex ratio at birth in the world in 2014 was 1.07. In most Black African nations or Black majority nations, it is 1.03 or less. Among the factors presented for this development are: historical fluctuations of sex ratio at birth; geography and ethnicity; male preference/chasing a son; Age of parents; high death rates of male infants and males in general; and wealth/socioeconomic status. Among the potential implications are: young and poor men in Nigeria may not be able to find brides and form families due to a potential shortage of females; emigration of young and poor Nigerian men to West (Africa) and elsewhere to seek brides and form families; immigration of marriage age women from West (Africa) and around the world to Nigeria to seek husbands; and low contraceptive use and high fertility rates in Nigeria. PMID:26506655

  16. Lipoprotein (a), lipids, and lipoproteins in patients with rheumatoid arthritis.

    PubMed Central

    Rantapää-Dahlqvist, S; Wållberg-Jonsson, S; Dahlén, G

    1991-01-01

    Lipoprotein (a), (Lp(a)), an independent atherogenic factor, was significantly increased in 93 patients with classical, seropositive rheumatoid arthritis of median disease activity. In the patients with Lp(a) concentrations above the upper reference value of 480 mg/l there was a significant correlation between Lp(a) and the concentration of orosomucoid, erythrocyte sedimentation rate, and the platelet count. The plasma concentrations of cholesterol and high density lipoprotein-cholesterol in both male and female patients were significantly lower than in controls. Apolipoprotein B and apolipoprotein AI in the patients correlated significantly with total cholesterol and high density lipoprotein-cholesterol respectively. PMID:1829348

  17. Regulation of Plasma Cholesterol by Lipoprotein Receptors

    NASA Astrophysics Data System (ADS)

    Brown, Michael S.; Kovanen, Petri T.; Goldstein, Joseph L.

    1981-05-01

    The lipoprotein transport system holds the key to understanding the mechanisms by which genes, diet, and hormones interact to regulate the plasma cholesterol level in man. Crucial components of this system are lipoprotein receptors in the liver and extrahepatic tissues that mediate the uptake and degradation of cholesterol-carrying lipoproteins. The number of lipoprotein receptors, and hence the efficiency of disposal of plasma cholesterol, can be increased by cholesterol-lowering drugs. Regulation of lipoprotein receptors can be exploited pharmacologically in the therapy of hypercholesterolemia and atherosclerosis in man.

  18. Participation of decreased serum cholesteryl ester transfer activity, independent of increased serum lipoprotein(a), in angina pectoris in normolipemic elderly subjects.

    PubMed

    Miyashita, Y; Morimoto, S; Fukuo, K; Imanaka, S; Koh, E; Tamatani, M; Ogihara, T

    1992-01-01

    The cholesteryl ester transfer activity (CETA) is a measurement of the transfer of cholesteryl ester from HDL to VLDL, LDL or peripheral cells. Its role in the development of early coronary heart disease is not clear. In the present study, serum levels of CETA, lipoprotein(a) [Lp(a)] and other lipid-related factors were compared in 10 normal young subjects, 28 healthy elderly subjects and 14 normolipemic elderly patients with angina pectoris. Compared to the young normals and healthy elderly subjects, the elderly patients with angina pectoris showed significantly decreased mean serum CETA levels, and significantly increased mean serum levels of Lp(a) and apoprotein B. These results may indicate that decreased serum values of CETA participate in the development of angina pectoris in normolipemic elderly patients. PMID:1427124

  19. Phytosterols, Phytostanols, and Lipoprotein Metabolism

    PubMed Central

    Gylling, Helena; Simonen, Piia

    2015-01-01

    The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL) cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%–10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a) or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL) cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein particles will be

  20. Effects of hormones on lipids and lipoproteins

    SciTech Connect

    Krauss, R.M.

    1991-12-01

    Levels of plasma lipids and lipoproteins are strong predictors for the development of atherosclerotic cardiovascular disease in postmenopausal women. In women, as in men, numerous factors contribute to variations in plasma lipoproteins that may affect cardiovascular disease risk. These include age, dietary components, adiposity, genetic traits, and hormonal changes. Each of these factors may operate to varying degrees in determining changes in plasma lipoprotein profiles accompanying menopause- Cross-sectional and longitudinal studies have suggested increases in levels of cholesterol, low density lipoproteins (LDL) and triglyceride-rich lipoproteins associated with menopause. High density lipoproteins (HDL), which are higher in women than men and are thought to contribute to relative protection of premenopausal women from cardiovascular disease, remain relatively constant in the years following menopause, although small, and perhaps transient reductions in the HDL{sub 2} subfraction have been reported in relation to reduced estradiol level following menopause. Despite these associations, it has been difficult to determine the role of endogenous hormones in influencing the plasma lipoproteins of postmenopausal women. In principle, the effects of hormone replacement should act to reverse any alterations in lipoprotein metabolism that are due to postmenopausal hormone changes. While there may be beneficial effects on lipoproteins, hormone treatment does not restore a premenopausal lipoprotein profile. Furthermore, it is not dear to what extent exogenous hormone-induced lipoprotein changes contribute to the reduced incidence of cardiovascular disease with hormone replacement therapy.

  1. Metabolism of lipoproteins by human fetal hepatocytes

    SciTech Connect

    Carr, B.R.

    1987-12-01

    The rate of clearance of lipoproteins from plasma appears to play a role in the development of atherogenesis. The liver may account for as much as two thirds of the removal of low-density lipoprotein and one third of the clearance of high-density lipoprotein in certain animal species and humans, mainly by receptor-mediated pathways. The purpose of the present investigation was to determine if human fetal hepatocytes maintained in vitro take up and degrade lipoproteins. We first determined that the maximal binding capacity of iodine 125-iodo-LDL was approximately 300 ng of low-density lipoprotein protein/mg of membrane protein and an apparent dissociation constant of approximately 60 micrograms low-density lipoprotein protein/ml in membranes prepared from human fetal liver. We found that the maximal uptake of (/sup 125/I)iodo-LDL and (/sup 125/I)iodo-HDL by fetal hepatocytes occurred after 12 hours of incubation. Low-density lipoprotein uptake preceded the appearance of degradation products by 4 hours, and thereafter the degradation of low-density lipoprotein increased linearly for at least 24 hours. In contrast, high-density lipoprotein was not degraded to any extent by fetal hepatocytes. (/sup 125/I)Iodo-LDL uptake and degradation were inhibited more than 75% by preincubation with low-density lipoprotein but not significantly by high-density lipoprotein, whereas (/sup 125/I)iodo-HDL uptake was inhibited 70% by preincubation with high-density lipoprotein but not by low-density lipoprotein. In summary, human fetal hepatocytes take up and degrade low-density lipoprotein by a receptor-mediated process similar to that described for human extrahepatic tissues.

  2. Increased hepatic cholesterol esterification with essential fatty acid deficiency (EFAD): relationship to plasma lipoprotein (LP) cholesterol content

    SciTech Connect

    Ney, D.M.; Ziboh, V.A.; Schneeman, B.O.

    1986-03-01

    EFAD in the rat is associated with hepatic accumulation of esterified cholesterol and altered distribution of cholesterol between plasma and hepatic tissue. Little is known regarding the impact of EFAD on LP composition. To determine the relationship between hepatic cholesterol esterification and plasma lP composition in control (C) and EFAD male Wistar rats, the authors induced EFAD with continuous intragastric (IG) infusion of EFA-free solutions containing 3.5% of calories as triolein for 7 and 14 days. C animals received IG infusion of solutions containing 3.5% of calories as linoleic acid. Data in the EFAD groups reveal: (i) marked decreases in hepatic EFAs and increases in monoenoic acids; (ii) progressive increases in hepatic content of triglyceride and esterified cholesterol with 7 and 14 days of feeding; (iii) assay of acyl CoA:cholesterol acyltransferase activity in hepatic tissue using /sup 14/C-cholesterol demonstrates an increase in hepatic cholesterol esterification when compared to C animals. Increased hepatic cholesterol esterification correlates with elevated levels of esterified cholesterol in plasma VLDL and HDL particles. These data indicate that the elevated levels of cholesterol esters in LP particles is due, at least in part, to increased hepatic cholesterol esterification with EFAD.

  3. Calmodulin antagonists increase the amount of mRNA for the low-density-lipoprotein receptor in skin fibroblasts.

    PubMed Central

    Eckardt, H; Filipovic, I; Hasilik, A; Buddecke, E

    1988-01-01

    The effects of calmodulin antagonists on the amount of LDL receptor (LDL-R) mRNA in cultured human fibroblasts was examined by hybridization with a fragment of LDL-R cDNA. In a 'Northern' blot the fragment hybridized to a 5.3-kilobase RNA, as expected for LDL-R mRNA. The concentration of this RNA was increased in preparations from cells that were treated with trifluoperazine or W-7 [N-(6-aminohexyl)-5-chloronaphthalene-1-sulphonamide]. The selectivity of the increase was established by using a probe for beta-actin mRNA. In dot-blot hybridization it was observed that the calmodulin antagonists cause 2-4-fold relative increase in the amount of LDL-R mRNA. Images Fig. 1. Fig. 2. Fig. 3. PMID:3421929

  4. A diet rich in monounsaturated rapeseed oil reduces the lipoprotein cholesterol concentration and increases the relative content of n-3 fatty acids in serum in hyperlipidemic subjects.

    PubMed

    Gustafsson, I B; Vessby, B; Ohrvall, M; Nydahl, M

    1994-03-01

    The effects of 3 wk on a diet rich in monounsaturated rapeseed oil were compared with those of a diet containing sunflower oil within a lipid-lowering diet. Ninety-five subjects with moderate hyperlipoproteinemia were randomly assigned to one of the two well-controlled diets prepared at the hospital kitchen. Total serum, low-density- and high-density-lipoprotein cholesterol concentrations decreased by 15%, 16%, and 11% (P < 0.001), respectively, on the rapeseed oil diet and by 16%, 14%, and 13% (P < 0.001) on the sunflower oil diet. Serum triglycerides decreased more markedly (by 29%, P < 0.001) on the sunflower oil than on the rapeseed oil diet (14%, P < 0.01). The n-3 fatty acids (20:5 and 22:5) in the serum phospholipids increased significantly on the rapeseed oil diet but decreased on the sunflower oil diet. There was an increase in the alpha-tocopherol concentrations after both diets. The findings indicate that low erucic acid rapeseed oil can replace oils and fats rich in polyunsaturated fatty acids in a lipid-lowering diet. PMID:8116547

  5. Obesity development in neuron-specific lipoprotein lipase deficient mice is not responsive to increased dietary fat content or change in fat composition.

    PubMed

    Wang, Hong; Taussig, Matthew D; DiPatrizio, Nicholas V; Bruce, Kimberley; Piomelli, Daniele; Eckel, Robert H

    2016-07-01

    We have previously reported that mice with neuron-specific LPL deficiency (NEXLPL-/-) become obese by 16weeks of age on chow. Moreover, these mice had reduced uptake of triglyceride (TG)-rich lipoprotein-derived fatty acids and lower levels of n-3 long chain polyunsaturated fatty acids (n-3 PUFAs) in the hypothalamus. Here, we asked whether increased dietary fat content or altered dietary composition could modulate obesity development in NEXLPL-/- mice. Male NEXLPL-/- mice and littermate controls (WT) were randomly assigned one of three synthetic diets; a high carbohydrate diet (HC, 10% fat), a high-fat diet (HF, 45% fat), or a HC diet supplemented with n-3 PUFAs (HCn-3, 10% fat, Lovaza, GSK®). After 42weeks of HC feeding, body weight and fat mass were increased in the NEXLPL-/- mice compared to WT. WT mice fed a HF diet displayed typical diet-induced obesity, but weight gain was only marginal in HF-fed NEXLPL-/- mice, with no significant difference in body composition. Dietary n-3 PUFA supplementation did not prevent obesity in NEXLPL-/- mice, but was associated with differential modifications in hypothalamic gene expression and PUFA concentration compared to WT mice. Our findings suggest that neuronal LPL is involved in the regulation of body weight and composition in response to either the change in quantity (HF feeding) or quality (n-3 PUFA-enriched) of dietary fat. The precise role of LPL in lipid sensing in the brain requires further investigation. PMID:27282869

  6. The hypertriglyceridemia of acquired immunodeficiency syndrome is associated with an increased prevalence of low density lipoprotein subclass pattern B

    SciTech Connect

    Feingold, K.R.; Krauss, R.M.; Pang, M.; Doerrler, W.; Jensen, P.; Grunfeld, C. Lawrence Berkeley Lab., CA )

    1993-06-01

    To better define the role of environmental factors on LDL phenotypic expression, the authors determined LDL patterns in patients with acquired immunodeficiency syndrome (AIDS), and infection characterized by hypertriglyceridemia and weight loss. Similar to previous studies, plasma triglyceride levels were increased, whereas plasma cholesterol, LDL cholesterol, and HDL cholesterol levels were decreased in the AIDS subjects compared to those in age-matched controls. The percentage of AIDS subjects with the LDL B phenotype was increased 2.5-fold, demonstrating an increased prevalence of the LDL B phenotype in an acquired form of hypertriglyceridemia. For each LDL phenotype in AIDS, serum triglyceride levels were higher than the same phenotypic pattern in controls, with the most marked elevations in triglycerides found in AIDS subjects with the LDL B phenotype. In contrast to what was observed in controls, HDL cholesterol levels were decreased in all AIDS subjects and were unrelated to LDL pattern. Total and LDL cholesterol levels were higher in controls with the LDL B phenotype than in those with the LDL A phenotype, but there was no difference in total and LDL cholesterol in AIDS subjects with LDL B compared to A. On multiple regression analysis in subjects with AIDS, plasma triglyceride levels, age, and HDL cholesterol all contribute to the occurrence of the LDL B phenotype, but elevations in plasma triglyceride levels are the strongest independent predictor. Body mass index was not a predictor of LDL B phenotype in AIDS. These results suggest that disturbances in triglyceride metabolism that are caused by AIDS lead to the appearance of the LDL subclass B phenotype and provide further evidence that environmental or disease states that perturb lipid metabolism can produce an increased prevalence of the LDL B phenotype. 35 refs., 1 fig., 5 tabs.

  7. Interferon-Free Treatment of Hepatitis C Virus in HIV/Hepatitis C Virus-Coinfected Subjects Results in Increased Serum Low-Density Lipoprotein Concentration.

    PubMed

    Townsend, Kerry; Meissner, Eric G; Sidharthan, Sreetha; Sampson, Maureen; Remaley, Alan T; Tang, Lydia; Kohli, Anita; Osinusi, Anu; Masur, Henry; Kottilil, Shyam

    2016-05-01

    Chronic hepatitis C virus (HCV) infection is associated with lower serum concentration of low-density lipoprotein (LDL-C), the primary cholesterol metabolite targeted pharmaceutically to modulate cardiovascular risk. Chronic infection with human immunodeficiency virus (HIV) and treatment with antiretrovirals (ARVs) are associated with dyslipidemia and increased risk of cardiovascular disease. In subjects coinfected with HIV and HCV, lipid abnormalities associated with either infection alone are often attenuated. Treatment of chronic HCV infection in HIV/HCV-coinfected subjects is now possible with interferon (IFN)-free regimens composed of directly acting antivirals (DAAs). We previously observed a marked increase in serum LDL-C in HCV-monoinfected subjects treated with sofosbuvir and ribavirin (SOF/RBV) that correlated with viral decline in serum, suggesting a direct influence of HCV clearance on serum cholesterol. In the present study, we assessed longitudinal changes in cholesterol in HIV/HCV-coinfected subjects during treatment of HCV genotype-1 (GT1) infection with combination DAA therapy. We report a rapid increase in LDL-C and LDL particle size by week 2 of treatment that was sustained during and after treatment in HIV/HCV-coinfected subjects. No change in serum LDL-C was observed at day 3 of treatment, in spite of a marked reduction in serum HCV viral load, suggesting LDL-C increases do not directly reflect HCV clearance as measured in peripheral blood. After effective DAA therapy for HCV, an increase in LDL should be anticipated in HIV/HCV-coinfected subjects. PMID:26559180

  8. Does plasticity in plant physiological traits explain the rapid increase in water use efficiency? An ecohydrological modeling approach

    NASA Astrophysics Data System (ADS)

    Mastrotheodoros, Theodoros; Fatichi, Simone; Pappas, Christoforos; Molnar, Peter; Burlando, Paolo

    2016-04-01

    The rise of atmospheric CO2 concentration is expected to stimulate plant productivity by enhancing photosynthesis and reducing stomatal conductance and thus increasing plant water use efficiency (WUE) worldwide. An analysis of eddy covariance flux tower data from 21 forested ecosystems across the north hemisphere detected an unexpectedly large increase in WUE (Keenan et al, 2013), which was six times larger than the increase found by most previous studies based on controlled experiments (e.g., FACE), leaf-scale analyses, and numerical modelling. This increase could be solely attributed to the increase in atmospheric CO2 since other confounding factors were ruled out. Here, we investigate the potential contribution of plant plasticity, reflected in the temporal adjustment of major plant physiological traits, on changes in WUE using the ecohydrological model Tethys and Chloris (T&C). We hypothesize that the increase in WUE can be attributed to small variations in plant physiological traits, undetectable through observations, eventually triggered by the atmospheric CO2 increase. Data from the 21 sites in the above mentioned study are used to force the model. Simulation results with and without plasticity in the physiological traits (i.e., model parameters in our numerical experiments) are compared with the observed trends in WUE. We test several plant adaptation strategies in being effective in explaining the observed increase in WUE using a multifactorial numerical experiment in which we perturb in a systematic way selected plant parameters. Keenan, T. F., Hollinger, D. Y., Bohrer, G., Dragoni, D., Munger, J. W., Schmid, H. P., and Richardson, A. D. (2013). Increase in forest water-use efficiency as atmospheric carbon dioxide concentrations rise. Nature, 499(7458), 324-7.

  9. Increased plasma total cholesterol and high density lipoprotein levels produced by the crude extract from the leaves of Viscum album (mistletoe).

    PubMed

    Ben, E E; Eno, A E; Ofem, O E; Aidem, U; Itam, E H

    2006-01-01

    The effect of an aqueous extract prepared from the leaves of Viscum album (Mistletoe) on plasma cholesterol and albumin levels in male Wistar rats was studied. Lethality studies revealed that the extract had an LD50 value of 417.0 mg/kg mice, intraperitoneally. The rats were randomly divided into seven (7) groups of 5 rats per group with one animal per metabolic cage. Group one served as the control (C1), groups two to six were treated with extract (200 mg/kg body weight orally and daily) for a maximum of ten (10) weeks, whereas, group seven (C2) received no extract treatment but was fed on normal rat chow. All the rats had free access to rat food and drinking water. The first group (C1) was sacrificed a fortnight after the commencement of the experiment, while group seven (C2) was sacrificed at the end (10th week) of the experiment. The extract-treated groups were sacrificed respectively in the order two, four, six, eight and ten week of extract administration. Whole blood was collected from these groups for analysis. Results showed significant [P < 0.01] increases in the level of total cholesterol (TC) from 1.92 +/- 0.11 mMol/L to 2.59 +/- 0.02 mMol/L (about 35% increase) and high-density lipoproteins (HDL) from 0.95 +/- 0.02 mMol/L to 1.50 +/- 0.08 mMol/L (about 58.50% increase) at week ten. The LDL levels, the total protein and albumin levels did not show any significant change from the control values. From the results, it is suggested that the crude aqueous extract from mistletoe leaf may be relatively safe for therapeutic use as it neither predisposes to cardiovascular risk nor adversely affects protein metabolism following prolonged period of administration. PMID:17242719

  10. Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels.

    PubMed

    Berge, Kjetil; Musa-Veloso, Kathy; Harwood, Melody; Hoem, Nils; Burri, Lena

    2014-02-01

    The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150-499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings. PMID:24461313

  11. Apolipoprotein E isoform-specific effects on lipoprotein receptor processing

    PubMed Central

    Bachmeier, Corbin; Shackleton, Ben; Ojo, Joseph; Paris, Daniel; Mullan, Michael; Crawford, Fiona

    2014-01-01

    Recent findings indicate an isoform-specific role for apolipoprotein E (apoE) in the elimination of beta-amyloid (Aβ) from the brain. ApoE is closely associated with various lipoprotein receptors, which contribute to Aβ brain removal via metabolic clearance or transit across the blood-brain barrier (BBB). These receptors are subject to ectodomain shedding at the cell surface, which alters endocytic transport and mitigates Aβ elimination. To further understand the manner in which apoE influences Aβ brain clearance, these studies investigated the effect of apoE on lipoprotein receptor shedding. Consistent with prior reports, we observed an increased shedding of the low density lipoprotein receptor (LDLR) and the LDLR-related protein 1 (LRP1) following Aβ exposure in human brain endothelial cells. When Aβ was co-treated with each apoE isoform, there was a reduction in Aβ-induced shedding with apoE2 and apoE3, while lipoprotein receptor shedding in the presence of apoE4 remained elevated. Likewise, intracranial administration of Aβ to apoE targeted replacement mice (expressing the human apoE isoforms) resulted in an isoform-dependent effect on lipoprotein receptor shedding in the brain (apoE4>apoE3>apoE2). Moreover, these results show a strong inverse correlation with our prior work in apoE transgenic mice in which apoE4 animals showed reduced Aβ clearance across the BBB compared to apoE3 animals. Based on these results, apoE4 appears less efficient than other apoE isoforms in regulating lipoprotein receptor shedding, which may explain the differential effects of these isoforms in removing Aβ from the brain. PMID:25015123

  12. Species-specific adaptations explain resilience of herbaceous understorey to increased precipitation variability in a Mediterranean oak woodland.

    PubMed

    Jongen, Marjan; Hellmann, Christine; Unger, Stephan

    2015-10-01

    To date, the implications of the predicted greater intra-annual variability and extremes in precipitation on ecosystem functioning have received little attention. This study presents results on leaf-level physiological responses of five species covering the functional groups grasses, forbs, and legumes in the understorey of a Mediterranean oak woodland, with increasing precipitation variability, without altering total annual precipitation inputs. Although extending the dry period between precipitation events from 3 to 6 weeks led to increased soil moisture deficit, overall treatment effects on photosynthetic performance were not observed in the studied species. This resilience to prolonged water stress was explained by different physiological and morphological strategies to withstand periods below the wilting point, that is, isohydric behavior in Agrostis, Rumex, and Tuberaria, leaf succulence in Rumex, and taproots in Tolpis. In addition, quick recovery upon irrigation events and species-specific adaptations of water-use efficiency with longer dry periods and larger precipitation events contributed to the observed resilience in productivity of the annual plant community. Although none of the species exhibited a change in cover with increasing precipitation variability, leaf physiology of the legume Ornithopus exhibited signs of sensitivity to moisture deficit, which may have implications for the agricultural practice of seeding legume-rich mixtures in Mediterranean grassland-type systems. This highlights the need for long-term precipitation manipulation experiments to capture possible directional changes in species composition and seed bank development, which can subsequently affect ecosystem state and functioning. PMID:26664676

  13. Lipoprotein(a) metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein. The metabolism of this lipoprotein is still not well understood. It has long been known that the plasma concentration of Lp(a) is highly heritable, with its genetic determinants located in the apo(a) locus and regulating the rate of hepatic apo(a...

  14. Model to explain the effects of halide ions on the increase in surface enhanced Raman spectral intensity over time

    NASA Astrophysics Data System (ADS)

    Cole, Michael A.

    Understanding the mechanisms responsible for the large increase in spectral intensity when molecules are adsorbed to nanoparticle surfaces such as occurs during surface enhanced Raman (SER) spectroscopy will allow scientists to probe ever smaller scales, even allowing single molecule detection. One particular scenario that increased the SER scattering efficiency was the addition of halide ions to Rhodamine 6G (R6G)-ethanol solution. This thesis presents a theoretical model explaining the effects of halide ions on the SER spectral intensity of the Rhodamine 6G (R6G) molecule when co-adsorbed to a silver nanoparticle surface. Glaspell et al. 2005, found a linear correlation between the increase in spectral intensities of selected vibrational normal modes of R6G over time and the polarizabilities of co-adsorbed halide ions. When the R6G molecule co-adsorbs to the silver nanoparticle surface with the halide ions, the molecule is exposed to three external electric fields that add vectorially, creating a total external electric field. Modelling the fields from the halide ions and the silver nanoparticles as electric dipole fields introduces the polarizability of the halide ion linearly into the Raman spectral intensity equation. This model also shows that there is a necessary interaction between the halide ions and the silver nanoparticle surface in order to see the effects as described by Glaspell et al. Furthermore, we will present experimental results that show that there is a necessary interaction between the halide ions and the nanoparticle surface. Without this interaction there was no increase in the SER spectral intensity of R6G or pyridine molecules in solution with the halide ions but without the silver nanoparticles.

  15. Different Mechanisms Must Be Considered to Explain the Increase in Hippocampal Neural Precursor Cell Proliferation by Physical Activity

    PubMed Central

    Overall, Rupert W.; Walker, Tara L.; Fischer, Tim J.; Brandt, Moritz D.; Kempermann, Gerd

    2016-01-01

    The number of proliferating neural precursor cells in the adult hippocampus is strongly increased by physical activity. The mechanisms through which this behavioral stimulus induces cell proliferation, however, are not yet understood. In fact, even the mode of proliferation of the stem and progenitor cells is not exactly known. Evidence exists for several mechanisms including cell cycle shortening, reduced cell death and stem cell recruitment, but as yet no model can account for all observations. An appreciation of how the cells proliferate, however, is crucial to our ability to model the neurogenic process and predict its behavior in response to pro-neurogenic stimuli. In a recent study, we addressed modulation of the cell cycle length as one possible mode of regulation of precursor cell proliferation in running mice. Our results indicated that the observed increase in number of proliferating cells could not be explained through a shortening of the cell cycle. We must therefore consider other mechanisms by which physical activity leads to enhanced precursor cell proliferation. Here we review the evidence for and against several different hypotheses and discuss the implications for future research in the field. PMID:27536215

  16. Effect of serum lipoproteins on the adenylate cyclase activity of rat liver plasma membranes.

    PubMed Central

    Ghiselli, G; Sirtori, C R; Nicosia, S

    1981-01-01

    Four rat lipoprotein classes [lymph chylomicrons, VLD (very-low-density), LD (low-density) and HD (high-density) lipoproteins] were tested for their ability to affect basal adenylate cyclase (EC 4.6.1.1) activity of rat liver plasma membranes. All the lipoproteins, with the exception of lymph chylomicrons, effectively increase the enzyme activity. VLD lipoproteins are the most active class (67% maximal increase), followed by HD lipoproteins (33%) and LD lipoproteins (23%). The effect of VLD lipoproteins is additive to that elicited by GTP or GTP plus glucagon (at least within a certain concentration range). VLD lipoproteins affect only the Vmax. of the enzyme, not the Km. PMID:7317023

  17. Increased {beta}-amyloid levels in the choroid plexus following lead exposure and the involvement of low-density lipoprotein receptor protein-1

    SciTech Connect

    Behl, Mamta; Zhang Yanshu; Monnot, Andrew D.; Jiang, Wendy; Zheng Wei

    2009-10-15

    The choroid plexus, a barrier between the blood and cerebrospinal fluid (CSF), is known to accumulate lead (Pb) and also possibly function to maintain brain's homeostasis of A{beta}, an important peptide in the etiology of Alzheimer's disease. This study was designed to investigate if Pb exposure altered A{beta} levels at the blood-CSF barrier in the choroid plexus. Rats received ip injection of 27 mg Pb/kg. Twenty-four hours later, a FAM-labeled A{beta} (200 pmol) was infused into the lateral ventricle and the plexus tissues were removed to quantify A{beta} accumulation. Results revealed a significant increase in intracellular A{beta} accumulation in the Pb-exposed animals compared to controls (p < 0.001). When choroidal epithelial Z310 cells were treated with 10 {mu}M Pb for 24 h and 48 h, A{beta} (2 {mu}M in culture medium) accumulation was significantly increased by 1.5 fold (p < 0.05) and 1.8 fold (p < 0.05), respectively. To explore the mechanism, we examined the effect of Pb on low-density lipoprotein receptor protein-1 (LRP1), an intracellular A{beta} transport protein. Following acute Pb exposure with the aforementioned dose regimen, levels of LRP1 mRNA and proteins in the choroid plexus were decreased by 35% (p < 0.05) and 31.8% (p < 0.05), respectively, in comparison to those of controls. In Z310 cells exposed to 10 {mu}M Pb for 24 h and 48 h, a 33.1% and 33.4% decrease in the protein expression of LRP1 was observed (p < 0.05), respectively. Knocking down LRP1 resulted in even more substantial increases of cellular accumulation of A{beta}, from 31% in cells without knockdown to 72% in cells with LRP1 knockdown (p < 0.05). Taken together, these results suggest that the acute exposure to Pb results in an increased accumulation of intracellular A{beta} in the choroid plexus; the effect appears to be mediated, at least in part, via suppression of LRP1 production following Pb exposure.

  18. BMP4 is increased in the aortas of diabetic ApoE knockout mice and enhances uptake of oxidized low density lipoprotein into peritoneal macrophages

    PubMed Central

    2013-01-01

    Background BMP4, a member of the transforming growth factor-beta superfamily, is upregulated in the aortas of diabetic db/db mice. However, little is known about its role in diabetic atherosclerosis. Therefore, we examined the roles of BMP4 in the formation of diabetic atherosclerosis in apolipoprotein E knockout (ApoE KO) mice and in the uptake of oxidized low density lipoprotein (oxLDL) in peritoneal macrophages of wild-type mice. Methods To induce diabetes, ApoE KO mice were intraperitoneally injected with streptozotocin. Diabetic and non-diabetic ApoE KO mice were then fed a high-fat diet for 4 weeks. Next, to investigate a role of BMP4 in the peritoneal macrophages, we examined the uptake of oxLDL in BMP4-treated macrophages. Results Diabetic ApoE KO mice showed accelerated progression of aortic plaques accompanied by increased luminal plaque area. Western blot analysis showed that BMP4 expression in the whole aorta was greatly increased in diabetic ApoE KO mice, than non-diabetic mice. Western blot analysis showed that the BMP4/SMAD1/5/8 signaling pathway was strongly activated in the aorta from diabetic ApoE KO mice, compared with control ApoE KO mice. Double immunofluorescence staining showed that BMP4 was expressed in MOMA2-labeled macrophage in the aortic lesions of ApoE KO mice. BMP4 significantly increased the uptake of oxLDL into peritoneal macrophages in vitro. Conclusion We show that in the aorta of diabetic ApoE KO mice, BMP4 is increased and activates SMAD1/5/8. Our in vitro findings indicate that BMP4 enhances oxLDL uptake in mouse peritoneal macrophages, suggesting BMP4 may be involved in aortic plaque formation in diabetic ApoE KO mice. Targeting BMP4 may offer a new strategy for inhibition of plaque progression and stabilization of atherosclerotic lesions. PMID:24107300

  19. A computational model for the analysis of lipoprotein distributions in the mouse: translating FPLC profiles to lipoprotein metabolism.

    PubMed

    Sips, Fianne L P; Tiemann, Christian A; Oosterveer, Maaike H; Groen, Albert K; Hilbers, Peter A J; van Riel, Natal A W

    2014-05-01

    Disturbances of lipoprotein metabolism are recognized as indicators of cardiometabolic disease risk. Lipoprotein size and composition, measured in a lipoprotein profile, are considered to be disease risk markers. However, the measured profile is a collective result of complex metabolic interactions, which complicates the identification of changes in metabolism. In this study we aim to develop a method which quantitatively relates murine lipoprotein size, composition and concentration to the molecular mechanisms underlying lipoprotein metabolism. We introduce a computational framework which incorporates a novel kinetic model of murine lipoprotein metabolism. The model is applied to compute a distribution of plasma lipoproteins, which is then related to experimental lipoprotein profiles through the generation of an in silico lipoprotein profile. The model was first applied to profiles obtained from wild-type C57Bl/6J mice. The results provided insight into the interplay of lipoprotein production, remodelling and catabolism. Moreover, the concentration and metabolism of unmeasured lipoprotein components could be determined. The model was validated through the prediction of lipoprotein profiles of several transgenic mouse models commonly used in cardiovascular research. Finally, the framework was employed for longitudinal analysis of the profiles of C57Bl/6J mice following a pharmaceutical intervention with a liver X receptor (LXR) agonist. The multifaceted regulatory response to the administration of the compound is incompletely understood. The results explain the characteristic changes of the observed lipoprotein profile in terms of the underlying metabolic perturbation and resultant modifications of lipid fluxes in the body. The Murine Lipoprotein Profiler (MuLiP) presented here is thus a valuable tool to assess the metabolic origin of altered murine lipoprotein profiles and can be applied in preclinical research performed in mice for analysis of lipid fluxes and

  20. Lipoprotein sorting in bacteria.

    PubMed

    Okuda, Suguru; Tokuda, Hajime

    2011-01-01

    Bacterial lipoproteins are synthesized as precursors in the cytoplasm and processed into mature forms on the cytoplasmic membrane. A lipid moiety attached to the N terminus anchors these proteins to the membrane surface. Many bacteria are predicted to express more than 100 lipoproteins, which play diverse functions on the cell surface. The Lol system, composed of five proteins, catalyzes the localization of Escherichia coli lipoproteins to the outer membrane. Some lipoproteins play vital roles in the sorting of other lipoproteins, lipopolysaccharides, and β-barrel proteins to the outer membrane. On the basis of results from biochemical, genetic, and structural studies, we discuss the biogenesis of lipoproteins in bacteria, their importance in cellular functions, and the molecular mechanisms underlying efficient sorting of hydrophobic lipoproteins to the outer membrane through the hydrophilic periplasm. PMID:21663440

  1. Central Nervous System Lipoproteins

    PubMed Central

    Mahley, Robert W.

    2016-01-01

    ApoE on high-density lipoproteins is primarily responsible for lipid transport and cholesterol homeostasis in the central nervous system (CNS). Normally produced mostly by astrocytes, apoE is also produced under neuropathologic conditions by neurons. ApoE on high-density lipoproteins is critical in redistributing cholesterol and phospholipids for membrane repair and remodeling. The 3 main structural isoforms differ in their effectiveness. Unlike apoE2 and apoE3, apoE4 has markedly altered CNS metabolism, is associated with Alzheimer disease and other neurodegenerative disorders, and is expressed at lower levels in brain and cerebrospinal fluid. ApoE4-expressing cultured astrocytes and neurons have reduced cholesterol and phospholipid secretion, decreased lipid-binding capacity, and increased intracellular degradation. Two structural features are responsible for apoE4 dysfunction: domain interaction, in which arginine-61 interacts ionically with glutamic acid-255, and a less stable conformation than apoE3 and apoE2. Blocking domain interaction by gene targeting (replacing arginine-61 with threonine) or by small-molecule structure correctors increases CNS apoE4 levels and lipid-binding capacity and decreases intracellular degradation. Small molecules (drugs) that disrupt domain interaction, so-called structure correctors, could prevent the apoE4-associated neuropathology by blocking the formation of neurotoxic fragments. Understanding how to modulate CNS cholesterol transport and metabolism is providing important insights into CNS health and disease. PMID:27174096

  2. Fat utilization during exercise: adaptation to a fat-rich diet increases utilization of plasma fatty acids and very low density lipoprotein-triacylglycerol in humans

    PubMed Central

    Helge, Jørn W; Watt, Peter W; Richter, Erik A; Rennie, Michael J; Kiens, Bente

    2001-01-01

    This study was carried out to test the hypothesis that the greater fat oxidation observed during exercise after adaptation to a high-fat diet is due to an increased uptake of fat originating from the bloodstream. Of 13 male untrained subjects, seven consumed a fat-rich diet (62% fat, 21% carbohydrate) and six consumed a carbohydrate-rich diet (20% fat, 65% carbohydrate). After 7 weeks of training and diet, 60 min of bicycle exercise was performed at 68 ± 1% of maximum oxygen uptake. During exercise [1-13C]palmitate was infused, arterial and venous femoral blood samples were collected, and blood flow was determined by the thermodilution technique. Muscle biopsy samples were taken from the vastus lateralis muscle before and after exercise. During exercise, the respiratory exchange ratio was significantly lower in subjects consuming the fat-rich diet (0.86 ± 0.01, mean ±s.e.m.) than in those consuming the carbohydrate-rich diet (0.93 ± 0.02). The leg fatty acid (FA) uptake (183 ± 37 vs. 105 ± 28 μmol min−1) and very low density lipoprotein-triacylglycerol (VLDL-TG) uptake (132 ± 26 vs. 16 ± 21 μmol min−1) were both higher (each P < 0.05) in the subjects consuming the fat-rich diet. Whole-body plasma FA oxidation (determined by comparison of 13CO2 production and blood palmitate labelling) was 55-65% of total lipid oxidation, and was higher after the fat-rich diet than after the carbohydrate-rich diet (13.5 ± 1.2 vs. 8.9 ± 1.1 μmol min−1 kg−1; P < 0.05). Muscle glycogen breakdown was significantly lower in the subjects taking the fat-rich diet than those taking the carbohydrate-rich diet (2.6 ± 0.5 vs. 4.8 ± 0.5 mmol (kg dry weight)−1 min−1, respectively; P < 0.05), whereas leg glucose uptake was similar (1.07 ± 0.13 vs. 1.15 ± 0.13 mmol min−1). In conclusion, plasma VLDL-TG appears to be an important substrate source during aerobic exercise, and in combination with the higher plasma FA uptake it accounts for the increased fat oxidation

  3. Increased levels of low-density lipoprotein cholesterol within the normal range as a risk factor for nonalcoholic fatty liver disease

    PubMed Central

    Zhu, Gui-Qi; Braddock, Martin; Zhang, Dong-Chu; Shi, Ke-Qing; Song, Dan; Zheng, Ming-Hua

    2016-01-01

    Objectives Dyslipidemia exists within the setting of NAFLD and the relationship of a normal level of low-density lipoprotein cholesterol (LDL-c) with NAFLD is largely unknown. This large population-based study aimed to investigate the association between LDL-c levels within the normal range and the incidence of NAFLD. Methods A total of 60527 subjects from 2 medical centers who had undergone liver ultrasonography were initially enrolled into this study. NAFLD was defined by ultrasonographic detection of steatosis in the absence of other liver disease. Subjects were divided into 4 groups (Q1 to Q4) by normal LDL-c quartiles : Q1: ≤ 2.00, Q2: 2.10-2.35, Q3: 2.36-2.68 and Q4: 2.69-3.12 mmol/L. The odds ratios (OR), hazard ratio (HR) and 95% confidence intervals (CIs) for NAFLD were calculated across each quartile of LDL-c, using the Q1 as reference. Results The prevalence rates of NAFLD in a cross-sectional population from Q1 to Q4 were 19.34%, 25.86%, 35.65% and 42.08%, respectively. The OR for NAFLD in the cross-sectional population were 1.31 (95% CI 1.14-1.54), 1.73 (95% CI 1.46-2.04), and 1.82 (95% CI 1.49-2.23), respectively, after adjusting for known confounding variables. The HR for NAFLD in the longitudinal population were 1.23 (95% CI 1.12-1.35), 1.57 (95% CI 1.44-1.72) and 2.02 (95% CI 1.86-2.21), compared with Q1. Subjects with higher LDL-c level within the normal range had an increased cumulative incidence rate of NAFLD. Conclusions Increased levels of LDL-c within the normal range may play a significant role in the prevalence and incidence of NAFLD, independent of other confounding factors. PMID:26735337

  4. Cholesteryl-ester transfer protein enhances the ability of high-density lipoprotein to inhibit low-density lipoprotein oxidation.

    PubMed

    Hine, David; Mackness, Bharti; Mackness, Mike

    2011-09-01

    Therapeutic strategies to increase high-density lipoprotein (HDL) to treat or prevent vascular disease include the use of cholesteryl-ester transfer protein (CETP) inhibitors. Here, we show, to the best of our knowledge for the first time, that addition of CETP to HDL enhances the ability of HDL to inhibit low-density lipoprotein oxidation by ∼ 30% for total HDL and HDL(2) (both P < 0.05) and 75% for HDL(3) (P < 0.01). Therefore, CETP inhibition may be detrimental to the antiatherosclerotic properties of HDL, and these findings may partly explain the failure of the CETP inhibitor, torcetrapib, treatment to retard vascular disease despite large increases in HDL, in addition to its "off target" toxicity, a property which appears not to be shared by other members of this class of CETP inhibitor currently under clinical trial. Further, detailed studies are urgently required. PMID:21815241

  5. [Lipoproteins, free radicals and atherosclerosis].

    PubMed

    Manso, C

    1990-10-01

    The Author reviews vascular, lipidic and oxidative factors in the genesis of atherosclerosis. He admits the possibility that an alteration in the arterial wall, an increase in circulating lipids or an oxidative stress may influence the precocity of atherosclerosis. The transport of lipoperoxides or of oxidized cholesterol by lipoproteins renders them toxic and susceptible to aggravate atherosclerosis. PMID:2291852

  6. Lipoproteins of bacterial pathogens.

    PubMed

    Kovacs-Simon, A; Titball, R W; Michell, S L

    2011-02-01

    Bacterial lipoproteins are a set of membrane proteins with many different functions. Due to this broad-ranging functionality, these proteins have a considerable significance in many phenomena, from cellular physiology through cell division and virulence. Here we give a general overview of lipoprotein biogenesis and highlight examples of the roles of lipoproteins in bacterial disease caused by a selection of medically relevant Gram-negative and Gram-positive pathogens: Mycobacterium tuberculosis, Streptococcus pneumoniae, Borrelia burgdorferi, and Neisseria meningitidis. Lipoproteins have been shown to play key roles in adhesion to host cells, modulation of inflammatory processes, and translocation of virulence factors into host cells. As such, a number of lipoproteins have been shown to be potential vaccines. This review provides a summary of some of the reported roles of lipoproteins and of how this knowledge has been exploited in some cases for the generation of novel countermeasures to bacterial diseases. PMID:20974828

  7. Arachnid lipoproteins: comparative aspects.

    PubMed

    Cunningham, Mónica; Garcia, Fernando; Pollero, Ricardo J

    2007-01-01

    Findings on hemolymph lipoproteins in the class Arachnida are reviewed in relation to their lipid and protein compositions, hydrated densities, the capacity of apoproteins to bind lipids, and the influence of xenobiotics on their structures and functionality. The occurrence of hemolymphatic lipoproteins in arachnids has been reported in species belonging to the orders Araneida, Scorpionida, Solpugida and Acarina. However, lipoproteins were properly characterized in only three species, Eurypelma californicum, Polybetes pythagoricus and Latrodectus mirabilis. Like insect and crustaceans the arachnids examined contain high density lipoproteins (HDLs) as predominant circulating lipoproteins. Although in most arachnids these particles resemble those of insect HDLs called "lipophorins", in two arachnid species they differ from lipophorins in their apoproteins, total mass and lipid composition. The hemolymph of P. pythagoricus and L. mirabilis contains another HDL of higher density, while P. pythagoricus and E. californicum hemolymph contain a third lipoprotein of very high density (VHDL). Composition of arachnid lipoproteins regarding apoprotein classes as well as lipid classes differ among species. Hemocyanin, in addition to the classical role of this protein as respiratory pigment, is presented here performing the function of apolipoprotein in some arachnid species. Reports on experiments demonstrating the capacity of hemocyanin to bind neutral and polar lipid classes, including ecdysteroids, are commented. Recent works about the changes evoked by a phosphorous pesticide on the structures and functionality of spider lipoproteins are also reviewed. PMID:16887396

  8. Can increased nitrogen uptake at elevated CO2 be explained by an hypothesis of optimal root function?

    NASA Astrophysics Data System (ADS)

    McMurtrie, R. E.; Norby, R. J.; Näsholm, T.; Iversen, C.; Dewar, R. C.; Medlyn, B. E.

    2011-12-01

    Forest free-air CO2 enrichment (FACE) experiments have shown that annual nitrogen (N) uptake increases when trees are grown at elevated CO2 (eCO2) and that increased N uptake is critical for a sustained growth response to eCO2. Processes contributing to increased N uptake at eCO2 may include: accelerated decomposition of soil organic matter due to enhanced root carbon (C) exudation (so-called rhizosphere priming); increased C allocation to fine roots and increased root production at depth, both of which enhance N acquisition; differences in soil N availability with depth; changes in the abundance of N in chemical forms with differing mobility in soil; and reduced N concentrations, reduced maintenance respiration rates, and increased longevities of deeper roots. These processes have been synthesised in a model of annual N uptake in relation to the spatial distribution of roots. We hypothesise that fine roots are distributed spatially in order to maximise annual N uptake. The optimisation hypothesis leads to equations for the optimal vertical distribution of root biomass in relation to the distribution of available soil N and for maximum annual N uptake. We show how maximum N uptake and rooting depth are related to total root mass, and compare the optimal solution with an empirical function that has been fitted to root-distribution data from all terrestrial biomes. Finally, the model is used to explore the consequences of rhizosphere priming at eCO2 as observed at the Duke forest FACE experiment (Drake et al. 2011, Ecology Letters 14: 349-357) and of increasing N limitation over time as observed at the Oak Ridge FACE experiment (Norby et al. 2010, Proc. Nat. Acad. Sci. USA 107: 19368-19373).

  9. [The high content of palmitinic fatty acid in food as a major cause of increase of concentration of cholesterol and low density lipoproteins and atheromatous plaques of arteries' intima].

    PubMed

    Titov, V N

    2013-02-01

    The positioning of individual triglycerides of blood serum in palmitinic and oleic lipoproteins ofvery low density in the order ofincrease of the rate constant of their hydrolysis under action of post-heparin lipoprotein leads to the sequence as follows: palmitoil-palmitoil-palmitate-->palmitoil-palmitoil-oleate-->palmitoil-oleil-palmitat-->oleil-palmitoil-palmitate-->oleil-palmitate-palmitate-->oleil-oleil-palmitate-->oleil-oleil-oleate. The shift to the left and to the right is discerned with this spectrum of isoforms of triglycerides. The shift to the left into direction of palmitinicc triglycerides occurs in case of eating of animal food (i.e. beef andfoodstuf of fat saw milk) when the content of palmitinic saturated fatty acid supersedes 15% of fatty acids total and under the development of endogenic syndrome of insulin resistance. The content of low density lipoproteins cholesterol is high in blood The shift to the right with prevalence of oleinic triglycerides occurs in case of low content of beef and foodstuff of fat saw milk in food, fish eating, seafood and olive oil. The physiologic levels of carbohydrates in food and insulin function are present too. The shift to the right initiates the action of insulin, ometa-3 essential polyenic fatty acids, glytazones and fibrates. They increase the activity of delta9-stearil-KoA-desaturase-2 and the transformation of palmitine saturated fatty acid into mono unsaturated oleinic fatty acid. The shift to the left forms the palmitine alternative of metabolism of substrate to supply cells with energy. The shift to the right is a more effective oleinic alternative. PMID:23808000

  10. Familial lipoprotein lipase deficiency

    MedlinePlus

    ... and white-colored blood vessels in the retinas Pancreatitis that keeps returning Yellowing of the eyes and ... discuss your diet needs with a registered dietitian. Pancreatitis that is related to lipoprotein lipase deficiency responds ...

  11. Thermal stability of human plasma electronegative low-density lipoprotein: A paradoxical behavior of low-density lipoprotein aggregation.

    PubMed

    Rull, Anna; Jayaraman, Shobini; Gantz, Donald L; Rivas-Urbina, Andrea; Pérez-Cuellar, Montserrat; Ordóñez-Llanos, Jordi; Sánchez-Quesada, Jose Luis; Gursky, Olga

    2016-09-01

    Low-density lipoprotein (LDL) aggregation is central in triggering atherogenesis. A minor fraction of electronegative plasma LDL, termed LDL(-), plays a special role in atherogenesis. To better understand this role, we analyzed the kinetics of aggregation, fusion and disintegration of human LDL and its fractions, LDL(+) and LDL(-). Thermal denaturation of LDL was monitored by spectroscopy and electron microscopy. Initially, LDL(-) aggregated and fused faster than LDL(+), but later the order reversed. Most LDL(+) disintegrated and precipitated upon prolonged heating. In contrast, LDL(-) partially retained lipoprotein morphology and formed soluble aggregates. Biochemical analysis of all fractions showed no significant degradation of major lipids, mild phospholipid oxidation, and an increase in non-esterified fatty acid (NEFA) upon thermal denaturation. The main baseline difference between LDL subfractions was higher content of NEFA in LDL(-). Since NEFA promote lipoprotein fusion, increased NEFA content can explain rapid initial aggregation and fusion of LDL(-) but not its resistance to extensive disintegration. Partial hydrolysis of apoB upon heating was similar in LDL subfractions, suggesting that minor proteins importantly modulate LDL disintegration. Unlike LDL(+), LDL(-) contains small amounts of apoA-I and apoJ. Addition of exogenous apoA-I to LDL(+) hampered lipoprotein aggregation, fusion and precipitation, while depletion of endogenous apoJ had an opposite effect. Therefore, the initial rapid aggregation of LDL(-) is apparently counterbalanced by the stabilizing effects of minor proteins such as apoA-I and apoJ. These results help identify key determinants for LDL aggregation, fusion and coalescence into lipid droplets in vivo. PMID:27233433

  12. Lipoproteins, nutrition, and heart disease.

    PubMed

    Schaefer, Ernst J

    2002-02-01

    This article reviews the current status of our knowledge of lipoproteins, nutrition, and coronary heart disease (CHD). Special emphasis is placed on CHD risk assessment, dietary intervention studies, diet-gene interactions, and current dietary guidelines and the contributions of my laboratory to these areas. CHD remains a major cause of death and disability, and risk factors include age, sex, hypertension, smoking, diabetes, elevated serum LDL cholesterol, and low HDL cholesterol. Emerging independent risk factors include elevated serum concentrations of lipoprotein(a), remnant lipoproteins, and homocysteine. The cornerstone of CHD prevention is lifestyle modification. Dietary intervention studies support the concepts that restricting saturated fat and cholesterol and increasing the intake of essential fatty acids, especially n - 3 fatty acids, reduces CHD risk. The variability in LDL-cholesterol response to diet is large, related in part to APOE and APOA4 genotype. The use of antioxidants in intervention studies has not been shown to reduce CHD risk. Compliance with dietary recommendations remains a major problem, and directly altering the food supply may be the most effective way to ensure compliance. The available data indicate that the recommendation to use fats, oils, and sugars sparingly for CHD prevention should be modified to a recommendation to use animal, dairy, and hydrogenated fats; tropical oils; egg yolks; and sugars sparingly and to increase the use of vegetables, fruit, and whole grains. PMID:11815309

  13. Lipoprotein Lipase releases esterified oxylipins from Very Low Density Lipoproteins

    PubMed Central

    Shearer, Gregory C.; Newman, John W.

    2009-01-01

    We previously demonstrated that defects in lipoprotein metabolism alter the distribution of oxygenated polyunsaturated fatty acids (PUFAs) in lipoprotein particles. If these oxidation products are released by lipoprotein lipase (LpL), then their delivery to peripheral tissues with bulk lipids could influence cellular function. Using 26 week old normolipidemic and hyperlipidemic Zucker rats, we measured PUFA alcohols, epoxides, diols, ketones and triols (i.e. oxylipins) in esterified and non-esterified fractions of whole plasma, VLDL, and LpL-generated VLDL-lipolysates. Whole plasma, VLDL, and lipolysate oxylipin profiles were distinct and altered by hyperlipidemia. While >90% of the whole plasma oxylipins were esterified, the fraction of each oxylipin class in the VLDL varied: 46% of alcohols, 30% of epoxides, 19% of diols, <10% of ketones, <1% triols. Whole plasma was dominated by arachidonate alcohols, while the linoleate alcohols, epoxides and ketones showed an increased prevalence in VLDL. LpL-mediated VLDL lipolysis of PUFA alcohols, diols and ketones was detected and the relative abundance of oxygenated linoleates was enhanced in the lipolysates, relative to their corresponding VLDL. In summary esterified oxylipins were seen to be LpL substrates with heterogeneous distributions among lipoprotein classes. Moreover, oxylipin distributions are changes within the context of obesity-associated dyslipidemia. These results support the notion that the VLDL-LpL axis may facilitate the delivery of plasma oxylipins to the periphery. The physiological implication of these findings are yet to be elucidated, however these molecules are plausible indicators of systemic oxidative stress, and could report this status to the peripheral tissues. PMID:19042114

  14. The association between advanced maternal and paternal ages and increased adult mortality is explained by early parental loss

    PubMed Central

    Elo, Irma T.; Kohler, Iliana; Martikainen, Pekka

    2015-01-01

    The association between advanced maternal and paternal ages at birth and increased mortality among adult offspring is often attributed to parental reproductive ageing, e.g., declining oocyte or sperm quality. Less attention has been paid to alternative mechanisms, including parental socio-demographic characteristics or the timing of parental death. Moreover, it is not known if the parental age-adult mortality association is mediated by socioeconomic attainment of the children, or if it varies over the lifecourse of the adult children. We used register-based data drawn from the Finnish 1950 census (sample size 89,737; mortality follow-up 1971–2008) and discrete-time survival regression with logit link to analyze these alternative mechanisms in the parental age-offspring mortality association when the children were aged 35–49 and 50–72. Consistent with prior literature, we found that adult children of older parents had increased mortality relative to adults whose parents were aged 25–29 at the time of birth. For example, maternal and paternal ages 40–49 were associated with mortality odds ratios (ORs)of 1.31 (p<.001) and 1.22 (p<.01), respectively, for offspring mortality at ages 35–49. At ages 50–72 advanced parental age also predicted higher mortality, though not as strongly. Adjustment for parental socio-demographic characteristics (education, occupation, family size, household crowding, language) weakened the associations only slightly. Adjustment for parental survival, measured by whether the parents were alive when the child reached age 35, reduced the advanced parental age coefficients substantially and to statistically insignificant levels. These results indicate that the mechanism behind the advanced parental age-adult offspring mortality association is mainly social, reflecting early parental loss and parental characteristics, rather than physiological mechanisms reflecting reproductive ageing. PMID:24997641

  15. The association between advanced maternal and paternal ages and increased adult mortality is explained by early parental loss.

    PubMed

    Myrskylä, Mikko; Elo, Irma T; Kohler, Iliana V; Martikainen, Pekka

    2014-10-01

    The association between advanced maternal and paternal ages at birth and increased mortality among adult offspring is often attributed to parental reproductive aging, e.g., declining oocyte or sperm quality. Less attention has been paid to alternative mechanisms, including parental socio-demographic characteristics or the timing of parental death. Moreover, it is not known if the parental age-adult mortality association is mediated by socioeconomic attainment of the children, or if it varies over the lifecourse of the adult children. We used register-based data drawn from the Finnish 1950 census (sample size 89,737; mortality follow-up 1971-2008) and discrete-time survival regression with logit link to analyze these alternative mechanisms in the parental age-offspring mortality association when the children were aged 35-49 and 50-72. Consistent with prior literature, we found that adult children of older parents had increased mortality relative to adults whose parents were aged 25-29 at the time of birth. For example, maternal and paternal ages 40-49 were associated with mortality odds ratios (ORs) of 1.31 (p<.001) and 1.22 (p<.01), respectively, for offspring mortality at ages 35-49. At ages 50-72 advanced parental age also predicted higher mortality, though not as strongly. Adjustment for parental socio-demographic characteristics (education, occupation, family size, household crowding, language) weakened the associations only slightly. Adjustment for parental survival, measured by whether the parents were alive when the child reached age 35, reduced the advanced parental age coefficients substantially and to statistically insignificant levels. These results indicate that the mechanism behind the advanced parental age-adult offspring mortality association is mainly social, reflecting early parental loss and parental characteristics, rather than physiological mechanisms reflecting reproductive aging. PMID:24997641

  16. Insulin response dysregulation explains abnormal fat storage and increased risk of diabetes mellitus type 2 in Cohen Syndrome.

    PubMed

    Limoge, Floriane; Faivre, Laurence; Gautier, Thomas; Petit, Jean-Michel; Gautier, Elodie; Masson, David; Jego, Gaëtan; El Chehadeh-Djebbar, Salima; Marle, Nathalie; Carmignac, Virginie; Deckert, Valérie; Brindisi, Marie-Claude; Edery, Patrick; Ghoumid, Jamal; Blair, Edward; Lagrost, Laurent; Thauvin-Robinet, Christel; Duplomb, Laurence

    2015-12-01

    Cohen Syndrome (CS) is a rare autosomal recessive disorder, with defective glycosylation secondary to mutations in the VPS13B gene, which encodes a protein of the Golgi apparatus. Besides congenital neutropenia, retinopathy and intellectual deficiency, CS patients are faced with truncal obesity. Metabolism investigations showed abnormal glucose tolerance tests and low HDL values in some patients, and these could be risk factors for the development of diabetes mellitus and/or cardiovascular complications. To understand the mechanisms involved in CS fat storage, we used two models of adipogenesis differentiation: (i) SGBS pre-adipocytes with VPS13B invalidation thanks to siRNA delivery and (ii) CS primary fibroblasts. In both models, VPS13B invalidation led to accelerated differentiation into fat cells, which was confirmed by the earlier and increased expression of specific adipogenic genes, consequent to the increased response of cells to insulin stimulation. At the end of the differentiation protocol, these fat cells exhibited decreased AKT2 phosphorylation after insulin stimulation, which suggests insulin resistance. This study, in association with the in-depth analysis of the metabolic status of the patients, thus allowed us to recommend appropriate nutritional education to prevent the occurrence of diabetes mellitus and to put forward recommendations for the follow-up of CS patients, in particular with regard to the development of metabolic syndrome. We also suggest replacing the term obesity by abnormal fat distribution in CS, which should reduce the number of inappropriate diagnoses in patients who are referred only on the basis of intellectual deficiency associated with obesity. PMID:26358774

  17. Mechanically induced structural changes during dynamic compression of engineered cartilaginous constructs can potentially explain increases in bulk mechanical properties

    PubMed Central

    Nagel, Thomas; Kelly, Daniel J.

    2012-01-01

    Several studies on chondrocyte-seeded hydrogels in bioreactor culture report increased mechanical properties of mechanically loaded constructs compared with unloaded free swelling controls despite no significant differences in biochemical composition. One possible explanation is that changes in the collagen architecture of dynamically compressed constructs lead to improved mechanical properties. Collagen molecules are incorporated locally into the extracellular matrix with individual stress-free configurations and orientations. In this study, we computationally investigated possible influences of loading on the collagen architecture in chondrocyte-seeded hydrogels and their resulting mechanical properties. Both the collagen orientation and its stress-free configuration were hypothesized to depend on the local mechanical environment. Reorientation of the collagen network alone in response to dynamic compression leads to a prediction of constructs with lower compressive properties. In contrast, remodelling of the stress-free configuration of the collagen fibres was predicted to result in a more compacted tissue with higher swelling pressures and an altered pre-stressed state within the collagen network. Combining both mechanisms resulted in predictions of construct geometry and mechanical properties in agreement with experimental observations. This study provides support for the hypothesis that structural changes to the collagen network contribute to the enhanced mechanical properties of cartilaginous tissues engineered in bioreactors. PMID:21900321

  18. The affective reactivity of psychotic speech: The role of internal source monitoring in explaining increased thought disorder under emotional challenge.

    PubMed

    de Sousa, Paulo; Sellwood, William; Spray, Amy; Bentall, Richard P

    2016-04-01

    Thought disorder (TD) has been shown to vary in relation to negative affect. Here we examine the role internal source monitoring (iSM, i.e. ability to discriminate between inner speech and verbalized speech) in TD and whether changes in iSM performance are implicated in the affective reactivity effect (deterioration of TD when participants are asked to talk about emotionally-laden topics). Eighty patients diagnosed with schizophrenia-spectrum disorder and thirty healthy controls received interviews that promoted personal disclosure (emotionally salient) and interviews on everyday topics (non-salient) on separate days. During the interviews, participants were tested on iSM, self-reported affect and immediate auditory recall. Patients had more TD, poorer ability to discriminate between inner and verbalized speech, poorer immediate auditory recall and reported more negative affect than controls. Both groups displayed more TD and negative affect in salient interviews but only patients showed poorer performance on iSM. Immediate auditory recall did not change significantly across affective conditions. In patients, the relationship between self-reported negative affect and TD was mediated by deterioration in the ability to discriminate between inner speech and speech that was directed to others and socially shared (performance on the iSM) in both interviews. Furthermore, deterioration in patients' performance on iSM across conditions significantly predicted deterioration in TD across the interviews (affective reactivity of speech). Poor iSM is significantly associated with TD. Negative affect, leading to further impaired iSM, leads to increased TD in patients with psychosis. Avenues for future research as well as clinical implications of these findings are discussed. PMID:26851142

  19. Black-white differences in postprandial triglyceride response and postheparin lipoprotein lipase and hepatic triglyceride lipase among young men.

    PubMed

    Friday, K E; Srinivasan, S R; Elkasabany, A; Dong, C; Wattigney, W A; Dalferes, E; Berenson, G S

    1999-06-01

    Black-white differences in serum triglycerides and high-density lipoprotein (HDL) cholesterol concentrations are known. However, the metabolic basis for these differences is not clear. This study determined the magnitude of postprandial triglyceride concentrations, lipoprotein lipase and hepatic triglyceride lipase activities in postheparin plasma, and serum lipid and lipoprotein cholesterol concentrations in healthy young adult black men (n = 22) and white men (n = 28). Postprandial triglyceride concentrations were measured at 2, 3, 4, 5, 6, and 8 hours after a standardized test meal. Serum lipid and lipoprotein cholesterol concentrations were similar between the races in this study sample. However, incremental (above basal) increases in triglycerides were significantly greater in white men versus black men at 2 hours (P = .01) and tended to be greater at 3 hours (P = .12) and 4 hours (P = .06) after the fat load. In a multivariate analysis that included age, race, apolipoprotein E (apoE) genotype, fasting triglycerides, obesity measures, alcohol intake, and cigarette use, fasting triglycerides (P = .04) and, to a lesser extent, race (P = .07) were associated independently with the 2-hour incremental increase in triglycerides. The incremental triglyceride response correlated inversely with HDL cholesterol in both whites (r = -.38, P = .04) and blacks (r = -.59, P = .004). Lipoprotein lipase activity was higher (P = .049) and hepatic triglyceride lipase activity lower (P = .0001) in black men compared with white men; racial differences persisted after adjusting for the covariates. While lipoprotein lipase activity tended to associate inversely with the postprandial triglyceride concentration in both races, hepatic triglyceride lipase activity tended to correlate positively in whites and inversely in blacks. These results suggest that compared with whites, blacks may have an efficient lipid-clearing mechanism that could explain the black-white differences in

  20. A vanadyl sulfate-bovine serum albumin complex stimulates the release of lipoprotein lipase activity from isolated rat fat pads through an increase in the cellular content of cAMP and myo-inositol 1,4,5-trisphosphate.

    PubMed

    Motoyashiki, T; Miyake, M; Yoshida, A; Morita, T; Ueki, H

    1999-08-01

    A vanadyl sulfate-bovine serum albumin complex (vanadyl-BSA) prolonged the stability of the V4+ oxidation state, although vanadyl alone can readily change the oxidation state from V4+ to V5+ under physiological conditions. Vanadyl-BSA stimulated the release of lipoprotein lipase (LPL) activity from isolated rat fat pads and increased the cellular LPL activity in a time-dependent manner. These effects were independent of protein synthesis. Propranolol, quin 2-AM, ruthenium red, and neomycin all inhibited LPL release more potently than the increase in activity. In contrast, potent inhibition of the increase effect was observed with genistein and wortmannin. Short-term incubation of the fat pads with vanadyl-BSA showed a transient increase in the cellular content of cAMP and myo-inositol 1,4,5-trisphosphate (IP3), which was inhibited by propranolol and neomycin, respectively. These results suggest that vanadyl-BSA stimulates the release of LPL activity through an increase in the cellular content of cAMP and IP3, leading to an increased intracellular Ca2+ concentration, and that it also increases cellular LPL activity via process(es) sensitive to genistein and wortmannin. PMID:10480313

  1. Revisiting the Gram-Negative Lipoprotein Paradigm

    PubMed Central

    LoVullo, Eric D.; Wright, Lori F.; Isabella, Vincent; Huntley, Jason F.

    2015-01-01

    ABSTRACT The processing of lipoproteins (Lpps) in Gram-negative bacteria is generally considered an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein N-acyltransferase. The mature lipoproteins are then sorted by the Lol system, with most Lpps inserted into the outer membrane (OM). We demonstrate here that the lnt gene is not essential to the Gram-negative pathogen Francisella tularensis subsp. tularensis strain Schu or to the live vaccine strain LVS. An LVS Δlnt mutant has a small-colony phenotype on sucrose medium and increased susceptibility to globomycin and rifampin. We provide data indicating that the OM lipoprotein Tul4A (LpnA) is diacylated but that it, and its paralog Tul4B (LpnB), still sort to the OM in the Δlnt mutant. We present a model in which the Lol sorting pathway of Francisella has a modified ABC transporter system that is capable of recognizing and sorting both triacylated and diacylated lipoproteins, and we show that this modified system is present in many other Gram-negative bacteria. We examined this model using Neisseria gonorrhoeae, which has the same Lol architecture as that of Francisella, and found that the lnt gene is not essential in this organism. This work suggests that Gram-negative bacteria fall into two groups, one in which full lipoprotein processing is essential and one in which the final acylation step is not essential, potentially due to the ability of the Lol sorting pathway in these bacteria to sort immature apolipoproteins to the OM. IMPORTANCE This paper describes the novel finding that the final stage in lipoprotein processing (normally considered an essential process) is not required by Francisella tularensis or Neisseria gonorrhoeae. The paper provides a potential reason for this and shows that it may be widespread in other Gram-negative bacteria. PMID:25755189

  2. Metabolism of apoprotein B of plasma very low density lipoproteins in the rat.

    PubMed Central

    Faergeman, O; Sata, T; Kane, J P; Havel, R J

    1975-01-01

    As an extension of metabolic studies of the cholesteryl ester component of rat very low density lipoproteins, we have studied the metabolism of the B apoprotein component labeled by intravenous injection of [3H]lysine. The B apoprotein separated from other apoproteins by delipidation and selective precipitation with tetramethylurea could not be distinguished from B apoprotein prepared by the conventional gel filtration technique. After injection of [3H]lysine, specific activity of B apoprotein was maximal in very low density and low density lipoproteins 1 and 11/2-h later, respectively, in a manner consistent with a precursor-product relationship. When protein-labeled very low density lipoproteins were injected into rats, the relationships of specific activity again indicated that B apoprotein of very low density lipoproteins may be the sole precursor of that of low density lipoproteins. However, less than 10% of the B apoprotein that disappeared from very low density lipoproteins appeared in density lipoproteins. To evaluate the sites of removal of B aproprotein of very low density lipoproteins from plasma, protein-labeled very low density lipoproteins were incubated with unlabeled high density lipoproteins to reduce radioactivity in non-B apoproteins selectively by molecular exchange. Most of the B apoprotein was rapidly removed by the liver. The extensive hepatic uptake of both the cholesteryl ester and B apoprotein components of rat very low density lipoproteins may explain the characteristically low concentrations of plasma low density lipoproteins in the rat. PMID:172530

  3. High-Density Lipoprotein, Lecithin: Cholesterol Acyltransferase, and Atherosclerosis

    PubMed Central

    Ossoli, Alice; Pavanello, Chiara

    2016-01-01

    Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system. PMID:27302716

  4. High-Density Lipoprotein, Lecithin: Cholesterol Acyltransferase, and Atherosclerosis.

    PubMed

    Ossoli, Alice; Pavanello, Chiara; Calabresi, Laura

    2016-06-01

    Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system. PMID:27302716

  5. Lipoprotein marker for hypertriglyceridemia

    DOEpatents

    Cubicciotti, Roger S.; Karu, Alexander E.; Krauss, Ronald M.

    1986-01-01

    Methods and compositions are provided for the detection of a particular low density lipoprotein which has been found to be a marker for patients suffering from type IV hypertriglyceridemia. A monoclonal antibody capable of specifically binding to a characteristic epitopic site on this LDL subspecies can be utilized in a wide variety of immunoassays. Hybridoma cell line SPL.IVA5A1 was deposited at the American Type Culture Collection on Mar. 29, 1984, and granted accession no. HB 8535.

  6. Beneficial effects of weight loss associated with moderate calorie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum urate and lipoprotein levels in gout: a pilot study

    PubMed Central

    Dessein, P; Shipton, E; Stanwix, A; Joffe, B; Ramokgadi, J

    2000-01-01

    OBJECTIVES—Insulin resistance (IR) has been increasingly implicated in the pathogenesis of gout. The lipoprotein abnormalities described in hyperuricaemic subjects are similar to those associated with IR, and insulin influences renal urate excretion. In this study it was investigated whether dietary measures, reported to be beneficial in IR, have serum uric acid (SU) and lipid lowering effects in gout.
METHODS—Thirteen non-diabetic men (median age 50, range 38-62) were enrolled. Each patient had had at least two gouty attacks during the four months before enrolment. Dietary recommendations consisted of calorie restriction to 6690 kJ (1600 kcal) a day with 40% derived from carbohydrate, 30% from protein, and 30% from fat; replacement of refined carbohydrates with complex ones and saturated fats with mono- and polyunsaturated ones. At onset and after 16 weeks, fasting blood samples were taken for determination of SU, serum cholesterol (C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TGs). Results were expressed as median (SD).
RESULTS—At onset, the body mass index (BMI) was 30.5 (8.1) kg/m2. Dietary measures resulted in weight loss of 7.7 (5.4) kg (p=0.002) and a decrease in the frequency of monthly attacks from 2.1 (0.8) to 0.6 (0.7) (p=0.002). The SU decreased from 0.57 (0.10) to 0.47 (0.09) mmol/l (p=0.001) and normalised in 7 (58%) of the 12 patients with an initially raised level. Serum cholesterol decreased from 6.0 (1.7) to 4.7 (0.9) mmol/l (p=0.002), LDL-C from 3.5 (1.2) to 2.7 (0.8) mmol/l (p=0.004), TGs from 4.7 (4.2) to 1.9 (1.0) mmol/l (p=0.001), and C:HDL-C ratios from 6.7 (1.7) to 5.2 (1.0) (p=0.002). HDL-C levels increased insignificantly. High baseline SU, frequency of attacks, total cholesterol, LDL-C and TG levels, and total C:HDL-C ratios correlated with higher decreases in the respective variables upon dietary intervention (p<0.05).

  7. Softness of atherogenic lipoproteins: a comparison of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) using elastic incoherent neutron scattering (EINS).

    PubMed

    Mikl, Christian; Peters, Judith; Trapp, Marcus; Kornmueller, Karin; Schneider, Wolfgang J; Prassl, Ruth

    2011-08-31

    Apolipoprotein B100 (apoB100)-containing plasma lipoproteins (LDL and VLDL) supply tissues and cells with cholesterol and fat. During lipolytic conversion from VLDL to LDL the size and chemical composition of the particles change, but the apoB100 molecule remains bound to the lipids and regulates the receptor mediated uptake. The molecular physical parameters which control lipoprotein remodeling and enable particle stabilization by apoB100 are largely unknown. Here, we have compared the molecular dynamics and elasticities of VLDL and LDL derived by elastic neutron scattering temperature scans. We have determined thermal motions, dynamical transitions, and molecular fluctuations, which reflect the temperature-dependent motional coupling between lipid and protein. Our results revealed that lipoprotein particles are extremely soft and flexible. We found substantial differences in the molecular resiliences of lipoproteins, especially at higher temperatures. These discrepancies not only can be explained in terms of lipid composition and mobility but also suggest that apoB100 displays different dynamics dependent on the lipoprotein it is bound to. Hence, we suppose that the inherent conformational flexibility of apoB100 permits particle stabilization upon lipid exchange, whereas the dynamic coupling between protein and lipids might be a key determinant for lipoprotein conversion and atherogenicity. PMID:21790144

  8. A Cross-Sectional Study Demonstrating Increased Serum Amyloid A Related Inflammation in High-Density Lipoproteins from Subjects with Type 1 Diabetes Mellitus and How This Association Was Augmented by Poor Glycaemic Control

    PubMed Central

    McEneny, Jane; Daniels, Jane-Ann; McGowan, Anne; Gunness, Anjuli; Moore, Kevin; Stevenson, Michael; Young, Ian S.; Gibney, James

    2015-01-01

    Inflammatory atherosclerosis is increased in subjects with type 1 diabetes mellitus (T1DM). Normally high-density lipoproteins (HDL) protect against atherosclerosis; however, in the presence of serum amyloid-A- (SAA-) related inflammation this property may be reduced. Fasting blood was obtained from fifty subjects with T1DM, together with fifty age, gender and BMI matched control subjects. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Serum-hsCRP and serum-, HDL2-, and HDL3-SAA were measured by ELISAs. Compared to control subjects, SAA was increased in T1DM subjects, nonsignificantly in serum (P = 0.088), and significantly in HDL2(P = 0.003) and HDL3(P = 0.005). When the T1DM group were separated according to mean HbA1c (8.34%), serum-SAA and HDL3-SAA levels were higher in the T1DM subjects with HbA1c ≥ 8.34%, compared to when HbA1c was <8.34% (P < 0.05). Furthermore, regression analysis illustrated, that for every 1%-unit increase in HbA1c, SAA increased by 20% and 23% in HDL2 and HDL3, respectively, independent of BMI. HsCRP did not differ between groups (P > 0.05). This cross-sectional study demonstrated increased SAA-related inflammation in subjects with T1DM that was augmented by poor glycaemic control. We suggest that SAA is a useful inflammatory biomarker in T1DM, which may contribute to their increased atherosclerosis risk. PMID:26557720

  9. The fibrate drug gemfibrozil disrupts lipoprotein metabolism in rainbow trout

    SciTech Connect

    Prindiville, John S. Mennigen, Jan A.; Zamora, Jake M.; Moon, Thomas W.; Weber, Jean-Michel

    2011-03-15

    Gemfibrozil (GEM) is a fibrate drug consistently found in effluents from sewage treatment plants. This study characterizes the pharmacological effects of GEM on the plasma lipoproteins of rainbow trout (Oncorhynchus mykiss). Our goals were to quantify the impact of the drug on: 1) lipid constituents of lipoproteins (phospholipids (PL), triacylglycerol (TAG), and cholesterol), 2) lipoprotein classes (high, low and very low density lipoproteins), and 3) fatty acid composition of lipoproteins. Potential mechanisms of GEM action were investigated by measuring lipoprotein lipase activity (LPL) and the hepatic gene expression of LPL and of the peroxisome proliferator-activated receptor (PPAR) {alpha}, {beta}, and {gamma} isoforms. GEM treatment resulted in decreased plasma lipoprotein levels (- 29%) and a reduced size of all lipoprotein classes (lower PL:TAG ratios). However, the increase in HDL-cholesterol elicited by GEM in humans failed to be observed in trout. Therefore, HDL-cholesterol cannot be used to assess the impact of the drug on fish. GEM also modified lipoprotein composition by reducing the abundance of long-chain n-3 fatty acids, thereby potentially reducing the nutritional quality of exposed fish. The relative gene expression of LPL was increased, but the activity of the enzyme was not, and we found no evidence for the activation of PPAR pathways. The depressing effects of GEM on fish lipoproteins demonstrated here may be a concern in view of the widespread presence of fibrates in aquatic environments. Work is needed to test whether exposure to environmental concentrations of these drugs jeopardizes the capacity of fish for reproduction, temperature acclimation or migratory behaviors.

  10. Lipoprotein Metabolism during Acute Inhibition of Hepatic Triglyceride Lipase in the Cynomolgus Monkey

    PubMed Central

    Goldberg, Ira J.; Le, Ngoc-Anh; Paterniti, James R.; Ginsberg, Henry N.; Lindgren, Frank T.; Brown, W. Virgil

    1982-01-01

    The role of the enzyme hepatic triglyceride lipase was investigated in a primate model, the cynomolgus monkey. Antisera produced against human postheparin hepatic lipase fully inhibited cynomolgus monkey posttheparin plasma hepatic triglyceride lipase activity. Lipoprotein lipase activity was not inhibited by this antisera. Hepatic triglyceride lipase activity in liver biopsies was decreased by 65-90% after intravenous infusion of this antisera into the cynomolgus monkey. After a 3-h infusion of the antisera, analytic ultracentrifugation revealed an increase in mass of very low density lipoproteins (Sf 20-400). Very low density lipoprotein triglyceride isolated by isopycnic ultracentrifugation increased by 60-300%. Analytic ultracentrifugation revealed an increase in mass of lipoproteins with flotation greater than Sf 9 (n = 4). The total mass of intermediate density lipoproteins (Sf 12-20) approximately doubled during the 3 h of in vivo enzyme inhibition. While more rapidly floating low density lipoproteins (Sf 9-12) increased, the total mass of low density lipoproteins decreased after infusion of the antibodies. The changes in high density lipoproteins did not differ from those in control experiments. In order to determine whether the increases of plasma concentrations of very low density lipoproteins were due to an increase in the rate of synthesis or a decrease in the rate of clearance of these particles, the metabolism of radiolabeled homologous very low density lipoproteins was studied during intravenous infusion of immunoglobulin G prepared from the antisera against hepatic triglyceride lipase (n = 3) or preimmune goat sera (n = 3). Studies performed in the same animals during saline infusion were used as controls for each immunoglobulin infusion. There was a twofold increase in the apparent half-life of the very low density lipoprotein apolipoprotein-B tracer in animals receiving the antibody, consistent with a decreased catabolism of very low density

  11. Endogenously produced glycosaminoglycans affecting the release of lipoprotein lipase from macrophages and the interaction with lipoproteins.

    PubMed

    Zimmermann, R; Sartipy, P; Winkler, R; Zechner, R; Hurt-Camejo, E; Kostner, G M

    2000-04-12

    Macrophages are intimately involved in the pathogenesis of atherosclerotic diseases. A key feature of this process is their uptake of various lipoproteins and subsequent transformation to foam cells. Since lipoprotein lipase (LPL) is believed to play a role in foam cell formation, we investigated if endogenously produced proteoglycans (PGs) affect the release of this enzyme from macrophages. The human leukaemic cell line THP-1 which differentiates into macrophages by treatment with phorbol ester (phorbol 12-myristate 13-acetate) served as a model. The differentiation of THP-1 macrophages promoted the release of PGs into the cell medium which caused the detachment of LPL activity from the cell surface, and prevented LPL re-uptake and inactivation. These PGs were mainly composed of chondroitin sulfate type and exerted a heparin-like effect on LPL release. LPL is known to increase the cell association of lipoproteins by the well known bridging function. Exogenous bovine LPL at a concentration of 1 microg/ml enhanced low density lipoprotein (LDL)-binding 10-fold. Endogenously produced PGs reduced LPL-mediated binding of LDL. It is proposed that the differentiation-dependent increase in the release of PGs interferes with binding of LPL and reduces lipoprotein-binding to macrophages. PMID:10760480

  12. Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids

    SciTech Connect

    Saxena, U.; Witte, L.D.; Goldberg, I.J.

    1989-03-15

    Lipoprotein lipase (LPL) bound to the lumenal surface of vascular endothelial cells is responsible for the hydrolysis of triglycerides in plasma lipoproteins. Studies were performed to investigate whether human plasma lipoproteins and/or free fatty acids would release LPL which was bound to endothelial cells. Purified bovine milk LPL was incubated with cultured porcine aortic endothelial cells resulting in the association of enzyme activity with the cells. When the cells were then incubated with media containing chylomicrons or very low density lipoproteins (VLDL), a concentration-dependent decrease in the cell-associated LPL enzymatic activity was observed. In contrast, incubation with media containing low density lipoproteins or high density lipoproteins produced a much smaller decrease in the cell-associated enzymatic activity. The addition of increasing molar ratios of oleic acid:bovine serum albumin to the media also reduced enzyme activity associated with the endothelial cells. To determine whether the decrease in LPL activity was due to release of the enzyme from the cells or inactivation of the enzyme, studies were performed utilizing radioiodinated bovine LPL. Radiolabeled LPL protein was released from endothelial cells by chylomicrons, VLDL, and by free fatty acids (i.e. oleic acid bound to bovine serum albumin). The release of radiolabeled LPL by VLDL correlated with the generation of free fatty acids from the hydrolysis of VLDL triglyceride by LPL bound to the cells. Inhibition of LPL enzymatic activity by use of a specific monoclonal antibody, reduced the extent of release of /sup 125/I-LPL from the endothelial cells by the added VLDL. These results demonstrated that LPL enzymatic activity and protein were removed from endothelial cells by triglyceride-rich lipoproteins (chylomicrons and VLDL) and oleic acid.

  13. Lipoprotein ApoC-II activation of lipoprotein lipase. Modulation by apolipoprotein A-IV.

    PubMed

    Goldberg, I J; Scheraldi, C A; Yacoub, L K; Saxena, U; Bisgaier, C L

    1990-03-15

    Lipoprotein lipase (LPL)-mediated hydrolysis of triglycerides (TG) contained in chylomicrons requires the presence of a cofactor, apolipoprotein (apo) C-II. The physiological mechanism by which chylomicrons gain apoC-II necessary for LPL activation in whole plasma is not known. Using a gum arabic stabilized TG emulsion, activation of LPL by lipoprotein apoC-II was studied. Hydrolysis of TG by LPL was greater in the presence of serum than with addition of either high density lipoproteins (HDL) or very low density lipoproteins (VLDL). LPL activation by either VLDL or HDL increased with addition of the lipoprotein-free fraction of plasma. A similar increase in LPL activity by addition of the lipoprotein-free fraction together with HDL or VLDL was observed when another TG emulsion (Intralipid) or TG-rich lipoproteins from an apoC-II deficient subject were used as a substrate. Human apoA-IV, apoA-I, apoE, and cholesteryl ester transfer protein were assessed for their ability to increase LPL activity in the presence of VLDL. At and below physiological concentrations, only apoA-IV increased LPL activity. One hundred percent of LPL activity measured in the presence of serum was achieved using VLDL plus apoA-IV. In the absence of an apoC-II source, apoA-IV had no effect on LPL activity. Removal of greater than 80% of the apoA-IV from the nonlipoprotein-containing fraction of plasma by incubation with Intralipid markedly reduced its ability to activate LPL in the presence of VLDL or HDL. Gel filtration chromatography demonstrated that incubation of the nonlipoprotein-containing fraction of plasma with HDL and the TG emulsion caused increased transfer of apoC-II to the emulsion and association of apoA-IV with HDL. Our studies demonstrate that apoA-IV increases LPL activation in the presence of lipoproteins. We hypothesize that apoA-IV is required for efficient release of apoC-II from either HDL or VLDL, which then allows for LPL-mediated hydrolysis of TG in nascent

  14. Raising highly desirable lipoprotein versus lowering deleterious lipoprotein.

    PubMed

    Cheung, Bernard My; Kumana, Cyrus R

    2010-03-01

    Evaluation of: Taylor AJ, Villines TC, Stanek EJ et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N. Engl. J. Med. 361(22), 2113-2122 (2009). Epidemiological evidence suggests that elevated low-density lipoprotein cholesterol (LDL-C) and reduced high-density lipoprotein cholesterol (HDL-C) are both factors causing coronary heart disease. These authors compared extended-release niacin, which raises HDL-C, with ezetimibe, which lowers LDL-C, in a study named Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies (ARBITER 6-HALTS). The study was terminated early and only 208 patients were included in the analysis. Ezetimibe decreased LDL-C by 19.2%, to 66 mg/dl (1.7 mmol/l), whereas niacin increased HDL-C by 18.4%. Ezetimibe did not reduce carotid intima-media thickness, whereas niacin decreased it significantly. Moreover, major adverse cardiovascular events occurred in 5% of the ezetimibe group but only 1% of the niacin group (p = 0.04). The study suggests that niacin may be more effective than ezetimibe as an adjunct to statin in regressing atherosclerosis and in preventing cardiovascular events. This small study of short duration reported a very large treatment effect, so the findings need to be confirmed in a larger longer trial. Nevertheless, it provides the evidence that we now have an additional class of drugs besides statins that can reduce atherosclerosis and cardiovascular events. PMID:22111565

  15. Explaining Global Increases in Water Use Efficiency: Why Have We Overestimated Responses to Rising Atmospheric CO2 in Natural Forest Ecosystems?

    PubMed Central

    Silva, Lucas C. R.; Horwath, William R.

    2013-01-01

    Background The analysis of tree-ring carbon isotope composition (δ13C) has been widely used to estimate spatio-temporal variations in intrinsic water use efficiency (iWUE) of tree species. Numerous studies have reported widespread increases in iWUE coinciding with rising atmospheric CO2 over the past century. While this could represent a coherent global response, the fact that increases of similar magnitude were observed across biomes with no apparent effect on tree growth raises the question of whether iWUE calculations reflect actual physiological responses to elevated CO2 levels. Methodology/Results Here we use Monte Carlo simulations to test if an artifact of calculation could explain observed increases in iWUE. We show that highly significant positive relationships between iWUE and CO2 occur even when simulated data (randomized δ13C values spanning the observed range) are used in place of actual tree-ring δ13C measurements. From simulated data sets we calculated non-physiological changes in iWUE from 1900 to present and across a 4000 m altitudinal range. This generated results strikingly similar to those reported in recent studies encompassing 22 species from tropical, subtropical, temperate, boreal and mediterranean ecosystems. Only 6 of 49 surveyed case studies showed increases in iWUE significantly higher than predicted from random values. Conclusions/Significance Our results reveal that increases in iWUE estimated from tree-ring δ13C occur independently of changes in 13C discrimination that characterize physiological responses to elevated CO2. Due to a correlation with CO2 concentration, which is used as an independent factor in the iWUE calculation, any tree-ring δ13C data set would inevitably generate increasing iWUE over time. Therefore, although consistent, previously reported trends in iWUE do not necessarily reflect a coherent global response to rising atmospheric CO2. We discuss the significance of these findings and suggest ways to distinguish

  16. Colistin-resistant, lipopolysaccharide-deficient Acinetobacter baumannii responds to lipopolysaccharide loss through increased expression of genes involved in the synthesis and transport of lipoproteins, phospholipids, and poly-β-1,6-N-acetylglucosamine.

    PubMed

    Henry, Rebekah; Vithanage, Nuwan; Harrison, Paul; Seemann, Torsten; Coutts, Scott; Moffatt, Jennifer H; Nation, Roger L; Li, Jian; Harper, Marina; Adler, Ben; Boyce, John D

    2012-01-01

    We recently demonstrated that colistin resistance in Acinetobacter baumannii can result from mutational inactivation of genes essential for lipid A biosynthesis (Moffatt JH, et al., Antimicrob. Agents Chemother. 54:4971-4977). Consequently, strains harboring these mutations are unable to produce the major Gram-negative bacterial surface component, lipopolysaccharide (LPS). To understand how A. baumannii compensates for the lack of LPS, we compared the transcriptional profile of the A. baumannii type strain ATCC 19606 to that of an isogenic, LPS-deficient, lpxA mutant strain. The analysis of the expression profiles indicated that the LPS-deficient strain showed increased expression of many genes involved in cell envelope and membrane biogenesis. In particular, upregulated genes included those involved in the Lol lipoprotein transport system and the Mla-retrograde phospholipid transport system. In addition, genes involved in the synthesis and transport of poly-β-1,6-N-acetylglucosamine (PNAG) also were upregulated, and a corresponding increase in PNAG production was observed. The LPS-deficient strain also exhibited the reduced expression of genes predicted to encode the fimbrial subunit FimA and a type VI secretion system (T6SS). The reduced expression of genes involved in T6SS correlated with the detection of the T6SS-effector protein AssC in culture supernatants of the A. baumannii wild-type strain but not in the LPS-deficient strain. Taken together, these data show that, in response to total LPS loss, A. baumannii alters the expression of critical transport and biosynthesis systems associated with modulating the composition and structure of the bacterial surface. PMID:22024825

  17. Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase.

    PubMed

    Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M; Brown, Robert J

    2014-09-01

    Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL. PMID:25130461

  18. Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase

    SciTech Connect

    Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M.; Brown, Robert J.

    2014-09-05

    Highlights: • Lipoprotein hydrolysis products were produced by lipoprotein lipase. • Hydrolysis products lowers expression of macrophage cholesterol transporters. • Hydrolysis products reduces expression of select nuclear receptors. • Fatty acid products lowers cholesterol transporters and select nuclear receptors. • Fatty acid products reduces cholesterol efflux from macrophages. - Abstract: Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL.

  19. Explaining happiness.

    PubMed

    Easterlin, Richard A

    2003-09-16

    What do social survey data tell us about the determinants of happiness? First, that the psychologists' setpoint model is questionable. Life events in the nonpecuniary domain, such as marriage, divorce, and serious disability, have a lasting effect on happiness, and do not simply deflect the average person temporarily above or below a setpoint given by genetics and personality. Second, mainstream economists' inference that in the pecuniary domain "more is better," based on revealed preference theory, is problematic. An increase in income, and thus in the goods at one's disposal, does not bring with it a lasting increase in happiness because of the negative effect on utility of hedonic adaptation and social comparison. A better theory of happiness builds on the evidence that adaptation and social comparison affect utility less in the nonpecuniary than pecuniary domains. Because individuals fail to anticipate the extent to which adaptation and social comparison undermine expected utility in the pecuniary domain, they allocate an excessive amount of time to pecuniary goals, and shortchange nonpecuniary ends such as family life and health, reducing their happiness. There is need to devise policies that will yield better-informed individual preferences, and thereby increase individual and societal well-being. PMID:12958207

  20. Myeloperoxidase-mediated oxidation of high-density lipoproteins: fingerprints of newly recognized potential proatherogenic lipoproteins.

    PubMed

    Malle, Ernst; Marsche, Gunther; Panzenboeck, Ute; Sattler, Wolfgang

    2006-01-15

    Substantial evidence supports the notion that oxidative processes participate in the pathogenesis of atherosclerotic heart disease. Major evidence for myeloperoxidase (MPO) as enzymatic catalyst for oxidative modification of lipoproteins in the artery wall has been suggested in numerous studies performed with low-density lipoprotein. In contrast to low-density lipoprotein, plasma levels of high-density lipoprotein (HDL)-cholesterol and apoAI, the major apolipoprotein of HDL, inversely correlate with the risk of developing coronary artery disease. These antiatherosclerotic effects are attributed mainly to HDL's capacity to transport excess cholesterol from arterial wall cells to the liver during 'reverse cholesterol transport'. There is now strong evidence that HDL is a selective in vivo target for MPO-catalyzed oxidation impairing the cardioprotective and antiinflammatory capacity of this antiatherogenic lipoprotein. MPO is enzymatically active in human lesion material and was found to be associated with HDL extracted from human atheroma. MPO-catalyzed oxidation products are highly enriched in circulating HDL from individuals with cardiovascular disease where MPO concentrations are also increased. The oxidative potential of MPO involves an array of intermediate-generated reactive oxygen and reactive nitrogen species and the ability of MPO to generate chlorinating oxidants-in particular hypochlorous acid/hypochlorite-under physiological conditions is a unique and defining activity for this enzyme. All these MPO-generated reactive products may affect structure and function of HDL as well as the activity of HDL-associated enzymes involved in conversion and remodeling of the lipoprotein particle, and represent clinically useful markers for atherosclerosis. PMID:16171772

  1. Consuming a buttermilk drink containing lutein-enriched egg yolk daily for 1 year increased plasma lutein but did not affect serum lipid or lipoprotein concentrations in adults with early signs of age-related macular degeneration.

    PubMed

    van der Made, Sanne M; Kelly, Elton R; Berendschot, Tos T J M; Kijlstra, Aize; Lütjohann, Dieter; Plat, Jogchum

    2014-09-01

    Dietary lutein intake is postulated to interfere with the development of age-related macular degeneration (AMD). Because egg yolk-derived lutein has a high bioavailability, long-term consumption of lutein-enriched eggs might be effective in preventing AMD development, but alternatively might increase cardiovascular disease risk. Here, we report the effect of 1-y daily consumption of a buttermilk drink containing 1.5 lutein-rich egg yolks on serum lipid and lipoprotein and plasma lutein concentrations. Additionally, subgroups that could potentially benefit the most from the intervention were identified. Men and women who had early signs of AMD in at least 1 eye, but were otherwise healthy, participated in a 1-y randomized, placebo-controlled parallel intervention trial. At the start of the study, 101 participants were included: 52 in the experimental (Egg) group and 49 in the control (Con) group. Final analyses were performed with 45 participants in the Egg group and 43 participants in the Con group. As expected, the increase in plasma lutein concentrations in the Egg group was 83% higher than that in the Con group (P < 0.001). Changes in serum total, HDL, and LDL cholesterol, as well as the ratio of total cholesterol to HDL cholesterol, were not different between the 2 groups. Interestingly, participants classified as cholesterol absorbers had higher serum HDL cholesterol concentrations than participants classified as cholesterol synthesizers or participants with average campesterol-to-lathosterol ratios (P < 0.05) at baseline. In addition, cholesterol absorbers had a 229% higher increase in plasma lutein concentrations than participants who were classified as having an average campesterol-to-lathosterol ratio upon consumption of the lutein-enriched egg yolk drink (P < 0.05). Moreover, the change in serum HDL cholesterol upon consumption was significantly different between these 3 groups (P < 0.05). We suggest that cholesterol absorbers particularly might benefit

  2. Lipoprotein abnormalities in South Asians and its association with cardiovascular disease: Current state and future directions

    PubMed Central

    Bilen, Ozlem; Kamal, Ayeesha; Virani, Salim S

    2016-01-01

    South Asians have a high prevalence of coronary heart disease (CHD) and suffer from early-onset CHD compared to other ethnic groups. Conventional risk factors may not fully explain this increased CHD risk in this population. Indeed, South Asians have a unique lipid profile which may predispose them to premature CHD. Dyslipidemia in this patient population seems to be an important contributor to the high incidence of coronary atherosclerosis. The dyslipidemia in South Asians is characterized by elevated levels of triglycerides, low levels of high-density lipoprotein (HDL) cholesterol, elevated lipoprotein(a) levels, and a higher atherogenic particle burden despite comparable low-density lipoprotein cholesterol levels compared with other ethnic subgroups. HDL particles also appear to be smaller, dysfunctional, and proatherogenic in South Asians. Despite the rapid expansion of the current literature with better understanding of the specific lipid abnormalities in this patient population, studies with adequate sample sizes are needed to assess the significance and contribution of a given lipid parameter on overall cardiovascular risk in this population. Specific management goals and treatment thresholds do not exist for South Asians because of paucity of data. Current treatment recommendations are mostly extrapolated from Western guidelines. Lastly, large, prospective studies with outcomes data are needed to assess cardiovascular benefit associated with various lipid-lowering therapies (including combination therapy) in this patient population. PMID:27022456

  3. Abnormal high density lipoproteins in cerebrotendinous xanthomatosis

    SciTech Connect

    Shore, V.; Salen, G.; Cheng, F.W.; Forte, T.; Shefer, S.; Tint, G.S.

    1981-11-01

    The plasma lipoprotein profiles and high density lipoproteins (HDL) were characterized in patients with the genetic disease cerebrotendinous xanthomatosis (CTX). The mean HDL-cholesterol concentration in the CTX plasmas was 14.5 +/- 3.2 mg/dl, about one-third the normal value. The low HDL-cholesterol reflects a low concentration and an abnormal lipid composition of the plasma HDL. Relative to normal HDL, the cholesteryl esters are low, free cholesterol and phospholipids essentially normal, and triglycerides increased. The ratio of apoprotein (apo) to total cholesterol in the HDL of CTX was two to three times greater than normal. In the CTX HDL, the ratio of apoAI to apoAII was high, the proportion of apoC low, and a normally minor form of apoAI increased relative to other forms. The HDL in electron micrographs appeared normal morphologically and in particle size. The adnormalities in lipoprotein distribution profiles and composition of the plasma HDL result from metabolic defects that are not understood but may be linked to the genetic defect in bile acid synthesis in CTX. As a consequence, it is probable that the normal functions of the HDL, possibly including modulation of LDL-cholesterol uptake and the removal of excess cholesterol from peripheral tissues, are perturbed significantly in this disease.

  4. Regulation of hepatic lipase activity by sphingomyelin in plasma lipoproteins.

    PubMed

    Yang, Peng; Subbaiah, Papasani V

    2015-10-01

    Hepatic lipase (HL) is an important enzyme in the clearance of triacylglycerol (TAG) from the circulation, and has been proposed to have pro-atherogenic as well as anti-atherogenic properties. It hydrolyzes both phospholipids and TAG of lipoproteins, and its activity is negatively correlated with HDL levels. Although it is known that HL acts preferentially on HDL lipids, the basis for this specificity is not known, since it does not require any specific apoprotein for activity. In this study, we tested the hypothesis that sphingomyelin (SM), whose concentration is much higher in VLDL and LDL compared to HDL, is an inhibitor of HL, and that this could explain the lipoprotein specificity of the enzyme. The results presented show that the depletion of SM from normal lipoproteins activated the HL roughly in proportion to their SM content. SM depletion stimulated the hydrolysis of both phosphatidylcholine (PC) and TAG, although the PC hydrolysis was stimulated more. In the native lipoproteins, HL showed specificity for PC species containing polyunsaturated fatty acids at sn-2 position, and produced more unsaturated lyso PC species. The enzyme also showed preferential hydrolysis of certain TAG species over others. SM depletion affected the specificity of the enzyme towards PC and TAG species modestly. These results show that SM is a physiological inhibitor of HL activity in lipoproteins and that the specificity of the enzyme towards HDL is at least partly due to its low SM content. PMID:26193433

  5. Excessive centrifugal fields damage high density lipoprotein[S

    PubMed Central

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

    2015-01-01

    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

  6. Effect of cobalt chloride on content of lipids and lipoproteins in serum and liver of rats.

    PubMed

    Kaliman, P A; Shalamov, R V; Zagaiko, A L

    1997-07-01

    Lipids and the composition of lipoproteins in blood serum and liver cytosol, total lipid, and phospholipid contents in liver subcellular fractions and the spectrum of microsomal liver lipids were studied in male Wistar rats after a single injection of cobalt chloride. Virtually all lipid and lipoprotein fractions in blood and liver were increased and lipoprotein composition was changes. The lipid composition of liver microsomes did not change under these conditions. Thus, microsomal membranes are stable under developing oxidative stress. PMID:9331964

  7. Metabolism of triglyceride-rich lipoproteins during alimentary lipemia.

    PubMed Central

    Karpe, F; Steiner, G; Olivecrona, T; Carlson, L A; Hamsten, A

    1993-01-01

    The metabolism of chylomicron remnants and VLDL was studied in healthy controls and normo- (NTG) and hypertriglyceridemic (HTG) patients with coronary artery disease after intake of an oral fat load. Specific determination of apo B-48 and B-100 enabled separation of the respective contribution of the two lipoprotein species. The postprandial plasma levels of small (Sf 20-60) and large (Sf 60-400) chylomicron remnants increased in controls and NTG patients. In contrast, only large chylomicron remnants increased in the HTG patients. An increase of large VLDL was seen in response to the oral fat load in all groups, whereas small VLDL were either unchanged in the controls and the NTG patients, or decreased in the HTG patient group. The whole plasma concentration of C apolipoproteins was essentially uninfluenced by the oral fat load, whereas the content in large triglyceride-rich lipoproteins paralleled the apo B elevations in controls and NTG patients. An even more prominent increase of apo B in large triglyceride-rich lipoproteins in the HTG group was not accompanied by an increase of C apolipoproteins. These findings indicate that chylomicrons compete with VLDL for removal of triglycerides by lipoprotein lipase and that the postprandial metabolism of triglyceride-rich lipoproteins is severely defective in hypertriglyceridemia. PMID:8450056

  8. Lipoproteins: When size really matters.

    PubMed

    German, J Bruce; Smilowitz, Jennifer T; Zivkovic, Angela M

    2006-06-01

    The field of nanoscience is extending the applications of physics, chemistry and biology into previously unapproached infinitesimal length scales. Understanding the behavior and manipulating the positions and properties of single atoms and molecules hold great potential to improve areas of science as disparate as medicine and computation, and communication and orbiting satellites. Yet, in the race to develop novel, previously unavailable nanoparticles, there is an opportunity for scientists in this field to digress and to apply their growing understanding of nanoscience and the tools of nanotechnology to one of the most pressing problems in all of human biology-diseases related to lipoproteins. Although not appreciated outside the field of lipoprotein biology, variations in the compositions, structures and properties of these nanoscale-sized, blood-borne particles are responsible for most of the variations in health, morbidity and mortality in the Western world. If the lipoproteins could be understood at the nanometer length scale with precise details of their structures and functions, scientists could understand a wide range of perplexing physiological processes and also address the dysfunctions in normal lipoprotein biology that lead to such diseases as hypercholesterolemia, heart disease, stroke and neurodegenerative diseases. Furthermore, if the capabilities of nanoscience to assemble and manipulate nanometer-sized particles could be recruited to studies of lipoproteins, these biological particles would provide a new dimension to therapeutic agents, and these natural particles could be designed to carry out many specialized beneficial tasks. PMID:20592953

  9. Low-density lipoprotein apheresis: an overview.

    PubMed

    Bambauer, Rolf; Schiel, Ralf; Latza, Reinhard

    2003-08-01

    Atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lpa) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL adsorption and LDL hemoperfusion. Regarding the different LDL apheresis systems used, there is no significant difference with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein (HDL), or triglyceride concentrations. With respect to elevated Lpa levels, however, the immunoadsorption method seems to be the most effective. In 45 patients (25 women, 20 men) suffering from familial hypercholesterolemia resistant to diet and lipid lowering drugs, low-density lipoprotein (LDL) apheresis was performed over 95.6 +/- 44.7 months. Four different systems (Liposorber, 32 of 45, Kaneka, Osaka, Japan; Therasorb, 6 of 45, Baxter, Munich, Germany; Lipopak, 2 of 45, Pocard, Moscow, Russia; and Dali, 5 of 45, Fresenius, St. Wendel, Germany) were used. With all methods, average reductions of 57% for total cholesterol, 55.9% for LDL, 75.8% for lipoprotein a (Lpa), and 45.9% for triglycerides, and an average increase of 14.3% for HDL were reached. Severe side-effects such as shock or allergic reactions were very rare (0.3%) in all methods. In the course of treatment, an improvement

  10. A lipidomic analysis approach in patients undergoing lipoprotein apheresis.

    PubMed

    Schmöcker, C; Kassner, U; Kiesler, S; Bismarck, M; Rothe, M; Steinhagen-Thiessen, E; Weylandt, K H

    2016-06-01

    Lipoprotein apheresis such as heparin-induced extracorporal LowDensityLipoprotein (LDL) Cholesterol precipitation (HELP) reduces apolipoprotein B-containing lipoproteins, most importantly low-density-lipoprotein (LDL), and lipoprotein (a) [Lp(a)]. It is used in patients with atherosclerotic disease and therapy-refractory hypercholesterolemia or progressive atherosclerotic disease in patients with elevated Lp(a). While lipid-lowering effects of lipoprotein apheresis are well-established, there are only sparse data regarding the effect of apheresis on individual omega-6 and omega-3 polyunsaturated fatty acids (n-6 PUFA and n-3 PUFA), such as arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which could increase (AA) or decrease (EPA and DHA) cardiovascular risk. Here we analyzed different omega-6 and omega-3 fatty acids in the blood of patients undergoing a single HELP apheresis procedure using gas chromatography (GC). Furthermore, we assessed the effect of HELP treatment on formation of lipid metabolites and mediators arising from these polyunsaturated fatty acids in the plasma by LC/ESI-MS/MS. Lipoprotein apheresis reduced the concentrations of fatty acids analyzed in the plasma by 40-50%. This was similar for AA, EPA and DHA. The reduction in fatty acid plasma levels was similar to the reduction of total triglycerides. However there was a trend towards an increase of PUFA metabolites associated with platelet activation, such as 12-hydroxyeicosatetraenoic acid (12-HETE) and 14-hydroxydocosahexaenoic acid (14-HDHA). These data indicate that HELP apheresis could interfere with achieving higher levels of n-3 PUFA in the plasma. Lipid apheresis treatment might also increase the formation of potentially pro- as well as anti-inflammatory lipid mediators derived from AA or EPA and DHA. PMID:27062407

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

    PubMed Central

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

    1991-01-01

    OBJECTIVE--To investigate long term changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations and in measures of other risk factors for coronary heart disease and to assess their importance for the development of coronary heart disease in Scottish men. DESIGN--Longitudinal study entailing follow up in 1988-9 of men investigated during a study in 1976. SETTING--Edinburgh, Scotland. SUBJECTS--107 men from Edinburgh who had taken part in a comparative study of risk factors for heart disease with Swedish men in 1976 when aged 40. INTERVENTION--The men were invited to attend a follow up clinic in 1988-9 for measurement of cholesterol concentrations and other risk factor measurements. Eighty three attended and 24 refused to or could not attend. MAIN OUTCOME MEASURES--Changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations, body weight, weight to height index, prevalence of smoking, and alcohol intake; number of coronary artery disease events. RESULTS--Mean serum total cholesterol concentration increased over the 12 years mainly due to an increase in the low density lipoprotein cholesterol fraction (from 3.53 (SD 0.09) to 4.56 (0.11) mmol/l) despite a reduction in high density lipoprotein cholesterol concentration. Body weight and weight to height index increased. Fewer men smoked more than 15 cigarettes/day in 1988-9 than in 1976. Blood pressure remained stable and fasting triglyceride concentrations did not change. The frequency of corneal arcus doubled. Alcohol consumption decreased significantly. Eleven men developed clinical coronary heart disease. High low density lipoprotein and low high density lipoprotein cholesterol concentrations in 1976, but not total cholesterol concentration, significantly predicted coronary heart disease (p = 0.05). Almost all of the men who developed coronary heart disease were smokers (91% v 53%, p less than

  12. [Lipoprotein lipase and diabetic cardiomyopathy].

    PubMed

    Liu, Xiang-Yu; Yin, Wei-Dong; Tang, Chao-Ke

    2014-02-01

    Lipoprotein lipase (LPL) hydrolyzes plasma triglyceride-rich lipoproteins into free fatty acids (FFA) to provide energy for cardiac tissue. During diabetes, cardiac energy supply is insufficient due to defected utilization of glucose. As a compensation of cardiac energy supply, FFAs are released through the hydrolysis of very low density lipoprotein (VLDL) and chylomicrons (CM) due to activation of LPL activity. In diabetic patients, activated LPL activity and elevated FFAs result in the intracellular accumulation of reactive oxygen species and lipids in myocardium and potentially induce the diabetic cardiomyopathy (DCM). The present review summarizes the regulatory mechanisms of myocardial LPL and the pathogenesis of DCM induced by LPL and provides novel therapeutic targets and pathways for DCM. PMID:24873138

  13. Ion mobility analysis of lipoproteins

    DOEpatents

    Benner, W. Henry; Krauss, Ronald M.; Blanche, Patricia J.

    2007-08-21

    A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

  14. Aerosol preparation of intact lipoproteins

    DOEpatents

    Benner, W. Henry; Krauss, Ronald M; Blanche, Patricia J

    2012-01-17

    A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

  15. Role of caveolin-1 in the regulation of lipoprotein metabolism

    PubMed Central

    Frank, Philippe G.; Pavlides, Stephanos; Cheung, Michelle W.-C.; Daumer, Kristin; Lisanti, Michael P.

    2008-01-01

    Lipoprotein metabolism plays an important role in the development of several human diseases, including coronary artery disease and the metabolic syndrome. A good comprehension of the factors that regulate the metabolism of the various lipoproteins is therefore key to better understanding the variables associated with the development of these diseases. Among the players identified are regulators such as caveolins and caveolae. Caveolae are small plasma membrane invaginations that are observed in terminally differentiated cells. Their most important protein marker, caveolin-1, has been shown to play a key role in the regulation of several cellular signaling pathways and in the regulation of plasma lipoprotein metabolism. In the present paper, we have examined the role of caveolin-1 in lipoprotein metabolism using caveolin-1-deficient (Cav-1−/−) mice. Our data show that, while Cav-1−/− mice show increased plasma triglyceride levels, they also display reduced hepatic very low-density lipoprotein (VLDL) secretion. Additionally, we also found that a caveolin-1 deficiency is associated with an increase in high-density lipoprotein (HDL), and these HDL particles are enriched in cholesteryl ester in Cav-1−/− mice when compared with HDL obtained from wild-type mice. Finally, our data suggest that a caveolin-1 deficiency prevents the transcytosis of LDL across endothelial cells, and therefore, that caveolin-1 may be implicated in the regulation of plasma LDL levels. Taken together, our studies suggest that caveolin-1 plays an important role in the regulation of lipoprotein metabolism by controlling their plasma levels as well as their lipid composition. Thus caveolin-1 may also play an important role in the development of atherosclerosis. PMID:18508910

  16. Increased temperature tolerance of the air-breathing Asian swamp eel Monopterus albus after high-temperature acclimation is not explained by improved cardiorespiratory performance.

    PubMed

    Lefevre, S; Findorf, I; Bayley, M; Huong, D T T; Wang, T

    2016-01-01

    This study investigated the hypothesis that in the Asian swamp eel Monopterus albus, an air-breathing fish from south-east Asia that uses the buccopharyngeal cavity for oxygen uptake, the upper critical temperature (TU) is increased by acclimation to higher temperature, and that the increased TU is associated with improved cardiovascular and respiratory function. Monopterus albus were therefore acclimated to 27° C (current average) and 32° C (current maximum temperature as well as projected average within 100-200 years), and both the effect of acclimation and acute temperature increments on cardiovascular and respiratory functions were investigated. Two weeks of heat acclimation increased upper tolerated temperature (TU ) by 2° C from 36·9 ± 0·1° C to 38·9 ± 0·1° C (mean ± s.e.). Oxygen uptake (M˙O2) increased with acclimation temperature, accommodated by increases in both aerial and aquatic respiration. Overall, M˙O2 from air (M˙O2a ) was predominant, representing 85% in 27° C acclimated fish and 80% in 32° C acclimated fish. M˙O2 increased with acute increments in temperature and this increase was entirely accommodated by an increase in air-breathing frequency and M˙O2a . Monopterus albus failed to upregulate stroke volume; rather, cardiac output was maintained through increased heart rate with rising temperature. Overall, acclimation of M. albus to 32° C did not improve its cardiovascular and respiratory performance at higher temperatures, and cardiovascular adaptations, therefore, do not appear to contribute to the observed increase in TU. PMID:26563596

  17. Genetics Home Reference: familial lipoprotein lipase deficiency

    MedlinePlus

    ... tissue. This enzyme helps break down fats called triglycerides, which are carried by molecules called lipoproteins . Mutations ... which prevents the enzyme from effectively breaking down triglycerides. As a result, triglycerides attached to lipoproteins build ...

  18. Characterization of metabolic interrelationships and in silico phenotyping of lipoprotein particles using self-organizing maps[S

    PubMed Central

    Kumpula, Linda S.; Mäkelä, Sanna M.; Mäkinen, Ville-Petteri; Karjalainen, Anna; Liinamaa, Johanna M.; Kaski, Kimmo; Savolainen, Markku J.; Hannuksela, Minna L.; Ala-Korpela, Mika

    2010-01-01

    Plasma lipid concentrations cannot properly account for the complex interactions prevailing in lipoprotein (patho)physiology. Sequential ultracentrifugation (UCF) is the gold standard for physical lipoprotein isolations allowing for subsequent analyses of the molecular composition of the particles. Due to labor and cost issues, however, the UCF-based isolations are usually done only for VLDL, LDL, and HDL fractions; sometimes with the addition of intermediate density lipoprotein (IDL) particles and the fractionation of HDL into HDL2 and HDL3 (as done here; n = 302). We demonstrate via these data, with the lipoprotein lipid concentration and composition information combined, that the self-organizing map (SOM) analysis reveals a novel data-driven in silico phenotyping of lipoprotein metabolism beyond the experimentally available classifications. The SOM-based findings are biologically consistent with several well-known metabolic characteristics and also explain some apparent contradictions. The novelty is the inherent emergence of complex lipoprotein associations; e.g., the metabolic subgrouping of the associations between plasma LDL cholesterol concentrations and the structural subtypes of LDL particles. Importantly, lipoprotein concentrations cannot pinpoint lipoprotein phenotypes. It would generally be beneficial to computationally enhance the UCF-based lipoprotein data as illustrated here. Particularly, the compositional variations within the lipoprotein particles appear to be a fundamental issue with metabolic and clinical corollaries. PMID:19734566

  19. Bath and Shower Effects in the Rat Parotid Gland Explain Increased Relative Risk of Parotid Gland Dysfunction After Intensity-Modulated Radiotherapy

    SciTech Connect

    Luijk, Peter van Faber, Hette; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; Meertens, Harm; Coppes, Robert P.

    2009-07-15

    Purpose: To assess in a rat model whether adding a subtolerance dose in a region adjacent to a high-dose irradiated subvolume of the parotid gland influences its response (bath-and-shower effect). Methods and Materials: Irradiation of the whole, cranial 50%, and/or the caudal 50% of the parotid glands of Wistar rats was performed using 150-MeV protons. To determine suitable (i.e., subtolerance) dose levels for a bath-dose, both whole parotid glands were irradiated with 5 to 25 Gy. Subsequently groups of Wistar rats received 30 Gy to the caudal 50% (shower) and 0 to 10 Gy to the cranial 50% (bath) of both parotid glands. Stimulated saliva flow rate (function) was measured before and up to 240 days after irradiation. Results: Irradiation of both glands up to a dose of 10 Gy did not result in late loss of function and is thus regarded subtolerance. Addition of a dose bath of 1 to 10 Gy to a high-dose in the caudal 50% of the glands resulted in enhanced function loss. Conclusion: Similar to the spinal cord, the parotid gland demonstrates a bath and shower effect, which may explain the less-than-expected sparing of function after IMRT.

  20. Fungal-mediated mortality explains the different effects of dung leachates on the germination response of grazing increaser and decreaser species

    NASA Astrophysics Data System (ADS)

    Carmona, Carlos P.; Navarro, Elena; Peco, Begoña

    2016-01-01

    Depending on their response to grazing, grassland species can be categorized as grazing increasers or decreasers. Grazing by livestock includes several different activities that can impact species differently. Recent evidence suggest that one of these actions, dung deposition, can reduce the germinative performance of decreaser species, thus favouring increasers. The present study tested the hypothesis that decreased germinative success of decreaser species is caused by a greater activity of fungal pathogens under the influence of dung leachates. We performed a phytotron experiment analysing the germination and fungal infections of fourteen species from Mediterranean grasslands. Species were grouped into phylogenetically-related pairs, composed of an increaser and a decreaser species. Seeds of each species were germinated under four different treatments (control, dung leachate addition, fungicide addition and dung leachate and fungicide addition), and the differences in germination percentage, germination speed and infection rate between each increaser species and its decreaser counterpart were analysed. Decreaser species were more affected by mortality than increaser ones, and these differences were higher under the presence of dung leachates. The differences in germinative performance after excluding the effect of seed mortality did not differ between treatments, showing that the main mechanism by which dung leachates favour increaser species is through increased mortality of the seeds of decreaser species. Drastic reductions in the number of dead seeds in the treatments including fungicide addition further revealed that fungal pathogens are responsible for these differences between species with different grazing response. The different vulnerabilities of increaser and decreaser species to the increased activity of fungal pathogens under the presence of dung leachates seems the main reason behind the differential effect of these leachates on species with

  1. Revisiting the gram-negative lipoprotein paradigm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The processing of lipoproteins (lpps) in Gram-negative bacteria is generally considered to be an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein n-acyltransferase. The mature lipoproteins are then sorted...

  2. Regulation of high density lipoprotein levels

    SciTech Connect

    Krauss, R.M.

    1982-03-01

    An increasing awareness of the physiologic and pathologic importance of serum high density lipoproteins (HDL) has led to a large number of observations regarding factors which influence their concentrations. HDL consists of a heterogeneous collection of macromolecules with diverse physical properties and chemical constituents. While laboratory techniques have made it possible to measure HDL and their individual components, there are as yet large gaps in our knowledge of the biochemical mechanisms and clinical significance of changes in these laboratory parameters. In this review, current concepts of the structure and metabolism of HDL will be briefly summarized, and the factors influencing their levels in humans will be surveyed. 313 references.

  3. Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions.

    PubMed

    Burstein, M; Scholnick, H R; Morfin, R

    1970-11-01

    Procedures are described for the isolation of lipoproteins from human serum by precipitation with polyanions and divalent cations. A mixture of low and very low density lipoproteins can be prepared without ultracentrifugation by precipitation with heparin and either MnCl(2) alone or MgCl(2) plus sucrose. In both cases the precipitation is reversible, selective, and complete. The highly concentrated isolated lipoproteins are free of other plasma proteins as judged by immunological and electrophoretic methods. The low density and very low density lipoproteins can then be separated from each other by ultracentrifugation. The advantage of the method is that large amounts of lipoproteins can be prepared with only a single preparative ultracentrifugation. Polyanions other than heparin may also be used; when the precipitation of the low and very low density lipoproteins is achieved with dextran sulfate and MnCl(2), or sodium phosphotungstate and MgCl(2), the high density lipoproteins can subsequently be precipitated by increasing the concentrations of the reagents. These lipoproteins, containing small amounts of protein contaminants, are further purified by ultracentrifugation at d 1.22. With a single preparative ultracentrifugation, immunologically pure high density lipoproteins can be isolated from large volumes of serum. PMID:4100998

  4. In vitro studies on the distribution of probucol among human plasma lipoproteins

    SciTech Connect

    Urien, S.; Riant, P.; Albengres, E.; Brioude, R.; Tillement, J.P.

    1984-09-01

    The role of human plasma lipoproteins as carriers in the blood transport of the cholesterol-lowering and water-insoluble drug, probucol, was investigated in in vitro studies. (/sup 14/C)Probucol was incubated in whole human blood, a serum pool, individual diluted sera, and isolated protein and lipoprotein fractions. In whole blood, about 90% partitioned in plasma. Following ultracentrifugal fractionation of the serum, it was found that less than 5% distributed in the d greater than 1.20 protein fraction (albumin-rich fraction) and more than 95% in the lipoprotein fractions. The distribution of probucol in the lipoprotein fractions correlated with the lipoprotein total lipid volume under saturation conditions (incubation of isolated lipoprotein fractions) as well as nonsaturation conditions (fractionation of serum exposed to (/sup 14/C)probucol). Incubation of the albumin-rich fraction and of apolipoproteins originating from the isolated lipoprotein fractions showed that they account for a negligible part in the interaction of probucol with blood components. The probucol uptake of individual sera was shown to be correlated to the lipid content of the serum. When probucol was incubated in erythrocyte suspensions containing variable amounts of lipoproteins, probucol partitioned less in erythrocytes as the lipoprotein concentration increased in the suspension.

  5. Does Increasing Reliance on Student Debt Explain Declines in Entrepreneurial Activity? Posing the Question, Gathering Evidence, Considering Policy Options. Research Report

    ERIC Educational Resources Information Center

    Baum, Sandy

    2015-01-01

    In recent years, concerns have emerged both about declines in entrepreneurial activity, and about increases in the amount students borrow to finance postsecondary education--in the aggregate as well as on average. Because the financial obligations associated with student debt could limit access to credit for individuals seeking to start…

  6. Increased accumulation of fumonisin B1, sphingoid bases and sphingoid base 1-phosphates: explaining the differential sensitivity of rat kidney and liver to fumonisin toxicity.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisins are mycotoxins in maize and inhibitors of ceramide synthase a key enzyme in the de novo sphingolipid biosynthesis pathway. In liver and kidney inhibition of ceramide synthase results in a marked increase in the ceramide precursor sphinganine. This study was conducted to investigate the di...

  7. Consistently high plasma high-density lipoprotein-cholesterol levels in children in Spain, a country with low cardiovascular mortality.

    PubMed

    Garcés, Carmen; Gil, Angel; Benavente, Mercedes; Viturro, Enrique; Cano, Beatriz; de Oya, Manuel

    2004-08-01

    Coronary heart disease (CHD) mortality is relatively low in Spain compared with other developed countries and has remained low despite an apparent increase in mean plasma cholesterol concentration in adults over the last several years. It is accepted that pathologic processes related to arteriosclerosis development begin in childhood and seem to be related to the presence of cardiovascular risk factors at this age. High-density lipoprotein-cholesterol (HDL-C) levels in children have been inversely correlated with the incidence of coronary heart disease in the different countries studied. Childhood plasma lipoprotein profile might contribute to the low coronary heart disease mortality in Spain. Thus, we analyzed data on lipid levels over time in schoolchildren in Spain in the last decade. Plasma lipid levels were analyzed in prepuberal children (6 to 8 years) in 3 school-based surveys performed by our group in Madrid in 1987, 1993, and 1999. A significant increase in plasma total cholesterol (P < .05) and low-density lipoprotein-cholesterol (LDL-C) (P < .01) levels in prepuberal children was observed over the last decade. However, the mean concentration of plasma HDL-C remained stable and very high. These high levels of plasma HDL-C in Spanish school children may help to explain why the coronary heart disease mortality rate in Spain is low compared with that in other developed countries. PMID:15281016

  8. A mechanistic study explaining the synergistic viscosity increase obtained from polyethylene oxide (PEO) and {beta}-naphthalene sulfonate (BNS) in shotcrete

    SciTech Connect

    Pickelmann, J.; Plank, J.

    2012-11-15

    In shotcrete, a combination of polyethylene oxide (PEO) and {beta}-naphthalene sulfonate (BNS) is commonly applied to reduce rebound. Here, the mechanism for the synergistic viscosity increase resulting from this admixture combination was investigated via x-ray diffraction (XRD), infrared and nuclear magnetic resonance (NMR) spectroscopy. It was found that the electron-rich aromatic rings present in BNS donate electrons to the alkyl protons of PEO and thus increase the electron density there. This rare interaction is known as CH-{pi} interaction and leads to the formation of a supramolecular structure whereby PEO chains bind weakly to BNS molecules. Through this mechanism a polymer network exhibiting exceptionally high molecular weight and thus viscosity is formed. Among polycondensates, sulfanilic acid-phenol-formaldehyde (SPF) provides even higher synergy with PEO than BNS while melamine (PMS), acetone (AFS) or polycarboxylate (PCE) based superplasticizers do not work at all. Effectiveness of lignosulfonates is dependent on their degree of sulfonation.

  9. Increase in dance imprecision with decreasing foraging distance in the honey bee Apis mellifera L. is partly explained by physical constraints.

    PubMed

    Beekman, Madeleine; Doyen, Laurent; Oldroyd, Benjamin P

    2005-12-01

    Honey bee foragers communicate the direction and distance of both food sources and new nest sites to nest mates by means of a symbolic dance language. Interestingly, the precision by which dancers transfer directional information is negatively correlated with the distance to the advertised food source. The 'tuned-error' hypothesis suggests that colonies benefit from this imprecision as it spreads recruits out over a patch of constant size irrespective of the distance to the advertised site. An alternative to the tuned-error hypothesis is that dancers are physically incapable of dancing with great precision for nearby sources. Here we revisit the tuned-error hypothesis by studying the change in dance precision with increasing foraging distance over relatively short distances while controlling for environmental influences. We show that bees indeed increase their dance precision with the increase in foraging distance. However, we also show that dance performed by swarm-scouts for a nearby (30 m) nest site, where there could be no benefit to imprecision, are either without or with only limited directional information. This result suggests that imprecision in dance communication is caused primarily by physical constraints in the ability of dancers to turn around quickly enough when the advertised site is nearby. PMID:16049698

  10. Searching for events in Chinese ancient records to explain the increase in 14C from AD 774-775 and AD 993-994

    NASA Astrophysics Data System (ADS)

    Chai, Ya-Ting; Zou, Yuan-Chuan

    2015-09-01

    According to analysis of the 14C content in two Japanese trees, that grew over a period of approximately 3000 years, with high time resolution, Miyake et al. found a rapid increase at AD 774-775 and another one at AD 993-994. These increases correspond to high-energy events that happened within those years and radiated γ-ray energy of about 7×1024 erg toward the Earth. The origin of these events is a mystery. Such strong events should have an unusual optical counterpart, and have been recorded in historical literatures. We searched Chinese historical materials around AD 744-775 and AD 993-994, but no remarkable event was found except for a violent thunderstorm in AD 775. However, the possibility of a thunderstorm containing so much energy is unlikely. We conclude that the events, which caused the 14C increase, are still unclear. These events most probably had no optical counterpart, and a short gamma-ray burst, giant flare of a soft gamma-ray repeater or a terrestrial γ-ray flash could all be candidates.

  11. Increased neurotrophic factor levels in ventral mesencephalic cultures do not explain the protective effect of osteopontin and the synthetic 15-mer RGD domain against MPP+ toxicity.

    PubMed

    Broom, Lauren; Jenner, Peter; Rose, Sarah

    2015-01-01

    The synthetic 15-mer arginine-glycine-aspartic acid (RGD) domain of osteopontin (OPN) is protective in vitro and in vivo against dopaminergic cell death and this protective effect may be mediated through interaction with integrin receptors to regulate neurotrophic factor levels. We now examine this concept in rat primary ventral mesencephalic (VM) cultures. 1-Methyl-4-phenylpyridinium (MPP+) exposure reduced tyrosine hydroxylase (TH)-positive cell number and activated glial cells as shown by increased glial fibrillary acidic protein (GFAP), oxycocin-42 (OX-42) and ectodermal dysplasia 1 (ED-1) immunoreactivity. Both OPN and the RGD domain of OPN were equally protective against MPP+ toxicity in VM cultures and both increased glial-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) levels. The effects of OPN and the RGD domain were accompanied by a decrease in numbers of activated microglia but with no change in astrocyte number. However, full-length OPN and the RGD domain of OPN remained protective against MPP+ toxicity in the presence of a GDNF neutralising antibody. This suggests that increased GDNF levels do not underlie the protective effect observed with OPN. Rather, OPN's protective effect may be mediated through decreased glial cell activation. PMID:25218309

  12. Structural stability and functional remodeling of high-density lipoproteins.

    PubMed

    Gursky, Olga

    2015-09-14

    Lipoproteins are protein-lipid nanoparticles that transport lipids in circulation and are central in atherosclerosis and other disorders of lipid metabolism. Apolipoproteins form flexible structural scaffolds and important functional ligands on the particle surface and direct lipoprotein metabolism. Lipoproteins undergo multiple rounds of metabolic remodeling that is crucial to lipid transport. Important aspects of this remodeling, including apolipoprotein dissociation and particle fusion, are mimicked in thermal or chemical denaturation and are modulated by free energy barriers. Here we review the biophysical studies that revealed the kinetic mechanism of lipoprotein stabilization and unraveled its structural basis. The main focus is on high-density lipoprotein (HDL). An inverse correlation between stability and functions of various HDLs in cholesterol transport suggests the functional role of structural disorder. A mechanism for the conformational adaptation of the major HDL proteins, apoA-I and apoA-II, to the increasing lipid load is proposed. Together, these studies help understand why HDL forms discrete subclasses separated by kinetic barriers, which have distinct composition, conformation and functional properties. Understanding these properties may help improve HDL quality and develop novel therapies for cardiovascular disease. PMID:25749369

  13. Characterization of chick serum lipoproteins isolated by density gradient ultracentrifugation.

    PubMed

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

    1992-01-01

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

  14. Biogenesis and Membrane Targeting of Lipoproteins.

    PubMed

    Narita, Shin-Ichiro; Tokuda, Hajime

    2010-09-01

    Bacterial lipoproteins represent a unique class of membrane proteins, which are anchored to membranes through triacyl chains attached to the amino-terminal cysteine. They are involved in various functions localized in cell envelope. Escherichia coli possesses more than 90 species of lipoproteins, most of which are localized in the outer membrane, with others being in the inner membrane. All lipoproteins are synthesized in the cytoplasm with an N-terminal signal peptide, translocated across the inner membrane by the Sec translocon to the periplasmic surface of the inner membrane, and converted to mature lipoproteins through sequential reactions catalyzed by three lipoprotein-processing enzymes: Lgt, LspA, and Lnt. The sorting of lipoproteins to the outer membrane requires a system comprising five Lol proteins. An ATP-binding cassette transporter, LolCDE, initiates the sorting by mediating the detachment of lipoproteins from the inner membrane. Formation of the LolA-lipoprotein complex is coupled to this LolCDE-dependent release reaction. LolA accommodates the amino-terminal acyl chain of lipoproteins in its hydrophobic cavity, thereby generating a hydrophilic complex that can traverse the periplasmic space by diffusion. Lipoproteins are then transferred to LolB on the outer membrane and anchored to the inner leaflet of the outer membrane by the action of LolB. In contrast, since LolCDE does not recognize lipoproteins possessing Asp at position +2, these lipoproteins remain anchored to the inner membrane. Genes for Lol proteins are widely conserved among gram-negative bacteria, and Lol-mediated outer membrane targeting of lipoproteins is considered to be the general lipoprotein localization mechanism. PMID:26443779

  15. The role of lipoprotein(a) in clotting reactions during lipoprotein apheresis-A case report.

    PubMed

    Matney, Kathryn; Berg, Mary; Falko, James M; Draper, Nicole L

    2016-01-01

    In individuals with familial hypercholesterolemia (FH) who are unable to reach a target low-density lipoprotein level on a drug regimen, lipoprotein apheresis (LA) may be the treatment of choice. Severe reactions involving clotting during LA are not well described in the literature. We report a case of a 63-year-old woman with FH and markedly elevated lipoprotein(a) (Lp[a]) levels who experienced such a reaction while undergoing LA with a dextran-sulfate cellulose column on the Kaneka MA-01 Liposorber system. Owing to the clotting as well as a blood pressure drop to <100 mm Hg systolic, the procedure was stopped early. Before her second procedure, she was given an increased loading dose of unfractionated heparin. She did not develop clotting during this second procedure. A growing body of literature on the role of Lp(a) in atherothrombotic complications and hemostasis supports a possible mechanism by which clotting in the instrument could occur during apheresis. Our patient's initial pretreatment Lp(a) was 3.5 times greater than the mean Lp(a) levels in patients with FH. This theory is consistent with our case in that the patient's Lp(a) levels progressively declined with each procedure, and she had no subsequent clotting. PMID:27055976

  16. Increased Proportion of Variance Explained and Prediction Accuracy of Survival of Breast Cancer Patients with Use of Whole-Genome Multiomic Profiles.

    PubMed

    Vazquez, Ana I; Veturi, Yogasudha; Behring, Michael; Shrestha, Sadeep; Kirst, Matias; Resende, Marcio F R; de Los Campos, Gustavo

    2016-07-01

    Whole-genome multiomic profiles hold valuable information for the analysis and prediction of disease risk and progression. However, integrating high-dimensional multilayer omic data into risk-assessment models is statistically and computationally challenging. We describe a statistical framework, the Bayesian generalized additive model ((BGAM), and present software for integrating multilayer high-dimensional inputs into risk-assessment models. We used BGAM and data from The Cancer Genome Atlas for the analysis and prediction of survival after diagnosis of breast cancer. We developed a sequence of studies to (1) compare predictions based on single omics with those based on clinical covariates commonly used for the assessment of breast cancer patients (COV), (2) evaluate the benefits of combining COV and omics, (3) compare models based on (a) COV and gene expression profiles from oncogenes with (b) COV and whole-genome gene expression (WGGE) profiles, and (4) evaluate the impacts of combining multiple omics and their interactions. We report that (1) WGGE profiles and whole-genome methylation (METH) profiles offer more predictive power than any of the COV commonly used in clinical practice (e.g., subtype and stage), (2) adding WGGE or METH profiles to COV increases prediction accuracy, (3) the predictive power of WGGE profiles is considerably higher than that based on expression from large-effect oncogenes, and (4) the gain in prediction accuracy when combining multiple omics is consistent. Our results show the feasibility of omic integration and highlight the importance of WGGE and METH profiles in breast cancer, achieving gains of up to 7 points area under the curve (AUC) over the COV in some cases. PMID:27129736

  17. Enhanced Botrytis cinerea Resistance of Arabidopsis Plants Grown in Compost May Be Explained by Increased Expression of Defense-Related Genes, as Revealed by Microarray Analysis

    PubMed Central

    Segarra, Guillem; Santpere, Gabriel; Elena, Georgina; Trillas, Isabel

    2013-01-01

    Composts are the products obtained after the aerobic degradation of different types of organic matter waste and can be used as substrates or substrate/soil amendments for plant cultivation. There is a small but increasing number of reports that suggest that foliar diseases may be reduced when using compost, rather than standard substrates, as growing medium. The purpose of this study was to examine the gene expression alteration produced by the compost to gain knowledge of the mechanisms involved in compost-induced systemic resistance. A compost from olive marc and olive tree leaves was able to induce resistance against Botrytis cinerea in Arabidopsis, unlike the standard substrate, perlite. Microarray analyses revealed that 178 genes were differently expressed, with a fold change cut-off of 1, of which 155 were up-regulated and 23 were down-regulated in compost-grown, as against perlite-grown plants. A functional enrichment study of up-regulated genes revealed that 38 Gene Ontology terms were significantly enriched. Response to stress, biotic stimulus, other organism, bacterium, fungus, chemical and abiotic stimulus, SA and ABA stimulus, oxidative stress, water, temperature and cold were significantly enriched, as were immune and defense responses, systemic acquired resistance, secondary metabolic process and oxireductase activity. Interestingly, PR1 expression, which was equally enhanced by growing the plants in compost and by B. cinerea inoculation, was further boosted in compost-grown pathogen-inoculated plants. Compost triggered a plant response that shares similarities with both systemic acquired resistance and ABA-dependent/independent abiotic stress responses. PMID:23405252

  18. Increased Proportion of Variance Explained and Prediction Accuracy of Survival of Breast Cancer Patients with Use of Whole-Genome Multiomic Profiles

    PubMed Central

    Vazquez, Ana I.; Veturi, Yogasudha; Behring, Michael; Shrestha, Sadeep; Kirst, Matias; Resende, Marcio F. R.; de los Campos, Gustavo

    2016-01-01

    Whole-genome multiomic profiles hold valuable information for the analysis and prediction of disease risk and progression. However, integrating high-dimensional multilayer omic data into risk-assessment models is statistically and computationally challenging. We describe a statistical framework, the Bayesian generalized additive model ((BGAM), and present software for integrating multilayer high-dimensional inputs into risk-assessment models. We used BGAM and data from The Cancer Genome Atlas for the analysis and prediction of survival after diagnosis of breast cancer. We developed a sequence of studies to (1) compare predictions based on single omics with those based on clinical covariates commonly used for the assessment of breast cancer patients (COV), (2) evaluate the benefits of combining COV and omics, (3) compare models based on (a) COV and gene expression profiles from oncogenes with (b) COV and whole-genome gene expression (WGGE) profiles, and (4) evaluate the impacts of combining multiple omics and their interactions. We report that (1) WGGE profiles and whole-genome methylation (METH) profiles offer more predictive power than any of the COV commonly used in clinical practice (e.g., subtype and stage), (2) adding WGGE or METH profiles to COV increases prediction accuracy, (3) the predictive power of WGGE profiles is considerably higher than that based on expression from large-effect oncogenes, and (4) the gain in prediction accuracy when combining multiple omics is consistent. Our results show the feasibility of omic integration and highlight the importance of WGGE and METH profiles in breast cancer, achieving gains of up to 7 points area under the curve (AUC) over the COV in some cases. PMID:27129736

  19. Enhanced Botrytis cinerea resistance of Arabidopsis plants grown in compost may be explained by increased expression of defense-related genes, as revealed by microarray analysis.

    PubMed

    Segarra, Guillem; Santpere, Gabriel; Elena, Georgina; Trillas, Isabel

    2013-01-01

    Composts are the products obtained after the aerobic degradation of different types of organic matter waste and can be used as substrates or substrate/soil amendments for plant cultivation. There is a small but increasing number of reports that suggest that foliar diseases may be reduced when using compost, rather than standard substrates, as growing medium. The purpose of this study was to examine the gene expression alteration produced by the compost to gain knowledge of the mechanisms involved in compost-induced systemic resistance. A compost from olive marc and olive tree leaves was able to induce resistance against Botrytis cinerea in Arabidopsis, unlike the standard substrate, perlite. Microarray analyses revealed that 178 genes were differently expressed, with a fold change cut-off of 1, of which 155 were up-regulated and 23 were down-regulated in compost-grown, as against perlite-grown plants. A functional enrichment study of up-regulated genes revealed that 38 Gene Ontology terms were significantly enriched. Response to stress, biotic stimulus, other organism, bacterium, fungus, chemical and abiotic stimulus, SA and ABA stimulus, oxidative stress, water, temperature and cold were significantly enriched, as were immune and defense responses, systemic acquired resistance, secondary metabolic process and oxireductase activity. Interestingly, PR1 expression, which was equally enhanced by growing the plants in compost and by B. cinerea inoculation, was further boosted in compost-grown pathogen-inoculated plants. Compost triggered a plant response that shares similarities with both systemic acquired resistance and ABA-dependent/independent abiotic stress responses. PMID:23405252

  20. Effect of dietary Fatty acids on human lipoprotein metabolism: a comprehensive update.

    PubMed

    Ooi, Esther M M; Watts, Gerald F; Ng, Theodore W K; Barrett, P Hugh R

    2015-06-01

    Dyslipidemia is a major risk factor for cardiovascular disease (CVD). Dietary fatty-acid composition regulates lipids and lipoprotein metabolism and may confer CVD benefit. This review updates understanding of the effect of dietary fatty-acids on human lipoprotein metabolism. In elderly participants with hyperlipidemia, high n-3 polyunsaturated fatty-acids (PUFA) consumption diminished hepatic triglyceride-rich lipoprotein (TRL) secretion and enhanced TRL to low-density lipoprotein (LDL) conversion. n-3 PUFA also decreased TRL-apoB-48 concentration by decreasing TRL-apoB-48 secretion. High n-6 PUFA intake decreased very low-density lipoprotein (VLDL) cholesterol and triglyceride concentrations by up-regulating VLDL lipolysis and uptake. In a study of healthy subjects, the intake of saturated fatty-acids with increased palmitic acid at the sn-2 position was associated with decreased postprandial lipemia. Low medium-chain triglyceride may not appreciably alter TRL metabolism. Replacing carbohydrate with monounsaturated fatty-acids increased TRL catabolism. Trans-fatty-acid decreased LDL and enhanced high-density lipoprotein catabolism. Interactions between APOE genotype and n-3 PUFA in regulating lipid responses were also described. The major advances in understanding the effect of dietary fatty-acids on lipoprotein metabolism has centered on n-3 PUFA. This knowledge emphasizes the importance of regulating lipoprotein metabolism as a mode to improve plasma lipids and potentially CVD risk. Additional studies are required to better characterize the cardiometabolic effects of other dietary fatty-acids. PMID:26043038

  1. Prothrombotic lipoprotein patterns in stroke.

    PubMed

    Podrez, Eugene A; Byzova, Tatiana V

    2016-03-10

    The importance of research focused on the final events of atherothrombosis cannot be overestimated. Platelet hyperreactivity leading to thrombosis is the main reason for mortality and morbidity in patients with cardiovascular disease and stroke, which together remain a leading cause of death in developed countries. In this issue of Blood, Shen et al1 establish another functional link between proatherogenic lipoproteins and platelet-mediated thrombus formation with a specific focus on stroke. In their model, the initiating component is L5, the electronegative subfraction of low-density lipoproteins (LDLs), which was shown to be substantially elevated in patients with ischemic stroke. L5 was shown to activate platelets via its receptor, lectin-like oxidized LDL receptor-1 (LOX-1), and αβ amyloid peptide, which together contribute to platelet hyperreactivity and stroke complications. PMID:26965920

  2. Lipoprotein (a): impact by ethnicity and environmental and medical conditions.

    PubMed

    Enkhmaa, Byambaa; Anuurad, Erdembileg; Berglund, Lars

    2016-07-01

    Levels of lipoprotein (a) [Lp(a)], a complex between an LDL-like lipid moiety containing one copy of apoB, and apo(a), a plasminogen-derived carbohydrate-rich hydrophilic protein, are primarily genetically regulated. Although stable intra-individually, Lp(a) levels have a skewed distribution inter-individually and are strongly impacted by a size polymorphism of the LPA gene, resulting in a variable number of kringle IV (KIV) units, a key motif of apo(a). The variation in KIV units is a strong predictor of plasma Lp(a) levels resulting in stable plasma levels across the lifespan. Studies have demonstrated pronounced differences across ethnicities with regard to Lp(a) levels and some of this difference, but not all of it, can be explained by genetic variations across ethnic groups. Increasing evidence suggests that age, sex, and hormonal impact may have a modest modulatory influence on Lp(a) levels. Among clinical conditions, Lp(a) levels are reported to be affected by kidney and liver diseases. PMID:26637279

  3. Explaining Increases in Higher Education Costs

    ERIC Educational Resources Information Center

    Archibald, Robert B.; Feldman, David H.

    2008-01-01

    The real cost of higher education per full-time equivalent student has grown substantially over the last 75 years, and the rapid rise since the early 1980s is a cause of considerable public concern. Opinion surveys consistently find that how much one has to pay for a college education is a serious national issue. In his July 1996 congressional…

  4. Regulation of high-density lipoprotein metabolism.

    PubMed

    Rye, Kerry-Anne; Barter, Philip J

    2014-01-01

    There is compelling evidence from human population studies that plasma levels of high-density lipoprotein (HDL) cholesterol correlate inversely with cardiovascular risk. Identification of this relationship has stimulated research designed to understand how HDL metabolism is regulated. The ultimate goal of these studies has been to develop HDL-raising therapies that have the potential to decrease the morbidity and mortality associated with atherosclerotic cardiovascular disease. However, the situation has turned out to be much more complex than originally envisaged. This is partly because the HDL fraction consists of multiple subpopulations of particles that vary in terms of shape, size, composition, and surface charge, as well as in their potential cardioprotective properties. This heterogeneity is a consequence of the continual remodeling and interconversion of HDL subpopulations by multiple plasma factors. Evidence that the remodeling of HDLs may impact on their cardioprotective properties is beginning to emerge. This serves to highlight the importance of understanding not only how the remodeling and interconversion of HDL subpopulations is regulated but also how these processes are affected by agents that increase HDL levels. This review provides an overview of what is currently understood about HDL metabolism and how the subpopulation distribution of these lipoproteins is regulated. PMID:24385508

  5. Advanced glycation endproduct changes to Bruch's membrane promotes lipoprotein retention by lipoprotein lipase.

    PubMed

    Cano, Marisol; Fijalkowski, Natalia; Kondo, Naoshi; Dike, Sonny; Handa, James

    2011-08-01

    Lipoprotein particles accumulate in Bruch's membrane before the development of basal deposits and drusen, two histopathologic lesions that define age-related macular degeneration (AMD). We therefore, sought to determine which molecules could participate in lipoprotein retention. Wild-type or lipoprotein lipase-deficient mice were injected with low-dose D-galactose or PBS subcutaneously for 8 weeks to induce advanced glycation endproduct (AGE) formation. Some mice were also injected with the AGE breaker phenacylphiazolium bromide and D-galactose. Rhodamine-labeled low-density lipoproteins were injected into mice, and the fluorescence was measured up to 72 hours later. AGEs, proteoglycans, and other lipid-retaining molecules were evaluated by IHC. Lipoprotein lipase distribution was assessed in AMD samples by IHC. D-galactose-treated mice retained lipoproteins in the retinal pigment epithelial and Bruch's membrane to a greater extent than either PBS- or phenacylphiazolium bromide/D-galactose-treated mice at 24 and 72 hours after injection (P ≤ 0.04). Immunolabeling for carboxymethyllysine, biglycan, and lipoprotein lipase was found in D-galactose-treated mice only. Mice deficient for lipoprotein lipase treated with D-galactose did not retain lipoproteins to any measureable extent. Human AMD samples had lipoprotein lipase labeling within drusen, basal deposits, and the choroid. Mice treated with D-galactose to induce AGE formation in Bruch's membrane retain intravenously injected lipoproteins. Our results suggest that lipoprotein retention in Bruch's membrane is mediated by lipoprotein lipase. PMID:21801873

  6. Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice.

    PubMed Central

    Harris, H W; Grunfeld, C; Feingold, K R; Rapp, J H

    1990-01-01

    Endotoxemia stimulates many physiologic responses including disturbances in lipid metabolism. We hypothesized that this lipemia may be part of a defensive mechanism by which the body combats the toxic effects of circulating endotoxin. We tested the effects of mixtures of endotoxin, lipoproteins, and lipoprotein-free plasma and determined the ability of varying concentrations of human very low density lipoproteins (VLDL) and chylomicrons, as well as low density lipoproteins (LDL) and high density lipoproteins (HDL), and of the synthetic lipid emulsion SOYACAL to prevent endotoxin-induced death in mice. This study demonstrates that the triglyceride-rich VLDL and chylomicrons, as well as cholesterol-rich LDL and HDL, and cholesterol-free SOYACAL can protect against endotoxin-induced death. Protection required small amounts of lipoprotein-free plasma, and depended on the incubation time and the concentration of lipoprotein lipid. Despite stringent techniques to prevent exogenous endotoxin contamination eight of ten duplicate VLDL preparations contained endotoxin (5,755 +/- 3,514 ng endotoxin/mg triglyceride, mean +/- SEM) making the isolation of endotoxin-free VLDL difficult. In contrast, simultaneous preparations of LDL and HDL were relatively free of endotoxin contamination (3 +/- 3 and 320 +/- 319 ng/mg total cholesterol, respectively), suggesting that the contamination of VLDL occurs in vivo and not during the isolation procedure. These observations suggest a possible role for increased triglyceride-rich lipoproteins in the host's defense against endotoxemia and infection. Images PMID:2394827

  7. Once-daily niacin extended release/lovastatin combination tablet has more favorable effects on lipoprotein particle size and subclass distribution than atorvastatin and simvastatin.

    PubMed

    Bays, Harold E; McGovern, Mark E

    2003-01-01

    Standard lipoprotein measurements may not adequately reflect the increased atherogenic risk found in patients with abnormalities in lipoprotein particle size and subfraction distribution such as disproportionate amounts of small, dense low-density lipoprotein particles, small high-density lipoprotein particles, or large very-low-density lipoprotein particles. Measurement or anticipation of patients most susceptible to lipoprotein subfraction abnormalities may influence therapeutic choices for the optimal management of dyslipidemia. Previously, the ADvicor Vs. Other Cholesterol-modulating Agents Trial Evaluation demonstrated that niacin extended release/lovastatin provided greater global improvement in lipid parameters such as low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, lipoprotein (a), apolipoprotein B, and apolipoprotein A-I blood levels compared with atorvastatin and simvastatin monotherapies. In this report, niacin extended release/lovastatin was also more effective than atorvastatin and simvastatin monotherapies in reducing small, dense low-density lipoprotein particles and improving low-density lipoprotein phenotype pattern at relative starting doses, and was more effective in increasing the proportion of high-density lipoprotein in the potentially cardioprotective 2b subclass at all doses. PMID:14605511

  8. A more flexible lipoprotein sorting pathway.

    PubMed

    Chahales, Peter; Thanassi, David G

    2015-05-01

    Lipoprotein biogenesis in Gram-negative bacteria occurs by a conserved pathway, each step of which is considered essential. In contrast to this model, LoVullo and colleagues demonstrate that the N-acyl transferase Lnt is not required in Francisella tularensis or Neisseria gonorrhoeae. This suggests the existence of a more flexible lipoprotein pathway, likely due to a modified Lol transporter complex, and raises the possibility that pathogens may regulate lipoprotein processing to modulate interactions with the host. PMID:25755190

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

    PubMed Central

    Hatch, Nicholas W.; Srodulski, Sarah J.; Chan, Huei-Wei; Zhang, Xuan; Tannock, Lisa R.; King, Victoria L.

    2012-01-01

    Background Despite numerous clinical and animal studies, the role of sex steroid hormones on lipoprotein metabolism and atherosclerosis remain controversial. Objective We sought to determine the effects of endogenous estrogen and testosterone on lipoprotein levels and atherosclerosis using mice fed a low-fat diet with no added cholesterol. Methods Male and female low-density lipoprotein receptor-deficient mice were fed an open stock low-fat diet (10% of kcals from fat) for 2, 4, or 17 weeks. Ovariectomy, orchidectomy, or sham surgeries were performed to evaluate the effects of the presence or absence of endogenous hormones on lipid levels, lipoprotein distribution, and atherosclerosis development. Results Female mice fed the study diet for 17 weeks had a marked increase in levels of total cholesterol, triglycerides, apolipoprotein-B containing lipoproteins, and atherosclerosis compared with male mice. Surprisingly, ovariectomy in female mice had no effect on any of these parameters. In contrast, castration of male mice markedly increased total cholesterol concentrations, triglycerides, apolipoprotein B-containing lipoproteins, and atherosclerotic lesion formation compared with male and female mice. Conclusions These data suggest that endogenous androgens protect against diet-induced increases in cholesterol concentrations, formation of proatherogenic lipoproteins, and atherosclerotic lesions formation. Conversely orchidectomy, which decreases androgen concentrations, promotes increases in cholesterol concentrations, proatherogenic lipoprotein formation, and atherosclerotic lesion formation in lowdensity lipoprotein receptor-deficient mice in response to a low-fat diet. PMID:22981166

  10. Obesity and Insulin Resistance Are the Main Determinants of Postprandial Lipoprotein Dysmetabolism in Polycystic Ovary Syndrome

    PubMed Central

    Phelan, Niamh; Boran, Gerard; O'Connor, Anna-Louise; Gibney, James

    2016-01-01

    Postprandial dyslipidaemia may be a plausible mechanism by which polycystic ovary syndrome (PCOS) increases cardiovascular risk. We sought to investigate whether the postprandial glucose and insulin and lipid and lipoprotein responses, including that of apolipoprotein B-48 (apoB-48) containing chylomicrons, to a mixed meal are different in obese PCOS women when compared to obese control subjects and whether differences, if any, are related to obesity, insulin resistance (IR), hyperandrogenaemia, or PCOS status. 26 women with PCOS (age 30.4 ± 1.2 years (mean ± SEM), body mass index (BMI) 36.8 ± 1.5 kg/m2) and 26 non-PCOS subjects (age 34.1 ± 0.9 years, BMI 31.5 ± 1.0 kg/m2) were studied before and up to 8 hours following a standard mixed meal. AUC-triglyceride (AUC-TG) was higher and AUC-high-density lipoprotein (AUC-HDL) lower in PCOS women. These differences were not apparent when BMI was accounted for. Insulin sensitivity (SI), AUC-apoB-48, and AUC-apolipoprotein B (AUC-apoB) were found to be independent predictors of AUC-TG, accounting for 55% of the variance. Only AUC-insulin remained significantly elevated following adjustment for BMI. Obesity related IR explains postprandial hypertriglyceridaemia and hyperinsulinaemic responses. Management of obesity in premenopausal women with PCOS is likely to reduce their cardiovascular risk burden. PMID:26989412

  11. Lipoprotein lipase activity is required for cardiac lipid droplet production.

    PubMed

    Trent, Chad M; Yu, Shuiqing; Hu, Yunying; Skoller, Nathan; Huggins, Lesley A; Homma, Shunichi; Goldberg, Ira J

    2014-04-01

    The rodent heart accumulates TGs and lipid droplets during fasting. The sources of heart lipids could be either FFAs liberated from adipose tissue or FAs from lipoprotein-associated TGs via the action of lipoprotein lipase (LpL). Because circulating levels of FFAs increase during fasting, it has been assumed that albumin transported FFAs are the source of lipids within heart lipid droplets. We studied mice with three genetic mutations: peroxisomal proliferator-activated receptor α deficiency, cluster of differentiation 36 (CD36) deficiency, and heart-specific LpL deletion. All three genetically altered groups of mice had defective accumulation of lipid droplet TGs. Moreover, hearts from mice treated with poloxamer 407, an inhibitor of lipoprotein TG lipolysis, also failed to accumulate TGs, despite increased uptake of FFAs. TG storage did not impair maximal cardiac function as measured by stress echocardiography. Thus, LpL hydrolysis of circulating lipoproteins is required for the accumulation of lipids in the heart of fasting mice. PMID:24493834

  12. LIPOPROTEIN LIPASE RELEASES ESTERIFIED OXYLIPINS FROM VERY LOW-DENSITY LIPOPROTEINS.

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    SciTech Connect

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

    1987-01-01

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

  14. Transfer of fatty acids from the 1-position of phosphatidyl-ethanolamine to the major outer membrane lipoprotein of E coli

    SciTech Connect

    Jackowski, S.; Rock, C.O.

    1986-05-01

    The fatty acids esterified to Braun's lipoprotein are derived from the phospholipid pool in E. coli. Mutants lacking acyl-CoA synthetase activity (fadD) incorporated extracellular fatty acids specifically into the 1-position of phosphatidylethanolamine (PtdEtn). This pathway was blocked by chloramphenicol and was depressed by preventing the acylation of the amino terminus of the lipoprotein with globomycin. Transfer of fatty acids to lipoprotein was investigated in fadD mutants harboring hybrid plasmids containing either the lipoprotein gene or a lipoprotein-..beta..-lactamase gene fusion under control of the lactose promoter. Labeling of the 1-position of the PtdEtn pool prior to induction of lipoprotein biosynthesis resulted in the transfer of fatty acids from PtdEtn to the lipoproteins. Induction of lipoprotein synthesis in the presence of exogenous (1-/sup 14/C)palmitate increased the amount of radioactivity entering the PtdEtn pool and efficiently labeled lipoprotein acyl moieties. Lipoprotein fatty acids derived from the 1-position of PtdEtn were resistant to hydroxylamine hydrolysis, and globomycin reduced the incorporation of exogenous (1-/sup 14/C)palmitic acid into lipoproteins by 80% suggesting that the fatty acid is attached to the amino terminus. These data illustrate the metabolic relationship between turnover of fatty acids in the 1-position of PtdEtn and the maturation of the major outer membrane lipoprotein.

  15. Endotoxin suppresses rat hepatic low-density lipoprotein receptor expression.

    PubMed Central

    Liao, W; Rudling, M; Angelin, B

    1996-01-01

    Endotoxin induces hyperlipidaemia in experimental animals. In the current study, we investigated whether endotoxin alters hepatic low-density lipoprotein (LDL) receptor expression in rats. Endotoxin treatment suppressed hepatic LDL receptor expression in a dose- and time-dependent manner. Eighteen hours after intraperitoneal injection of increasing amounts of endotoxin, LDL receptor and its mRNA levels were determined by ligand blot and solution hybridization respectively. LDL receptor expression was inhibited by about 70% at a dose of 500 micrograms/100 g body weight. However, LDL receptor mRNA levels were markedly increased in all endotoxin-treated groups at this time point (by 83-136%; P < 0.001). Time-course experiments showed that LDL receptor expression was already reduced by 48% 4 h after endotoxin injection and was maximally reduced (by 63-65%) between 8 and 18 h. Changes in hepatic LDL receptor mRNA showed a different pattern. By 4 h after endotoxin injection, LDL receptor mRNA had decreased by 78% (P < 0.001). However, by 8 h after endotoxin injection, LDL receptor mRNA had returned to levels similar to controls, and 18 and 24 h after endotoxin injection, they were increased by about 60% (P < 0.05). Separation of plasma lipoproteins by FPLC demonstrated that endotoxin-induced changes in plasma triacylglycerols and cholesterol were due to accumulation of plasma apolipoprotein B-containing lipoproteins among very-low-density lipoprotein, intermediate-density lipoprotein and LDL. It is concluded that endotoxin suppresses hepatic LDL receptor expression in vivo in rats. PMID:8611169

  16. Low-Density Lipoprotein Apheresis

    PubMed Central

    2007-01-01

    are approximately 765 refractory HTZ FH patients in Ontario, of which 115 are diagnosed and 650 are undiagnosed. Drug therapy is less effective in HMZ FH patients since the effects of the majority of cholesterol-lowering drugs are mediated by the upregulation of LDL receptors, which are often absent or function poorly in HMZ FH patients. Some HMZ FH patients may still benefit from drug therapy, however this rarely reduces LDL-C levels to targeted levels. Existing Technology: Plasma Exchange An option currently available in Ontario for FH patients who do not respond to standard diet and drug therapy is plasma exchange (PE). Patients are treated with this lifelong therapy on a weekly or biweekly basis with concomitant drug therapy. Plasma exchange is nonspecific and eliminates virtually all plasma proteins such as albumin, immunoglobulins, coagulation factors, fibrinolytic factors and HDL-C, in addition to acutely lowering LDL-C by about 50%. Blood is removed from the patient, plasma is isolated, discarded and replaced with a substitution fluid. The substitution fluid and the remaining cellular components of the blood are then returned to the patient. The major limitation of PE is its nonspecificity. The removal of HDL-C prevents successful vascular remodeling of the areas stenosed by atherosclerosis. In addition, there is an increased susceptibility to infections, and costs are incurred by the need for replacement fluid. Adverse events can be expected to occur in 12% of procedures. Other Alternatives Surgical alternatives for FH patients include portocaval shunt, ileal bypass and liver transplantation. However, these are risky procedures and are associated with a high morbidity rate. Results with gene therapy are not convincing to date. The Technology Being Reviewed: LDL Apheresis An alternative to PE is LDL apheresis. Unlike PE, LDL apheresis is a selective treatment that removes LDL-C and other atherogenic lipoproteins from the blood while minimally impacting other

  17. Altered Serum Lipoprotein Profiles in Male and Female Power Lifters Ingesting Anabolic Steroids.

    ERIC Educational Resources Information Center

    Cohen, Jonathan C.; And Others

    1986-01-01

    Serum lipoprotein profiles were measured in nine male and three female weightlifters who were taking anabolic steroids. The profiles suggest that steriod users may face an increased risk of coronary artery disease. (Author/MT)

  18. Metabolism of very low density lipoproteins--effect of sardine oil.

    PubMed

    Anil, K; Abraham, R; Kumar, G S; Sudhakaran, P R; Kurup, P A

    1992-06-01

    The effect of feeding fish oil on the metabolism of lipoproteins was studied in rats. Rats were fed diet containing 10% sardine or groundnut oil for 6 weeks. There was a significant decrease in the total cholesterol, phospholipids and triglycerides as well as the amount of the lipids associated with VLDL and LDL in serum in fish oil-fed rats. The synthesis and secretion of lipoproteins particularly apoB containing lipoproteins by primary cultures of hepatocytes from these rats were studied by 14(C)-acetate or 3(H)-leucine labelling. Primary cultures of hepatocytes derived from sardine oil-fed rats showed reduced incorporation of 3(H)-leucine into apoB containing lipoproteins secreted into the medium when compared to those fed groundnut oil, indicating a decreased synthesis and secretion of apoB. This was further confirmed by significantly lower incorporation of 14(C)-radioactivity into total and individual lipids of VLDL secreted into the medium, as well as that associated with different lipids in cell layer. The activity of lipoprotein lipase in adipose tissue and aorta was significantly higher in rats fed sardine oil which may cause an increased clearance of triglyceride-rich lipoproteins from circulation. These results indicate that the fish oil exerts hypolipidemic effect particularly by decreasing the synthesis and secretion of VLDL by liver and possibly by an increased clearance of triglyceride-rich lipoproteins from circulation. PMID:1506035

  19. Intestinal Lipid Absorption and Lipoprotein Formation

    PubMed Central

    Hussain, M. Mahmood

    2014-01-01

    Purpose of review The purpose of this review is to summarize evidence for the presence of two pathways of lipid absorption and their regulation. Recent findings Lipid absorption involves hydrolysis of dietary fat in the lumen of the intestine followed by the uptake of hydrolyzed products by enterocytes. Lipids are re-synthesized in the endoplasmic reticulum and are either secreted with chylomicrons and high density lipoproteins or stored as cytoplasmic lipid droplets. Lipids in the droplets are hydrolyzed and are secreted at a later time. Secretion of lipids by the chylomicron and HDL pathways are critically dependent on MTP and ABCA1, respectively, and are regulated independently. Gene ablation studies showed that MTP function and chylomicron assembly is essential for the absorption of triglyceride and retinyl esters. Ablation of MTP abolishes triglyceride absorption and results in massive triglyceride accumulation in enterocytes. Although majority of phospholipid, cholesterol and vitamin E are absorbed through the chylomicron pathway, a significant amount of these lipids are also absorbed via the HDL pathway. Chylomicron assembly and secretion is increased by the enhanced availability of fatty acids, whereas HDL pathway is upregulated by LXR agonists. Intestinal insulin resistance increases chylomicron and might reduce HDL production. Summary Triglycerides are exclusively transported via the chylomicron pathway and this process is critically dependent on MTP. Besides chylomicrons, absorption of phospholipids, free cholesterol, retinol, and vitamin E also involves high density lipoproteins. These two pathways are complementary and are regulated independently. They may be targeted to lower lipid absorption in order to control hyperlipidemia, obesity, metabolic syndrome, steatosis, insulin resistance, atherosclerosis and other disorders. PMID:24751933

  20. Historical perspectives on lipoprotein research and methodology

    SciTech Connect

    Lindgren, F.T.

    1990-03-01

    Since the early history of lipoprotein isolation and characterization dates back more than 60 years, it would be helpful to describe some of the landmarks occurring before about 1965. This document contains historical perspectives and information on lipoprotein research and methodology. 35 refs., 9 figs., 1 tab.

  1. Computational studies of plasma lipoprotein lipids.

    PubMed

    Pan, Lurong; Segrest, Jere P

    2016-10-01

    Plasma lipoproteins are macromolecular assemblies of proteins and lipids found in the blood. The lipid components of lipoproteins are amphipathic lipids such as phospholipids (PLs), and unesterified cholesterols (UCs) and hydrophobic lipids such as cholesteryl esters (CEs) and triglycerides (TGs). Since lipoproteins are soft matter supramolecular assemblies easily deformable by thermal fluctuations and they also exist in varying densities and protein/lipid components, a detailed understanding of their structure/function is experimentally difficult. Molecular dynamics (MD) simulation has emerged as a particularly promising way to explore the structure and dynamics of lipoproteins. The purpose of this review is to survey the current status of computational studies of the lipid components of the lipoproteins. Computational studies aim to explore three levels of complexity for the 3-dimensional structural dynamics of lipoproteins at various metabolic stages: (i) lipoprotein particles consist of protein with minimal lipid; (ii) lipoprotein particles consist of PL-rich discoidal bilayer-like lipid particles; (iii) mature circulating lipoprotein particles consist of CE-rich or TG-rich spheroidal lipid-droplet-like particles. Due to energy barriers involved in conversion between these species, other biomolecules also participate in lipoprotein biological assembly. For example: (i) lipid-poor apolipoprotein A-I (apoA-I) interacts with ATP-binding cassette transporter A1 (ABCA1) to produce nascent discoidal high density lipoprotein (dHDL) particles; (ii) lecithin-cholesterol acyltransferase (LCAT) mediates the conversion of UC to CE in dHDL, driving spheroidal HDL (sHDL) formation; (iii) transfer proteins, cholesterol ester transfer protein (CETP) and phospholipid transfer protein (PLTP), transfer both CE and TG and PL, respectively, between lipoprotein particles. Computational studies have the potential to explore different lipoprotein particles at each metabolic stage in

  2. The iron-regulated staphylococcal lipoproteins

    PubMed Central

    Sheldon, Jessica R.; Heinrichs, David E.

    2012-01-01

    Lipoproteins fulfill diverse roles in antibiotic resistance, adhesion, protein secretion, signaling and sensing, and many also serve as the substrate binding protein (SBP) partner to ABC transporters for the acquisition of a diverse array of nutrients including peptides, sugars, and scarcely abundant metals. In the staphylococci, the iron-regulated SBPs are significantly upregulated during iron starvation and function to sequester and deliver iron into the bacterial cell, enabling staphylococci to circumvent iron restriction imposed by the host environment. Accordingly, this subset of lipoproteins has been implicated in staphylococcal pathogenesis and virulence. Lipoproteins also activate the host innate immune response, triggered through Toll-like receptor-2 (TLR2) and, notably, the iron-regulated subset of lipoproteins are particularly immunogenic. In this review, we discuss the iron-regulated staphylococcal lipoproteins with regard to their biogenesis, substrate specificity, and impact on the host innate immune response. PMID:22919632

  3. The pathophysiology of intestinal lipoprotein production

    PubMed Central

    Giammanco, Antonina; Cefalù, Angelo B.; Noto, Davide; Averna, Maurizio R.

    2015-01-01

    Intestinal lipoprotein production is a multistep process, essential for the absorption of dietary fats and fat-soluble vitamins. Chylomicron assembly begins in the endoplasmic reticulum with the formation of primordial, phospholipids-rich particles that are then transported to the Golgi for secretion. Several classes of transporters play a role in the selective uptake and/or export of lipids through the villus enterocytes. Once secreted in the lymph stream, triglyceride-rich lipoproteins (TRLs) are metabolized by Lipoprotein lipase (LPL), which catalyzes the hydrolysis of triacylglycerols of very low density lipoproteins (VLDLs) and chylomicrons, thereby delivering free fatty acids to various tissues. Genetic mutations in the genes codifying for these proteins are responsible of different inherited disorders affecting chylomicron metabolism. This review focuses on the molecular pathways that modulate the uptake and the transport of lipoproteins of intestinal origin and it will highlight recent findings on TRLs assembly. PMID:25852563

  4. Lipoprotein Kinetics in the Metabolic Syndrome: Pathophysiological and Therapeutic Lessons from Stable Isotope Studies

    PubMed Central

    Chan, Dick C; Barrett, P Hugh R; Watts, Gerald F

    2004-01-01

    Dyslipoproteinaemia is a cardinal feature of the metabolic syndrome that accelerates atherosclerosis. It is usually characterised by high plasma concentrations of triglyceride-rich and apolipoprotein (apo) B-containing lipoproteins, with depressed concentrations of high-density lipoprotein (HDL). Dysregulation of lipoprotein metabolism in these subjects may be due to a combination of overproduction of very-low-density lipoprotein (VLDL) apoB-100, decreased catabolism of apoB-containing particles, and increased catabolism of HDL apoA-I particles. These abnormalities may be consequent on a global metabolic effect of insulin resistance that increases the flux of fatty acids from adipose tissue to the liver, the accumulation of fat in the liver, the increased hepatic secretion of VLDL-triglycerides and the remodelling of both low-density lipoprotein (LDL) and HDL particles in the circulation; perturbations in lipolytic enzymes and lipid transfer proteins contribute to the dyslipidaemia. Our in vivo understanding of the kinetic defects in lipoprotein metabolism in the metabolic syndrome has been chiefly achieved by ongoing developments in the use of stable isotope tracers and mathematical modelling. Knowledge of the pathophysiology of lipoprotein metabolism in the metabolic syndrome is well complemented by extensive cell biological data. Nutritional modifications and increased physical exercise may favourably alter lipoprotein transport in the metabolic syndrome by collectively decreasing the hepatic secretion of VLDL-apoB and the catabolism of HDL apoA-I, as well as by increasing the clearance of LDL-apoB. Pharmacological treatments, such as statins, fibrates or fish oils, can also correct the dyslipidaemia by several mechanisms of action including decreased secretion and increased catabolism of apoB, as well as increased secretion and decreased catabolism of apoA-I. The complementary mechanisms of action of lifestyle and drug therapies support the use of combination

  5. The relationship among brain natriuretic peptide (BNP), cholesterol and lipoprotein

    PubMed Central

    Takeuchi, Hidekazu; Sata, Masataka

    2012-01-01

    Objective To study the relationship among brain natriuretic peptide (BNP), cholesterol and lipoprotein. Design A retrospective, cross-sectional study. Setting Tokushima University Hospital area. Patients A retrospective study of 46 patients (nine inpatients and 37 outpatients) with angina pectoris or arrhythmias who were seen at Tokushima University Hospital Cardiovascular Division and had measurements of their BNP, fatty acid and lipid profile. The average age of patients was 57±17 years, and 39% were male subjects. Main outcome measures BNP, dihomo-γ-linolenic acid, arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), apolipoproteinA1, apolipoprotein A2 (ApoA2), apolipoprotein B (ApoB), apolipoprotein C2, apolipoprotein C3, apolipoprotein E, total cholesterol (TC), triglyceride, high density lipoprotein cholesterol and low density lipoprotein cholesterol. Results The baseline characteristics of the patients were shown in table 1 and the data of lipoprotein were shown in table 2. Table 3 shows the relationship among BNP, cholesterol and lipoprotein. The authors found significant negative correlation between serum levels of BNP and ApoA2 (figure 1; r=−0.458, p=0.001), serum levels of BNP and ApoB (figure 2; r=−0.328, p=0.026) and serum levels of BNP and TC (figure 3; r=-0.383, p=0.010). There is a possibility that dietary EPA and DHA may modulate cardiac mitochondrial and autonomic nervous system dysfunction via fatty-acids-PPARs-PTEN-PI3K/Akt-SREBPs system and affect serum BNP levels indirectly. Conclusion BNP had significant negative correlation with ApoA2, ApoB and TC. The findings suggest that increasing serum levels of ApoA2, ApoB and TC may have an effect on improving heart function. But the mechanism is presently unclear. PMID:27326018

  6. Characterization of biophysical properties of baboon lipoproteins: modulation by dietary fat and cholesterol

    SciTech Connect

    Babiak, J.

    1984-04-01

    The serum lipoproteins of baboons fed diets containing differing types and amounts of fat and varying amounts of cholesterol were examined by analytic ultracentrifugation, gradient gel electrophoresis, density gradient ultracentrifugation, sodium dodecyl sulfate-polyacrylamide electrophoresis, electron microscopy, and standard protein and lipid composition assays. These studies characterized the lipoproteins of the baboon, observed how concentrations and physical-chemical properties of the lipoproteins are modulated by dietary fat and cholesterol and described the suitability of the baboon as an animal model of human lipoprotein metabolism. Results indicate that baboon high density lipoproteins (HDL), though higher in total serum concentration than human HDL, are remarkably similar to human HDL. The concentration of baboon HDL is increased by dietary saturated fat but decreased by the addition of cholesterol. While serum concentrations of low density lipoproteins (LDL) tend to be lower in baboons, the physical-chemical properties of the LDL of baboons and humans are comparable. The LDL of both species contains apolipoprotein B as their major apolipoprotein and exhibit considerable polydispersity in particle size. LDL of both species consists of seven discrete subpopulations. The analytical and statistical data presented in this dissertation indicate that the baboon is a good model for studying the role of lipoproteins in the development of atherosclerosis. 125 references, 31 figures, 28 tables.

  7. Oscillatory changes in muscle lipoprotein lipase activity of fed and starved rats.

    PubMed

    Kotlar, T J; Borensztajn, J

    1977-10-01

    Lipoprotein lipase activity was measured at short time intervals in cardiac and skeletal muscles of normal and streptozotocin-treated diabetic rats fed ad libitum or deprived of food. In normal animals fed ad libitum, lipoprotein lipase activities of heart, diaphragm, soleus, and fast-twitch red fibers of the quadriceps muscle showed rhythmic oscillations that appeared to coincide with the nocturnal feeding habits of the animals. During the day (7 A.M. to 7 P.M.), when food consumption by the rats was greatly reduced, lipoprotein lipase activity in all muscles increased, followed by a decline to basal levels during the night. Similar oscillatory changes in lipoprotein lipase activity were observed in the muscles of diabetic rats fed ad libitum. In normal rats deprived of food, however, the oscillatory changes in muscle lipoprotein lipase activity were not abolished and persisted for at least 48 h. In diabetic rats starved during a 48-h period, the oscillatory changes in muscle lipoprotein lipase activity were markedly altered. In all animals, muscle lipoprotein lipase activities were not correlated to plasma glucagon levels. PMID:143895

  8. Lipoprotein lipase enhances binding of lipoproteins to heparan sulfate on cell surfaces and extracellular matrix.

    PubMed Central

    Eisenberg, S; Sehayek, E; Olivecrona, T; Vlodavsky, I

    1992-01-01

    Lipoprotein lipase enhances binding at 4 degrees C of human plasma lipoproteins (chylomicrons, VLDL, intermediate density lipoprotein, LDL, and HDL3) to cultured fibroblasts and hepG-2 cells and to extracellular matrix. Heparinase treatment of cells and matrix reduces the lipoprotein lipase enhanced binding by 90-95%. Lipoprotein lipase causes only a minimal effect on the binding of lipoproteins to heparan sulfate deficient mutant Chinese hamster ovary cells while it promotes binding to wild type cells that is abolished after heparinase treatment. With 125I-LDL, lipoprotein lipase also enhances uptake and proteolytic degradation at 37 degrees C by normal human skin fibroblasts but has no effect in heparinase-treated normal cells or in LDL receptor-negative fibroblasts. These observations prove that lipoprotein lipase causes, predominantly, binding of lipoproteins to heparan sulfate at cell surfaces and in extracellular matrix rather than to receptors. This interaction brings the lipoproteins into close proximity with cell surfaces and may promote metabolic events that occur at the cell surface, including facilitated transfer to cellular receptors. Images PMID:1430223

  9. Hydrolysis of bovine and caprine milk fat globules by lipoprotein lipase. Effects of heparin and skim milk on lipase distribution and on lipolysis

    SciTech Connect

    Sundheim, G.; Bengtsson-Olivecrona, G.

    1987-12-01

    Heparin can dissociate lipoprotein lipase from casein micelles, and addition of heparin enhances lipolysis in bovine but not in caprine milk. Heparin shortened the lag-time for binding of lipoprotein lipase to milk fat globules and for lipolysis. Heparin counteracted the inhibitory effects of skim milk on binding of lipase and on lipolysis. Heparin stimulated lipolysis in all bovine milk samples when added before cooling and in spontaneously lipolytic milk samples also when added after cooling. Heparin enhanced lipolysis of isolated milk fat globules. Hence, its effect is not solely due to dissociation of lipoprotein lipase from the casein micelles. Cooling of goat milk caused more marked changes in the distribution of lipase than cooling of bovine milk; the fraction of added /sup 125/I-labeled lipase that bound to cream increased from about 8 to 60%. In addition, caprine skim milk caused less inhibition of lipolysis than bovine skim milk. These observations provide an explanation for the high degree of cold storage lipolysis in goat milk. Heparin had only small effects on the distribution of lipoprotein lipase in caprine milk, which explains why heparin has so little effect on lipolysis in caprine milk. The distribution of /sup 35/S-labeled heparin in bovine milk was studied. In warm milk less than 10% bound to the cream fraction, but when milk was cooled, binding of heparin to cream increased to 45%. These results suggest that there exists in the skim fraction a relatively small amount of a heparin-binding protein, which on cooling of milk adsorbs to the milk fat, or suggests that cooling induces a conformational change in a membrane protein such that its affinity for heparin increases.

  10. Cellular uptake of lipoproteins and persistent organic compounds-An update and new data

    SciTech Connect

    Hjelmborg, Philip Sebastian; Andreassen, Thomas Kjaergaard; Bonefeld-Jorgensen, Eva Cecilie

    2008-10-15

    There are a number of interactions related to the transport of lipophilic xenobiotic compounds in the blood stream of mammals. This paper will focus on the interactions between lipoproteins and persistent organic pollutants (POPs) and how these particles are taken up by cells. A number of POPs including the pesticide p,p'-dichlorodiphenyltrichloroethane (DDT), and especially its metabolite p,p'-dichlorodiphenyldichloroethene (DDE), interacts with nuclear hormone receptors causing these to malfunction, which in turn results in a range of deleterious health effects in humans. The aim of the present study was to determine the role of lipoprotein receptors in mouse embryonic fibroblast (MEF) cells in conjunction with uptake of DDT-lipoprotein complexes from supplemented media in vitro. Uptake of DDT by MEF cells was investigated using MEF1 cells carrying the receptors low-density lipoprotein receptor-related protein (LRP) and low-density lipoprotein receptor (LDLR) present and MEF4 cells with no LRP and LDLR expression. Cells were incubated together with the complex of low-density lipoproteins (LDL) and [{sup 14}C]DDT. The receptor function was further evaluated by adding the 40 kDa receptor-associated protein (RAP) which blocks receptor activity. The results showed that [{sup 14}C]DDT uptake was decreasing when the LDL concentration was increasing. There was no strong evidence for a receptor-mediated uptake of the [{sup 14}C]DDT-lipoprotein complex. To conclude, DDT travels in the blood stream and can cross cell membranes while being transported as a DDT-lipoprotein complex. The lipoproteins do not need receptors to cross cell membranes since passive diffusion constitutes a major passageway.

  11. Metabolism and Modification of Apolipoprotein B-Containing Lipoproteins Involved in Dyslipidemia and Atherosclerosis.

    PubMed

    Morita, Shin-ya

    2016-01-01

    Increased levels of apolipoprotein B (apoB)-containing lipoproteins, such as low density lipoproteins (LDL) and chylomicron remnants, are associated with the development of atherosclerosis. Chylomicrons containing apoB-48 are secreted from the intestine during the postprandial state, whereas very low density lipoproteins (VLDL) containing apoB-100 are constitutively formed in the liver. Chylomicron remnants and VLDL remnants are produced by the lipoprotein lipase-mediated lipolysis of triglycerides, which is activated by apolipoprotein C-II bound on the particle surfaces. The hepatic uptake of these remnants is facilitated by apolipoprotein E (apoE), but is inhibited by apolipoproteins C-I, C-II and C-III. In the plasma, VLDL remnants are further converted into LDL by the hydrolysis of triglycerides. ApoB-100 is responsible for the hepatic uptake of LDL. LDL receptor, LDL receptor-related protein and heparan sulfate proteoglycans are involved in the hepatic clearance of lipoproteins containing apoB-100 and/or apoE. The subendothelial retention and modification of apoB-containing lipoproteins are crucial events in the initiation of atherosclerosis. In the subendothelium, the uptake of modified lipoproteins by macrophages leads to the formation of foam cells storing excess amounts of cholesteryl esters and subsequently to apoptosis. This review describes the current knowledge about the metabolism and modification of apoB-containing lipoproteins involved in dyslipidemia and atherogenesis. In particular, I focus on the effects of apolipoproteins, lipid composition and particle size on lipoprotein metabolism and on the roles of cholesterol, sphingomyelinase and apoB denaturation in macrophage foam cell formation and apoptosis. A detailed understanding of these mechanisms will help to develop new therapeutic strategies. PMID:26725424

  12. Efcts of chronic ethanol feeding on serum lipoprotein metabolism in the rat.

    PubMed

    Baraona, E; Lieber, C S

    1970-04-01

    In rats, chronic ethanol feeding was found to enhance the postprandial hyperlipemia and to increase the incorporation of dietary palmitic acid-(3)H and intravenously injected L-lysine-(14)C into serum lipoproteins. The main increases of total amount, labeling, and specific activity of lipid and protein occurred in the d < 1.019 lipoprotein fraction. Fat absorption and the clearance of injected chylomicrons were not affected by ethanol feeding. Blocking of lipoprotein and chylomicron removal with Triton did not prevent the action of ethanol on serum lipids, indicating that the ethanol effect is not likely due to defective removal of lipids from the circulation. Ethanol enhanced the incorporation of chylomicron fatty acids into newly synthetized very low density lipoproteins, as shown by an increased reappearance of the fatty acid label into the lipids of this fraction after injection of palmitate-(14)C/glycerol-(3)H doubly labeled chylomicrons. These results indicate that alcoholic hyperlipemia is due, at least in part, to an increase in newly synthetized lipoproteins. The hyperlipemia produced by ethanol was accompanied by hepatic steatosis. The simultaneous production of fatty liver and hyperlipemia makes it unlikely that defective lipoprotein synthesis or secretion is a primary mechanism for the pathogenesis of the alcoholic fatty liver. PMID:5443177

  13. Lipoprotein Metabolism and Inflammation in Patients With Psoriasis.

    PubMed

    Armstrong, Ehrin J; Krueger, James G

    2016-08-15

    Psoriasis is a chronic inflammatory disease associated with a variety of co-morbid conditions, including cardiovascular disease. Advancements in our understanding of the cellular and molecular mechanisms of psoriasis have led to a better understanding regarding its pathogenesis, which in turn has stimulated ongoing research to identify the underlying pathophysiology responsible for the increased risk of cardiovascular events associated with psoriasis. Although not yet fully elucidated, emerging evidence points to immune-mediated inflammation as a process that contributes to endothelial cell dysfunction, dyslipidemia, and atherosclerosis as key processes influencing cardiovascular disease in psoriasis. In particular, the dyslipidemia present in psoriasis may be associated with altered lipoprotein function and increased atherogenicity. Here, we review how the cytokine networks involved in lipoprotein metabolism and inflammation could impact on the cardiovascular disease risk for patients with psoriasis. PMID:27392508

  14. Recent advances in physiological lipoprotein metabolism.

    PubMed

    Ramasamy, Indra

    2014-12-01

    Research into lipoprotein metabolism has developed because understanding lipoprotein metabolism has important clinical indications. Lipoproteins are risk factors for cardiovascular disease. Recent advances include the identification of factors in the synthesis and secretion of triglyceride rich lipoproteins, chylomicrons (CM) and very low density lipoproteins (VLDL). These included the identification of microsomal transfer protein, the cotranslational targeting of apoproteinB (apoB) for degradation regulated by the availability of lipids, and the characterization of transport vesicles transporting primordial apoB containing particles to the Golgi. The lipase maturation factor 1, glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 and an angiopoietin-like protein play a role in lipoprotein lipase (LPL)-mediated hydrolysis of secreted CMs and VLDL so that the right amount of fatty acid is delivered to the right tissue at the right time. Expression of the low density lipoprotein (LDL) receptor is regulated at both transcriptional and post-transcriptional level. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has a pivotal role in the degradation of LDL receptor. Plasma remnant lipoproteins bind to specific receptors in the liver, the LDL receptor, VLDL receptor and LDL receptor-like proteins prior to removal from the plasma. Reverse cholesterol transport occurs when lipid free apoAI recruits cholesterol and phospholipid to assemble high density lipoprotein (HDL) particles. The discovery of ABC transporters (ABCA1 and ABCG1) and scavenger receptor class B type I (SR-BI) provided further information on the biogenesis of HDL. In humans HDL-cholesterol can be returned to the liver either by direct uptake by SR-BI or through cholesteryl ester transfer protein exchange of cholesteryl ester for triglycerides in apoB lipoproteins, followed by hepatic uptake of apoB containing particles. Cholesterol content in cells is regulated by several

  15. Understanding Lipoproteins as Transporters of Cholesterol and Other Lipids

    ERIC Educational Resources Information Center

    Biggerstaff, Kyle D.; Wooten, Joshua S.

    2004-01-01

    A clear picture of lipoprotein metabolism is essential for understanding the pathophysiology of atherosclerosis. Many students are taught that low-density lipoprotein-cholesterol is "bad" and high-density lipoprotein-cholesterol is "good." This misconception leads to students thinking that lipoproteins are types of cholesterol rather than…

  16. Enhanced delivery of lipophilic nutrients to the infant brain via high density lipoprotein.

    PubMed

    Naberhuis, J K; Lai, C-S

    2015-11-01

    Lipoproteins are the primary carriers of lipophilic cognitive nutrients such as docosahexaenoic acid, lutein, and α-tocopherol within circulation. The critical roles these nutrients play in growth and development are well established, and as such, their efficient delivery to the infant brain is crucial. Given the selectivity of the blood brain barrier, the lipoprotein fraction primarily responsible for brain delivery of these nutrients must be determined so that efforts aimed at increasing brain nutrient uptake, via lipoprotein profile manipulation, can be appropriately focused. Based on the preclinical and clinical data reviewed here, we hypothesize that high density lipoprotein is the fraction chiefly responsible for delivery of docosahexaenoic acid, lutein, and α-tocopherol to the infant brain. As high density lipoprotein levels tend to be lower in preterm, formula-fed infants as compared to their full-term, breast-fed counterparts, efforts aimed at increasing circulating high density lipoprotein levels, and subsequent delivery of cognitive lipophilic nutrients to the brain via manipulation of formula composition, may be most effective if targeted to this group. These efforts include (1) limiting the polyunsaturated: saturated fatty acid ratio; (2) increasing the casein: whey ratio; (3) altering the proportion of saturated fatty acids found in the sn-2 position of the parent triglyceride; (4) cholesterol supplementation; and (5) nucleotide supplementation. PMID:26323246

  17. Effects of obeticholic acid on lipoprotein metabolism in healthy volunteers.

    PubMed

    Pencek, R; Marmon, T; Roth, J D; Liberman, A; Hooshmand-Rad, R; Young, M A

    2016-09-01

    The bile acid analogue obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist in development for treatment of several chronic liver diseases. FXR activation regulates lipoprotein homeostasis. The effects of OCA on cholesterol and lipoprotein metabolism in healthy individuals were assessed. Two phase I studies were conducted to evaluate the effects of repeated oral doses of 5, 10 or 25 mg OCA on lipid variables after 14 or 20 days of consecutive administration in 68 healthy adults. Changes in HDL and LDL cholesterol levels were examined, in addition to nuclear magnetic resonance analysis of particle sizes and sub-fraction concentrations. OCA elicited changes in circulating cholesterol and particle size of LDL and HDL. OCA decreased HDL cholesterol and increased LDL cholesterol, independently of dose. HDL particle concentrations declined as a result of a reduction in medium and small HDL. Total LDL particle concentrations increased because of an increase in large LDL particles. Changes in lipoprotein metabolism attributable to OCA in healthy individuals were found to be consistent with previously reported changes in patients receiving OCA with non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. PMID:27109453

  18. The antigenic similarity of human low density lipoproteins.

    PubMed

    LEVINE, L; KAUFFMAN, D L; BROWN, R K

    1955-08-01

    THE FOLLOWING HUMAN LOW DENSITY LIPOPROTEINS WERE PREPARED: beta-lipoproteins of densities greater than 1.040 (A, B,C) a beta-lipoprotein of -S(1.063) = 5 (D), a lipoprotein of -S(1.063) = 19 (E), and a lipoprotein of -S(1.063) = 70 (F). Data are presented which show the immunochemical homogeneity of the D lipoprotein rabbit-anti-D lipoprotein system. Cross-reactions between antibody to A and D lipoproteins and the above lipoproteins have been demonstrated by quantitative precipitation, quanitative complement fixation, and single and double diffusion in agar. The antigenic similarities appear to be associated with the protein portions of the molecule. The antisera produced did not differentiate the low density lipoprotein classes. PMID:13242737

  19. The Human Pathogen Streptococcus pyogenes Releases Lipoproteins as Lipoprotein-rich Membrane Vesicles*

    PubMed Central

    Biagini, Massimiliano; Garibaldi, Manuela; Aprea, Susanna; Pezzicoli, Alfredo; Doro, Francesco; Becherelli, Marco; Taddei, Anna Rita; Tani, Chiara; Tavarini, Simona; Mora, Marirosa; Teti, Giuseppe; D'Oro, Ugo; Nuti, Sandra; Soriani, Marco; Margarit, Immaculada; Rappuoli, Rino; Grandi, Guido; Norais, Nathalie

    2015-01-01

    Bacterial lipoproteins are attractive vaccine candidates because they represent a major class of cell surface-exposed proteins in many bacteria and are considered as potential pathogen-associated molecular patterns sensed by Toll-like receptors with built-in adjuvanticity. Although Gram-negative lipoproteins have been extensively characterized, little is known about Gram-positive lipoproteins. We isolated from Streptococcus pyogenes a large amount of lipoproteins organized in vesicles. These vesicles were obtained by weakening the bacterial cell wall with a sublethal concentration of penicillin. Lipid and proteomic analysis of the vesicles revealed that they were enriched in phosphatidylglycerol and almost exclusively composed of lipoproteins. In association with lipoproteins, a few hypothetical proteins, penicillin-binding proteins, and several members of the ExPortal, a membrane microdomain responsible for the maturation of secreted proteins, were identified. The typical lipidic moiety was apparently not necessary for lipoprotein insertion in the vesicle bilayer because they were also recovered from the isogenic diacylglyceryl transferase deletion mutant. The vesicles were not able to activate specific Toll-like receptor 2, indicating that lipoproteins organized in these vesicular structures do not act as pathogen-associated molecular patterns. In light of these findings, we propose to name these new structures Lipoprotein-rich Membrane Vesicles. PMID:26018414

  20. Contribution of lipoproteins and lipoprotein processing to endocarditis virulence in Streptococcus sanguinis.

    PubMed

    Das, Sankar; Kanamoto, Taisei; Ge, Xiuchun; Xu, Ping; Unoki, Takeshi; Munro, Cindy L; Kitten, Todd

    2009-07-01

    Streptococcus sanguinis is an important cause of infective endocarditis. Previous studies have identified lipoproteins as virulence determinants in other streptococcal species. Using a bioinformatic approach, we identified 52 putative lipoprotein genes in S. sanguinis strain SK36 as well as genes encoding the lipoprotein-processing enzymes prolipoprotein diacylglyceryl transferase (lgt) and signal peptidase II (lspA). We employed a directed signature-tagged mutagenesis approach to systematically disrupt these genes and screen each mutant for the loss of virulence in an animal model of endocarditis. All mutants were viable. In competitive index assays, mutation of a putative phosphate transporter reduced in vivo competitiveness by 14-fold but also reduced in vitro viability by more than 20-fold. Mutations in lgt, lspA, or an uncharacterized lipoprotein gene reduced competitiveness by two- to threefold in the animal model and in broth culture. Mutation of ssaB, encoding a putative metal transporter, produced a similar effect in culture but reduced in vivo competiveness by >1,000-fold. [(3)H]palmitate labeling and Western blot analysis confirmed that the lgt mutant failed to acylate lipoproteins, that the lspA mutant had a general defect in lipoprotein cleavage, and that SsaB was processed differently in both mutants. These results indicate that the loss of a single lipoprotein, SsaB, dramatically reduces endocarditis virulence, whereas the loss of most other lipoproteins or of normal lipoprotein processing has no more than a minor effect on virulence. PMID:19395487

  1. Regulation of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Activity in Human Fibroblasts by Lipoproteins

    PubMed Central

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

    1973-01-01

    The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34), the rate-limiting enzyme of hepatic cholesterol biosynthesis, is suppressed in human fibroblasts cultured in the presence of serum. This enzyme activity increases by more than 10-fold after the removal of serum from the medium. The rise in enzyme activity requires de novo protein synthesis and is not accompanied by changes in the activities of several other cellular enzymes. The factor responsible for the suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured fibroblasts is present in the sera of at least four mammalian species, and in human serum it is found in the low-density lipoproteins. Human high-density lipoproteins, very low-density lipoproteins from chicken egg yolk, and the fraction of human serum containing no lipoproteins do not suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase. PMID:4352976

  2. A brief history of lipid and lipoprotein measurements and their contribution to clinical chemistry.

    PubMed

    McNamara, Judith R; Warnick, G Russell; Cooper, Gerald R

    2006-07-23

    The study of modern lipid chemistry began in the 17th and 18th centuries with early observations by Robert Boyle, Poulletier de la Salle, Antoine François de Fourcroy and others. The 19th century chemist, Chevreul, identified several fatty acids, suggested the name 'cholesterine' for the fatty substance in gallstones, coined the word 'glycerine', and showed that fats were comprised of glycerol and fatty acids. The 20th century brought many advances in the understanding of lipoprotein structure and function, and explored relationships between lipoproteins and disease states. The development of the ultracentrifuge and other lipoprotein separation techniques, and reagents for accurate, standardized quantitative measurement have steadily increased our understanding of the important role of lipoprotein metabolism in both healthy and disease states. PMID:16740255

  3. Is the atherosclerotic phenotype of preeclamptic placentas due to altered lipoprotein concentrations and placental lipoprotein receptors? Role of a small-for-gestational-age phenotype

    PubMed Central

    Hentschke, Marta R.; Poli-de-Figueiredo, Carlos E.; Pinheiro da Costa, Bartira E.; Kurlak, Lesia O.; Williams, Paula J.; Mistry, Hiten D.

    2013-01-01

    Atherosis of spiral arteries in uteroplacental beds from preeclamptic women resemble those of atherosclerosis, characterized by increased plasma lipids and lipoproteins. We hypothesized that: 1) lipoprotein receptors/transporters in the placenta would be upregulated in preeclampsia, associated with increased maternal and fetal lipoprotein concentrations; and 2) expression of these would be reduced in preeclamptic placentae from women delivering small-for-gestational-age (SGA) infants. Placental biopsies and maternal and umbilical serum samples were taken from 27 normotensive and 24 preeclamptic women. Maternal/umbilical cord serum LDL, HDL, total cholesterol, and triglycerides were measured. Placental mRNA expression of lipoprotein receptors/transporters were quantified using quantitative RT-PCR. Protein localization/expression of LDL receptor-related protein 1 (LRP-1) in the preeclamptic placentae with/without SGA was measured by immunohistochemistry. Placental mRNA expression of all genes except paraoxonase-1 (PON-1), microsomal triglyceride transfer protein (MTTP), and protein disulfide isomerase family A member 2 (PDIA2) were observed. No differences for any lipoprotein receptors/transporters were found between groups; however, in the preeclamptic group placental LRP-1 expression was lower in SGA delivering mothers (n = 7; P = 0.036). LRP-1 protein was localized around fetal vessels and Hofbauer cells. This is the first detailed study of maternal/fetal lipoprotein concentrations and placental lipoprotein receptor mRNA expression in normotensive and preeclamptic pregnancies. These findings do not support a role of altered lipid metabolism in preeclampsia, but may be involved in fetal growth. PMID:23898049

  4. Association between lipids, lipoproteins composition of HDL particles and triglyceride-rich lipoproteins, and LCAT and CETP activity in post-renal transplant patients.

    PubMed

    Kimak, Elżbieta; Bylina, Jerzy; Solski, Janusz; Hałabiś, Magdalena; Baranowicz-Gąszczyk, Iwona; Książek, Andrzej

    2013-11-01

    High-density lipoprotein (HDL) remodeling within the plasma compartment and the association between lecithin-cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) activity, and lipid, lipoprotein concentrations and composition were investigated. The aim was to examine the high sensitivity of C-reactive protein (hsCRP), lipid, apolipoprotein B (apoB), apoAI, total apoAII, apoAIInonB, apoB-containing apoAII (apoB:AII), total apoCIII, apoCIIInonB, apoB-containing apoCIII (apoB:CIII) concentration and LCAT and CETP activity to gain an insight into the association between them and LCAT and CETP, 57 post-renal transplant (Tx) patients with and without statin therapy and in 15 healthy subjects. Tx patients had moderate hypertriglyceridemia, hypercholesterolemia, and dyslipoproteinemia, disturbed triglyceride-rich lipoproteins (TRLs) and HDL composition, decreased LCAT, and slightly increased hsCRP but no CETP activity. Spearman's correlation test showed the association between lipids and lipoproteins and LCAT or CETP, and multiple ridge stepwise forward regression showed that immunosuppressive therapy in Tx patients can disturb HDL and TRLs composition. The results suggest that inhibition or activation of LCAT is due, in part, to HDL-associated lipoprotein. Lipoprotein composition of apoAI, apoAIInonB, and apoCIIInonB in HDL particle and apoB:AII TRLs can contribute to decrease LCAT mass in Tx patients. Tx patients without statin and with lower triglycerides but higher HDL cholesterol concentration and disturbed lipoprotein composition of ApoAI and apoAII in HDL particle can decrease LCAT, increase LDL cholesterol, aggravate renal graft, and accelerate atherosclerosis and chronic heart diseases. PMID:23479335

  5. Cholesterol in serum lipoprotein fractions after spaceflight

    NASA Technical Reports Server (NTRS)

    Leach, Carolyn S.; Johnson, Philip C., Jr.; Krauhs, Jane M.; Cintron, Nitza M.

    1988-01-01

    Results are reported from blood-lipid measurements obtained from 125 Space Shuttle crew members before and after space flight. The data are presented in tables and discussed in detail. The main differences noted between preflight and postflight values are a 12.8-percent decrease in high-density lipoproteins on postflight day 1 and significant decreases in total cholesterol and both high- and low-density lipoproteins later in the 23-day postflight period.

  6. 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.

  7. Lifestyle and Metformin Treatment Favorably Influence Lipoprotein Subfraction Distribution in the Diabetes Prevention Program

    PubMed Central

    Temprosa, M.; Otvos, J.; Brunzell, J.; Marcovina, S.; Mather, K.; Arakaki, R.; Watson, K.; Horton, E.; Barrett-Connor, E.

    2013-01-01

    Context: Although intensive lifestyle change (ILS) and metformin reduce diabetes incidence in subjects with impaired glucose tolerance (IGT), their effects on lipoprotein subfractions have not been studied. Objective: The objective of the study was to characterize the effects of ILS and metformin vs placebo interventions on lipoprotein subfractions in the Diabetes Prevention Program. Design: This was a randomized clinical trial, testing the effects of ILS, metformin, and placebo on diabetes development in subjects with IGT. Participants: Selected individuals with IGT randomized in the Diabetes Prevention Program participated in the study. Interventions: Interventions included randomization to metformin 850 mg or placebo twice daily or ILS aimed at a 7% weight loss using a low-fat diet with increased physical activity. Main Outcome Measures: Lipoprotein subfraction size, density, and concentration measured by magnetic resonance and density gradient ultracentrifugation at baseline and 1 year were measured. Results: ILS decreased large and buoyant very low-density lipoprotein, small and dense low-density lipoprotein (LDL), and small high-density lipoprotein (HDL) and raised large HDL. Metformin modestly reduced small and dense LDL and raised small and large HDL. Change in insulin resistance largely accounted for the intervention-associated decreases in large very low-density lipoprotein, whereas changes in body mass index (BMI) and adiponectin were strongly associated with changes in LDL. Baseline and a change in adiponectin were related to change in large HDL, and BMI change associated with small HDL change. The effect of metformin to increase small HDL was independent of adiponectin, BMI, and insulin resistance. Conclusion: ILS and metformin treatment have favorable effects on lipoprotein subfractions that are primarily mediated by intervention-related changes in insulin resistance, BMI, and adiponectin. Interventions that slow the development of diabetes may also

  8. Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data.

    PubMed Central

    Craig, W. Y.; Palomaki, G. E.; Haddow, J. E.

    1989-01-01

    To examine the association between cigarette smoking in adults and serum lipid and lipoprotein concentrations the results of 54 published studies were analysed. Overall, smokers had significantly higher serum concentrations of cholesterol (3.0%), triglycerides (9.1%), very low density lipoprotein cholesterol (10.4%), and low density lipoprotein cholesterol (1.7%) and lower serum concentrations of high density lipoprotein cholesterol (-5.7%) and apolipoprotein AI (-4.2%) compared with nonsmokers. Among non-smokers and light, moderate, and heavy smokers a significant dose response effect was present for cholesterol (0, 1.8, 4.3, and 4.5% respectively), triglycerides (0, 10.7, 11.5, and 18.0%), very low density lipoprotein cholesterol (0, 7.2, 44.4, and 39.0%), low density lipoprotein cholesterol (0, -1.1, 1.4, and 11.0%), high density lipoprotein cholesterol (0, -4.6, -6.3, and -8.9%), and apolipoprotein AI (0, -3.7 and -5.7% in non-smokers and light and heavy smokers). These dose response effects may provide new evidence for a causal relation between exposure to cigarette smoke and changes in serum lipid and lipoprotein concentrations whether as a direct result of physiological changes or of dietary changes induced by smoking. Adequate prospective data to estimate the excess risk of coronary artery disease existed only for cholesterol concentration. When that information was combined with data from the present study, and given that smokers as a group face an average overall excess risk of coronary artery disease of 70%, it was estimated that the observed increased serum cholesterol concentration in smokers may account for at least 9% of that excess risk. Furthermore, the dose response effect of smoking on serum cholesterol concentration suggests a gradient of increased absolute risk of coronary artery disease between light and heavy smokers. PMID:2496857

  9. Acrolein consumption induces systemic dyslipidemia and lipoprotein modification

    SciTech Connect

    Conklin, Daniel J.; Barski, Oleg A.; Lesgards, Jean-Francois; Juvan, Peter; Rezen, Tadeja; Rozman, Damjana; Prough, Russell A.; Vladykovskaya, Elena; Liu, SiQi; Srivastava, Sanjay; Bhatnagar, Aruni

    2010-02-15

    Aldehydes such as acrolein are ubiquitous pollutants present in automobile exhaust, cigarette, wood, and coal smoke. Such aldehydes are also constituents of several food substances and are present in drinking water, irrigation canals, and effluents from manufacturing plants. Oral intake represents the most significant source of exposure to acrolein and related aldehydes. To study the effects of short-term oral exposure to acrolein on lipoprotein levels and metabolism, adult mice were gavage-fed 0.1 to 5 mg acrolein/kg bwt and changes in plasma lipoproteins were assessed. Changes in hepatic gene expression related to lipid metabolism and cytokines were examined by qRT-PCR analysis. Acrolein feeding did not affect body weight, blood urea nitrogen, plasma creatinine, electrolytes, cytokines or liver enzymes, but increased plasma cholesterol and triglycerides. Similar results were obtained with apoE-null mice. Plasma lipoproteins from acrolein-fed mice showed altered electrophoretic mobility on agarose gels. Chromatographic analysis revealed elevated VLDL cholesterol, phospholipids, and triglycerides levels with little change in LDL or HDL. NMR analysis indicated shifts from small to large VLDL and from large to medium-small LDL with no change in the size of HDL particles. Increased plasma VLDL was associated with a significant decrease in post-heparin plasma hepatic lipase activity and a decrease in hepatic expression of hepatic lipase. These observations suggest that oral exposure to acrolein could induce or exacerbate systemic dyslipidemia and thereby contribute to cardiovascular disease risk.

  10. Acrolein Consumption Induces Systemic Dyslipidemia and Lipoprotein Modification

    PubMed Central

    Conklin, Daniel J.; Barski, Oleg A.; Lesgards, Jean-Francois; Juvan, Peter; Rezen, Tadeja; Rozman, Damjana; Prough, Russell A.; Vladykovskaya, Elena; Liu, SiQi; Srivastava, Sanjay; Bhatnagar, Aruni

    2010-01-01

    Aldehydes such as acrolein are ubiquitous pollutants present in automobile exhaust, cigarette, wood, and coal smoke. Such aldehydes are also constituents of several food substances and are present in drinking water, irrigation canals, and effluents from manufacturing plants. Oral intake represents the most significant source of exposure to acrolein and related aldehydes. To study the effects of short-term oral exposure to acrolein on lipoprotein levels and metabolism, adult mice were gavage fed 0.1 to 5 mg acrolein/kg bwt and changes in plasma lipoproteins were assessed. Changes in hepatic gene expression related to lipid metabolism and cytokines were examined by qRT-PCR analysis. Acrolein feeding did not affect body weight, BUN, plasma creatinine, electrolytes, cytokines or liver enzymes, but increased plasma cholesterol and triglycerides. Similar results were obtained with apoE-null mice. Plasma lipoproteins from acrolein-fed mice showed altered electrophoretic mobility on agarose gels. Chromatographic analysis revealed elevated VLDL cholesterol, phospholipids, and triglycerides levels with little change in LDL or HDL. NMR analysis indicated shifts from small to large VLDL and from large to medium-small LDL with no change in the size of HDL particles. Increased plasma VLDL was associated with a significant decrease in post-heparin plasma hepatic lipase activity and a decrease in hepatic expression of hepatic lipase. These observations suggest that oral exposure to acrolein could induce or exacerbate systemic dyslipidemia and thereby contribute to cardiovascular disease risk. PMID:20034506

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

    PubMed

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

    1986-01-01

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

  12. Lgt Processing Is an Essential Step in Streptococcus suis Lipoprotein Mediated Innate Immune Activation

    PubMed Central

    Wichgers Schreur, Paul J.; Rebel, Johanna M. J.; Smits, Mari A.; van Putten, Jos P. M.; Smith, Hilde E.

    2011-01-01

    Background Streptococcus suis causes invasive infections in pigs and occasionally in humans. The host innate immune system plays a major role in counteracting S. suis infections. The main components of S. suis able to activate the innate immune system likely include cell wall constituents that may be released during growth or after cell wall integrity loss, however characterization of these components is still limited. Methology/Principal Findings A concentrated very potent innate immunity activating supernatant of penicillin-treated S. suis was SDS-PAGE fractionated and tested for porcine peripheral blood mononucleated cell (PBMC) stimulating activity using cytokine gene transcript analysis. More than half of the 24 tested fractions increased IL-1β and IL-8 cytokine gene transcript levels in porcine PBMCs. Mass spectrometry of the active fractions indicated 24 proteins including 9 lipoproteins. Genetic inactivation of a putative prolipoprotein diacylglyceryl transferase (Lgt) gene resulted in deficient lipoprotein synthesis as evidenced by palmitate labeling. The Lgt mutant showed strongly reduced activation of porcine PBMCs, indicating that lipoproteins are dominant porcine PBMC activating molecules of S. suis. Conclusion/Significance This study for the first time identifies and characterizes lipoproteins of S. suis as major activators of the innate immune system of the pig. In addition, we provide evidence that Lgt processing of lipoproteins is required for lipoprotein mediated innate immune activation. PMID:21811583

  13. Assessment of permeation of lipoproteins in human carotid tissue

    NASA Astrophysics Data System (ADS)

    Ghosn, Mohamad G.; Syed, Saba H.; Leba, Michael; Morrisett, Joel D.; Tuchin, Valery V.; Larin, Kirill V.

    2010-02-01

    Cardiovascular disease is among the leading causes of death in the United States. Specifically, atherosclerosis is an increasingly devastating contributor to the tally and has been found to be a byproduct of arterial permeability irregularities in regards to lipoprotein penetration. To further explore arterial physiology and molecular transport, the imaging technique of Optical Coherence Tomography (OCT) was employed. With OCT, the permeation of glucose (MW = 180 Da), low density lipoprotein (LDL; MW = 2.1 × 106 Da), and high density lipoprotein (HDL; MW = 2.5 × 105 Da) in human carotid tissue was studied to determine the effect of different molecular characteristics on permeation in atherosclerotic tissues. The permeability rates calculated from the diffusion of the molecular agents into the abnormal carotid tissue samples is compared to those of normal, healthy tissue. The results show that in the abnormal tissue, the permeation of agents correlate to the size constraints. The larger molecules of LDL diffuse the slowest, while the smallest molecules of glucose diffuse the fastest. However, in normal tissue, LDL permeates at a faster rate than the other two agents, implying the existence of a transport mechanism that facilitates the passage of LDL molecules. These results highlight the capability of OCT as a sensitive and specific imaging technique as well as provide significant information to the understanding of atherosclerosis and its effect on tissue properties.

  14. Autophagy-mediated longevity is modulated by lipoprotein biogenesis

    PubMed Central

    Seah, Nicole E.; de Magalhaes Filho, C. Daniel; Petrashen, Anna P.; Henderson, Hope R.; Laguer, Jade; Gonzalez, Julissa; Dillin, Andrew; Hansen, Malene; Lapierre, Louis R.

    2016-01-01

    ABSTRACT Autophagy-dependent longevity models in C. elegans display altered lipid storage profiles, but the contribution of lipid distribution to life-span extension is not fully understood. Here we report that lipoprotein production, autophagy and lysosomal lipolysis are linked to modulate life span in a conserved fashion. We find that overexpression of the yolk lipoprotein VIT/vitellogenin reduces the life span of long-lived animals by impairing the induction of autophagy-related and lysosomal genes necessary for longevity. Accordingly, reducing vitellogenesis increases life span via induction of autophagy and lysosomal lipolysis. Life-span extension due to reduced vitellogenesis or enhanced lysosomal lipolysis requires nuclear hormone receptors (NHRs) NHR-49 and NHR-80, highlighting novel roles for these NHRs in lysosomal lipid signaling. In dietary-restricted worms and mice, expression of VIT and hepatic APOB (apolipoprotein B), respectively, are significantly reduced, suggesting a conserved longevity mechanism. Altogether, our study demonstrates that lipoprotein biogenesis is an important mechanism that modulates aging by impairing autophagy and lysosomal lipolysis. PMID:26671266

  15. Low-Density Lipoprotein Sensor Based on Molecularly Imprinted Polymer.

    PubMed

    Chunta, Suticha; Suedee, Roongnapa; Lieberzeit, Peter A

    2016-01-19

    Increased level of low-density lipoprotein (LDL) strongly correlates with incidence of coronary heart disease. We synthesized novel molecularly imprinted polymers (MIP) as biomimetic specific receptors to establish rapid analysis of LDL levels. For that purpose the ratios of monomers acrylic acid (AA), methacrylic acid (MAA), and N-vinylpyrrolidone (VP), respectively, were screened on 10 MHz dual-electrode quartz crystal microbalances (QCM). Mixing MAA and VP in the ratio 3:2 (m/m) revealed linear sensor characteristic to LDL cholesterol (LDL-C) from 4 to 400 mg/dL or 0.10-10.34 mmol/L in 100 mM phosphate-buffered saline (PBS) without significant interference: high-density lipoprotein (HDL) yields 4-6% of the LDL signal, very-low-density-lipoprotein (VLDL) yields 1-3%, and human serum albumin (HSA) yields 0-2%. The LDL-MIP sensor reveals analytical accuracy of 95-96% at the 95% confidence interval with precision at 6-15%, respectively. Human serum diluted 1:2 with PBS buffer was analyzed by LDL-MIP sensors to demonstrate applicability to real-life samples. The sensor responses are excellently correlated to the results of the standard technique, namely, a homogeneous enzymatic assay (R(2) = 0.97). This demonstrates that the system can be successfully applied to human serum samples for determining LDL concentrations. PMID:26643785

  16. Triglyceride-Rich Lipoproteins and Remnants: Targets for Therapy?

    PubMed

    Dallinga-Thie, Geesje M; Kroon, Jeffrey; Borén, Jan; Chapman, M John

    2016-07-01

    It is now evident that elevated circulating levels of triglycerides in the non-fasting state, a marker for triglyceride (TG)-rich remnant particles, are associated with increased risk of premature cardiovascular disease (CVD). Recent findings from basic and clinical studies have begun to elucidate the mechanisms that contribute to the atherogenicity of these apoB-containing particles. Here, we review current knowledge of the formation, intravascular remodelling and catabolism of TG-rich lipoproteins and highlight (i) the pivotal players involved in this process, including lipoprotein lipase, glycosylphosphatidylinositol HDL binding protein 1 (GPIHBP1), apolipoprotein (apo) C-II, apoC-III, angiopoietin-like protein (ANGPTL) 3, 4 and 8, apoA-V and cholesteryl ester transfer protein; (ii) key determinants of triglyceride (TG) levels and notably rates of production of very-low-density lipoprotein 1 (VLDL1) particles; and (iii) the mechanisms which underlie the atherogenicity of remnant particles. Finally, we emphasise the polygenic nature of moderate hypertriglyceridemia and briefly discuss modalities for its clinical management. Several new therapeutic strategies to attenuate hypertriglyceridemia have appeared recently, among which those targeted to apoC-III appear to hold considerable promise. PMID:27216847

  17. Lipoprotein(a) Serum Levels in Diabetic Patients with Retinopathy

    PubMed Central

    Malaguarnera, Giulia; Gagliano, Caterina; Vacante, Marco; Malaguarnera, Michele; Leonardi, Daniela Giovanna; Motta, Massimo; Drago, Filippo; Avitabile, Teresio

    2013-01-01

    Background. Atherogenic lipoproteins, such as total cholesterol, LDL cholesterol, oxidized low density lipoprotein, and triglycerides, are associated with progression of retinopathy. Aim. To evaluate the relationship between lipoprotein(a) and retinopathy in patients with type 2 diabetes mellitus. Materials and Methods. We enrolled 145 diabetic consecutive patients (82 females, 63 males; mean age 66.8 ± 12 years, mean duration of diabetes 9.4 ± 6.8 years). Presence and severity of retinopathy were evaluated. Serum lipid profile, including Lp(a) level, was assessed. Results. High Lp(a) levels have been observed in 54 (78.3%) subjects and normal levels in 13 (18.85%) subjects as regards diabetic patients with retinopathy. Lp(a) levels were high in 15 subjects (21.75%) and normal in 63 subjects (91.35%) as regards patients without retinopathy. Conclusions. Lp(a) levels are increased in a significant percentage of patients with retinopathy compared to diabetic patients without retinopathy. The impact of Lp(a) levels on diabetic retinopathy needs to be further investigated. PMID:23862162

  18. Effects of lipoprotein(a) on thrombolysis.

    PubMed

    von Hodenberg, E; Pestel, E; Kreuzer, J; Freitag, M; Bode, C

    1994-01-01

    Lipoprotein(a) (Lp(a)) and plasminogen share a high degree of structural homology. Therefore it has been suggested that elevated levels of Lp(a) may inhibit the profibrinolytic activity at the cell surface and increase the risk of thrombosis by competitive inhibition of plasminogen. In the present study we evaluated whether high levels of Lp(a) affect thrombolytic therapy in patients with acute myocardial infarction. Forty-one patients with acute myocardial infarction were treated with a combination of recombinant tissue-type plasminogen activator and human single-chain urokinase-type plasminogen activator. Coronary patency was assessed angiographically 90 min after initiation of treatment. Thrombolysis was successful in 30 and unsuccessful in 11 patients. Patients with high Lp(a) levels (> 25 mg/dl) (n = 9) responded equally well to thrombolytic therapy (8 of 9, patency 89%) as did patients with normal or low levels of Lp(a) (22 of 32, patency 70%, difference P > 0.1). The results demonstrate that high levels of Lp(a) do not influence thrombolysis in patients with acute myocardial infarction when low-dose pharmacologic concentrations of recombinant tissue-type plasminogen activator and human single chain urokinase-type plasminogen activator are applied in combination. PMID:8187238

  19. The two-receptor model of lipoprotein clearance: tests of the hypothesis in "knockout" mice lacking the low density lipoprotein receptor, apolipoprotein E, or both proteins.

    PubMed Central

    Ishibashi, S; Herz, J; Maeda, N; Goldstein, J L; Brown, M S

    1994-01-01

    Apolipoprotein E (apoE) is hypothesized to mediate lipoprotein clearance by binding to two receptors: (i) the low density lipoprotein receptor (LDLR) and (ii) a chylomicron remnant receptor. To test this hypothesis, we have compared plasma lipoproteins in mice that are homozygous for targeted disruptions of the genes for apoE [apoE(-/-)], the LDLR [LDLR(-/-)], and both molecules [poE(-/-); LDLR(-/-)]. On a normal chow diet, apoE(-/-) mice had higher mean plasma cholesterol levels than LDLR(-/-) mice (579 vs. 268 mg/dl). Cholesterol levels in the apoE(-/-); LDLR(-/-) mice were not significantly different from those in the apoE(-/-) mice. LDLR(-/-) mice had a relatively isolated elevation in plasma LDL, whereas apoE(-/-) mice had a marked increase in larger lipoproteins corresponding to very low density lipoproteins and chylomicron remnants. The lipoprotein pattern in apoE(-/-); LDLR(-/-) mice resembled that of apoE(-/-) mice. The LDLR(-/-) mice had a marked elevation in apoB-100 and a modest increase in apoB-48. In contrast, the apoE(-/-) mice had a marked elevation in apoB-48 but not in apoB-100. The LDLR(-/-); apoE(-/-) double homozygotes had marked elevations of both apolipoproteins. The observation that apoB-48 increases more dramatically with apoE deficiency than with LDLR deficiency supports the notion that apoE binds to a second receptor in addition to the LDLR. This conclusion is also supported by the observation that superimposition of a LDLR deficiency onto an apoE deficiency [apoE(-/-); LDLR(-/-) double homozygotes] does not increase hypercholesterolemia beyond the level observed with apoE deficiency alone. Images PMID:8183926

  20. 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

  1. Re-sequencing of the APOAI promoter region and the genetic association of the -75G > A polymorphism with increased cholesterol and low density lipoprotein levels among a sample of the Kuwaiti population

    PubMed Central

    2013-01-01

    Background APOAI, a member of the APOAI/CIII/IV/V gene cluster on chromosome 11q23-24, encodes a major protein component of HDL that has been associated with serum lipid levels. The aim of this study was to determine the genetic association of polymorphisms in the APOAI promoter region with plasma lipid levels in a cohort of healthy Kuwaiti volunteers. Methods A 435 bp region of the APOAI promoter was analyzed by re-sequencing in 549 Kuwaiti samples. DNA was extracted from blood taken from 549 healthy Kuwaiti volunteers who had fasted for the previous 12 h. Univariate and multivariate analysis was used to determine allele association with serum lipid levels. Results The target sequence included a partial segment of the promoter region, 5’UTR and exon 1 located between nucleotides −141 to +294 upstream of the APOAI gene on chromosome 11. No novel single nucleotide polymorphisms (SNPs) were observed. The sequences obtained were deposited with the NCBI GenBank with accession number [GenBank: JX438706]. The allelic frequencies for the three SNPs were as follows: APOAI rs670G = 0.807; rs5069C = 0.964; rs1799837G = 0.997 and found to be in HWE. A significant association (p < 0.05) was observed for the APOAI rs670 polymorphism with increased serum LDL-C. Multivariate analysis showed that APOAI rs670 was an independent predictive factor when controlling for age, sex and BMI for both LDL-C (OR: 1.66, p = 0.014) and TC (OR: 1.77, p = 0.006) levels. Conclusion This study is the first to report sequence analysis of the APOAI promoter in an Arab population. The unexpected positive association found between the APOAI rs670 polymorphism and increased levels of LDL-C and TC may be due to linkage disequilibrium with other polymorphisms in candidate and neighboring genes known to be associated with lipid metabolism and transport. PMID:24028463

  2. [Position of lipoprotein apheresis in present].

    PubMed

    Bláha, Vladimír; Bláha, Milan; Lánská, Miriam; Havel, Eduard; Vyroubal, Pavel; Zadák, Zdeněk; Vrablík, Michal; Piťha, Jan; Žák, Pavel; Sobotka, Luboš

    2015-11-01

    Lipoprotein apheresis (LA) is an effective treatment method the patients with severe hypercholesterolemia, resistant to the standard therapy. LA is an extracorporeal elimination technique, which specifically removes low density lipoprotein (LDL) cholesterol from the circulation. At present, lipoprotein apheresis, combined with high-dose statin and ezetimibe therapy, is the best available means of treating patients with homozygous and statin refractory heterozygous familial hypercholesterolaemia (FH). However, the extent of cholesterol-lowering achieved is often insufficient to meet the targets set by current guidelines. The recent advent of new classes of lipid-lowering agents provides new hope that the latter objective may now be achievable. These compounds act either by reducing low density lipoprotein (LDL) cholesterol production by inhibiting apolipoprotein B synthesis with an antisense oligonucleotide (mipomersen), or by inhibiting microsomal triglyceride transfer protein (lomitapid), or by enhancing LDL catabolism via monoclonal antibody-mediated inhibition of the activity of proprotein convertase subtilisin/kexin 9 (PCSK9-alirocumab, evolocumab etc). The promising is the combination of LDL-apheresis with new drugs, namely for its potential to further decrease of LDL-cholesterol between apheresis. Depending on the outcome of current trials, it seems likely that these compounds, used alone or combined with lipoprotein apheresis, will markedly improve the management of refractory FH. PMID:26652784

  3. Regulation of Mammary and Adipose Tissue Lipoprotein Lipase and Blood Triacylglycerol in Rats during Late Pregnancy

    PubMed Central

    Spooner, Peter M.; Garrison, Mary M.; Scow, Robert O.

    1977-01-01

    The effects of several prostaglandins on lipoprotein lipase activity of mammary gland and adipose tissue and serum triacylglycerol were studied during late pregnancy in rats. Prostaglandins were injected twice daily for 2 days before and once on the day of analysis. In rats pregnant 20 days, prostaglandin F2α (PGF2α) increased the activity of lipoprotein lipase in mammary gland fourfold, reduced the activity in adipose tissue about 60%, and decreased serum concentration of triacylglycerol 50%. PGF2α also reduced serum concentration of progesterone 90% and increased that of prolactin fivefold, but had no effect on serum concentrations of either immuno-reactive insulin or 17β-estradiol. Injections of 13,14-dihydro-15-keto PGF2α, a metabolite of PGF2α, had similar effects in rats pregnant 20 days, whereas prostaglandins E1 and E2 did not. In rats pregnant 16 days, PGF2α did not affect lipoprotein lipase activity in the tissues or the concentration of triacylglycerol and prolactin in serum, although it decreased serum progesterone 80%. 2-Br-α-ergocryptine prevented the increase in serum prolactin in response to PGF2α, but did not alter the effect of PGF2α on lipoprotein lipase activity or serum triacylglycerol. Progesterone completely blocked the effects of PGF2α on lipoprotein lipase activity and serum triacylglycerol and prolactin concentrations. These findings indicate that the changes in lipoprotein lipase activity and serum triacylglycerol in PGF2α-treated rats are probably related to the inhibitory action of PGF2α on progesterone secretion. They also suggest that endogenous F prostaglandins may play a role in the regulation of lipoprotein lipase activity in mammary gland and adipose tissue near parturition. PMID:893673

  4. Immunogenic integral membrane proteins of Borrelia burgdorferi are lipoproteins.

    PubMed

    Brandt, M E; Riley, B S; Radolf, J D; Norgard, M V

    1990-04-01

    The pathogenic spirochete Borrelia burgdorferi contains a set of integral membrane proteins which were selectively extracted into the detergent phase upon solubilization of intact B. burgdorferi with the nonionic detergent Triton X-114. Virtually all of these hydrophobic proteins were recognized by antibodies in pooled sera from patients with chronic Lyme arthritis, demonstrating that proteins partitioning into the detergent phase of Triton X-114 encompass the major B. burgdorferi immunogens. Furthermore, most of these immunogenic proteins, including the previously characterized OspA and OspB membrane antigens, could be biosynthetically labeled when B. burgdorferi was incubated in vitro with [3H]palmitate. The OspA and OspB antigens were radioimmunoprecipitated from [3H]palmitate-labeled detergent-phase proteins with monoclonal antibodies, and [3H]palmitate was recovered unaltered from these proteins after sequential alkaline and acid hydrolyses. The combined results provide formal confirmation that the major B. burgdorferi immunogens extracted by Triton X-114 are lipoproteins. The demonstration that B. burgdorferi integral membrane antigens are lipoproteins may explain the basis of their immunogenicity and may help to improve our understanding of the surface topology of B. burgdorferi. PMID:2318538

  5. Lipids and lipoproteins in Friedreich's ataxia.

    PubMed Central

    Walker, J L; Chamberlain, S; Robinson, N

    1980-01-01

    Friedreich's ataxia is an autosomal recessively inherited disease affecting the nervous system with a high incidence of heart involvement. Abnormalities of lipid metabolism are known to be associated with several progressive ataxic conditions. In this study of 46 Friedreich's ataxia patients, serum lipids, fatty acids and lipoproteins were assayed and compared with some earlier findings on Friedreich's ataxia and related disorders. Abnormalities of low and high density lipoproteins suggestive of a major defect have been reported; in the present study the level and chemical composition of high density lipoprotein has been assessed in 20 Friedreich's ataxia patients but previous abnormalities could not be substantiated. Lipid compositional analysis of Friedreich's ataxia central nervous tissue and heart, which has not been previously reported, did not markedly differ from control tissue. PMID:7359148

  6. Dietary fat, carbohydrate and protein: effects on plasma lipoprotein profiles fat, carbohydrate and protein and plasma lipids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In general, under isoweight conditions, different types of dietary protein or individual amino acids have little effect on lipoprotein patterns. Dietary carbohydrate tends to increase plasma triglyceride when it displaces fat, accompanied by a decrease in HDL cholesterol concentrations. Potential ...

  7. Explaining cloud chamber tracks

    SciTech Connect

    Broyles, A.A.

    1992-06-16

    The operation of many detection devices is usually explained in terms of the ionization tracks produced by particles despite the fact that the corresponding incident wave functions extended over the entire sensitive regions of the detectors. The mechanisms by which the wave function appears to collapse to a track is analyzed here.

  8. Explaining the Interpretive Mind.

    ERIC Educational Resources Information Center

    Brockmeier, Jens

    1996-01-01

    Examines two prominent positions in the epistemological foundations of psychology--Piaget's causal explanatory claims and Vygotsky's interpretive understanding; contends that they need to be placed in their wider philosophical contexts. Argues that the danger of causally explaining cultural practices through which human beings construct and…

  9. Suppression of diet-induced atherosclerosis in low density lipoprotein receptor knockout mice overexpressing lipoprotein lipase.

    PubMed Central

    Shimada, M; Ishibashi, S; Inaba, T; Yagyu, H; Harada, K; Osuga, J I; Ohashi, K; Yazaki, Y; Yamada, N

    1996-01-01

    Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. Conflicting results have been reported concerning its role in atherogenesis. To determine the effects of the overexpressed LPL on diet-induced atherosclerosis, we have generated low density lipoprotein receptor (LDLR) knockout mice that overexpressed human LPL transgene (LPL/LDLRKO) and compared their plasma lipoproteins and atherosclerosis with those in nonexpressing LDLR-knockout mice (LDLRKO). On a normal chow diet, LPL/LDLRKO mice showed marked suppression of mean plasma triglyceride levels (32 versus 236 mg/dl) and modest decrease in mean cholesterol levels (300 versus 386 mg/dl) as compared with LDLRKO mice. Larger lipoprotein particles of intermediate density lipoprotein (IDL)/LDL were selectively reduced in LPL/LDLRKO mice. On an atherogenic diet, both mice exhibited severe hypercholesterolemia. But, mean plasma cholesterol levels in LPL/ LDLRKO mice were still suppressed as compared with that in LDLRKO mice (1357 versus 2187 mg/dl). Marked reduction in a larger subfraction of IDL/LDL, which conceivably corresponds to remnant lipoproteins, was observed in the LPL/LDLRKO mice. LDLRKO mice developed severe fatty streak lesions in the aortic sinus after feeding with the atherogenic diet for 8 weeks. In contrast, mean lesion area in the LPL/LDLRKO mice was 18-fold smaller than that in LDLRKO mice. We suggest that the altered lipoprotein profile, in particular the reduced level of remnant lipoproteins, is mainly responsible for the protection by LPL against atherosclerosis. Images Fig. 1 Fig. 3 PMID:8692976

  10. HIV/HCV coinfection ameliorates the atherogenic lipoprotein abnormalities of HIV infection

    PubMed Central

    WHEELER, Amber L.; SCHERZER, Rebecca; LEE, Daniel; DELANEY, Joseph A. C.; BACCHETTI, Peter; SHLIPAK, Michael G.; SIDNEY, Stephen; GRUNFELD, Carl; TIEN, Phyllis C.

    2014-01-01

    Background Higher levels of small low-density lipoprotein (LDL) and lower levels of high-density lipoprotein (HDL) subclasses have been associated with increased risk of cardiovascular disease. The extent to which HIV infection and HIV/HCV coinfection are associated with abnormalities of lipoprotein subclasses is unknown. Methods Lipoprotein subclasses were measured by nuclear magnetic resonance (NMR) spectroscopy in plasma samples from 569 HIV-infected and 5948 control participants in the FRAM, CARDIA and MESA studies. Multivariable regression was used to estimate the association of HIV and HIV/HCV coinfection with lipoprotein measures with adjustment for demographics, lifestyle factors, and waist-to-hip ratio. Results Relative to controls, small LDL levels were higher in HIV-monoinfected persons (+381 nmol/L, p<.0001), with no increase seen in HIV/HCV coinfection (−16.6 nmol/L). Levels of large LDL levels were lower (−196 nmol/L, p<.0001) and small HDL were higher (+8.2 μmol/L, p<.0001) in HIV-monoinfection with intermediate values seen in HIV/HCV-coinfection. Large HDL levels were higher in HIV/HCV-coinfected persons relative to controls (+1.70 μmol/L, p<.0001), whereas little difference was seen in HIV-monoinfected persons (+0.33, p=0.075). Within HIV-infected participants, HCV was associated independently with lower levels of small LDL (−329 nmol/L, p<.0001) and small HDL (−4.6 μmol/L, p<.0001), even after adjusting for demographic and traditional cardiovascular risk factors. Conclusion HIV-monoinfected participants had worse levels of atherogenic LDL lipoprotein subclasses compared with controls. HIV/HCV coinfection attenuates these changes, perhaps by altering hepatic factors affecting lipoprotein production and/or metabolism. The effect of HIV/HCV coinfection on atherosclerosis and the clinical consequences of low small subclasses remain to be determined. PMID:24136113

  11. Analysis of individual lipoproteins and liposomes

    SciTech Connect

    Robbins, D.L.; Keller, R.A.; Nolan, J.P.

    1997-08-01

    We describe the application of single molecule detection (SMD) technologies for the analysis of natural (serum lipoproteins) and synthetic (liposomes) transport systems. The need for advanced analytical procedures of these complex and important systems is presented with the specific enhancements afforded by SMD with flowing sample streams. In contrast to bulk measurements which yield only average values, measurement of individual species allows creation of population histograms from heterogeneous samples. The data are acquired in minutes and the analysis requires relatively small sample quantities. Preliminary data are presented from the analysis of low density lipoprotein, and multilamellar and unilamellar vesicles.

  12. Binding of temoporfin to the lipoprotein fractions of human serum.

    PubMed Central

    Michael-Titus, A T; Whelpton, R; Yaqub, Z

    1995-01-01

    The binding of a new photosensitizer, temoporfin, to human serum lipoproteins was investigated. [14C]-Temoporfin (0.1-10 micrograms ml-1) was incubated with human serum for 30 min at room temperature or for 20 h at 4 degrees C, prior to stepwise density flotation to separate the lipoprotein fractions. The distribution of the drug was independent of the initial concentration or time and temperature of the incubation. The proportion of temoporfin in each fraction was: very low density lipoprotein 6%, low density lipoprotein 22%, lipoprotein(a) 17%, high density lipoprotein 39% and lipoprotein deficient serum 16%. Autoradiography of agarose gels showed that the drug was associated with the lipoprotein in the fractions. Fractionation of plasma samples collected from a patient after an intravenous infusion of temoporfin revealed a binding profile similar to that obtained in the in vitro study. Images Figure 1 PMID:8703668

  13. Age related changes in the lipoprotein substrates for the esterification of plasma cholesterol in rats.

    PubMed

    Lee, S M; Kudchodkar, B J; Lacko, A G

    1991-11-15

    The activity of the enzyme lecithin:cholesterol acyltransferase (LCAT) and the properties of its lipoprotein substrates have been investigated in 6- and 19-month-old Fischer-344 rats. These studies were carried out to determine the nature of the relationship between the observed hypercholesterolemia and the age-related decrease in the fractional rate of lipoprotein cholesterol esterification. The distribution of LCAT activity of plasma fractions was determined following gel chromatography and ultracentrifugation respectively. LCAT activity was found to be associated with the high density lipoprotein (HDL) fraction when rat plasma was passed through a Bio-Gel A-5 M column. Upon density gradient ultracentrifugation for 24 h it was found associated with HDL fraction; d = 1.125-1.21 g/ml. However, following prolonged ultracentrifugation (40 h), the majority of the LCAT activity was displaced into the lipoprotein-free infranatant (d greater than 1.225 g/ml). The dissociation of LCAT from its complex with HDL occurred to a smaller extent in aged rat plasma than in young rat plasma. Substrate specificity studies indicated that HDL was a considerably better substrate for LCAT than very low density lipoproteins (VLDL) in both young and aged rats. In addition, HDL from young rats was a better substrate for LCAT than the HDL from aged rats. Incubation experiments followed by the isolation of lipoproteins and the subsequent analyses of their cholesterol contents revealed that the age-related hypercholesterolemia was mainly due to an increase in the cholesterol carried by lipoprotein fractions d = 1.025 -1.07 g/ml (LDL + HDL1). These and other low density lipoproteins (d less than 1.025 g/ml) were poor substrates for LCAT. However, these lipoproteins could provide free cholesterol for esterification by first transferring it to HDL (d = 1.07-1.21). The HDL isolated from the plasma of aged rats was enriched with apolipoprotein (apo) E and these lipoprotein particles were found to

  14. Lipoprotein Profiles in Class III Obese Caucasian and African American Women with Nonalcoholic Fatty Liver Disease

    PubMed Central

    Garcia, Anna E.; Kasim, Nader; Tamboli, Robyn A.; Gonzalez, Raul S.; Antoun, Joseph; Eckert, Emily A.; Marks-Shulman, Pamela A.; Dunn, Julia; Wattacheril, Julia; Wallen, Taylor; Abumrad, Naji N.; Flynn, Charles Robb

    2015-01-01

    Triglyceride content in the liver is regulated by the uptake, production and elimination of lipoproteins, and derangements in these processes contribute to nonalcoholic fatty liver disease (NAFLD). Previous studies show a direct relationship between intrahepatic fat and production of apolipoprotein B100 (apoB100) containing particles, VLDL and LDL, but little consensus exists regarding changes in lipoprotein production in the development of simple steatosis (SS) versus nonalcoholic steatohepatitis (NASH). Further, ethnic variations in lipoproteins among SS and NASH are unknown as is how such variations might contribute to the differential prevalence of disease among Caucasians versus African Americans. In this study, we assessed plasma lipoprotein profiles by nuclear magnetic resonance (NMR) spectroscopy in 70 non-diabetic class III obese females recruited from the surgical weight loss clinic. Of these, 51 females were stratified by biopsy-staged NAFLD severity (histologically normal, SS, or NASH). NASH females displayed increased circulating triglycerides and increased VLDL particle number and size relative to those with histologically normal livers, while total and large LDL concentration decreased in SS versus NASH and correlated with increased insulin resistance (via HOMA2-IR). When Caucasian women were examined alone (n = 41), VLDL and triglycerides increased between normal and SS, while total LDL and apoB100 decreased between SS and NASH along with increased insulin resistance. Compared to Caucasians with SS, African American women with SS displayed reduced triglycerides, VLDL, and small LDL and a more favorable small to large HDL ratio despite having increased BMI and HOMA2-IR. These findings suggest that ApoB100 and lipoprotein subclass particle number and size can delineate steatosis from NASH in obese Caucasian females, but should be interpreted with caution in other ethnicities as African Americans with SS display relatively improved lipoprotein profiles

  15. Triacylglycerol kinetics in endotoxic rats with suppressed lipoprotein lipase activity

    SciTech Connect

    Bagby, G.J.; Corll, C.B.; Martinez, R.R.

    1987-07-01

    Hypertriglyceridemia observed in animals after bacterial endotoxin administration and some forms of sepsis can result from increased hepatic triacylglycerol (TG) output or decreased TG clearance by extrahepatic tissues. To differentiate between these two possibilities, TG and free fatty acid (FFA) kinetics were determined in control and endotoxin-injected rats 18 h after treatment. Plasma TG and FFA kinetics were assessed by a constant intravenous infusion with (9,10-/sup 3/H)palmitate-labeled very low-density lipoprotein and (1-/sup 14/C)palmitate bound to albumin, respectively. In addition, lipoprotein lipase (LPL) activity was determined in heart, skeletal muscle, and adipose tissue as well as in postheparin plasma of functionally hepatectomized, adrenalectomized, and gonadectomized rats. Plasma FFA acid concentrations were slightly increased in endotoxin-treated rats but their turnover did not differ from control. Endotoxin-treated rats had a threefold increase in plasma TG concentrations and decreased heart, skeletal muscle, and post-heparin plasma LPL activity. Plasma TG turnover was decreased, indicating that hypertriglyceridemia was not due to an increased TG output by the liver. Instead, the endotoxin-induced increase in plasma TG concentration was consequence of the 80% reduction in TG metabolic clearance rate. Thus, suppression of LPL activity in endotoxic animals impairs TG clearance resulting in hypertriglyceridemia. Furthermore, endotoxin administration reduced the delivery of TG-FFA to extrahepatic tissues because hepatic synthesis and secretion of TG from plasma FFA was decreased and LPL activity was suppressed.

  16. Limitations of automated remnant lipoprotein cholesterol assay for diagnostic use

    Technology Transfer Automated Retrieval System (TEKTRAN)

    I wish to comment on the limitations of automated remnant lipoprotein cholesterol (RemL-C) assay reported in Clinical Chemistry. Remnants are lipoprotein particles produced after newly formed triglyceride-rich lipoproteins (TRLs) of either hepatic or intestinal origin enter the plasma space and unde...

  17. Lipoprotein-associated lysolipids are differentially involved in high-density lipoprotein- and its oxidized form-induced neurite remodeling in PC12 cells.

    PubMed

    Sato, Koichi; Tobo, Masayuki; Mogi, Chihiro; Murata, Naoya; Kotake, Mie; Kuwabara, Atsushi; Im, Dong-Soon; Okajima, Fumikazu

    2014-03-01

    Oxidatively damaged proteins and lipid peroxidation products have been shown to accumulate in the brain of neurodegenerative diseases, such as Alzheimer's disease and multiple sclerosis, and oxidized lipoprotein is considered to be toxic and neurodegenerative. However, the role of lipoprotein and its oxidized form in neurite remodeling has not been well understood. In the present study, we have aimed to clarify whether and, if so, how high-density lipoprotein (HDL) and oxidized HDL (oxHDL) affect neuritogenesis. In the presence of nerve growth factor, exposure of PC12 cells to either HDL or oxHDL induces a rapid neurite retraction, which is followed by re-outgrowth of neurites in either case; however, oxHDL-treated cells exhibit much longer outgrowths than do basal and HDL-treated cells. Thus, processes in the morphological changes of neuronal cells after lipoprotein treatment are composed of two phases: the reversible retraction phase and the extension phase. Characterization of the active fractions of lipids and experiments with desensitization and knockdown of receptors have indicated that the reversible retraction phase involves mainly sphingosine 1-phosphate for HDL and lysophosphatidic acid for oxHDL. The change in the components responsible for the retraction response is comparable with the change in sphingosine 1-phosphate and lysophosphatidic acid contents by the oxidation of HDL. In the extension phase, lysophosphatidylcholine, which is increased by the oxidation of HDL, may play a stimulatory role in neurite outgrowth. We conclude that lipoprotein and its oxidized form differentially regulate neuritogenesis through lipoprotein-associated lysolipid molecules. PMID:24589770

  18. Cultured human astrocytes secrete large cholesteryl ester- andtriglyceride-rich lipoproteins along with endothelial lipase

    SciTech Connect

    Yang, Lin; Liu, Yanzhu; Forte, Trudy M.; Chisholm, Jeffrey W.; Parks, John S.; Shachter, Neil S.

    2003-12-01

    We cultured normal human astrocytes and characterized their secreted lipoproteins. Human astrocytes secreted lipoproteins in the size range of plasma VLDL (Peak 1), LDL (Peak 2), HDL (Peak 3) and a smaller peak (Peak 4), as determined by gel filtration chromatography, nondenaturing gradient gel electrophoresis and transmission electron microscopy. Cholesterol enrichment of astrocytes led to a particular increase in Peak 1. Almost all Peak 2, 3 and 4 cholesterol and most Peak 1 cholesterol was esterified (unlike mouse astrocyte lipoproteins, which exhibited similar peaks but where cholesterol was predominantly non-esterified). Triglycerides were present at about 2/3 the level of cholesterol. LCAT was detected along with two of its activators, apolipoprotein (apo) A-IV and apoC-I. ApoA-I and apoA-II mRNA and protein were absent. ApoJ was present equally in all peaks but apoE was present predominantly in peaks 3 and 4. ApoB was not detected. The electron microscopic appearance of Peak 1 lipoproteins suggested partial lipolysis leading to the detection of a heparin-releasable triglyceride lipase consistent with endothelial lipase. The increased neuronal delivery of lipids from large lipoprotein particles, for which apoE4 has greater affinity than does apoE3, may be a mechanism whereby the apoE {var_epsilon}4 allele contributes to neurodegenerative risk.

  19. Nutrient intake comparisons between Framingham and rural and Urban Puriscal, Costa Rica. Associations with lipoproteins, apolipoproteins, and low density lipoprotein particle size.

    PubMed

    Campos, H; Willett, W C; Peterson, R M; Siles, X; Bailey, S M; Wilson, P W; Posner, B M; Ordovas, J M; Schaefer, E J

    1991-01-01

    To assess cross-cultural relations between dietary intake and plasma lipoproteins, we randomly selected 222 men and 243 women from the urban and rural areas of Puriscal, Costa Rica; related their dietary composition (assessed by a food-frequency questionnaire), fitness level, and body fat to plasma lipids, apolipoproteins, and low density lipoprotein (LDL) particle size; and compared these data with those from a subsample of 280 adults from the Framingham Offspring Study. Total cholesterol and LDL cholesterol levels were significantly (p less than 0.0001) higher in Framingham (207 and 137 mg/dl, respectively) than in Puriscal (184 and 114 mg/dl, respectively) residents. Elevated triglyceride and apolipoprotein (apo) B levels (25% and 16% higher), low HDL cholesterol and apo A-I levels (12% and 29% lower), and smaller LDL particles (17%) were more frequent in Puriscal than in Framingham residents. Urban Puriscal residents had a significantly lower fitness level; increased body fat, total cholesterol, and triglyceride levels; decreased HDL cholesterol in men; and higher apo B levels in women compared with rural Puriscal residents. Body fat, animal fat, and saturated fat intakes were significantly correlated with total cholesterol, LDL cholesterol, and apo B levels in both men and women in Puriscal. Intakes of protein and animal fat were higher among urban (10.7% and 14.1%, respectively) compared with rural (8.9% and 9.9%, respectively) Puriscal residents and in Framingham (16.0% and 20.8%, respectively) compared with Puriscal residents. No significant differences were found in dietary cholesterol. Saturated fat (largely from palm oil in Puriscal) intakes were significantly different among the three groups: rural Puriscal, 10.7% of calories; urban Puriscal, 11.6%; and Framingham residents, 12.9%. These data indicate that the more atherogenic plasma lipid profile among urban compared with Puriscal residents was largely explained by increased adiposity, decreased

  20. Subfraction analysis of circulating lipoproteins in a patient with Tangier disease due to a novel ABCA1 mutation.

    PubMed

    Murano, Takeyoshi; Yamaguchi, Takashi; Tatsuno, Ichiro; Suzuki, Masayo; Noike, Hirofumi; Takanami, Tarou; Yoshida, Tomoe; Suzuki, Mitsuya; Hashimoto, Ryuya; Maeno, Takatoshi; Terai, Kensuke; Tokuyama, Wataru; Hiruta, Nobuyuki; Schneider, Wolfgang J; Bujo, Hideaki

    2016-01-15

    Tangier disease, characterized by low or absent high-density lipoprotein (HDL), is a rare hereditary lipid storage disorder associated with frequent, but not obligatory, severe premature atherosclerosis due to disturbed reverse cholesterol transport from tissues. The reasons for the heterogeneity in atherogenicity in certain dyslipidemias have not been fully elucidated. Here, using high-performance liquid chromatography with a gel filtration column (HPLC-GFC), we have studied the lipoprotein profile of a 17-year old male patient with Tangier disease who to date has not developed manifest coronary atherosclerosis. The patient was shown to be homozygous for a novel mutation (Leu1097Pro) in the central cytoplasmic region of ATP-binding cassette transporter A1 (ABCA1). Serum total and HDL-cholesterol levels were 59mg/dl and 2mg/dl, respectively. Lipoprotein electrophoretic analyses on agarose and polyacrylamide gels showed the presence of massively abnormal lipoproteins. Further analysis by HPLC-GFC identified significant amounts of lipoproteins in low-density lipoprotein (LDL) subfractions. The lipoprotein particles found in the peak subfraction were smaller than normal LDL, were rich in triglycerides, but poor in cholesterol and phospholipids. These findings in an adolescent Tangier patient suggest that patients in whom these triglyceride-rich, cholesterol- and phospholipid-poor LDL-type particles accumulate over time, would experience an increased propensity for developing atherosclerosis. PMID:26616730

  1. Subfractions of high-density lipoprotein (HDL) and dysfunctional HDL in chronic kidney disease patients

    PubMed Central

    Banach, Maciej

    2016-01-01

    A number of studies have shown that chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease (CVD). Chronic kidney disease is characterized by significant disturbances in lipoprotein metabolism, including differences in quantitative and qualitative content of high-density lipoprotein (HDL) particles. Recent studies have revealed that serum HDL cholesterol levels do not predict CVD in CKD patients; thus CKD-induced modifications in high-density lipoprotein (HDL) may be responsible for the increase in CV risk in CKD patients. Various methods are available to separate several subclasses of HDL and confirm their atheroprotective properties. However, under pathological conditions associated with inflammation and oxidation, HDL can progressively lose normal biological activities and be converted into dysfunctional HDL. In this review, we highlight the current state of knowledge on subfractions of HDL and HDL dysfunction in CKD. PMID:27478466

  2. Subfractions of high-density lipoprotein (HDL) and dysfunctional HDL in chronic kidney disease patients.

    PubMed

    Rysz-Górzyńska, Magdalena; Banach, Maciej

    2016-08-01

    A number of studies have shown that chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease (CVD). Chronic kidney disease is characterized by significant disturbances in lipoprotein metabolism, including differences in quantitative and qualitative content of high-density lipoprotein (HDL) particles. Recent studies have revealed that serum HDL cholesterol levels do not predict CVD in CKD patients; thus CKD-induced modifications in high-density lipoprotein (HDL) may be responsible for the increase in CV risk in CKD patients. Various methods are available to separate several subclasses of HDL and confirm their atheroprotective properties. However, under pathological conditions associated with inflammation and oxidation, HDL can progressively lose normal biological activities and be converted into dysfunctional HDL. In this review, we highlight the current state of knowledge on subfractions of HDL and HDL dysfunction in CKD. PMID:27478466

  3. Alterations in lipoprotein profiles in dogs with lymphoma.

    PubMed

    Ogilvie, G K; Ford, R B; Vail, D M; Walters, L M; Salman, M D; Babineau, C; Fettman, M J

    1994-01-01

    After a 12-hour fast, blood samples were obtained from 31 dogs with previously untreated lymphoma. Blood samples were also collected from 16 of these dogs after up to 5 treatments with doxorubicin (30 mg/m2 intravenously every 3 weeks). All 16 dogs underwent complete remission. Five dogs were re-evaluated after relapse and after overt signs of cancer cachexia had become clinically apparent. Samples were assayed for 8 quantitative parameters: total cholesterol (T-CH) and total triglyceride (T-TG) concentrations, and the concentration of cholesterol and triglyceride in each of the three major lipoprotein fractions, very-low-density lipoprotein (LDL-CH and LDL-TG), and high-density lipoprotein (HDL-CH and HDL-TG). The results were compared with those from 20 healthy control dogs of similar weight and age before and 3 weeks after being given one dose of doxorubicin (30 mg/m2 intravenously). The administration of doxorubicin to control dogs resulted in a significant (P < .05) decrease in T-CH, LDL-CH, and HDL-CH, as well as a significant increase in VLDL-TG and HDL-TG. When compared with untreated controls, untreated dogs with lymphoma had significantly higher concentrations of VLDL-CH, T-TG, VLDL-TG, LDL-TG, and HDL-TG, and significantly lower concentrations of HDL-CH. HDL-TG and VLDL-TG concentrations from dogs with lymphoma were significantly increased above pretreatment values after relapse and development of overt signs of cancer cachexia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8176666

  4. Metabolomic analysis of polar metabolites in lipoprotein fractions identifies lipoprotein-specific metabolic profiles and their association with insulin resistance.

    PubMed

    Hyötyläinen, Tuulia; Mattila, Ismo; Wiedmer, Susanne K; Koivuniemi, Artturi; Taskinen, Marja-Riitta; Yki-Järvinen, Hannele; Orešič, Matej

    2012-10-01

    While the molecular lipid composition of lipoproteins has been investigated in detail, little is known about associations of small polar metabolites with specific lipoproteins. The aim of the present study was to investigate the profiles of polar metabolites in different lipoprotein fractions, i.e., very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and two sub-fractions of the high-density lipoprotein (HDL). The VLDL, IDL, LDL, HDL(2), and HDL(3) fractions were isolated from serum of sixteen individuals having a broad range of insulin sensitivity and characterized using comprehensive two-dimensional gas chromatography combined with time-of-flight mass spectrometry (GC×GC-TOFMS). The lipoprotein fractions had clearly different metabolite profiles, which correlated with the particle size and surface charge. Lipoprotein-specific associations of individual metabolites with insulin resistance were identified, particularly in VLDL and IDL fractions, even in the absence of such associations in serum. The results indicate that the polar molecules are strongly attached to the surface of the lipoproteins. Furthermore, strong lipoprotein-specific associations of metabolites with insulin resistance, as compared to their serum profiles, indicate that lipoproteins may be a rich source of tissue-specific metabolic biomarkers. PMID:22722885

  5. 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...

  6. Chronic hepatitis C virus infection and lipoprotein metabolism

    PubMed Central

    Aizawa, Yoshio; Seki, Nobuyoshi; Nagano, Tomohisa; Abe, Hiroshi

    2015-01-01

    Hepatitis C virus (HCV) is a hepatotrophic virus and a major cause of chronic liver disease, including hepatocellular carcinoma, worldwide. The life cycle of HCV is closely associated with the metabolism of lipids and lipoproteins. The main function of lipoproteins is transporting lipids throughout the body. Triglycerides, free cholesterol, cholesteryl esters, and phospholipids are the major components of the transported lipids. The pathway of HCV assembly and secretion is closely linked to lipoprotein production and secretion, and the infectivity of HCV particles largely depends on the interaction of lipoproteins. Moreover, HCV entry into hepatocytes is strongly influenced by lipoproteins. The key lipoprotein molecules mediating these interactions are apolipoproteins. Apolipoproteins are amphipathic proteins on the surface of a lipoprotein particle, which help stabilize lipoprotein structure. They perform a key role in lipoprotein metabolism by serving as receptor ligands, enzyme co-factors, and lipid transport carriers. Understanding the association between the life cycle of HCV and lipoprotein metabolism is important because each step of the life cycle of HCV that is associated with lipoprotein metabolism is a potential target for anti-HCV therapy. In this article, we first concisely review the nature of lipoprotein and its metabolism to better understand the complicated interaction of HCV with lipoprotein. Then, we review the outline of the processes of HCV assembly, secretion, and entry into hepatocytes, focusing on the association with lipoproteins. Finally, we discuss the clinical aspects of disturbed lipid/lipoprotein metabolism and the significance of dyslipoproteinemia in chronic HCV infection with regard to abnormal apolipoproteins. PMID:26420957

  7. A high-fat diet and the threonine-encoding allele (Thr54) polymorphism of fatty acid–binding protein 2 reduce plasma triglyceride–rich lipoproteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Thr54 allele of the fatty acid binding protein 2 (FABP2) DNA polymorphism is associated with increased triglyceride-rich lipoproteins and insulin resistance. We investigated whether the triglyceride-rich lipoprotein response to diets of varied fat content is affected by the fatty acid binding pr...

  8. Abnormalities of Lipoprotein Concentrations in Obstructive Sleep Apnea Are Related to Insulin Resistance

    PubMed Central

    Liu, Alice; Cardell, James; Ariel, Danit; Lamendola, Cindy; Abbasi, Fahim; Kim, Sun H.; Holmes, Tyson H.; Tomasso, Vanessa; Mojaddidi, Hafasa; Grove, Kaylene; Kushida, Clete A.; Reaven, Gerald M.

    2015-01-01

    Study Objective: Prevalence of cardiovascular disease (CVD) is increased in patients with obstructive sleep apnea (OSA), possibly related to dyslipidemia in these individuals. Insulin resistance is also common in OSA, but its contribution to dyslipidemia of OSA is unclear. The study's aim was to define the relationships among abnormalities of lipoprotein metabolism, clinical measures of OSA, and insulin resistance. Design: Cross-sectional study. OSA severity was defined by the apnea-hypopnea index (AHI) during polysomnography. Hypoxia measures were expressed as minimum and mean oxygen saturation, and the oxygen desaturation index. Insulin resistance was quantified by determining steady-state plasma glucose (SSPG) concentrations during the insulin suppression test. Fasting plasma lipid/lipoprotein evaluation was performed by vertical auto profile methodology. Setting: Academic medical center. Participants: 107 nondiabetic, overweight/obese adults. Measurements and Results: Lipoprotein particles did not correlate with AHI or any hypoxia measures, nor were there differences noted by categories of OSA severity. By contrast, even after adjustment for age, sex, and BMI, SSPG was positively correlated with triglycerides (r = 0.30, P < 0.01), very low density lipoprotein (VLDL) and its subclasses (VLDL1+2) (r = 0.21–0.23, P < 0.05), and low density lipoprotein subclass 4 (LDL4) (r = 0.30, P < 0.01). SSPG was negatively correlated with high density lipoprotein (HDL) (r = −0.38, P < 0.001) and its subclasses (HDL2 and HDL3) (r = −0.32, −0.43, P < 0.01), and apolipoprotein A1 (r = −0.33, P < 0.01). Linear trends of these lipoprotein concentrations across SSPG tertiles were also significant. Conclusions: Pro-atherogenic lipoprotein abnormalities in obstructive sleep apnea (OSA) are related to insulin resistance, but not to OSA severity or degree of hypoxia. Insulin resistance may represent the link between OSA-related dyslipidemia and increased cardiovascular disease

  9. Characterization of the serum lipoproteins and their apoproteins in hypercholesterolaemic guinea pigs.

    PubMed Central

    Chapman, M J; Mills, G L

    1977-01-01

    1. Hypercholesterolaemia was induced in male guinea pigs after 6 days on a chow diet supplemented with 1.6% (w/w) cholesterol and 15% (w/w) corn oil. Both the VLD (very-low-density) and LD (low-density) lipoproteins were increased in cholesterol-fed animals, although the low concentrations of HD (high-density) lipoproteins remained essentially unchanged. LD lipoproteins of d 1.019-1.100 were the major class, accounting for 74% of the total substances of d less than 1.100. 2. Both VLD and LD lipoproteins exhibited alterations in their chemical composition, physical properties and apolipoprotein content. The VLD lipoproteins in cholesterolaemic animals were rich in cholesterol (25.9%), deficient in protein (4.9%) and exhibited electrophoretic mobility greater than that of beta-globulin; their average particle size (64.5 nm) was larger than that in controls (46.3 nm). The LD lipoproteins in animals fed on the experimental diet were also richer in cholesterol (53.1%) and of larger diameter (24.3 nm) than in the control group (41.1% and 21.4 nm respectively). 3. The apolipoprotein-B content of both VLD and LD lipoproteins was elevated in cholesterolaemic animals, particularly in the VLD class, where it represented 74.8% of the total protein moiety. 4. Apo-VLD lipoprotein exhibited an increase from 6 to 19% in its complement of tetramethylurea-soluble apolipoproteins with low electrophoretic mobility (relative mobility less than 0.29); this was primarily accounted for by apolipoproteins characterized by high arginine (7.2 and 6.4% respectively) and glutamic acid (20.1 and 20.0% respectively) contents. 5. By contrast, there was little change in the soluble apolipoproteins of LD lipoproteins in hypercholesterolaemic animals.6. These studies show the response of the guinea pig to dietary fat and cholesterol to be distinct from that elicited by similar stimuli in the rabbit, rat, pig and dog. Images PLATE 1 PLATE 2 PLATE 3 PLATE 4 PMID:588269

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

    PubMed

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

    1982-05-01

    patients, the d > 1.006 g/ml unesterified cholesterol and triglyceride levels decreased, while esterified cholesterol, HDL-cholesterol, and apoA-I levels increased. The first HDL fractions to reappear were lipoproteins with HDL(2) density characteristics, as evidenced by simultaneous increases of apoA-I, apoA-II, cholesteryl esters and phospholipids. Lipoproteins with HDL(3) density characteristics appeared later. Long-term (6-10 months) follow-up studies indicated a substantial elevation of HDL cholesterol and apoA-I in three of the four patients that appeared to have resulted from further increases in their HDL(2)-like subspecies. The above results illustrate the diversity of abnormal lipoproteins in alcoholic hepatitis and the ability of density gradient ultra-centrifugation combined with lipid and apolipoprotein quantitation, electron microscopy, and polyacrylamide gel electrophoresis to partially resolve those lipoproteins in the d > 1.006 g/ml plasma fraction.-Weidman, S. W., J. B. Ragland, and S. M. Sabesin. Plasma lipoprotein composition in alcoholic hepatitis: accumulation of apolipoprotein E-rich high density lipoprotein and preferential reappearance of "light"-HDL during partial recovery. PMID:7097121

  11. Modulation of lipoprotein metabolism by inhibition of sphingomyelin synthesis in ApoE knockout mice.

    PubMed

    Park, Tae-Sik; Panek, Robert L; Rekhter, Mark D; Mueller, Sandra Bak; Rosebury, Wendy S; Robertson, Andrew; Hanselman, Jeffrey C; Kindt, Erick; Homan, Reynold; Karathanasis, Sotirios K

    2006-12-01

    Plasma sphingomyelin (SM) has been suggested as a risk factor for coronary heart disease independent of cholesterol levels. A decrease of SM in lipoproteins is known to improve the activities of lecithin:cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL) in vitro. Inhibition of SM biosynthesis may reduce lipoprotein SM content and thus improve cholesterol distribution in lipoproteins by enhancing reverse cholesterol transport and clearance of triglyceride-rich lipoproteins. To examine this hypothesis, ApoE KO mice were fed a western diet and treated for 4 weeks with various concentrations of myriocin, a specific inhibitor of serine palmitoyltransferase. Myriocin treatment lowered plasma cholesterol and TG levels in a dose-dependent manner. In addition, myriocin treatment reduced cholesterol contents in VLDL and LDL and elevated HDL-cholesterol. Observed lipid-lowering effects of myriocin were associated with suppression of HMG CoA reductase and fatty acid synthase via reduced levels of SREBP-1 RNA and protein. Induction of apoAI and lecithin:cholesterol acytransferase (LCAT) in the liver by myriocin was associated with an increased HDL. Lesion area and macrophage area were also diminished in the cuffed femoral artery of ApoE KO mice. In conclusion, inhibition of sphingolipid biosynthesis can be a novel therapeutic target for dyslipidemia and atherosclerosis. PMID:16458317

  12. Systemic Inflammatory Markers Are Closely Associated with Atherogenic Lipoprotein Subfractions in Patients Undergoing Coronary Angiography

    PubMed Central

    Zhang, Yan; Li, Sha; Xu, Rui-Xia; Zhu, Cheng-Gang; Guo, Yuan-Lin; Wu, Na-Qiong; Sun, Jing; Li, Jian-Jun

    2015-01-01

    Objective. To investigate the relationship between inflammatory markers and atherogenic lipoprotein subfractions. Methods. We studied 520 eligible subjects who were not receiving any lipid-lowering therapy. The inflammatory markers including white blood cell (WBC) count, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR), and D-dimer were measured. A multimarker inflammatory index was developed. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) separation processes were performed using Lipoprint System. Results. In age- and sex-adjusted analysis, several inflammatory markers (WBC count, hs-CRP, fibrinogen, and ESR) were positively related to circulating non-HDL cholesterol and remnant cholesterol (p < 0.05, all). Among lipoprotein subfractions, we observed a positive association of inflammatory markers with very low-density lipoprotein cholesterol, small LDL cholesterol, and LDL score (p < 0.05, all). Meanwhile, a negative association was detected between inflammatory markers and mean LDL particle size (p < 0.05) or large HDL cholesterol (p < 0.05). Moreover, we found that the relationships between multimarker index quartiles and small LDL cholesterol, LDL score, and mean LDL particle size were slightly stronger in patients with CAD. Conclusions. Systemic inflammatory markers are positively correlated with small LDL cholesterol and LDL score while being negatively linked with mean LDL particle size and large HDL cholesterol, highlighting the potential contribution to increased cardiovascular risk. PMID:26688615

  13. Females with angina pectoris have altered lipoprotein metabolism with elevated cholesteryl ester transfer protein activity and impaired high-density lipoproteins-associated antioxidant enzymes

    PubMed Central

    PARK, JUNGHO; KIM, JAE-RYONG; SHIN, DONG-GU; CHO, KYUNG-HYUN

    2012-01-01

    In order to investigate non-invasive biomarkers for angina pectoris (AP), we analyzed the lipid and protein composition in individual lipoproteins from females with angina pectoris (n=22) and age- and gender-matched controls (n=20). In the low-density lipoprotein (LDL) fraction, the triglycerides (TG) and protein content increased in the AP group compared to the control group. The AP group had lower total cholesterol (TC) and elevated TG in the high-density lipoprotein (HDL) fraction. In the AP group, cholesteryl ester transfer protein (CETP) activity was enhanced in HDL and LDL, while lecithin:cholesterol acyltransferase (LCAT) activity in HDL3 was almost depleted. Antioxidant activity was significantly decreased in the HDL3 fraction, with a decrease in the HDL2 particle size. In the HDL3 fraction, paraoxonase and platelet activating factor-acetylhydrolase (PAF-AH) activity were much lower and the levels of CETP and apoC-III were elevated in the AP group. The LDL from the AP group was more sensitive to cupric ion-mediated oxidation with faster mobility. In conclusion, the lipoprotein fractions in the AP group had impaired antioxidant activity and increased TG and apoC-III with structural and functional changes. PMID:22211242

  14. Plasma lipoprotein changes during abstinence in chronic alcoholics.

    PubMed

    Weidman, S W; Beard, J D; Sabesin, S M

    1984-08-01

    Plasma lipoprotein changes during a 2-week period of abstinence were followed in 6 male, chronic alcoholics without evidence of severe liver disease and with initial HDL cholesterol (HDL-CH) greater than 60 mg/dl. Fasting blood samples were obtained on days 1, 3, 7 and 14 of the study. Reference data were obtained from healthy non-alcoholic normolipidemic men who had abstained from alcohol for 10 days. At day 1, plasma- and HDL-CH (by the heparin-Mn2+ technique) were 17 and 69% higher, respectively, than those of controls. During abstinence, VLDL-CH increased 52% whereas HDL-CH decreased 30% compared to day 1 values. (IDL + LDL)-CH increased during abstinence to levels 33% higher than that of controls. Plasma, SF greater than 400, VLDL- and d greater than 1.006 g/ml-triglycerides (TG) were not significantly different from those of the control group. Only the d greater than 1.006 g/ml-TG showed a significant effect of abstinence, increasing by 37%. Initial plasma and d greater than 1.006 g/ml-phospholipid (PL) concentrations were 17 and 31% higher, respectively, than those of controls; and the latter was the only fraction to change significantly with abstinence, decreasing by 13%. Density gradient ultracentrifugation was employed to further resolve the d greater than 1.006 g/ml fraction into IDL, LDL, HDL and VHDL subfractions. Initial levels of IDL- and LDL-CH and -PL in the alcoholic group did not differ from those of controls. IDL-CH and -PL were invariant during abstinence, whereas LDL-CH and -PL levels increased 38 and 28%, during this period. Apo A-I, CH and PL contained in the 'lighter' density HDL region of the gradient (d = 1.063-1.125 g/ml) were 70-108% increased over the corresponding parameters for controls; and with abstinence decreased 30-40% between days 1 and 14. CH and PL in the 'heavier' density HDL region (d = 1.125-1.21 g/ml) were 30% increased over those of controls, while apo A-I levels were similar to controls. During abstinence, 'heavy' HDL

  15. Explaining wartime rape.

    PubMed

    Gottschall, Jonathan

    2004-05-01

    In the years since the first reports of mass rapes in the Yugoslavian wars of secession and the genocidal massacres in Rwanda, feminist activists and scholars, human rights organizations, journalists, and social scientists have dedicated unprecedented efforts to document, explain, and seek solutions for the phenomenon of wartime rape. While contributors to this literature agree on much, there is no consensus on causal factors. This paper provides a brief overview of the literature on wartime rape in historical and ethnographical societies and a critical analysis of the four leading explanations for its root causes: the feminist theory, the cultural pathology theory, the strategic rape theory, and the biosocial theory. The paper concludes that the biosocial theory is the only one capable of bringing all the phenomena associated with wartime rape into a single explanatory context. PMID:15326538

  16. Explaining moral religions.

    PubMed

    Baumard, Nicolas; Boyer, Pascal

    2013-06-01

    Moralizing religions, unlike religions with morally indifferent gods or spirits, appeared only recently in some (but not all) large-scale human societies. A crucial feature of these new religions is their emphasis on proportionality (between deeds and supernatural rewards, between sins and penance, and in the formulation of the Golden Rule, according to which one should treat others as one would like others to treat oneself). Cognitive science models that account for many properties of religion can be extended to these religions. Recent models of evolved dispositions for fairness in cooperation suggest that proportionality-based morality is highly intuitive to human beings. The cultural success of moralizing movements, secular or religious, could be explained based on proportionality. PMID:23664451

  17. Analyzing the molecular mechanism of lipoprotein localization in Brucella.

    PubMed

    Goolab, Shivani; Roth, Robyn L; van Heerden, Henriette; Crampton, Michael C

    2015-01-01

    Bacterial lipoproteins possess diverse structure and functionality, ranging from bacterial physiology to pathogenic processes. As such many lipoproteins, originating from Brucella are exploited as potential vaccines to countermeasure brucellosis infection in the host. These membrane proteins are translocated from the cytoplasm to the cell membrane where they are anchored peripherally by a multifaceted targeting mechanism. Although much research has focused on the identification and classification of Brucella lipoproteins and their potential use as vaccine candidates for the treatment of Brucellosis, the underlying route for the translocation of these lipoproteins to the outer surface of the Brucella (and other pathogens) outer membrane (OM) remains mostly unknown. This is partly due to the complexity of the organism and evasive tactics used to escape the host immune system, the variation in biological structure and activity of lipoproteins, combined with the complex nature of the translocation machinery. The biosynthetic pathway of Brucella lipoproteins involves a distinct secretion system aiding translocation from the cytoplasm, where they are modified by lipidation, sorted by the lipoprotein localization machinery pathway and thereafter equipped for export to the OM. Surface localized lipoproteins in Brucella may employ a lipoprotein flippase or the β-barrel assembly complex for translocation. This review provides an overview of the characterized Brucella OM proteins that form part of the OM, including a handful of other characterized bacterial lipoproteins and their mechanisms of translocation. Lipoprotein localization pathways in gram negative bacteria will be used as a model to identify gaps in Brucella lipoprotein localization and infer a potential pathway. Of particular interest are the dual topology lipoproteins identified in Escherichia coli and Haemophilus influenza. The localization and topology of these lipoproteins from other gram negative bacteria

  18. Analyzing the molecular mechanism of lipoprotein localization in Brucella

    PubMed Central

    Goolab, Shivani; Roth, Robyn L.; van Heerden, Henriette; Crampton, Michael C.

    2015-01-01

    Bacterial lipoproteins possess diverse structure and functionality, ranging from bacterial physiology to pathogenic processes. As such many lipoproteins, originating from Brucella are exploited as potential vaccines to countermeasure brucellosis infection in the host. These membrane proteins are translocated from the cytoplasm to the cell membrane where they are anchored peripherally by a multifaceted targeting mechanism. Although much research has focused on the identification and classification of Brucella lipoproteins and their potential use as vaccine candidates for the treatment of Brucellosis, the underlying route for the translocation of these lipoproteins to the outer surface of the Brucella (and other pathogens) outer membrane (OM) remains mostly unknown. This is partly due to the complexity of the organism and evasive tactics used to escape the host immune system, the variation in biological structure and activity of lipoproteins, combined with the complex nature of the translocation machinery. The biosynthetic pathway of Brucella lipoproteins involves a distinct secretion system aiding translocation from the cytoplasm, where they are modified by lipidation, sorted by the lipoprotein localization machinery pathway and thereafter equipped for export to the OM. Surface localized lipoproteins in Brucella may employ a lipoprotein flippase or the β-barrel assembly complex for translocation. This review provides an overview of the characterized Brucella OM proteins that form part of the OM, including a handful of other characterized bacterial lipoproteins and their mechanisms of translocation. Lipoprotein localization pathways in gram negative bacteria will be used as a model to identify gaps in Brucella lipoprotein localization and infer a potential pathway. Of particular interest are the dual topology lipoproteins identified in Escherichia coli and Haemophilus influenza. The localization and topology of these lipoproteins from other gram negative bacteria

  19. Lipoprotein Receptor LRP1 Regulates Leptin Signaling and Energy Homeostasis in the Adult Central Nervous System

    PubMed Central

    Liu, Qiang; Zhang, Juan; Zerbinatti, Celina; Zhan, Yan; Kolber, Benedict J.; Herz, Joachim; Muglia, Louis J.; Bu, Guojun

    2011-01-01

    Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system. PMID:21264353

  20. The role of PCSK9 in intestinal lipoprotein metabolism: synergism of statin and ezetimibe.

    PubMed

    Fazio, Sergio

    2015-02-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a major role in the regulation of lipoprotein metabolism, mostly through control of low-density lipoprotein receptor degradation. Depletion of cellular cholesterol causes a compensatory increase in plasma PCSK9 levels, which can diminish the cholesterol-lowering power of statins and may lead to the overproduction of intestinal lipoproteins, mainly thorough the up regulation of microsomal triglyceride transfer protein and the Niemann-Pick C1-like 1 protein, the target of ezetimibe. Thus, ezetimibe therapy may counter this unwanted effect of statins, providing an additional theoretical rationale for combining the effect of ezetimibe on intestinal cholesterol absorption and that of statins on cholesterol synthesis. PMID:25659873

  1. Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease.

    PubMed

    Sacks, Frank M; Katan, Martijn

    2002-12-30

    Several dietary approaches have reduced cardiovascular events in randomized clinical trials. Replacing saturated fat with polyunsaturated fat prevented coronary events in men, and a Mediterranean diet and fatty fish improved survival. None of these trials had much impact on total fat intake but rather increased vegetable oils, n-3 fatty acids, or many other plant foods or nutrients that are linked to coronary prevention. The reductions in cardiovascular disease (CVD) caused by these dietary therapies compare favorably with drug treatments for hyperlipidemia and hypertension. Improvement in blood lipid risk factors is an important mechanism to explain the results of trials of unsaturated fats. When saturated or trans unsaturated fats are replaced with monounsaturated or n-6 polyunsaturated fats from vegetable oils, primarily low-density lipoprotein (LDL) cholesterol decreases. The LDL to high-density lipoprotein (HDL) cholesterol ratio decreases. When carbohydrates are used to replace saturated fats, in a low-fat diet, LDL and HDL decrease similarly, and the ratio is not improved; triglycerides increase as well when carbohydrate increases, except when low glycemic index foods are used. The n-3 polyunsaturated fats in fish oils suppress cardiac arrhythmias and reduce triglycerides, but they have little effect on LDL or HDL cholesterol levels. The theme should be that diet has benefits that come directly from foods, as well as from the reduction in saturated fats, cholesterol, meats, and fatty dairy foods. It is likely that many diets could be designed that could prevent CVD. This potential diversity is crucial for engaging the diverse cultures and tastes of people worldwide in cardiovascular disease prevention. PMID:12566134

  2. [A history and review of cholesterol ester transfer protein inhibitors and their contribution to the understanding of the physiology and pathophysiology of high density lipoprotein].

    PubMed

    Corral, Pablo; Schreier, Laura

    2014-01-01

    There is irrefutable evidence that statins reduce the risk of cardiovascular events in a magnitude proportional to the intensity of the decrease in cholesterol transport by the low density lipoproteins. Despite this great advance there is still a residual risk of cardiovascular events. For this reason, an increase in the levels of high density lipoprotein is considered in order to boost the main action of this lipoprotein, which is reverse cholesterol transport. Distinct classes of evidence (epidemiological, genetic, and pathophysiological) show that the inhibition and/or modulation of cholesterol ester transfer protein increases plasma high density lipoprotein-cholesterol levels. The main reason for presenting this review is to look at the physiology of cholesterol ester transfer protein, its interrelationship with high density lipoproteins, and to give an update on the development of different cholesterol ester transfer protein inhibitor/modulator molecules. PMID:24094503

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

    SciTech Connect

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

    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.

  4. Lipid profiling of lipoprotein X: Implications for dyslipidemia in cholestasis.

    PubMed

    Heimerl, Susanne; Boettcher, Alfred; Kaul, Harald; Liebisch, Gerhard

    2016-08-01

    Lipoprotein X (Lp-X) is an abnormal lipoprotein that may typically be formed in intra- and extrahepatic cholestasis and potentially interfere with lipid analysis in the routine lab. To gain insight into lipid class and species composition, Lp-X, LDL and HDL from cholestatic and control serum samples were subjected to mass spectrometric analysis including phospholipids (PL), sphingolipids, free cholesterol (FC), cholesteryl esters (CE) and bile acids. Our analysis of Lp-X revealed a content of 46% FC, 49% PL with 34% phosphatidylcholine (PC) as main PL component. The lipid species pattern of Lp-X showed remarkable high fractions of mono-unsaturated species including PC 32:1 and PC 34:1 and phosphatidylethanolamine (PE) 32:1 and 34:1. LDL and HDL lipid composition in the same specimens strongly reflected the lipid composition of Lp-X with increased PC 32:1, PC 34:1, PE 32:1, PE 34:1 and FC accompanied by decreased CE compared to controls. Comparison of Lp-X and biliary lipid composition clearly indicates that Lp-X does not originate from a sole release of bile lipids. Moreover, these data present evidence for increased hepatic fatty acid and PL synthesis which may represent a reaction to high hepatic FC level observed during cholestasis. PMID:27112638

  5. (/sup 3/H)cholesteryl ester labeling and transfer among human and honhuman primate plasma lipoproteins

    SciTech Connect

    Thomas, M.S.; Rudel, L.L.

    1983-04-01

    Aliquots of human and nonhuman primate plasma containing 5,5'-dithiobis (2-nitrobenzoic acid) were incubated at 37/sup 0/C in tubes previously coated with trace amounts of tritium-labeled cholesteryl oleate ((/sup 3/H)CO). Initially, cholesteryl esters were transferred at a rapid rate into plasma after which the rate slowed. During 24 h of incubation, an average of 55% of the (/sup 3/H)CO transferred from the side of the tube into African green monkey plasma, 44% into human plasma and 21% into rat plasma. Greater than 98% of the radioactive ester transferred into plasma was found to be associated with plasma lipoproteins that were then rapidly separated using vertical rotor density gradient ultracentrifugation. In very low density lipoprotein (VLDL)-poor plasma after 30 min incubations, high density lipoproteins (HDL) contained most of the (/sup 3/H)CO while 5- to 24-h incubations resulted in increased labeling of low density proteins (LDL). In VLDL-rich plasma, it was found that in addition to the labeling of HDL, VLDL contained about 25% of the labeled cholesteryl esters after 30-min incubations and, as above, the proportion in LDL subsequently increased. Compositional analyses showed that intermediate-sized LDL (ILDL) were accumulating cholesteryl ester mass while transfer occurred. LDL labeled using this method were injected intravenously into monkeys and their removal from plasma was found to be similar to that found for LDL labeled in vivo. It was concluded that this method of plasma lipoprotein cholesteryl ester labeling, presumably a result of cholesteryl ester transfer protein activity, was efficient, resulted in lipoproteins labeled only in the cholesteryl ester moiety, and induced minimal modification of lipoprotein particles that did not alter their biological activity.

  6. Effect of plasma lipoproteins in gonadotropin stimulation of 17 beta-estradiol production in the ovarian follicle of rainbow trout (Salmo gairdneri).

    PubMed

    Babin, P J

    1986-12-01

    The effect of trout plasma lipoproteins on the production of 17 beta-estradiol by trout ovarian follicles is investigated in vitro. 17 beta-Estradiol secretion into the medium was assayed as a function of follicular diameter in the presence of lipoproteins with and without salmonid gonadotropin (SGA-GTH). The presence of very low-density lipoproteins (VLDL) + chylomicrons (Chy), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) amplified the SGA-GTH effect at the lowest concentrations tested (less than 50 micrograms protein/ml). HDL is the most effective for increasing hormone accumulation on a microgram lipoprotein sterol basis. Autoradiography of 125I-labeled LDL showed that they were preferentially bound by thecal cells. Kinetics of 17 beta-estradiol release indicated that lipoprotein amplification occurred especially after 15 hr and subsequent metabolism of 17 beta-estradiol by follicular layers also led to an equilibrium. At the end of vitellogenesis apoprotein B lipoproteins (VLDL + Chy, LDL) apparently inhibited SGA-GTH stimulation. N',O'-Dibutyryl cAMP (10 mM) considerably stimulated 17 beta-estradiol production but lipoprotein amplification did not occur. Chloroquine (30 microM) inhibition of LDL and HDL amplification indicates that this process requires lysosomal degradation. Plasma lipoproteins in trout modulate SGA-GTH stimulation of 17 beta-estradiol production during exogenous vitellogenesis. Due to the ease and frequency with which the experiments can be carried out, the ovarian follicle of salmonids is an excellent model for the study of the role of lipoproteins in the regulation of ovarian steroids biosynthesis. PMID:3026884

  7. Lipoprotein(a) in women twins: Heritability and relationship to apolipoprotein(a) phenotypes

    SciTech Connect

    Austin, M.A. ); Sandholzer, C.; Utermann, G. ); Selby, J.V. ); Newman, B. ); Krauss, R.M. )

    1992-10-01

    Lp(a) is a unique lipoprotein consisting of an LDL-like particle and a characteristic protein, apo(a). Increased levels of Lp(a) constitute a risk factor for coronary heart disease. Variation in the size of the apo(a) protein is a phenotype controlled by the apo(a) gene on chromosome 6 and is related to Lp(a) plasma levels. Based on 169 MZ and 125 DZ adult female twin pairs, this study's purpose was to estimate the proportion of the variation in Lp(a) levels that is due to genetic influences and to determine the extent to which the apo(a) locus explains this heritability. Lp(a) levels were significantly more similar in MZ twins than in DZ twins: mean co-twin differences were 3.9 [+-] 5.7 mg/dl and 16.0 [+-] 19.9 mg/dl (P < .001), respectively. Intraclass correlations were .94 in MZ twins and .32 in DZ twins, resulting in a heritability estimate of .94 (P < .001). Heritability was then calculated using only co-twins with the same apo(a) phenotype: the heritability estimate decreased to .45 but was still highly significant (P < .001). Therefore, on the basis of heritability analysis of women twins, Lp(a) levels are almost entirely genetically controlled. Variation at the apo(a) locus contributes to this heritability, although other genetic factors could be involved. 66 refs., 2 figs., 4 tabs.

  8. Serum and urinary lipoproteins in the human nephrotic syndrome: evidence for renal catabolism of lipoproteins

    SciTech Connect

    Shore, V.G.; Forte, T.; Licht, H.; Lewis, S.B.

    1982-03-01

    The urinary excretion of lipoproteins and the possibility of catabolic alterations on glomerular filtration were investigated in four nephrotic subjects difering in etiology, serum lipoprotein profile, and 24 hr urinary output of protein and lipids. The apolipoproteins and lipoproteins of urine were compared with those of serum with respect to distribution profile, physical properties, and composition. As expected from molecular sieving effects during glomerular filtration, the urinary HDL were more abundant than the lower density lipoproteins even when the plasma LDL was elevated markedly. Intact apolipoproteins were not found in the concentrated urinary fraction isolated by ultrafiltration between the limits of 10/sup 4/ and 5 x 10/sup 4/ daltons. On the basis of immunoreactivity, gel electrophoresis, and amino acid composition, apolipoproteins B and AI are the major and minor proteins, respectively, of urinary LDL, and apo B is the major protein of the urinary IDL and VLDL. Apolipoproteins AI, AII, CI, CIII, and possibly AIV were isolated from the urinary HDL. As much as 20% of the protein moiety of the urinary HDL appeared to be large apolipoprotien fragments with molecular weights and isoelectric points similar to those of apo CII and apo CIII. The lower density classes of urinary lipoproteins also appeared to have lost apo E and apo C's and to have undergone partial proteolysis.

  9. Moderate alcohol consumption and changes in postprandial lipoproteins of premenopausal and postmenopausal women: a diet-controlled, randomized intervention study.

    PubMed

    van der Gaag, M S; Sierksma, A; Schaafsma, G; van Tol, A; Geelhoed-Mieras, T; Bakker, M; Hendriks, H F

    2000-01-01

    Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Earlier studies in men have shown that moderate alcohol consumption affects lipoprotein metabolism and hemostasis. In this diet-controlled, randomized, crossover trial, we investigated the effect on lipoprotein metabolism of moderate consumption of red wine or red grape juice with evening dinner for 3 weeks in premenopausal women using oral contraceptives and in postmenopausal women. After 3 weeks, blood samples were collected 1 hour before dinner up to 19 hours after starting dinner at 2-hour or 4-hour intervals. Plasma triglyceride concentrations and very low density lipoprotein (VLDL) triglyceride levels peaked 3 hours after dinner with wine in both premenopausal and postmenopausal women. After wine consumption, the overall high-density lipoprotein (HDL) cholesterol level was increased in postmenopausal women (mean increase 0.17 mmol/L, or 12%, p = 0.03), and the plasma low-density lipoprotein (LDL) cholesterol level was reduced in premenopausal women (mean reduction 0.35 mmol/L, or 12%, p = 0.01) as compared with grape juice consumption. The findings suggest that postprandial lipoprotein metabolism after moderate alcohol consumption differs between oral contraceptive-using premenopausal women and postmenopausal women. The response of postmenopausal women to alcohol resembled the response found in earlier studies in men. PMID:10957749

  10. Essential protective role attributed to the surface lipoproteins of Borrelia burgdorferi against innate defenses

    PubMed Central

    Xu, Qilong; McShan, Kristy; Liang, Fang Ting

    2008-01-01

    Summary To initiate infection, a microbial pathogen must be able to evade innate immunity. Here we show that the Lyme disease spirochete Borrelia burgdorferi depends on its surface lipoproteins for protection against innate defenses. The deficiency for OspC, an abundantly expressed surface lipoprotein during early infection, led to quick clearance of B. burgdorferi after inoculation into the skin of SCID mice. Increasing expression of any of the four randomly chosen surface lipoproteins, OspA, OspE, VlsE or DbpA, fully protected the ospC mutant from elimination from the skin tissue of SCID mice; moreover, increased OspA, OspE, or VlsE expression allowed the mutant to cause disseminated infection and restored the ability to effectively colonize both joint and skin tissues, albeit the dissemination process was much slower than that of the mutant restored with OspC expression. When the ospC mutant was modified to express OspA under control of the ospC regulatory elements, it registered only a slight increase in the 50% infectious dose than the control in SCID mice but a dramatic increase in immunocompetent mice. Taken together, the study demonstrated that the surface lipoproteins provide B. burgdorferi with an essential protective function against host innate elimination. PMID:18452586

  11. Lipoprotein-induced phenoloxidase-activity in tarantula hemocyanin.

    PubMed

    Schenk, Sven; Schmidt, Juliane; Hoeger, Ulrich; Decker, Heinz

    2015-08-01

    Phenoloxidases play vital roles in invertebrate innate immune reactions, wound closure and sclerotization processes in arthropods. In chelicerates, where phenoloxidases are lacking, phenoloxidase-activity can be induced in the oxygen carrier hemocyanin in vitro by proteolytic cleavage, incubation with the artificial inducer SDS, or lipids. The role of protein-protein interaction has up to now received little attention. This is remarkable, as lipoproteins - complexes of proteins and lipids - are present at high concentrations in arthropod hemolymph. We characterized the three lipoproteins present in tarantula hemolymph, two high-density lipoproteins and one very high-density lipoprotein, and show that the two high-density lipoproteins have distinct structures: the more abundant high-density lipoprotein is an ellipsoid particle with axes of ~22.5 nm and ~16.8 nm, respectively. The second high-density lipoprotein, present only in trace amount, is a large discoidal lipoprotein with a diameter of ~38.4 nm and an on-edge thickness of ~7.1 nm. We further demonstrate that the interaction between lipoproteins and hemocyanin induces phenoloxidase activity in hemocyanin, and propose that this activation is due to protein-protein interaction rather than protein-lipid interaction, as neither lipid micelles nor lipid monomers were found to be activating. Activation was strongest in the presence of high-density lipoproteins; very high-density lipoproteins were found to be non-activating. This is the first time that the ability of lipoproteins to induce phenoloxidase activity of hemocyanin has been demonstrated, thus adding novel aspects to the function of lipoproteins apart from their known role in nutrient supply. PMID:25817204

  12. Hippocampal lipoprotein lipase regulates energy balance in rodents☆

    PubMed Central

    Picard, Alexandre; Rouch, Claude; Kassis, Nadim; Moullé, Valentine S.; Croizier, Sophie; Denis, Raphaël G.; Castel, Julien; Coant, Nicolas; Davis, Kathryn; Clegg, Deborah J.; Benoit, Stephen C.; Prévot, Vincent; Bouret, Sébastien; Luquet, Serge; Le Stunff, Hervé; Cruciani-Guglielmacci, Céline; Magnan, Christophe

    2013-01-01

    Brain lipid sensing is necessary to regulate energy balance. Lipoprotein lipase (LPL) may play a role in this process. We tested if hippocampal LPL regulated energy homeostasis in rodents by specifically attenuating LPL activity in the hippocampus of rats and mice, either by infusing a pharmacological inhibitor (tyloxapol), or using a genetic approach (adeno-associated virus expressing Cre-GFP injected into Lpllox/lox mice). Decreased LPL activity by either method led to increased body weight gain due to decreased locomotor activity and energy expenditure, concomitant with increased parasympathetic tone (unchanged food intake). Decreased LPL activity in both models was associated with increased de novo ceramide synthesis and neurogenesis in the hippocampus, while intrahippocampal infusion of de novo ceramide synthesis inhibitor myriocin completely prevented body weight gain. We conclude that hippocampal lipid sensing might represent a core mechanism for energy homeostasis regulation through de novo ceramide synthesis. PMID:24634821

  13. Change in composition of high density lipoprotein during gemfibrozil therapy.

    PubMed

    Sorisky, A; Ooi, T C; Simo, I E; Meuffels, M; Hindmarsh, J T; Nair, R

    1987-10-01

    We investigated the high density lipoprotein cholesterol (HDL-C) response in 20 middle-aged males during a 12-week course of gemfibrozil. Three aspects of the increase in HDL-C (25%) were studied and our observations are as follows: (1) subfraction analysis showed that HDL3-C rose earlier and to a larger extent (28%) than HDL2-C (15%), (2) analysis of variance group--time interaction effect and correlation studies of HDL-C and total triglycerides suggest the increase in HDL-C was due to a direct effect of gemfibrozil on HDL metabolism, and (3) HDL-C was the only one of 4 HDL components to increase. Apoprotein A-I (apo A-I) and HDL-phospholipid (HDL-PL) did not change, and HDL-triglyceride (HDL-TG) decreased. This pattern is consistent with a change in composition of HDL, i.e. cholesterol enrichment and triglyceride depletion. PMID:3118893

  14. Lipoprotein (a) and cardiovascular risk factors in children and adolescents

    PubMed Central

    Palmeira, Ástrid Camêlo; Leal, Adriana Amorim de F.; Ramos, Nathaly de Medeiros N.; de Alencar F., José; Simões, Mônica Oliveira da S.; Medeiros, Carla Campos M.

    2013-01-01

    OBJECTIVE: To review the relationship between lipoprotein (a) [Lp(a)] and other risk factors for cardiovascular disease (CVD) in children and adolescents. DATA SOURCES: This systematic review included studies from 2001 to 2011, a ten-year time period. Epidemiological studies with children and/or adolescents published in English, Portuguese or Spanish and fully available online were included. The searches were performed in Science Direct, PubMed/Medline, BVS (Biblioteca Virtual em Saúde) and Cochrane Library databases, using the following combination of key-words: "lipoprotein a" and "cardiovascular diseases" and "obesity". DATA SYNTHESIS: Overall, 672 studies were obtained but only seven were included. Some studies assessed the family history for CVD. In all of them, Lp(a) levels were increased in patients with family history for CVD. There was also a positive correlation between Lp(a) and LDL-cholesterol, total cholesterol, and apolipoprotein B levels, suggesting an association between Lp(a) levels and the lipid profile. CONCLUSIONS: The evidence that CVD may originate in childhood and adolescence leads to the need for investigating the risk factors during this period in order to propose earlier and possibly more effective interventions to reduce morbidity and mortality rates. PMID:24473960

  15. Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation.

    PubMed

    Sundaram, V; Hanna, A N; Koneru, L; Newman, H A; Falko, J M

    1997-10-01

    Hypothyroidism is frequently associated with hypercholesterolemia and an increased risk for atherosclerosis, whereas hyperthyroidism is known to precipitate angina or myocardial infarction in patients with underlying coronary heart disease. We have shown previously that L-T4 functions as an antioxidant in vitro and inhibits low density lipoprotein (LDL) oxidation in a dose-dependent fashion. The present study was designed to evaluate the changes in LDL oxidation in subjects with hypothyroidism and hyperthyroidism. Fasting blood samples for LDL oxidation analyses, lipoprotein determinations, and thyroid function tests were collected at baseline and after the patients were rendered euthyroid. The lag phase (mean +/- SEM hours) of the Cu+2-catalyzed LDL oxidation in the hypothyroid state and the subsequent euthyroid states were 4 +/- 0.0.65 and 14 +/- 0.68 h, respectively (P < 0.05). The lag phase during the hyperthyroid phase was 6 +/- 0.55 h, and that during the euthyroid phase was 12 +/- 0.66 h (P < 0.05). The total and LDL cholesterol levels were higher in hypothyroidism than in euthyroidism and were lower in hyperthyroidism than in the euthyroid state. We conclude that LDL has more susceptibility to oxidation in both the hypothyroid and hyperthyroid states. Thus, the enhanced LDL oxidation may play a role in the cardiac disease process in both hypothyroidism and hyperthyroidism. PMID:9329379

  16. Effect of ethinyl estradiol treatment on lipoproteins and LCAT activity in aged rats.

    PubMed

    Lee, S M; Kudchodkar, B J; Lacko, A G

    1992-06-01

    The induction of hepatic lipoprotein (apo B/E) have been investigated in Fischer-344 rats. These studies were aimed to determine the mechanism underlying the previously observed (Lee et al., Mech. Ageing Dev., 61 (1991) 85-98) hypercholesterolemia and the age-related decrease in the fractional rate of endogenous cholesterol esterification. Young (5 months) and aged (22 months) male Fischer-344 rats were treated with pharmacological doses (5 mg/kg per day) of ethinyl estradiol (EE) for 7 days. Reduction of plasma cholesterol (57% in young vs 47% in aged rats) and high density lipoprotein cholesterol (64% in young vs 63% in aged rats) occurred in both groups upon EE treatment. Initial low density lipoprotein levels were very low in the plasma of young rats and consequently were not affected by EE treatment. However, in aged rats, the low density lipoprotein levels were much higher initially and were markedly reduced by EE treatment. (18.0 vs 10.0 mg/dl). Very low density lipoproteins were about the same initially but increased in aged rats and decreased in young rats upon EE treatment. Both the lecithin:cholesterol acyltransferase (LCAT) activity (as determined with a proteoliposome substrate) and the fractional rate (FR) of the endogenous cholesterol esterification decreased in treated animals compared to controls. However, the differences in the FR of the endogenous cholesterol esterification between young and aged rats (observed before treatment) were nearly abolished upon treatment. These data suggest that the previously observed age related decrease in the FR of endogenous cholesterol esterification is due to the accumulation of apolipoprotein E-rich (apo E) lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1630152

  17. Mice with Chimeric Livers Are an Improved Model for Human Lipoprotein Metabolism

    PubMed Central

    Ellis, Ewa C. S.; Nauglers, Scott; Parini, Paolo; Mörk, Lisa-Mari; Jorns, Carl; Zemack, Helen; Sandblom, Anita Lövgren; Björkhem, Ingemar; Ericzon, Bo-Göran; Wilson, Elizabeth M.; Strom, Stephen C.; Grompe, Markus

    2013-01-01

    Objective Rodents are poor model for human hyperlipidemias because total cholesterol and low density lipoprotein levels are very low on a normal diet. Lipoprotein metabolism is primarily regulated by hepatocytes and we therefore assessed whether chimeric mice extensively repopulated with human cells can model human lipid and bile acid metabolism. Design FRG [Fah(−/−)Rag2(−/−)Il2rg(−/−)]) mice were repopulated with primary human hepatocytes. Serum lipoprotein lipid composition and distribution (VLDL, LDL, and HDL) was analyzed by size exclusion chromatography. Bile was analyzed by LC-MS or by GC-MS. RNA expression levels were measured by quantitative RT-PCR. Results Chimeric mice displayed increased LDL and VLDL fractions and a lower HDL fraction compared to wild type, thus significantly shifting the ratio of LDL/HDL towards a human profile. Bile acid analysis revealed a human-like pattern with high amounts of cholic acid and deoxycholic acid (DCA). Control mice had only taurine-conjugated bile acids as expcted, but highly repopulated mice had glycine-conjugated cholic acid as found in human bile. RNA levels of human genes involved in bile acid synthesis including CYP7A1, and CYP27A1 were significantly upregulated as compared to human control liver. However, administration of recombinant hFGF19 restored human CYP7A1 levels to normal. Conclusion Humanized-liver mice showed a typical human lipoprotein profile with LDL as the predominant lipoprotein fraction even on a normal diet. The bile acid profile confirmed presence of an intact enterohepatic circulation. Although bile acid synthesis was deregulated in this model, this could be fully normalized by FGF19 administration. Taken together these data indicate that chimeric FRG-mice are a useful new model for human lipoprotein and bile-acid metabolism. PMID:24223822

  18. Lipoprotein-mediated distribution of N-aspartyl chlorin-E6 in the mouse.

    PubMed

    Kessel, D; Whitcomb, K L; Schulz, V

    1992-07-01

    The localization of many photosensitizing agents has been attributed to distribution of low density lipoprotein (LDL)-bound drug as a function of the relative numbers of LDL receptors in different tissues. While the chlorin derivative NPe6 is a potent photosensitizing agent in the mouse, it binds mainly to mouse plasma high density lipoproteins (HDL) and albumin, with only 1% bound to LDL. This pattern suggests only a minor role for the LDL-receptor pathway with regard to N-aspartyl chlorin e6 (NPe6) biodistribution. Moreover, patterns of accumulation of radioactive NPe6, LDL and HDL in murine tissues are consistent with the suggestion that distribution of NPe6 to different tissues cannot be explained on the basis of an LDL-mediated mechanism. PMID:1508982

  19. The role of lipoprotein receptors on the physiological function of APP.

    PubMed

    Wagner, Timo; Pietrzik, Claus U

    2012-04-01

    In this review, we will primarily focus on the role of members of the low-density lipoprotein receptor (LDL-R) family that are involved in trafficking and processing of the amyloid precursor protein (APP). We will discuss the role of the LDL-receptor family members, low-density lipoprotein receptor-related protein 1 (LRP1), LRP1b, apolipoprotein E receptor 2, sortilin-related receptor (SorLA/LR11) and megalin/LRP2 on the physiological function of APP and its cellular localization. Additionally, we will focus on adaptor proteins that have been shown to influence the physiological function of LDL-R family members in combination with APP processing. The results in this review emphasize that the physiological function of APP cannot be explained by the focus on the APP protein alone but rather in combination with various direct or indirect interaction partners within the cellular environment. PMID:21947084

  20. Jupiter's Gossamer Rings Explained.

    NASA Astrophysics Data System (ADS)

    Hamilton, D. P.

    2003-05-01

    Over the past several years, Galileo measurements and groundbased imaging have drastically improved our knowledge of Jupiter's faint ring system. We now recognize that the ring consists of four components: a main ring 7000km wide, whose inner edge blossoms into a vertically-extended halo, and a pair of more tenuous Gossamer rings, one associated with each of the small moons Thebe and Amalthea. When viewed edge on, the Gossamer rings appear as diaphanous disks whose thicknesses agree with the vertical excursions of the inclined satellites from the equatorial plane. In addition, the brightness of each Gossamer ring drops off sharply outside the satellite orbits. These correlations allowed Burns etal (1999, Science, 284, 1146) to argue convincingly that the satellites act as sources of the dusty ring material. In addition, since most material is seen inside the orbits of the source satellites, an inwardly-acting dissipative force such as Poynting-Robertson drag is implicated. The most serious problem with this simple and elegant picture is that it is unable to explain the existence of a faint swath of material that extends half a jovian radius outward from Thebe. A key constraint is that this material has the same thickness as the rest of the Thebe ring. In this work, we identify the mechanism responsible for the outward extension: it is a shadow resonance, first investigated by Horanyi and Burns (1991, JGR, 96, 19283). When a dust grain enters Jupiter's shadow, photoelectric processes shut down and the grain's electric charge becomes more negative. The electromagnetic forces associated with the varying charge cause periodic oscillations in the orbital eccentricity and semimajor axis as the orbital pericenter precesses. This results in a ring which spreads both inward and outward of its source satellite while preserving its vertical thickness - just as is observed for the Thebe ring. Predictions of the model are: i) gaps of micron-sized material interior to Thebe and

  1. Correlation of Serum Lipoprotein Ratios with Insulin Resistance in Infertile Women with Polycystic Ovarian Syndrome: A Case Control Study

    PubMed Central

    Ghaffarzad, Aisa; Amani, Reza; Mehrzad Sadaghiani M.D.3, Mahzad; Darabi, Masoud; Cheraghian, Bahman

    2016-01-01

    Background Dyslipidemia and insulin resistance (IR), occurring in most infertile women with polycystic ovarian syndrome (PCOS), increase the risk of cardiovascular disease (CVD) and type 2 diabetes. This study aimed to assess the relationships between lipoprotein ratios and IR in PCOS women. Materials and Methods Thirty six infertile women with PCOS selected based on Androgen Excess Society (AES) criteria and 29 healthy women matched for age were recruited to this case-control study. After physical measurements, fasting serum glucose (Glu), insulin and lipid profile levels [triglycerides (TGs), total cholesterol (TC), low-density lipoproteincholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C)] were measured, while lipoprotein ratios (TC/HDL-C, LDL-C/HDL-C, TG/HDL-C) were calculated. IR was also calculated using homeostasis model assessment (HOMA)-IR. The optimal cutoffs of lipoprotein ratios in relation to HOMA-IR were calculated based on the Receiver Operating Characteristics (ROC) curve analysis using the area under curve (AUC). Results Waist circumference (WC), insulin levels, HOMA-IR, TG levels, and all lipoprotein ratios were significantly higher, while HDL-C was lower in PCOS group as compared to healthy controls. All lipoprotein ratios, TG levels, and WC are significantly correlated with insulin levels and HOMA-IR. Among lipoprotein ratios, the highest AUC of the ROC belonged to TG/HDL-C ratio with sensitivity of 63.6% and specificity of 84.4% (TG/HDL-C>3.19) as a marker of IR in infertile PCOS women. Conclusion Lipoprotein ratios, particularly TG/HDL-C, are directly correlated with insulin levels and can be used as a marker of IR (HOMA-IR) in infertile PCOS patients. PMID:27123197

  2. Impact of baseline lipoprotein and C-reactive protein levels on coronary atheroma regression following high-intensity statin therapy.

    PubMed

    Puri, Rishi; Nissen, Steven E; Shao, Mingyuan; Uno, Kiyoko; Kataoka, Yu; Kapadia, Samir R; Tuzcu, E Murat; Nicholls, Stephen J

    2014-11-15

    Guidelines now recommend high-intensity statin therapy in all patients with proven atherosclerotic disease. Yet the impact of baseline lipoprotein and C-reactive protein (CRP) levels on measures of disease regression to this therapy are unknown. The aim of this study was to test the hypothesis that high-intensity statin therapy causes equivalent degrees of coronary atheroma regression irrespective of baseline lipoprotein and CRP levels. In 8 prospective randomized trials using serial coronary intravascular ultrasound, 1,881 patients who maintained or switched to 18- to 24 months of high-intensity statin therapy (rosuvastatin 40 mg or atorvastatin 80 mg) were stratified according to baseline lipoprotein and CRP levels. Changes in coronary percentage atheroma volume (PAV) and total atheroma volume (TAV) were evaluated. High-intensity statin therapy produced significant reductions from baseline in low-density lipoprotein cholesterol by 38.4%, non-high-density lipoprotein (HDL) cholesterol by 33.6%, triglycerides by 13.1%, and CRP by 33.3%, while increasing HDL cholesterol by 11.7% (p <0.001 for all). This was associated with regression of PAV by 0.7% and of TAV by 8.2 mm(3) (p <0.001 for both). No significant differences of changes in PAV and TAV were observed across baseline quintiles of low-density lipoprotein cholesterol, HDL cholesterol, non-HDL cholesterol, triglycerides, or CRP. Moreover, across all measured lipoproteins and CRP, most patients demonstrated plaque regression (defined as any change from baseline in PAV or TAV <0). In conclusion, high-intensity statin therapy attenuated the natural progression of coronary atherosclerosis in all strata of patients with coronary artery disease irrespective of baseline lipoprotein or CRP levels. These findings provide support for the latest United States guideline recommendations for the broad use of high-intensity statin therapy in all patients with atherosclerosis, regardless of baseline lipid status. PMID:25282317

  3. Enterococcus faecalis Glycolipids Modulate Lipoprotein-Content of the Bacterial Cell Membrane and Host Immune Response

    PubMed Central

    Otto, Andreas; Sava, Irina G.; Wobser, Dominique; Bao, Yinyin; Hese, Katrin; Broszat, Melanie; Henneke, Philipp; Becher, Dörte; Huebner, Johannes

    2015-01-01

    In this study, we investigated the impact of the cell membrane composition of E. faecalis on its recognition by the host immune system. To this end, we employed an E. faecalis deletion mutant (ΔbgsA) that does not synthesize the major cell membrane glycolipid diglycosyl-diacylglycerol (DGlcDAG). Proteomic analysis revealed that 13 of a total of 21 upregulated surface-associated proteins of E. faecalis ΔbgsA were lipoproteins. This led to a total lipoprotein content in the cell membrane of 35.8% in ΔbgsA compared to only 9.4% in wild-type bacteria. Increased lipoprotein content strongly affected the recognition of ΔbgsA by mouse macrophages in vitro with an increased stimulation of TNF-α production by heat-fixed bacteria and secreted antigens. Inactivation of the prolipoprotein diacylglycerol transferase (lgt) in ΔbgsA abrogated TNF-α induction by a ΔbgsA_lgt double mutant indicating that lipoproteins mediate increased activation of mouse macrophages by ΔbgsA. Heat-fixed ΔbgsA bacteria, culture supernatant, or cell membrane lipid extract activated transfected HEK cells in a TLR2-dependent fashion; the same was not true of wild-type bacteria. In mice infected intraperitoneally with a sublethal dose of E. faecalis we observed a 70% greater mortality in mice infected with ΔbgsA compared with wild-type-infected mice. Increased mortality due to ΔbgsA infection was associated with elevated plasma levels of the inflammatory cytokines TNF-α, IL-6 and MIP-2. In summary, our results provide evidence that an E. faecalis mutant lacking its major bilayer forming glycolipid DGlcDAG upregulates lipoprotein expression leading to increased activation of the host innate immune system and virulence in vivo. PMID:26172831

  4. [Lack of association between the S447X variant of the lipoprotein lipase gene and plasma lipids. A preliminary study].

    PubMed

    Zambrano Morales, Mariana; Fernández Salgado, Erika; Balzán Urdaneta, Ligia; Labastidas, Neila; Aranguren-Méndez, José; Connell, Lissette; Molero Paredes, Tania; Rojas, Alicia; Panunzio, Amelia

    2014-06-01

    The increase in lipid plasma values is an important cardiovascular risk factor. Lipoprotein lipase (LPL) plays an important role in the lipoprotein metabolism and metabolic and genetic factors may influence its levels and functions. The S447X variant of the lipoprotein lipase gene is associated with changes in plasma lipids in different populations. The objective of this research was to analyze the S447X variant of the LPL gene and its relation with plasma lipids of individuals in Zulia state, Venezuela. With this purpose, we studied 75 individuals (34 men and 41 women) between 20 and 60 years of age. Each subject had a medical history which included family history, anthropometric characteristics, nutritional status evaluation and biochemical tests. Genomic DNA was extracted for the molecular study and the polymerase chain reaction was used, followed by enzyme digestion, for restriction fragments length polymorphisms using the Hinf I enzyme. The individuals studied had normal levels of blood glucose, triglycerides, total cholesterol and low density lipoproteins (LDL-C) and slightly decreased levels of high density lipoproteins (HDL-C). The genotypic distribution of the LPL gene S447X variant in the studied population was 90.6% for the homozygous genotype SS447 and 9.4% for the heterozygote SX447. The genotype 447XX was not identified. The population was found in Hardy Weinberg genetic equilibrium. No association between the S447X polymorphism of lipoprotein lipase gene and plasma lipids was observed. PMID:24974629

  5. Improved cholesterol phenotype analysis by a model relating lipoprotein life cycle processes to particle size[S

    PubMed Central

    van Schalkwijk, Daniël B.; de Graaf, Albert A.; van Ommen, Ben; van Bochove, Kees; Rensen, Patrick C. N.; Havekes, Louis M.; van de Pas, Niek C. A.; Hoefsloot, Huub C. J.; van der Greef, Jan; Freidig, Andreas P.

    2009-01-01

    Increased plasma cholesterol is a known risk factor for cardiovascular disease. Lipoprotein particles transport both cholesterol and triglycerides through the blood. It is thought that the size distribution of these particles codetermines cardiovascular disease risk. New types of measurements can determine the concentration of many lipoprotein size-classes but exactly how each small class relates to disease risk is difficult to clear up. Because relating physiological process status to disease risk seems promising, we propose investigating how lipoprotein production, lipolysis, and uptake processes depend on particle size. To do this, we introduced a novel model framework (Particle Profiler) and evaluated its feasibility. The framework was tested using existing stable isotope flux data. The model framework implementation we present here reproduced the flux data and derived lipoprotein size pattern changes that corresponded to measured changes. It also sensitively indicated changes in lipoprotein metabolism between patient groups that are biologically plausible. Finally, the model was able to reproduce the cholesterol and triglyceride phenotype of known genetic diseases like familial hypercholesterolemia and familial hyperchylomicronemia. In the future, Particle Profiler can be applied for analyzing detailed lipoprotein size profile data and deriving rates of various lipolysis and uptake processes if an independent production estimate is given. PMID:19515990

  6. Seasonal variation in plasma lipids, lipoproteins, apolipoprotein A-I and vitellogenin in the freshwater turtle, Chrysemys picta.

    PubMed

    Duggan, A; Paolucci, M; Tercyak, A; Gigliotti, M; Small, D; Callard, I

    2001-09-01

    An analysis of plasma lipids and lipoprotein fractions was performed over the course of the annual ovarian cycle of the female turtle, Chrysemys picta. Determinations of total plasma triglycerides, cholesterol, vitellogenin and apolipoprotein A-I (apoA-I) were made. The lipid and protein composition of the lipoprotein fractions [very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) and very high density lipoprotein (VHDL)] were also observed over the same period. Plasma triglyceride and vitellogenin levels were significantly increased in the spring preovulatory period and fall recrudescent phase. Total plasma cholesterol levels were significantly elevated only at the onset of the fall recrudescent phase and apoA-I levels were highest during the postoviposition/ovarian arrest phase. The triglyceride content of VLDL was highest in preovulatory animals and there were apparent seasonal changes in the expression of apoA-I and apoE of HDL/VHDL. We conclude that the coordinate regulation of lipids and protein contributes to seasonal ovarian growth and clearance of lipids from plasma, both of which are most likely under hormonal control. PMID:11544071

  7. 21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of...

  8. 21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of...

  9. 21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of...

  10. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Low-density lipoprotein immunological test system....5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein...

  11. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Low-density lipoprotein immunological test system....5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein...

  12. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Low-density lipoprotein immunological test system....5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein...

  13. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Low-density lipoprotein immunological test system....5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein...

  14. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Low-density lipoprotein immunological test system....5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein...

  15. Fish plasma lipoproteins--comparative observations in serranides and sparides.

    PubMed

    Santulli, A; Cusenza, L; Modica, A; Curatolo, A; D'Amelio, V

    1991-01-01

    1. Diet, time from last feeding, temperature, season and sexual stage are some of the factors influencing the lipoprotein pattern. 2. Keeping these factors constant species-specific differences observed among lipoprotein patterns of Sparus aurata, Puntazzo puntazzo, Diplodus sargus, Diplodus vulgaris and Dicentrarchus labrax are discussed. 3. Feeding habits and therefore lipid absorption and the rate of lipoprotein maturation process are the factors determining the observed differences. PMID:1764905

  16. Outer membrane lipoprotein biogenesis: Lol is not the end.

    PubMed

    Konovalova, Anna; Silhavy, Thomas J

    2015-10-01

    Bacterial lipoproteins are lipid-anchored proteins that contain acyl groups covalently attached to the N-terminal cysteine residue of the mature protein. Lipoproteins are synthesized in precursor form with an N-terminal signal sequence (SS) that targets translocation across the cytoplasmic or inner membrane (IM). Lipid modification and SS processing take place at the periplasmic face of the IM. Outer membrane (OM) lipoproteins take the localization of lipoproteins (Lol) export pathway, which ends with the insertion of the N-terminal lipid moiety into the inner leaflet of the OM. For many lipoproteins, the biogenesis pathway ends here. We provide examples of lipoproteins that adopt complex topologies in the OM that include transmembrane and surface-exposed domains. Biogenesis of such lipoproteins requires additional steps beyond the Lol pathway. In at least one case, lipoprotein sequences reach the cell surface by being threaded through the lumen of a beta-barrel protein in an assembly reaction that requires the heteropentomeric Bam complex. The inability to predict surface exposure reinforces the importance of experimental verification of lipoprotein topology and we will discuss some of the methods used to study OM protein topology. PMID:26370942

  17. Ethnic differences in serum lipids and lipoproteins in overweight/obese African-American and white American women with pre-diabetes: significance of NMR-derived lipoprotein particle concentrations and sizes

    PubMed Central

    Gaillard, Trudy; Osei, Kwame

    2016-01-01

    Objective African-American women (AAW) suffer disproportionately from higher rates of cardiovascular disease (CVD) mortality compared with white American women (WAW), despite favorable lipid and lipoprotein profile. Therefore, we used nuclear magnetic resonance (NMR) to examine lipoprotein particle concentrations and sizes in overweight/obese AAW and WAW with pre-diabetes. Participants and methods We studied 69 AAW and 41 WAW, with mean age 46.5±11.3 years and body mass index (BMI) 37.8±6.4 kg/m2. All participants completed standard oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIVGTT). Insulin sensitivity (Si) was calculated using MINIMOD method. Body composition was assessed using dual-energy X-ray absorptiometry (DEXA). Fasting blood was obtained for traditional lipids/lipoproteins and NMR-derived lipoprotein particle sizes and concentrations. Results We found that AAW with pre-diabetes were more obese (BMI 38.8±6.7 vs 36.0±5.4 kg/m2, p=0.02) than WAW. Mean Si was not significantly different. However, the mean serum triglycerides were lower, whereas the high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (Apo A1) were significantly higher in AAW versus WAW. The large HDL particle concentration (6.1±3.1 vs 4.6±3.1 µmol/L, p=0.02) was significantly higher in AAW versus WAW. Mean total very low-density lipoprotein (VLDL) particle concentration was lower in AAW versus WAW (39.9±24.4 vs 59.2±25.6 nmol/L, p≤0.001). While mean total LDL particle concentrations were not different, mean small LDL particle concentrations were lower in AAW versus WAW (538.8±294.1 vs 638.4±266 nmol/L, p=0.07). Conclusions We found a more favorable NMR-derived lipoprotein profile in AAW that extends the traditional antiatherogenic lipid/lipoprotein profiles. Clinically, these favorable lipid/lipoprotein profiles cannot explain the paradoxically higher CVD mortality in AAW than WAW and warrant further

  18. Binding of Salmonella typhimurium lipopolysaccharides to rat high-density lipoproteins.

    PubMed Central

    Munford, R S; Hall, C L; Dietschy, J M

    1981-01-01

    These studies were undertaken to investigate the binding of gram-negative bacterial lipopolysaccharides (LPS) to high-density lipoproteins (HDL) of rat plasma. Purified Salmonella typhimurium LPS, intrinsically labeled with [3H]-galactose, bound rapidly in vitro to isolated rat HDL. Maximal binding of LPS to HDL occurred when LPS and HDL were incubated with lipoprotein-free plasma (rho greater than 1.21 g/ml). Since LPS, when purified, form large aggregates, we tested the hypothesis that disaggregation of LPS enhances LPS-HDL binding. We found that calcium chloride (1 mM), an agent which prevents LPS disaggregation, inhibited binding of LPS to HDL by interfering with the modification of LPS by lipoprotein-free plasma. Conversely, sodium deoxycholate (0.15 g/dl), which disaggregates LPS, greatly increased binding of LPS to HDL in the absence of lipoprotein-free plasma. Analysis of labeled LPS by sodium deodecyl sulfate-polyacrylamide gel electrophoresis showed only minor differences in the sizes of LPS molecules before and after binding to HDL, suggesting that chemical modification of LPS is not required for binding. The results provide evidence that disaggregation increases the binding of LPS to HDL. PMID:7037642

  19. Effect of Extended-Release Niacin on High-Density Lipoprotein (HDL) Functionality, Lipoprotein Metabolism, and Mediators of Vascular Inflammation in Statin-Treated Patients

    PubMed Central

    Yadav, Rahul; Liu, Yifen; Kwok, See; Hama, Salam; France, Michael; Eatough, Ruth; Pemberton, Phil; Schofield, Jonathan; Siahmansur, Tarza J; Malik, Rayaz; Ammori, Basil A; Issa, Basil; Younis, Naveed; Donn, Rachelle; Stevens, Adam; Durrington, Paul; Soran, Handrean

    2015-01-01

    Background The aim of this study was to explore the influence of extended-release niacin/laropiprant (ERN/LRP) versus placebo on high-density lipoprotein (HDL) antioxidant function, cholesterol efflux, apolipoprotein B100 (apoB)-containing lipoproteins, and mediators of vascular inflammation associated with 15% increase in high-density lipoprotein cholesterol (HDL-C). Study patients had persistent dyslipidemia despite receiving high-dose statin treatment. Methods and Results In a randomized double-blind, placebo-controlled, crossover trial, we compared the effect of ERN/LRP with placebo in 27 statin-treated dyslipidemic patients who had not achieved National Cholesterol Education Program-ATP III targets for low-density lipoprotein cholesterol (LDL-C). We measured fasting lipid profile, apolipoproteins, cholesteryl ester transfer protein (CETP) activity, paraoxonase 1 (PON1) activity, small dense LDL apoB (sdLDL-apoB), oxidized LDL (oxLDL), glycated apoB (glyc-apoB), lipoprotein phospholipase A2 (Lp-PLA2), lysophosphatidyl choline (lyso-PC), macrophage chemoattractant protein (MCP1), serum amyloid A (SAA) and myeloperoxidase (MPO). We also examined the capacity of HDL to protect LDL from in vitro oxidation and the percentage cholesterol efflux mediated by apoB depleted serum. ERN/LRP was associated with an 18% increase in HDL-C levels compared to placebo (1.55 versus 1.31 mmol/L, P<0.0001). There were significant reductions in total cholesterol, triglycerides, LDL cholesterol, total serum apoB, lipoprotein (a), CETP activity, oxLDL, Lp-PLA2, lyso-PC, MCP1, and SAA, but no significant changes in glyc-apoB or sdLDL-apoB concentration. There was a modest increase in cholesterol efflux function of HDL (19.5%, P=0.045), but no change in the antioxidant capacity of HDL in vitro or PON1 activity. Conclusions ERN/LRP reduces LDL-associated mediators of vascular inflammation, but has varied effects on HDL functionality and LDL quality, which may counter its HDL

  20. Lipoprotein Receptors Redundantly Participate in Entry of Hepatitis C Virus

    PubMed Central

    Ono, Chikako; Uemura, Kentaro; Kawachi, Yukako; Shiokawa, Mai; Mori, Hiroyuki; Wada, Masami; Shima, Ryoichi; Okamoto, Toru; Hiraga, Nobuhiko; Suzuki, Ryosuke; Chayama, Kazuaki; Wakita, Takaji; Matsuura, Yoshiharu

    2016-01-01

    Scavenger receptor class B type 1 (SR-B1) and low-density lipoprotein receptor (LDLR) are known to be involved in entry of hepatitis C virus (HCV), but their precise roles and their interplay are not fully understood. In this study, deficiency of both SR-B1 and LDLR in Huh7 cells was shown to impair the entry of HCV more strongly than deficiency of either SR-B1 or LDLR alone. In addition, exogenous expression of not only SR-B1 and LDLR but also very low-density lipoprotein receptor (VLDLR) rescued HCV entry in the SR-B1 and LDLR double-knockout cells, suggesting that VLDLR has similar roles in HCV entry. VLDLR is a lipoprotein receptor, but the level of its hepatic expression was lower than those of SR-B1 and LDLR. Moreover, expression of mutant lipoprotein receptors incapable of binding to or uptake of lipid resulted in no or slight enhancement of HCV entry in the double-knockout cells, suggesting that binding and/or uptake activities of lipid by lipoprotein receptors are essential for HCV entry. In addition, rescue of infectivity in the double-knockout cells by the expression of the lipoprotein receptors was not observed following infection with pseudotype particles bearing HCV envelope proteins produced in non-hepatic cells, suggesting that lipoproteins associated with HCV particles participate in the entry through their interaction with lipoprotein receptors. Buoyant density gradient analysis revealed that HCV utilizes these lipoprotein receptors in a manner dependent on the lipoproteins associated with HCV particles. Collectively, these results suggest that lipoprotein receptors redundantly participate in the entry of HCV. PMID:27152966

  1. Methylation at CPT1A locus is associated with lipoprotein subfraction profiles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lipoprotein subfractions help discriminate cardiometabolic disease risk. Genetic loci validated as associating with lipoprotein measures do not account for a large proportion of the individual variation in lipoprotein measures. We hypothesized that DNA methylation levels across the genome contribute...

  2. Ambient Air Pollution and Lipoprotein-Associated Phospholipase A2 in Survivors of Myocardial Infarction

    PubMed Central

    Hampel, Regina; Baumgärtner, Zita; Rückerl, Regina; Greven, Sonja; Koenig, Wolfgang; Peters, Annette; Schneider, Alexandra

    2011-01-01

    Background: Increasing evidence suggests a proatherogenic role for lipoprotein-associated phospholipase A2 (Lp-PLA2). A meta-analysis of published cohorts has shown that Lp-PLA2 is an independent predictor of coronary heart disease events and stroke. Objective: In this study, we investigated whether the association between air pollution and cardiovascular disease might be partly explained by increased Lp-PLA2 mass in response to exposure. Methods: A prospective longitudinal study of 200 patients who had had a myocardial infarction was performed in Augsburg, Germany. Up to six repeated clinical examinations were scheduled every 4–6 weeks between May 2003 and March 2004. Supplementary to the multicenter AIRGENE protocol, we assessed repeated plasma Lp-PLA2 concentrations. Air pollution data from a fixed monitoring site representing urban background concentrations were collected. We measured hourly means of particle mass [particulate matter (PM) < 10 µm (PM10) and PM < 2.5 µm (PM2.5) in aerodynamic diameter] and particle number concentrations (PNCs), as well as the gaseous air pollutants carbon monoxide (CO), sulfur dioxide (SO2), ozone (O3), nitric oxide (NO), and nitrogen dioxide (NO2). Data were analyzed using mixed models with random patient effects. Results: Lp-PLA2 showed a positive association with PM10, PM2.5, and PNCs, as well as with CO, NO2, NO, and SO2 4–5 days before blood withdrawal (lag 4–5). A positive association with O3 was much more immediate (lag 0). However, inverse associations with some pollutants were evident at shorter time lags. Conclusion: These preliminary findings should be replicated in other study populations because they suggest that the accumulation of acute and subacute effects or the chronic exposure to ambient particulate and gaseous air pollution may result in the promotion of atherosclerosis, mediated, at least in part, by increased levels of Lp-PLA2. PMID:21356620

  3. Subcellular distribution of apolipoprotein E along the lipoprotein synthetic pathway of rat liver

    SciTech Connect

    Cole, T.G.; Stockhausen, D.C.

    1986-03-01

    Apolipoprotein E (apoE) is synthesized by the liver and is secreted as a component of VLDL. To define the intracellular locations of apoE, liver from 10 nonfasted male rats were removed and subcellular organelles prepared by differential pelleting through sucrose gradients. Mass of apoE was measured by radioimmunoassay. Approximately 10% of total hepatic apoE was recovered in rough endoplasmic reticulum (RER), smooth endoplasmic reticulum (SER) and Golgi fractions. Concentrations of apoE (ng/mg protein) were: homogenate, 302 +/- 59; RER, 653 +/- 251; SER, 1250 +/- 471; Golgi, 11,044 +/- 4291. Total apoE content of each reaction (..mu..g/organelle) was: homogenate (whole liver), 517 +/- 103; RER, 15 +/- 3; SER, 9 +/- 3; Golgi, 28 +/- 8. These data indicate that along the putative pathway of lipoprotein synthesis (RER->SER->Golgi), apoE concentration increases in each successive organelle and that flux of apoE is apparently most rapid through SER. Furthermore, the majority of apoE in the rat liver is apparently not directly associated with the lipoprotein synthetic pathway and may be associated with internalized lipoproteins or may be involved in non-lipoprotein related functions.

  4. Lipoprotein-Associated Oxidative Stress: A New Twist to the Postprandial Hypothesis

    PubMed Central

    Le, Ngoc-Anh

    2014-01-01

    Oxidative stress is recognized as one of the primary processes underlying the initiation and progression of atherosclerotic vascular disease. Under physiological conditions, the balance between reactive oxygen species (ROS) generation and ROS scavenging is tightly controlled. As part of normal cellular metabolism, regulated oxidative stress is responsible for a variety of cellular responses. Excess generation of ROS that could not be compensated by antioxidant system has been suggested to be responsible for a number of pathological conditions. Due to their short biological half-lives, direct measurement of ROS is not available and surrogate measures are commonly used. Plasma lipoproteins, by virtue of their close interactions with endothelial cells in the vasculature and the susceptibility of their surface lipids to oxidative modification, are perfect biological sensors of oxidative stress in the arterial wall. In particular, with each consumed meal, triglyceride-rich lipoproteins, secreted by the intestine into the circulation, are responsible for the delivery of 20–40 grams of fat to the peripheral tissues. This flux of dietary lipids is accompanied by concomitant increases in glucose, insulin and other meal-associated metabolites. The contribution of postprandial lipemia to the pathogenesis of atherosclerosis has been previously suggested by several lines of investigation. We have extended this hypothesis by demonstrating the acute generation of oxidative epitopes on plasma lipoproteins as well as transient changes in the oxidative susceptibility of plasma lipoproteins. PMID:25548897

  5. Imaging of hepatic low density lipoprotein receptors by radionuclide scintiscanning in vivo.

    PubMed

    Huettinger, M; Corbett, J R; Schneider, W J; Willerson, J T; Brown, M S; Goldstein, J L

    1984-12-01

    The low density lipoprotein (LDL) receptor mediates the cellular uptake of plasma lipoproteins that are derived from very low density lipoproteins (VLDL). Most of the functional LDL receptors in the body are located in the liver. Here, we describe a radionuclide scintiscanning technique that permits the measurement of LDL receptors in the livers of intact rabbits. 123I-labeled VLDL were administered intravenously, and scintigraphic images of the liver and heart were obtained at intervals thereafter. In seven normal rabbits, radioactivity in the liver increased progressively between 1 and 20 min after injection, while radioactivity in the heart (reflecting that in plasma) decreased concomitantly. In Watanabe-heritable hyperlipidemic rabbits, which lack LDL receptors on a genetic basis, there was little uptake of 123I-labeled VLDL into the liver and little decrease in cardiac radioactivity during this interval. These findings demonstrate that the LDL receptor is necessary for the hepatic uptake of VLDL-derived lipoproteins in the rabbit. Two conditions that diminish hepatic LDL receptor activity, cholesterol-feeding and prolonged fasting, also reduced the uptake of 123I-labeled VLDL in the liver as measured by scintiscanning. The data suggest that radionuclide scintiscanning can be used as a noninvasive method to quantify the number of LDL receptors expressed in the liver in vivo. PMID:6594702

  6. Lipoprotein glomerulopathy: a case report of a rare disease in a Brazilian child.

    PubMed

    Pêgas, Karla Lais; Rohde, Roberta; Garcia, Clotilde Druck; Bittencourt, Viviane de Barros; Keitel, Elizete; Poloni, José Antonio Tesser; Cambruzzi, Eduardo

    2014-01-01

    Lipoprotein glomerulopathy (LPG) is a rare autosomal recessive glomerulopathy associated with the deposition of lipoprotein thrombi in the capillary lumina due to apoE gene mutations. Abnormal plasma lipoprotein profile and marked increase in serum apoliprotein E (apoE) are characteristic clinical data. The compromised patients can present nephrotic syndrome, hematuria, and progressive renal failure. Herein, the authors present the first described case of LPG in a Brazilian male patient, 11 years, who presented with a steroid-resistant nephrotic syndrome. Renal function was normal. Kidney biopsy showed markedly enlarged glomerulus, with dilated capillary loops and weak eosinophilic lipoprotein thrombi in the capillary lumina. Interstitium, tubules, arteries, and veins showed normal histologic aspect. Genotypic study for the apoE gene showed the presence of the alleles E3 and E4. The diagnosis of LPG was then performed. The patient received lipid-lowering treatment. After 2 years of follow-up, renal function is gradually decreasing, with persisting heavy proteinuria, despite a marked decrease in serum cholesterol and triglycerides levels. PMID:24676620

  7. Lipoproteins and their subfractions in psoriatic arthritis: identification of an atherogenic profile with active joint disease

    PubMed Central

    Jones, S; Harris, C; Lloyd, J; Stirling, C; Reckless, J; McHugh, N

    2000-01-01

    OBJECTIVES—(a) To characterise the lipid profile in psoriatic arthritis and investigate whether there are similarities to the dyslipoproteinaemia reported in rheumatoid arthritis and other inflammatory forms of joint disease; (b) to investigate whether there is an atherogenic lipid profile in psoriatic arthritis, which may have a bearing on mortality.
METHODS—Fasting lipids, lipoproteins, and their subfractions were measured in 50 patients with psoriatic arthritis and their age and sex matched controls.
RESULTS—High density lipoprotein cholesterol (HDL cholesterol) and its third subfraction, HDL3 cholesterol, were significantly reduced and the most dense subfraction of low density lipoprotein (LDL), LDL3, was significantly increased in the patients with psoriatic arthritis. Twenty patients with active synovitis had significantly lower total cholesterol, LDL cholesterol, and HDL3 cholesterol than their controls. 25% of the patients with psoriatic arthritis had raised Lp(a) lipoprotein levels (>300 mg/l) compared with 19% of controls, but this was not statistically significant.
CONCLUSION—Raised levels of LDL3 and low levels of HDL cholesterol are associated with coronary artery disease. Such an atherogenic profile in a chronic inflammatory form of arthritis is reported, which may be associated with accelerated mortality.

 PMID:11053070

  8. Intermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea

    PubMed Central

    Drager, Luciano F.; Li, Jianguo; Shin, Mi-Kyung; Reinke, Christian; Aggarwal, Neil R.; Jun, Jonathan C.; Bevans-Fonti, Shannon; Sztalryd, Carole; O'Byrne, Sheila M.; Kroupa, Olessia; Olivecrona, Gunilla; Blaner, William S.; Polotsky, Vsevolod Y.

    2012-01-01

    Aims Delayed lipoprotein clearance is associated with atherosclerosis. This study examined whether chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnoea (OSA), can lead to hyperlipidaemia by inhibiting clearance of triglyceride rich lipoproteins (TRLP). Methods and results Male C57BL/6J mice on high-cholesterol diet were exposed to 4 weeks of CIH or chronic intermittent air (control). FIO2 was decreased to 6.5% once per minute during the 12 h light phase in the CIH group. After the exposure, we measured fasting lipid profile. TRLP clearance was assessed by oral gavage of retinyl palmitate followed by serum retinyl esters (REs) measurements at 0, 1, 2, 4, 10, and 24 h. Activity of lipoprotein lipase (LpL), a key enzyme of lipoprotein clearance, and levels of angiopoietin-like protein 4 (Angptl4), a potent inhibitor of the LpL activity, were determined in the epididymal fat pads, skeletal muscles, and heart. Chronic intermittent hypoxia induced significant increases in levels of total cholesterol and triglycerides, which occurred in TRLP and LDL fractions (P< 0.05 for each comparison). Compared with control mice, animals exposed to CIH showed increases in REs throughout first 10 h after oral gavage of retinyl palmitate (P< 0.05), indicating that CIH inhibited TRLP clearance. CIH induced a >5-fold decrease in LpL activity (P< 0.01) and an 80% increase in Angptl4 mRNA and protein levels in the epididymal fat, but not in the skeletal muscle or heart. Conclusions CIH decreases TRLP clearance and inhibits LpL activity in adipose tissue, which may contribute to atherogenesis observed in OSA. PMID:21478490

  9. The Impact of Cardiorespiratory Fitness on Age-Related Lipids and Lipoproteins

    PubMed Central

    Park, Yong-Moon Mark; Sui, Xuemei; Liu, Junxiu; Zhou, Haiming; Kokkinos, Peter F.; Lavie, Carl J.; Hardin, James W.; Blair, Steven N.

    2015-01-01

    Background Evidence on the effect of cardiorespiratory fitness (CRF) on age-related longitudinal changes of lipids and lipoproteins is scarce. Objectives This study sought to assess the longitudinal, aging trajectory of lipids and lipoproteins for the life course in adults, and to determine whether CRF modifies the age-associated trajectory of lipids and lipoproteins. Methods Data came from 11,418 men, 20 to 90 years of age, without known high cholesterol, high triglycerides, cardiovascular disease, and cancer at baseline and during follow-up from the Aerobics Center Longitudinal Study. There were 43,821 observations spanning 2 to 25 (mean 3.5) health examinations between 1970 and 2006. CRF was quantified by a maximal treadmill exercise test. Marginal models using generalized estimating equations were applied. Results Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C) presented similar inverted U-shaped quadratic trajectories with aging: gradual increases were noted until the mid-40s to early 50s, with subsequent declines (all p < 0.0001). Compared to men with higher CRF, those with lower CRF developed abnormal values earlier in life: TC (≥200 mg/dl), LDL-C (≥130 mg/dl), non-HDL-C (≥160 mg/dl), and TG/HDL-C ratio (≥3.0). Notably, abnormal values for TC and LDL-C in men with low CRF were observed around 15 years earlier than in those with high CRF. After adjusting for time-varying covariates, a significant interaction was found between age and CRF in each trajectory, indicating that CRF was more strongly associated with the aging trajectories of lipids and lipoproteins in young to middle-aged men than in older men. Conclusions Our investigation reveals a differential trajectory of lipids and lipoproteins with aging according to CRF in healthy men, and suggests that promoting increased CRF levels may help delay the development of dyslipidemia. PMID:25975472

  10. The effects of extended release niacin on lipoprotein sub-particle concentrations in HIV-infected patients.

    PubMed

    Lin, Chunrong; Grandinetti, Andrew; Shikuma, Cecilia; Souza, Scott; Parikh, Nisha; Nakamoto, Beau; Kallianpur, Kalpana J; Chow, Dominic

    2013-04-01

    With the advent of highly active antiretroviral therapy (HAART), Cardiovascular Disease (CVD) has emerged as the leading cause of death in Human Immunodeficiency Virus (HIV) infected patients. An atherogenic lipoprotein phenotype has been described in HIV- infected patients with a predominance of small, low density lipoprotein (SLDL) particles with accompanying elevated triglycerides and reduced high density lipoprotein cholesterol. This randomized controlled pilot study was conducted to evaluate the efficacy of Extended Release Niacin (ERN) in improving the lipid profile in HIV patients. A total of 17 HIV positive subjects on HAART therapy with High Density Lipoprotein Cholesterol (HDL) levels below 40mg/dl and Low Density Lipoprotein Cholesterol (LDL) below 130mg/dl were enrolled. Nine were randomized to be treated with ERN titrated from a starting level of 500mg/night and titrated to a level of 1500mg/night. Eight patients were assigned to the control arm. No placebo was used. Lipoprotein profiles of the subjects were analyzed at baseline and at the end of 12 weeks using Nuclear Magnetic Resonance (NMR) spectroscopy. At the end of 12 weeks, NMR spectroscopic analysis revealed a significant increase in overall LDL size (1.2% in ERN treated subjects vs 2.0% decrease in control patients, P=.04) and a decrease in small LDL particle concentration (17.0% in ERN treated subjects vs 21.4% increase in control patients, P=.03) in subjects receiving ERN as compared to those in the control group. Only 1 subject receiving ERN developed serious flushing which was attributed to an accidental overdose of the drug. This pilot study demonstrates that ERN therapy in HIV-infected patients with low HDL is safe and effective in improving the lipoprotein profile in these patients. PMID:23795312

  11. Lipoprotein Subfraction Cholesterol Distribution Is Proatherogenic in Women With Type 1 Diabetes and Insulin Resistance

    PubMed Central

    Maahs, David M.; Hokanson, John E.; Wang, Hong; Kinney, Gregory L.; Snell-Bergeon, Janet K.; East, Ashley; Bergman, Bryan C.; Schauer, Irene E.; Rewers, Marian; Eckel, Robert H.

    2010-01-01

    OBJECTIVE Individuals with type 1 diabetes have a less atherogenic fasting lipid profile than those without diabetes but paradoxically have increased rates of cardiovascular disease (CVD). We investigated differences in lipoprotein subfraction cholesterol distribution and insulin resistance between subjects with and without type 1 diabetes to better understand the etiology of increased CVD risk. RESEARCH DESIGN AND METHODS Fast protein liquid chromatography was used to fractionate lipoprotein cholesterol distribution in a substudy of the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study (n = 82, age 46 ± 8 years, 52% female, 49% with type 1 diabetes for 23 ± 8 years). Insulin resistance was assessed by a hyperinsulinemic-euglycemic clamp. RESULTS Among men, those with type 1 diabetes had less VLDL and more HDL cholesterol than control subjects (P < 0.05), but among women, those with diabetes had a shift in cholesterol to denser LDL, despite more statin use. Among control subjects, men had more cholesterol distributed as VLDL and LDL but less as HDL than women; however, among those with type 1 diabetes, there was no sex difference. Within sex and diabetes strata, a more atherogenic cholesterol distribution by insulin resistance was seen in men with and without diabetes, but only in women with type 1 diabetes. CONCLUSIONS The expected sex-based less atherogenic lipoprotein cholesterol distribution was not seen in women with type 1 diabetes. Moreover, insulin resistance was associated with a more atherogenic lipoprotein cholesterol distribution in all men and in women with type 1 diabetes. This lipoprotein cholesterol distribution may contribute to sex-based differences in CVD in type 1 diabetes. PMID:20393149

  12. Lifestyle intervention improves lipoprotein particle size and distribution without weight loss in obese Latino adolescents.

    PubMed

    Ryder, J R; Vega-López, S; Ortega, R; Konopken, Y; Shaibi, G Q

    2013-10-01

    Childhood obesity is associated with a pro-atherogenic phenotype contributing to increased cardiovascular disease (CVD) risk. This single-arm pilot study examined the effects of a lifestyle intervention on lipoprotein particle size and cholesterol distribution in obese Latino adolescents. Fifteen obese Latino adolescents (15.0 ± 1.0 years) completed a 12-week nutrition education and exercise intervention. Low-density lipoprotein (LDL) particle size and distribution of cholesterol in lipoprotein subclasses were determined via polyacrylamide gel electrophoresis. The intervention resulted in increases in mean LDL particle size (269.3 ± 3.4 to 271.6 ± 2.9 Å, P = 0.0003) and cholesterol in large high-density lipoprotein (HDL) subfractions (22.4 ± 11.2 to 26.8 ± 10.6% area, P = 0.007) along with decreases of cholesterol in small LDL (1.6 ± 2.0 to 0.6 ± 1.2% area, P < 0.01) and HDL subfractions (23.2 ± 9.4 to 19.0 ± 6.7% area, P = 0.05). These improvements were observed independent of changes in weight (90.7 ± 26.2 to 89.9 ± 27.8 kg, P > 0.05) and suggest that lifestyle modification in obese youth may reduce cardiovascular risk by shifting lipoprotein particle size and cholesterol distribution to a less atherogenic phenotype. PMID:23576420

  13. High-density lipoprotein subpopulations in pathologic conditions.

    PubMed

    Asztalos, Bela F; Schaefer, Ernst J

    2003-04-01

    The role of low-density lipoprotein (LDL) cholesterol in coronary artery disease (CAD) and the impact of therapeutic agents on LDL cholesterol are well established. Less is known about the role of high-density lipoprotein (HDL) cholesterol and even less about the role of the different HDL subspecies in CAD. HDL particles vary in size and density, mainly because of differences in the number of apolipoprotein (apo) particles and the amount of cholesterol ester in the core of HDL. Apo A-I is essential and, together with lipid, sufficient for the formation of HDL particles. Apo A-I-containing HDL particles play a primary role in cholesterol efflux from membranes, at least in part through interactions with the adenosine triphosphate-binding cassette transporter A1 (ABCA1). Patients with Tangier disease have mutations in the gene encoding ABCA1, which result in functionally impaired protein, a marked deficiency in HDL cholesterol, and a high risk of premature CAD. Our studies of apo A-I-containing HDL subpopulations in various patient populations reveal that patients homozygous for Tangier disease have only the pre-beta(1) HDL subspecies. Tangier heterozygotes are severely depleted in the larger alpha- and pre-alpha-mobility subspecies. Patients with low HDL cholesterol levels and those with CAD also show deficiencies in the alpha(1) and pre-alpha(1-3) HDL subspecies. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) increase the levels of the large alpha(1) and pre-alpha(1) subpopulations and decrease the level of the small alpha(3) subpopulation. Thus, atorvastatin, for example, significantly moves the distribution of HDL particles toward normal, followed by simvastatin, pravastatin, and lovastatin in decreasing order of efficiency. A new statin, rosuvastatin, produces greater increases in HDL cholesterol than atorvastatin, but its effect on HDL particle distribution is yet to be determined. PMID:12679198

  14. Hydrolysis products generated by lipoprotein lipase and endothelial lipase differentially impact THP-1 macrophage cell signalling pathways.

    PubMed

    Essaji, Yasmin; Yang, Yanbo; Albert, Carolyn J; Ford, David A; Brown, Robert J

    2013-08-01

    Macrophages express lipoprotein lipase (LPL) and endothelial lipase (EL) within atherosclerotic plaques; however, little is known about how lipoprotein hydrolysis products generated by these lipases might affect macrophage cell signalling pathways. We hypothesized that hydrolysis products affect macrophage cell signalling pathways associated with atherosclerosis. To test our hypothesis, we incubated differentiated THP-1 macrophages with products from total lipoprotein hydrolysis by recombinant LPL or EL. Using antibody arrays, we found that the phosphorylation of six receptor tyrosine kinases and three signalling nodes--most associated with atherosclerotic processes--was increased by LPL derived hydrolysis products. EL derived hydrolysis products only increased the phosphorylation of tropomyosin-related kinase A, which is also implicated in playing a role in atherosclerosis. Using electrospray ionization-mass spectrometry, we identified the species of triacylglycerols and phosphatidylcholines that were hydrolyzed by LPL and EL, and we identified the fatty acids liberated by gas chromatography-mass spectrometry. To determine if the total liberated fatty acids influenced signalling pathways, we incubated differentiated THP-1 macrophages with a mixture of the fatty acids that matched the concentrations of liberated fatty acids from total lipoproteins by LPL, and we subjected cell lysates to antibody array analyses. The analyses showed that only the phosphorylation of Akt was significantly increased in response to fatty acid treatment. Overall, our study shows that macrophages display potentially pro-atherogenic signalling responses following acute treatments with LPL and EL lipoprotein hydrolysis products. PMID:23794138

  15. Effects of extended-release niacin on lipoprotein particle size, distribution, and inflammatory markers in patients with coronary artery disease.

    PubMed

    Kuvin, Jeffrey T; Dave, Devang M; Sliney, Kathleen A; Mooney, Paula; Patel, Ayan R; Kimmelstiel, Carey D; Karas, Richard H

    2006-09-15

    In this study, niacin was added to existing therapy for 3 months in 54 subjects with stable coronary artery disease. Average total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were similar between groups. Three months of niacin treatment increased total HDL by 7.5% and decreased triglycerides by 15% compared with baseline values (p <0.005 for each), whereas total cholesterol and LDL levels remained unchanged. Addition of niacin resulted in a 32% increase in large-particle HDL (p <0.001), an 8% decrease in small-particle HDL (p = 0.0032), an 82% increase in large-particle LDL (p = 0.09), and a 12% decrease in small-particle LDL (p = 0.008). Niacin decreased lipoprotein-associated phospholipase A2 and C-reactive protein levels (20% and 15%, respectively, p <0.05 for the 2 comparisons). No significant changes from baseline were seen in any tested parameter in subjects who received placebo. In conclusion, addition of niacin to existing medical regimens for patients with coronary artery disease and already well-controlled LDL levels favorably improves the distribution of lipoprotein particle sizes and inflammatory markers in a manner that would be expected to confer atheroprotection. The effect of altering lipoprotein particle distribution and inflammatory markers on surrogate markers of atherosclerosis and clinical cardiovascular events in this population remains unclear. PMID:16950175

  16. A clustering analysis of lipoprotein diameters in the metabolic syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The presence of smaller low-density lipoproteins (LDL) has been associated with atherosclerosis risk, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-, low- and high-density lipoprotein (VLDL HDL) particle...

  17. 21 CFR 862.1475 - Lipoprotein test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lipoprotein test system. 862.1475 Section 862.1475 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1475 Lipoprotein test system....

  18. Study of soluble lipoprotein in rat liver mitochondria

    PubMed Central

    Koppikar, S. V.; Fatterpaker, P.; Sreenivasan, A.

    1971-01-01

    1. A water-soluble lipoprotein was isolated and purified from osmotically shocked preparations of rat liver mitochondria by using a technique of Sephadex-sandwich disc electrophoresis. 2. The purified lipoprotein migrates as a distinct sharp zone in high-resolution electrophoretic systems, indicating high degree of purity. 3. The lipoprotein resembles mitochondrial membranes with respect to lipid composition and lipid/protein ratio. 4. The lipoprotein and its apoprotein fraction obtained by delipidization at −18°C to −20°C have common properties with respect to their fluorescence spectra, instability to storage and electrophoretic mobility. 5. The purified lipoprotein has an excitation maximum at 325nm and a fluorescence maximum at 418nm. 6. Storage at 4°C for 4 days or repeated freezing and thawing results in 15–30% decrease in electrophoretic mobility. 7. The patterns of incorporation in vitro of [1-14C]leucine into proteins of the soluble lipoprotein and of mitochondrial membrane of isolated rat liver mitochondria suggest a probable precursor role for the apoprotein in the formation of mitochondrial membrane protein. 8. Lipoprotein preparations isolated from mitochondrial fractions of rat kidney, brain and heart and of chicken and mouse liver resemble closely that obtained from rat liver mitochondria, suggesting that the soluble lipoprotein could be a distinct entity of mitochondrial origin. ImagesFig. 4.Fig. 5. PMID:5114976

  19. Lipoprotein effects of incretin analogs and dipeptidyl peptidase 4 inhibitors

    PubMed Central

    Zhong, Jixin; Maiseyeu, Andrei; Rajagopalan, Sanjay

    2015-01-01

    Elevated post-prandial lipoprotein levels are common in patients with type 2 diabetes. Post-prandial lipoprotein alterations in type 2 diabetics are widely believed to drive inflammation and are considered a major risk factor for cardiovascular disease in diabetic patients. The incretins glucagon like peptide-1 (GLP-1) and glucose insulinotropic peptide (GIP) modulate post-prandial lipoproteins through a multitude of pathways that are independent of insulin and weight loss. Evidence from both animal models and humans seems to suggest an important effect on triglyceride rich lipoproteins (Apo48 containing) with little to no effects on other lipoproteins at least in humans. Dipeptidyl peptidase-4 (DPP4) inhibitors also appear to share these effects suggesting an important role for incretins in these effects. In this review, we will summarize lipid modulating effects of incretin analogs and DPP-4 inhibitors in both animal models and human studies and provide an overview of mechanisms responsible for these effects. PMID:26005496

  20. Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention

    PubMed Central

    Millán, Jesús; Pintó, Xavier; Muñoz, Anna; Zúñiga, Manuel; Rubiés-Prat, Joan; Pallardo, Luis Felipe; Masana, Luis; Mangas, Alipio; Hernández-Mijares, Antonio; González-Santos, Pedro; Ascaso, Juan F; Pedro-Botet, Juan

    2009-01-01

    Low-density lipoprotein (LDL) cholesterol concentration has been the prime index of cardiovascular disease risk and the main target for therapy. However, several lipoprotein ratios or “atherogenic indices” have been defined in an attempt to optimize the predictive capacity of the lipid profile. In this review, we summarize their pathophysiological aspects, and highlight the rationale for using these lipoprotein ratios as cardiovascular risk factors in clinical practice, specifying their cut-off risk levels and a target for lipid-lowering therapy. Total/high-density lipoprotein (HDL) cholesterol and LDL/HDL cholesterol ratios are risk indicators with greater predictive value than isolated parameters used independently, particularly LDL. Future recommendations regarding the diagnosis and treatment of dyslipidemia, including instruments for calculating cardiovascular risk or action guidelines, should include the lipoprotein ratios with greater predictive power which, in view of the evidence-based results, are none other than those which include HDL cholesterol. PMID:19774217

  1. Apolipoprotein AV Accelerates Plasma Hydrolysis OfTriglyceride-Rich Lipoproteins By Interaction With Proteoglycan BoundLipoprotein Lipase

    SciTech Connect

    Merkel, Martin; Loeffler, Britta; Kluger, Malte; Fabig, Nathalie; Geppert, Gesa; Pennacchio, Len A.; Laatsch, Alexander; Heeren, Joerg

    2005-02-22

    Apolipoprotein A5 (APOA5) is associated with differences intriglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasmatriglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In hAPOA5 transgenic mice(hAPOA5tr), catabolism of chylomicrons and VLDL was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL).Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by crossbreeding a human LPL transgene with the apoa5 knockout, and the hAPOA5tr to an LPL deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5 deficient mice,however, over expression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr HDL, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line.A direct interaction between LPL and apoAV was found by ligand blotting.It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycans bound LPL for lipolysis.

  2. Analytical capillary isotachophoresis: a routine technique for the analysis of lipoproteins and lipoprotein subfractions in whole serum.

    PubMed

    Schmitz, G; Borgmann, U; Assmann, G

    1985-02-22

    A capillary isotachophoretic separation technique was developed for lipoproteins in native serum which, compared with previous electrophoretic techniques, has negligible molecular sieve effects, does not need gel casting, is suitable for whole serum and has a high discriminative power for lipoprotein subfractions. The technique is based on pre-staining whole serum lipoproteins for 30 min at 4 degrees C before separation of 0.5 microliter of the sample in a free-flow capillary system (0.5 mm I.D.) with discontinuous buffer system. In normolipidaemic sera, high-density (HDL) and low-density lipoproteins (VLDL) are separated into two major subpopulations according to their net electric mobility. The identification of these fractions was confirmed by substitution with ultracentrifugally isolated lipoproteins and by their complete absence from Tangier and abetalipoproteinaemic serum. Triglyceride-rich very low-density lipoproteins (VLDL) revealed a defined zone between the HDL and LDL subpopulations. Our preliminary results indicate that the separation of human whole serum lipoproteins by capillary isotachophoresis is a promising method for the determination of lipoprotein subfractions. PMID:4030932

  3. Characterization of Lipoprotein Composition and Function in Pediatric Psoriasis Reveals a More Atherogenic Profile.

    PubMed

    Tom, Wynnis L; Playford, Martin P; Admani, Shehla; Natarajan, Balaji; Joshi, Aditya A; Eichenfield, Lawrence F; Mehta, Nehal N

    2016-01-01

    Psoriasis is associated with increased cardiovascular disease in adults, but the risk profile of children with psoriasis remains to be fully characterized. We measured lipoprotein composition and function in 44 patients with pediatric psoriasis and 44 age- and sex-matched healthy controls, using nuclear magnetic resonance spectroscopy and a validated ex vivo assay of high-density lipoprotein cholesterol efflux capacity. The mean age of the patients was 13 years and the population was ethnically diverse. Children with psoriasis had higher waist-to-hip ratios (0.85 vs. 0.80; P < 0.002) and insulin resistance measures (log-transformed homeostasis model assessment of insulin resistance 0.65 vs. 0.41; P = 0.07). Despite comparable traditional lipid values, having psoriasis was associated with higher apolipoprotein B concentrations (72.4 vs. 64.6; P = 0.02), decreased large high-density lipoprotein particles (5.3 vs. 6.7; P < 0.01), and reduced cholesterol efflux capacity after adjusting for age, sex, fasting glucose, homeostasis model assessment of insulin resistance, systolic blood pressure, body mass index, apolipoprotein A-1, and high-density lipoprotein cholesterol concentration (β -0.22; P = 0.02). Patients with pediatric psoriasis have a more atherogenic cardiometabolic risk profile, with evidence of insulin resistance and lipoprotein dysfunction by particle size, number, and functional assessment. These findings may provide a basis for the observed link later in life between psoriasis and cardiovascular disease, and support the need to screen and educate young patients to minimize later complications. PMID:26763425

  4. Hypertriglyceridemic very low density lipoproteins induce triglyceride synthesis and accumulation in mouse peritoneal macrophages.

    PubMed

    Gianturco, S H; Bradley, W A; Gotto, A M; Morrisett, J D; Peavy, D L

    1982-07-01

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

  5. Uptake of postprandial lipoproteins into bone in vivo: impact on osteoblast function.

    PubMed

    Niemeier, Andreas; Niedzielska, Dagmara; Secer, Rukiye; Schilling, Arndt; Merkel, Martin; Enrich, Carlos; Rensen, Patrick C N; Heeren, Joerg

    2008-08-01

    Dietary lipids and lipophilic vitamins are transported by postprandial lipoproteins and are required for bone metabolism. Despite that, it remains unknown whether bone cells are involved in the uptake of circulating postprandial lipoproteins in vivo. The current study was performed to investigate a putative participation of bone in the systemic postprandial lipoprotein metabolism in mice, to identify potentially involved cell type populations and to analyze whether lipoprotein uptake affects bone function in vivo. As a model for the postprandial state, chylomicron remnants (CR) were injected intravenously into mice. Next to the liver and compared to other organs, bone appeared to be the second most important organ for the clearance of radiolabeled CR particles from the circulation in vivo. In addition, uptake of radiolabeled CR by primary murine osteoblasts and hepatocytes was quantified to be in a similar range in vitro. A complementary approach with fluorescently labeled CR and immunohistochemical staining for apoE proved that intact CR particles were taken up into bone and liver. Electron microscopy localization studies of bone sections revealed CR uptake into sinusoidal endothelial cells, macrophages and osteoblasts. The relative amount of radiolabeled CR uptake into femoral cortical bone, representing predominantly osteoblasts, and bone marrow, representing predominantly non-osteoblast cells, was within the same range. Most importantly, the injection of vitamin K1-enriched CR resulted in an increase of the degree of osteocalcin carboxylation in vivo while total osteocalcin concentrations remained unaffected, giving functional proof that osteoblasts process CR in vivo. In conclusion, here we demonstrate that bone is involved in the postprandial lipoprotein metabolism in mice. Osteoblasts participate in CR clearance from the circulation, which has a direct impact on the secretory function of osteoblasts. PMID:18538644

  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. The Mayer Hashi Large-Scale Program to Increase Use of Long-Acting Reversible Contraceptives and Permanent Methods in Bangladesh: Explaining the Disappointing Results. An Outcome and Process Evaluation

    PubMed Central

    Rahman, Mizanur; Haider, M Moinuddin; Curtis, Sian L; Lance, Peter M

    2016-01-01

    ABSTRACT Background: Bangladesh has achieved a low total fertility rate of 2.3. Two-thirds of currently married women of reproductive age (CMWRA) want to limit fertility, and many women achieve their desired fertility before age 30. The incidence of unintended pregnancy and pregnancy termination is high, however. Long-acting reversible contraceptives (LARCs), consisting of the intrauterine device and implant, and permanent methods (PM), including female sterilization and vasectomy, offer several advantages in this situation, but only 8% of CMWRA or 13% of method users use these methods. Program: The Mayer Hashi (MH) program (2009–2013) aimed to improve access to and the quality of LARC/PM services in 21 of the 64 districts in Bangladesh. It was grounded in the SEED (supply–enabling environment–demand) Programming Model. Supply improvements addressed provider knowledge and skills, system strengthening, and logistics. Creating an enabling environment involved holding workshops with local and community leaders, including religious leaders, to encourage them to help promote demand for LARCs and PMs and overcome cultural barriers. Demand promotion encompassed training of providers in counseling, distribution of behavior change communication materials in the community and in facilities, and community mobilization. Methods: We selected 6 MH program districts and 3 nonprogram districts to evaluate the program. We used a before–after and intervention–comparison design to measure the changes in key contraceptive behavior outcomes, and we used a difference-in-differences (DID) specification with comparison to the nonprogram districts to capture the impact of the program. In addition to the outcome evaluation, we considered intermediate indicators that measured the processes through which the interventions were expected to affect the use of LARCs and PMs. Results: The use of LARCs/PMs among CMWRA increased between 2010 and 2013 in both program (from 5.3% to 7.5%) and

  8. What explains consciousness? Or…What consciousness explains?

    PubMed

    Dulany, Donelson E

    2014-01-01

    In this invited commentary I focus on the topic addressed in three papers: De Sousa's (2013[1617]) Toward an Integrative Theory of Consciousness, a monograph with Parts 1 & 2, as well as commentaries by Pereira (2013a[59]) and Hirstein (2013[42]). All three are impressively scholarly and can stand-and shout-on their own. But theory of consciousness? My aim is to slice that topic into the two fundamentally different kinds of theories of consciousness, say what appears to be an ideology, out of behaviourism into cognitivism, now also influencing the quest for an "explanation of consciousness" in cognitive neuroscience. I will then say what can be expected given what we know of the complexity of brain structure, the richness of a conscious "vocabulary", and current technological limits of brain imaging. This will then turn to the strategy for examining "what consciousness explains"-metatheory, theories, mappings, and a methodology of competitive support, a methodology especially important where there are competing commitments. There are also increasingly common identifications of methodological bias in, along with failures to replicate, studies reporting unconscious controls in decision, social priming-as there have been in perception, learning, problem solving, etc. The literature critique has provided evidence taken as reducing, and in some cases eliminating, a role for conscious controls-a position consistent with that ideology out of behaviourism into cognitivism. It is an ideological position that fails to recognize the fundamental distinction between theoretical and metaphysical assertions. PMID:24891796

  9. Isolation of plasma lipoproteins by zonal ultracentrifugation in the B14 and B15 titanium rotors.

    PubMed

    Wilcox, H G; Heimberg, M

    1970-01-01

    Lipoproteins were isolated from plasma of man, dog, rabbit, rat, and chicken by ultracentrifugation in continuous density gradients using the B14 titanium and B15 titanium zonal rotors. Both the VLDL and the LDL of human plasma were separated easily from the HDL and from the other more plentiful plasma proteins by centrifugation for only 1 or 2 hr in the B14 or B15 rotor, respectively. Satisfactory separation of the HDL from the more dense plasma proteins was not achieved with these rotors. The human LDL achieved isopycnic equilibrium (d 1.04) on prolonged periods (> 24 hr) of centrifugation in a sucrose-KBr density gradient. The pattern of distribution of cholesterol and phospholipid throughout the density gradient coincided with the pattern of distribution of the lipoprotein-protein measured spectrophotometrically or chemically. The concentration of cholesterol and phospholipid in the lipoproteins isolated by zonal ultracentrifugation agreed with analyses reported for lipoproteins isolated by sequential centrifugation in solutions of increasing density. The lipoproteins isolated by zonal ultracentrifugation were characterized further by their electrophoretic behavior. The fractions which were identified as the LDL (d 1.04-1.05) from all species migrated on paper as a beta-globulin; the LDL from plasma of dogs contained an additional component which has been designated as an alpha(2)-globulin. The fractions which were identified as the HDL from all species migrated as an alpha(1)-globulin. Reaction of human LDL with either rabbit antihuman beta-lipoprotein or rabbit antihuman serum resulted in a single immunodiffusion band. The S(f, 1.063) of the human LDL was calculated to be 6.0. When plasma from humans or rabbits was centrifuged in the B15 rotor, the HDL was not visible as a distinct peak and was not separable from the bulk of the more dense plasma proteins; when plasma from dogs or chickens was centrifuged under identical conditions, the HDL was clearly

  10. Dynamics of lipoprotein level in blood plasma of pregnant women as a function of gestational age according to FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Korolik, E. V.; Korolenko, E. A.; Tretinnikov, O. N.; Kozlyakova, O. V.; Korolik, A. K.; Kirkovskiy, V. V.

    2013-01-01

    Results of an IR spectroscopic investigation of films of blood plasma taken from women of reproductive age, pregnant women with positive and negative Rh factors, and Rh-immunized women were presented as a function of gestational age. It was found that the lipoprotein content in blood plasma of all groups of pregnant women increased during the early stages of pregnancy (17-23 weeks) irrespective of the Rh factor and attained its peak value by weeks 30-35. It was shown that the lipoprotein level in blood plasma as a function of gestational age was quantitatively the same for pregnant women with positive and negative Rh factors. It was established for the first time that this dependence for Rh-immunized women featured a considerable increase of lipoprotein content at gestational age 30-32 weeks and declined acutely by week 36.

  11. Structure, function, and genetics of lipoprotein (a).

    PubMed

    Schmidt, Konrad; Noureen, Asma; Kronenberg, Florian; Utermann, Gerd

    2016-08-01

    Lipoprotein (a) [Lp(a)] has attracted the interest of researchers and physicians due to its intriguing properties, including an intragenic multiallelic copy number variation in the LPA gene and the strong association with coronary heart disease (CHD). This review summarizes present knowledge of the structure, function, and genetics of Lp(a) with emphasis on the molecular and population genetics of the Lp(a)/LPA trait, as well as aspects of genetic epidemiology. It highlights the role of genetics in establishing Lp(a) as a risk factor for CHD, but also discusses uncertainties, controversies, and lack of knowledge on several aspects of the genetic Lp(a) trait, not least its function. PMID:27074913

  12. Comparative studies of vertebrate lipoprotein lipase: a key enzyme of very low density lipoprotein metabolism.

    PubMed

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

    2011-06-01

    Lipoprotein lipase (LIPL or LPL; E.C.3.1.1.34) serves a dual function as a triglyceride lipase of circulating chylomicrons and very-low-density lipoproteins (VLDL) and facilitates receptor-mediated lipoprotein uptake into heart, muscle and adipose tissue. Comparative LPL amino acid sequences and protein structures and LPL gene locations were examined using data from several vertebrate genome projects. Mammalian LPL genes usually contained 9 coding exons on the positive strand. Vertebrate LPL sequences shared 58-99% identity as compared with 33-49% sequence identities with other vascular triglyceride lipases, hepatic lipase (HL) and endothelial lipase (EL). Two human LPL N-glycosylation sites were conserved among seven predicted sites for the vertebrate LPL sequences examined. Sequence alignments, key amino acid residues and conserved predicted secondary and tertiary structures were also studied. A CpG island was identified within the 5'-untranslated region of the human LPL gene which may contribute to the higher than average (×4.5 times) level of expression reported. Phylogenetic analyses examined the relationships and potential evolutionary origins of vertebrate lipase genes, LPL, LIPG (encoding EL) and LIPC (encoding HL) which suggested that these have been derived from gene duplication events of an ancestral neutral lipase gene, prior to the appearance of fish during vertebrate evolution. Comparative divergence rates for these vertebrate sequences indicated that LPL is evolving more slowly (2-3 times) than for LIPC and LIPG genes and proteins. PMID:21561822

  13. Associations of ApoAI and ApoB-containing Lipoproteins with AngII-induced Abdominal Aortic Aneurysms in Mice

    PubMed Central

    Liu, Jing; Lu, Hong; Howatt, Deborah A.; Balakrishnan, Anju; Moorleghen, Jessica J.; Sorci-Thomas, Mary; Cassis, Lisa A.; Daugherty, Alan

    2015-01-01

    Objective Dyslipidemia is implicated in abdominal aortic aneurysms (AAAs) in humans and angiotensin (Ang)II-infused mice. This study determined effects of major lipoprotein classes on AngII-induced AAAs using multiple mouse strains with dietary and pharmacological manipulations. Approach and Results Western diet had minor effects on plasma cholesterol concentrations and the low incidence of AngII-induced AAAs in C57BL/6J mice. Low incidence of AAAs in this strain was not attributed to protection from HDL, since apolipoprotein (apo)AI deficiency did not increase AngII-induced AAAs. ApoAI deletion also failed to alter AAA occurrence in hypercholesterolemic mice. Low density lipoprotein (LDL) receptor−/− mice fed normal diet had low incidence of AngII-induced AAAs. Western diet feeding of this strain provoked pronounced hypercholesterolemia due to increased apoB-containing lipoproteins with attendant increases of atherosclerosis in both genders, but AAAs only in male mice. ApoE−/− mice fed normal diet were modestly hypercholesterolemic, whereas this strain fed Western diet was severely hypercholesterolemic due to increased apoB-containing lipoprotein concentrations. The latter augmented atherosclerosis, but did not change the high incidence of AAAs in this strain. To determine whether reductions in apoB-containing lipoproteins influenced AngII-induced AAAs, ezetimibe was administered at a dose that partially reduced plasma cholesterol concentrations to apoE−/− mice fed Western diet. This decreased atherosclerosis, but not AAAs. This ezetimibe dose in apoE−/− mice fed normal diet significantly decreased plasma apoB-containing lipoprotein concentrations and reduced AngII-induced AAAs. Conclusions ApoB-containing lipoproteins contribute to augmentation of AngII-induced AAA in male mice. However, unlike atherosclerosis, AAA occurrence was not correlated with increases in plasma apoB-containing lipoprotein concentrations. PMID:26044581

  14. Lipoprotein(a) Catabolism Is Regulated by Proprotein Convertase Subtilisin/Kexin Type 9 through the Low Density Lipoprotein Receptor*

    PubMed Central

    Romagnuolo, Rocco; Scipione, Corey A.; Boffa, Michael B.; Marcovina, Santica M.; Seidah, Nabil G.; Koschinsky, Marlys L.

    2015-01-01

    Elevated levels of lipoprotein(a) (Lp(a)) have been identified as an independent risk factor for coronary heart disease. Plasma Lp(a) levels are reduced by monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9). However, the mechanism of Lp(a) catabolism in vivo and the role of PCSK9 in this process are unknown. We report that Lp(a) internalization by hepatic HepG2 cells and primary human fibroblasts was effectively reduced by PCSK9. Overexpression of the low density lipoprotein (LDL) receptor (LDLR) in HepG2 cells dramatically increased the internalization of Lp(a). Internalization of Lp(a) was markedly reduced following treatment of HepG2 cells with a function-blocking monoclonal antibody against the LDLR or the use of primary human fibroblasts from an individual with familial hypercholesterolemia; in both cases, Lp(a) internalization was not affected by PCSK9. Optimal Lp(a) internalization in both hepatic and primary human fibroblasts was dependent on the LDL rather than the apolipoprotein(a) component of Lp(a). Lp(a) internalization was also dependent on clathrin-coated pits, and Lp(a) was targeted for lysosomal and not proteasomal degradation. Our data provide strong evidence that the LDLR plays a role in Lp(a) catabolism and that this process can be modulated by PCSK9. These results provide a direct mechanism underlying the therapeutic potential of PCSK9 in effectively lowering Lp(a) levels. PMID:25778403

  15. Membrane topology of Borrelia burgdorferi and Treponema pallidum lipoproteins.

    PubMed Central

    Jones, J D; Bourell, K W; Norgard, M V; Radolf, J D

    1995-01-01

    A critical issue regarding the molecular architectures of Treponema pallidum and Borrelia burgdorferi, the agents of venereal syphilis and Lyme disease, respectively, concerns the membrane topologies of their major lipoprotein immunogens. A related question is whether these lipid-modified membrane proteins form intramembranous particles during freeze fracture electron microscopy. To address these issues, native borrelial and treponemal lipoproteins were reconstituted into liposomes of diverse composition. The importance of the covalently associated lipids for membrane association of lipoproteins was revealed by the observation that nonlipidated recombinant forms of both B. burgdorferi OspA and the T. pallidum 47-kDa immunogen (Tpp47) showed very weak or no binding to model bilayer vesicles. In contrast to control liposomes reconstituted with bacteriorhodopsin or bovine rhodopsin, two well-characterized transmembrane proteins, none of the lipoprotein-liposomes contained particles when examined by freeze fracture electron microscopy. To extend these findings to prokaryotic lipoproteins with relatively amphiphilic polypeptides, similar experiments were conducted with a recombinant nonlipidated form of Escherichia coli TraT, a lipoprotein which has putative transmembrane domains. The nonlipidated TraT oligomers bound vesicles derived from E. coli lipids but, surprisingly, did not form particles in the freeze-fractured liposomes. These findings support (i) a proposed topology of spirochetal lipoproteins in which the polypeptide is extrinsic to the membrane surface and (ii) the contention that particles visualized in freeze-fractured spirochetal membranes represent poorly characterized transmembrane proteins. PMID:7790053

  16. Fatty acids of Treponema pallidum and Borrelia burgdorferi lipoproteins.

    PubMed Central

    Belisle, J T; Brandt, M E; Radolf, J D; Norgard, M V

    1994-01-01

    A fundamental ultrastructural feature shared by the spirochetal pathogens Treponema pallidum subsp. pallidum (T. pallidum) and Borrelia burgdorferi, the etiological agents of venereal syphilis and Lyme disease, respectively, is that their most abundant membrane proteins contain covalently attached fatty acids. In this study, we identified the fatty acids covalently bound to lipoproteins of B. burgdorferi and T. pallidum and examined potential acyl donors to these molecules. Palmitate was the predominant fatty acid of both B. burgdorferi and T. pallidum lipoproteins. T. pallidum lipoproteins also contained substantial amounts of stearate, a fatty acid not typically prevalent in prokaryotic lipoproteins. In both spirochetes, the fatty acids of cellular lipids differed from those of their respective lipoproteins. To characterize phospholipids in these organisms, spirochetes were metabolically labeled with [3H]palmitate or [3H]oleate; B. burgdorferi contained only phosphatidylglycerol and phosphatidylcholine, while T. pallidum contained phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and cardiolipin. Although palmitate predominated in the lipoproteins, there were no apparent differences in the incorporation of these two fatty acids into phospholipids (putative acyl donors). Phospholipase A1 and A2 digestion of phosphatidylcholine from B. burgdorferi and T. pallidum labeled with either [3H]palmitate or [3H]oleate also revealed that neither fatty acid was incorporated preferentially into the 1 and 2 positions (potential acyl donor sites) of the glycerol backbone. The combined findings suggest that fatty acid utilization during lipoprotein synthesis is determined largely by the fatty acid specificities of the lipoprotein acyl transferases. These findings also provide the basis for ongoing efforts to elucidate the relationship between lipoprotein acylation and the physiological functions and inflammatory

  17. 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

  18. A MARCH6 and IDOL E3 Ubiquitin Ligase Circuit Uncouples Cholesterol Synthesis from Lipoprotein Uptake in Hepatocytes

    PubMed Central

    Loregger, Anke; Cook, Emma Claire Laura; Nelson, Jessica Kristin; Moeton, Martina; Sharpe, Laura Jane; Engberg, Susanna; Karimova, Madina; Lambert, Gilles; Brown, Andrew John

    2015-01-01

    Cholesterol synthesis and lipoprotein uptake are tightly coordinated to ensure that the cellular level of cholesterol is adequately maintained. Hepatic dysregulation of these processes is associated with pathological conditions, most notably cardiovascular disease. Using a genetic approach, we have recently identified the E3 ubiquitin ligase MARCH6 as a regulator of cholesterol biosynthesis, owing to its ability to promote degradation of the rate-limiting enzymes 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR) and squalene epoxidase (SQLE). Here, we present evidence for MARCH6 playing a multifaceted role in the control of cholesterol homeostasis in hepatocytes. We identify MARCH6 as an endogenous inhibitor of the sterol regulatory element binding protein (SREBP) transcriptional program. Accordingly, loss of MARCH6 increases expression of SREBP-regulated genes involved in cholesterol biosynthesis and lipoprotein uptake. Unexpectedly, this is associated with a decrease in cellular lipoprotein uptake, induced by enhanced lysosomal degradation of the low-density lipoprotein receptor (LDLR). Finally, we provide evidence that induction of the E3 ubiquitin ligase IDOL represents the molecular mechanism underlying this MARCH6-induced phenotype. Our study thus highlights a MARCH6-dependent mechanism to direct cellular cholesterol accretion that relies on uncoupling of cholesterol synthesis from lipoprotein uptake. PMID:26527619

  19. The effects of adrenocorticotrophic hormone and an equivalent dose of cortisol on the serum concentrations of lipids, lipoproteins, and apolipoproteins.

    PubMed

    Berg, Anna-Lena; Rafnsson, Arnar Thor; Johannsson, Magnus; Dallongeville, Jean; Arnadottir, Margret

    2006-08-01

    Previous studies have shown a strong lipid-lowering effect of adrenocorticotrophic hormone (ACTH) in healthy individuals and in patients with different kinds of dyslipoproteinemia. The mechanism behind this effect has not been established and its direct ACTH-specific nature has been questioned. Therefore, the present study was performed. Thirty healthy young males were randomized into 3 groups of equal size: one group received ACTH1-24 1 mg IM, daily for 4 days, another group was treated with cortisol 150 mg ID (50 mg tid) daily for 4 days, whereas a control group was observed for 4 days. Fasting blood samples were collected before and after treatment or observation. The serum concentrations of cholesterol (12%, P < .05), low-density lipoprotein cholesterol (24%, P < .01), and apolipoprotein (apo) B (31%, P < .01) decreased significantly in the ACTH group but not in the cortisol and control groups. The statistical workup confirmed that only ACTH had a lowering effect on the apo B-containing lipoproteins. In contrast, the results indicated conformity between the treatment groups with respect to increases in the serum apo E concentrations. There were inconsistent changes in the serum concentrations of the triglycerides, high-density lipoprotein cholesterol, apo A, and lipoprotein(a). The main results were clear: the lowering effect of ACTH on the serum concentration of apo B-containing lipoproteins could not be ascribed to cortisol. These, in combination with previous in vitro results, indicated an ACTH-specific effect. PMID:16839845

  20. Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise

    PubMed Central

    2012-01-01

    Background Many of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects. Methods Using a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL). Results The intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70–120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43–55 nm (medium) particle range. VLDL-TG in smaller particles (29–43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state. Conclusions These findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity. PMID

  1. Explaining the increased mortality in type 1 diabetes

    PubMed Central

    Mameli, Chiara; Mazzantini, Sara; Ben Nasr, Moufida; Fiorina, Paolo; Scaramuzza, Andrea E; Zuccotti, Gian Vincenzo

    2015-01-01

    Despite large improvements in the management of glucose levels and in the treatment of cardiovascular risk factors, the mortality rate in individuals with type 1 diabetes (T1D) is still high. Recently, Lind et al found that T1D individuals with glycated hemoglobin levels of 6.9% or lower had a risk of death from any cause or from cardiovascular causes that is twice as high as the risk for matched controls. T1D is a chronic disease with an early onset (e.g., pediatric age) and thus in order to establish a clear correlation between death rate and the glycometabolic control, the whole history of glycemic control should be considered; particularly in the early years of diabetes. The switch from a normo- to hyperglycemic milieu in an individual with T1D in the pediatric age, represents a stressful event that may impact outcomes and death rate many years later. In this paper we will discuss the aforementioned issues, and offer our view on these findings, paying a particular attention to the several alterations occurring in the earliest phases of T1D and to the many factors that may be associated with the chronic history of T1D. This may help us to better understand the recently published death rate data and to develop future innovative and effective preventive strategies. PMID:26185597

  2. Hepatitis C virus relies on lipoproteins for its life cycle

    PubMed Central

    Grassi, Germana; Di Caprio, Giorgia; Fimia, Gian Maria; Ippolito, Giuseppe; Tripodi, Marco; Alonzi, Tonino

    2016-01-01

    Hepatitis C virus (HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence and pathogenesis are due to the ability of HCV to deregulate specific host processes, mainly lipid metabolism and innate immunity. In particular, HCV exploits the lipoprotein machineries for almost all steps of its life cycle. The aim of this review is to summarize current knowledge concerning the interplay between HCV and lipoprotein metabolism. We discuss the role played by members of lipoproteins in HCV entry, replication and virion production. PMID:26877603

  3. 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

  4. 21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a...

  5. PLTP activity in premenopausal women. Relationship with lipoprotein lipase, HDL, LDL, body fat, and insulin resistance.

    PubMed

    Murdoch, S J; Carr, M C; Hokanson, J E; Brunzell, J D; Albers, J J

    2000-02-01

    Plasma phospholipid transfer protein (PLTP) is thought to play a major role in the facilitated transfer of phospholipids between lipoproteins and in the modulation of high density lipoprotein (HDL) particle size and composition. However, little has been reported concerning the relationships of PLTP with plasma lipoprotein parameters, lipolytic enzymes, body fat distribution, insulin, and glucose in normolipidemic individuals, particularly females. In the present study, 50 normolipidemic healthy premenopausal females were investigated. The relationships between the plasma PLTP activity and selected variables were assessed. PLTP activity was significantly and positively correlated with low density lipoprotein (LDL) cholesterol (r(s) = 0.53), apoB (r(s) = 0.44), glucose (r(s) = 0.40), HDL cholesterol (r(s) = 0.38), HDL(3) cholesterol (r(s) = 0.37), lipoprotein lipase activity (r(s) = 0.36), insulin (r(s) = 0.33), subcutaneous abdominal fat (r(s) = 0.36), intra-abdominal fat (r(s) = 0.29), and body mass index (r(s) = 0.29). HDL(2) cholesterol, triglyceride, and hepatic lipase were not significantly related to PLTP activity. As HDL(2) can be decreased by hepatic lipase and hepatic lipase is increased in obesity with increasing intra-abdominal fat, the participants were divided into sub-groups of non-obese (n = 35) and obese (n = 15) individuals and the correlation of PLTP with HDL(2) cholesterol was re-examined. In the non-obese subjects, HDL(2) cholesterol was found to be significantly and positively related to PLTP activity (r(s) = 0.44). Adjustment of the HDL(2) values for the effect of hepatic lipase activity resulted in a significant positive correlation between PLTP and HDL(2) (r(s) = 0.41), indicating that the strength of the relationship between PLTP activity and HDL(2) can be reduced by the opposing effect of hepatic lipase on HDL(2) concentrations. We conclude that PLTP-facilitated lipid transfer activity is related to HDL and LDL metabolism, as well as

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

    PubMed Central

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

    2014-01-01

    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 PPARα'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. PMID:24694979

  7. 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 PPARα'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.

  8. Lipids and lipoprotein profile in doxorubicin treated rats: influence of alpha-tocopherol administration.

    PubMed

    Geetha, A; Catherine, J; Sankar, R; Devi, C S

    1990-11-01

    The effect of doxorubicin (DXR) on the levels of heart, liver and plasma lipids and plasma lipoproteins were studied in rats. Rats were treated with DXR (2.5 mg/kg body weight weekly for 8 weeks, iv) with or without alpha-tocopherol (alpha-TPL) (400 mg/kg body wt daily for 60 days) co-administration. DXR treated rats showed increase in plasma total cholesterol, triglycerides and phospholipids. The activities of lecithin cholesterol-acyl transferase and hepatic and extrahepatic lipoprotein lipase were lowered significantly with concomitant increase in liver and heart lipid peroxide levels in DXR treatment. HDL cholesterol level was found to be decreased significantly in DXR treated rats as a result of which there was an increase of LDLc/HDLc ratio. alpha-TPL coadministration brought back the enzyme activity to near normal and reduced the level of lipid peroxides. The lipid changes were minimum in rats treated with both alpha-TPL and DXR. This study suggests that the toxicity of DXR is reflected in lipids and lipoprotein profile. PMID:2283173

  9. 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

  10. Effect of lithocholic acid feeding on plasma lipoproteins and binding of radioiodinated human lipoproteins to hepatic membranes in rats.

    PubMed

    Loo, G; Kessie, G; Berlin, E; Nair, P P

    1992-06-01

    1. Male Sprague-Dawley rats fed diets containing 0.25% lithocholic acid for 6 weeks exhibited elevated serum cholesterol. 2. The rats were fed diets containing 5 or 20% fat with and without the lithocholate and/or oxytetracycline-HCl. 3. The cholesterol elevation was associated with high density lipoprotein (HDL) and not very low density lipoprotein (VLDL) or low density lipoprotein (LDL). 4. Specific binding of human [125I]HDL to hepatic membranes was lowered in lithocholate-fed rats, but binding of human [125I]LDL to these membranes was not affected. PMID:1354585

  11. Your Radiologist Explains CT Colonography

    MedlinePlus Videos and Cool Tools

    ... About this Site RadiologyInfo.org is produced by: Image/Video Gallery Your Radiologist Explains CT Colonography (Virtual ... to allow for inflation with air while CT images are being taken. If you’re scheduled for ...

  12. Your Radiologist Explains Nuclear Medicine

    MedlinePlus Videos and Cool Tools

    ... by: Image/Video Gallery Your Radiologist Explains Nuclear Medicine Transcript Welcome to Radiology Info dot org Hello! ... d like to talk to you about nuclear medicine. Nuclear medicine offers the potential to identify disease ...

  13. Minimally modified low density lipoprotein stimulates monocyte endothelial interactions.

    PubMed Central

    Berliner, J A; Territo, M C; Sevanian, A; Ramin, S; Kim, J A; Bamshad, B; Esterson, M; Fogelman, A M

    1990-01-01

    The effect of minimally modified LDL (MM-LDL) on the ability of large vessel endothelial cells (EC) to interact with monocytes and neutrophils was examined. These LDL preparations, obtained by storage or by mild iron oxidation, were indistinguishable from native LDL to the LDL receptor and were not recognized by the scavenger receptor. Treatment of EC with as little as 0.12 micrograms/ml MM-LDL caused a significant increase in the production of chemotactic factor for monocytes (sevenfold) and increased monocyte binding (three- to fivefold). Monocyte binding was maximal after 4 h of EC exposure to MM-LDL, persisted for 48 h, and was inhibited by cycloheximide. In contrast, neutrophil binding was not increased after 1-24 h of exposure. Activity in the MM-LDL preparations was found primarily in the polar lipid fraction. MM-LDL was toxic for EC from one rabbit but not toxic for the cells from another rabbit or any human umbilical vein EC. The resistant cells became sensitive when incubated with lipoprotein in the presence of cycloheximide, whereas the sensitive strain became resistant when preincubated with sublethal concentrations of MM-LDL. We conclude that exposure of EC to sublethal levels of MM-LDL enhances monocyte endothelial interactions and induces resistance to the toxic effects of MM-LDL. Images PMID:2318980

  14. Effect of dietary vegetable oils on the fatty acid profile of plasma lipoproteins in dairy cows.

    PubMed

    Vargas-Bello-Pérez, Einar; Íñiguez-González, Gonzalo; Cancino-Padilla, Nathaly; Loor, Juan J; Garnsworthy, Philip C

    2016-08-01

    The aim of this study was to elucidate the effect of dietary supplementation of soybean oil (SO) and hydrogenated palm oil (HPO) on the transport of fatty acids (FA) within plasma lipoproteins in lactating and non-lactating cows. Three lactating and three non-lactating Holstein cows were used in two different 3 × 3 Latin square experiments that included three periods of 21 d. Dietary treatments for lactating cows consisted of a basal diet (control; no fat supplement) and fat-supplemented diets containing SO (500 g/d per cow) or HPO (500 g/d per cow). For non-lactating cows, dietary treatments consisted of a basal diet (control; no fat supplement) and fat-supplemented diets containing SO (170 g/d per cow) or HPO (170 g/d per cow). Compared with the control and SO diet, HPO addition increased (p < 0.05) the concentration of C16:0, C18:0, C18:2cis-9,12, C18:3cis-9,12,15 and total saturated and polyunsaturated FA in the plasma of lactating cows. In non-lactating cows, the SO addition increased the plasma concentration of C18:1trans-11. In lactating cows, concentrations of C16:0, C18:0 and total saturated FA were increased (p < 0.05) by HPO addition in the high-density lipoprotein (HDL). Total saturated FA were increased (p < 0.05) by HPO in very-low-density lipoprotein (VLDL). In non-lactating cows, the concentration of C18:0 was increased (p < 0.05) by HPO in HDL, whereas C18:1trans-11 was increased (p < 0.05) by SO in the low-density lipoprotein. Overall, it was found that distribution and transport of FA within the bovine plasma lipoproteins may be influenced by chain length and degree of unsaturation of dietary lipids. Also, the distribution of individual FA isomers such as C18:1trans-11 and C18:2cis-9,trans-11 may vary depending on the physiological state of the cow (lactating or non-lactating), and are increased in plasma (lactating cows) and the HDL (non-lactating cows) when cows are fed SO. PMID:27216557

  15. [Basic mechanisms: structure, function and metabolism of plasma lipoproteins].

    PubMed

    Errico, Teresa L; Chen, Xiangyu; Martin Campos, Jesús M; Julve, Josep; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2013-01-01

    The aim of this work is to present basic information on the lipoprotein physiology. The protein fraction of lipoproteins consists of several apolipoproteins and enzymes whose functions are lipid transport and metabolism. Classification of lipoproteins is based on their density. Chylomicrons, VLDL, IDL, LDL and HDL can be isolated by ultracentrifugation. Both chylomicrons- and VLDL-triglycerides are transported from the intestine and liver, respectively, to the peripheral tissues. The metabolism of VLDL originates IDL and LDL. LDL is the main transporter of cholesterol to extrahepatic tissues. HDL mobilizes cholesterol from peripheral tissues to the liver where it is secreted to bile as free cholesterol or bile salts, a process termed reverse cholesterol transport. Lipoprotein metabolism can be regulated by nuclear receptors that regulate the expression of genes involved in triglyceride and apolipoprotein metabolism. PMID:23769508

  16. Hypochlorite, oxidative modification of plasma lipoproteins, and atherosclerosis.

    PubMed

    Panasenko, O M; Sergienko, V I

    2001-05-01

    Hypochlorite produced in vivo by activated neutrophils, monocytes, and macrophages modifies blood lipoproteins and intensifies free radical lipid peroxidation, which probably plays a key role in the early stages of atherosclerotic vascular damages. PMID:11550040

  17. 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

  18. Catabolism of low density lipoproteins by perfused rabbit livers: cholestyramine promotes receptor-dependent hepatic catabolism of low density lipoproteins.

    PubMed

    Chao, Y S; Yamin, T T; Alberts, A W

    1982-07-01

    Rabbits fed a wheat starch/casein diet develop a marked hypercholesterolemia accompanied by a decrease in the number of EDTA-sensitive binding sites on plasma membrane fractions of the liver for low density lipoproteins (LDL) and beta-migrating very low density lipoproteins [Chao, Y.-S., Yamin, T.-T. & Alberts, A. W. (1982) J. Biol. Chem., in press]. Inclusion of 1% cholestyramine resin in this diet prevents the increase in plasma cholesterol, increases the removal of LDL from plasma, and increases the number of hepatic plasma membrane LDL-binding sites. To determine the functional role of hepatic LDL-binding sites in the catabolism of LDL, we studied the catabolism of (125)I-labeled LDL ((125)I-LDL) by in situ perfused rabbit livers in a recirculating system. The rate of catabolism was measured from the increment of nonprotein-bound radioiodine in the perfusate. The receptor-dependent catabolism of LDL by the liver was calculated from the difference of hepatic catabolism of (125)I-LDL and catabolism of (125)I-labeled cyclohexanedione-modified LDL, which does not bind to LDL receptors. The data show that about 74% of LDL catabolized by perfused livers from chow-fed rabbits is through the receptor-dependent pathway and 26% is through the receptor-independent pathway. In rabbits fed a cholesterol diet, the hepatic catabolism of (125)I-LDL is reduced, and the receptor-dependent catabolism of (125)I-LDL is abolished. In rabbits fed the wheat starch/casein diet, the receptor-dependent catabolism of (125)I-LDL is reduced by 40% when compared with hepatic catabolism in chow-fed rabbits. Perfused livers from rabbits fed the wheat starch/casein diet supplemented with 1% cholestyramine show a 5,4-fold increase of receptor-dependent catabolism of (125)I-LDL when compared with that of livers from rabbits fed the wheat starch/casein diet alone. Thus, these studies demonstrate that the change in the number of rabbit hepatic membrane LDL receptors induced by dietary manipulation

  19. Angiopoietin-like protein 4 inhibition of lipoprotein lipase: evidence for reversible complex formation.

    PubMed

    Lafferty, Michael J; Bradford, Kira C; Erie, Dorothy A; Neher, Saskia B

    2013-10-01

    Elevated triglycerides are associated with an increased risk of cardiovascular disease, and lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of triglycerides from circulating lipoproteins. The N-terminal domain of angiopoietin-like protein 4 (ANGPTL4) inhibits LPL activity. ANGPTL4 was previously described as an unfolding molecular chaperone of LPL that catalytically converts active LPL dimers into inactive monomers. Our studies show that ANGPTL4 is more accurately described as a reversible, noncompetitive inhibitor of LPL. We find that inhibited LPL is in a complex with ANGPTL4, and upon dissociation, LPL regains lipase activity. Furthermore, we have generated a variant of ANGPTL4 that is dependent on divalent cations for its ability to inhibit LPL. We show that LPL inactivation by this regulatable variant of ANGPTL4 is fully reversible after treatment with a chelator. PMID:23960078

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

    PubMed

    Drüeke, T B; Nguyen Khoa, T; Massy, Z A; Witko-Sarsat, V; Lacour, B; Descamps-Latscha, B

    2001-02-01

    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 that oxidation of LDL by hypochlorous acid (HOCl) in vitro, reflecting increased myeloperoxidase activity in vivo, leads to modifications of apoliproteins such that the latter in turn are capable of triggering macrophage nicotinamide adenine dinucleotide phosphate-oxidase activation. These oxidative changes of LDL protein moiety, if shown to occur to a significant extent in uremic patients in vivo, may represent an important alternative pathway in the pathogenesis of atheromatous lesions. PMID:11168995

  1. Structural and compositional changes attending the ultracentrifugation of very low density lipoproteins.

    PubMed

    Herbert, P N; Forte, T M; Shulman, R S; La Piana, M J; Gong, E L; Levy, R I; Fredrickson, D S; Nichols, A V

    1975-01-01

    The effects of repetitive ultracentrifugation on the physical and chemical properties of very low density lipoproteins (VLDL) were investigated. VLDL recentrifuged one to seven times were characterized by chemical analyses, analytical ultracentrifugation and electron microscopy. The VLDL content of triglyceride was increased and the proportion of phospholipid decreased by ultracentrifugation. Recentrifugation of VLDL decreased the number of Sf-o 20-100 particles and generated particles of Sf-o greater than 400. The bulk of the material removed from VLDL by ultracentrifugation was lipoprotein having pre-beta mobility on paper electrophoresis, flotation rates of Sf-o 10-100 and a particle size of 300-400 A-O. Two ultracentrifugations separated an average of 14% of the starting VLDL protein. Characterization of the apoproteins in this material by polyacrylamide gel electrophoresis, gel chromatography, immunoprecipitation and amino acid analysis demonstrated a relatively high proportion of beta-apoprotein and relatively little C-apoproteins. PMID:167365

  2. The use of transgenic animals to study lipoprotein metabolism

    SciTech Connect

    Rubin, E.M.; Plump, A.S.

    1993-12-01

    The application of transgenic technology to lipoprotein metabolism and atherosclerosis was first reported in 1988. Today, a large percentage of the genes involved in lipoprotein metabolism have been overexpressed in mice, and a substantial number of these same genes have been disrupted by homologous recombination in embryonic stem (ES) cells. The utility of animal models of lipoprotein metabolism and atherosclerosis is far-reaching given the complex nature of these systems. There are at least 17 known genes directly involved in lipoprotein metabolism and likely dozens more may be involved. This massive network of interacting factors has necessitated the development of in vivo systems which can be subject to genetic manipulation. The power of overexpression is obvious: elucidating function in a relatively controlled genetic environment in which the whole system is present and operational. The not-so-obvious problem with transgenics is ``background,`` or for purposes of the current discussion, the mouse`s own lipoprotein system. With the advent of gene knockout, we have been given the ability to overcome ``background.`` By recreating the genetic complement of the mouse we can alter a system in essentially any manner desired. As unique tools, and in combination with one another, the overexpression of foreign genes and the targeted disruption or alteration of endogenous genes has already and will continue to offer a wealth of information on the biology of lipoprotein metabolism and its effect on atherosclerosis susceptibility.

  3. Isolation and characterization of the haemolymph lipoproteins of Triatoma infestans.

    PubMed

    Fichera, L E; Brenner, R R

    1982-01-01

    1. Three lipoproteins differing in hydrated densities were isolated by ultracentrifugal procedures from the haemolymph of adult and fasted Triatoma infestans. 2. They are the high density lipoprotein HDL (d = 1.115-1.152) and the two very high density lipoproteins VHDL-I (d = 1.190-1.231) and VHDL-II (d = 1.245-1.260). HDL was the predominant lipoprotein. 3. The total lipid content expressed as % of lipoprotein weight in HDL, VHDL-I an VHDL-II was 30.1, 7.8 ad 2.9% respectively. Diacylglycerols are the predominant lipids of HDL (38.7%) and VHDL-I (27.0%) but only amount of 6.2% in VHDL-II. 4. Triacylglycerols are minor components (about 6.0%) of all fractions. 5. The phospholipids (phosphatidylethanolamine and phosphatidylcholine), sterols, sterol esters and hydrocarbons were present in all lipoprotein fractions. 6. Phospholipids and hydrocarbons were the most abundant lipids of VHDL-II. PMID:7049559

  4. A study of the abnormal lipoproteins in abetalipoproteinemia.

    PubMed Central

    Scanu, A M; Aggerbeck, L P; Kruski, A W; Lim, C T; Kayden, H J

    1974-01-01

    The serum lipoproteins of five patients with abetalipoproteinemia (ABL) were separated by ultracentrifugation and then analyzed either intact or after delipidation. In accord with previous findings, all of the patients lacked serum particles with the characteristics of normal low-density lipoproteins (LDL) and of the LDL apoprotein as assessed by immunochemical methods. Each patient exhibited on every examination an abnormal particle, "LDL", which had the flotational properties of LDL, the polypeptide makeup of high-density lipoproteins HDL, the spectral and morphological characteristics of neither LDL nor HDL, and a relatively low content of cholesteryl esters. The HDL were abnormal in having a marked decrease in their total plasma content, an altered proportion of the subclasses HDL2 and HDL3, and a peculiar polypeptide distribution, comprising both normal and additional components, usually not seen in normal controls. The patients also exhibited a decrease of plasma lecithin-cholesterol acyl transferase (LCAT) activity which probably accounted for the low content of cholesteryl esters in both "LDL" and HDL, and in turn for the unusual appearance of "LDL" on electron microscopy. It is concluded that ABL is a disorder affecting all serum lipoprotein classes. Whether the abetalipoproteinemia previously described and noted in the current studies is related to or independent of the abnormalities observed in the other lipoproteins was not established. How the deficiency of LCAT activity, observed in all patients studied, contributed to some of the observed structural lipoprotein abnormalities also remained undetermined. Images PMID:11344558

  5. The Cross-Talk between Spirochetal Lipoproteins and Immunity

    PubMed Central

    Kelesidis, Theodoros

    2014-01-01

    Spirochetal diseases such as syphilis, Lyme disease, and leptospirosis are major threats to public health. However, the immunopathogenesis of these diseases has not been fully elucidated. Spirochetes interact with the host through various structural components such as lipopolysaccharides (LPS), surface lipoproteins, and glycolipids. Although spirochetal antigens such as LPS and glycolipids may contribute to the inflammatory response during spirochetal infections, spirochetes such as Treponema pallidum and Borrelia burgdorferi lack LPS. Lipoproteins are most abundant proteins that are expressed in all spirochetes and often determine how spirochetes interact with their environment. Lipoproteins are pro-inflammatory, may regulate responses from both innate and adaptive immunity and enable the spirochetes to adhere to the host or the tick midgut or to evade the immune system. However, most of the spirochetal lipoproteins have unknown function. Herein, the immunomodulatory effects of spirochetal lipoproteins are reviewed and are grouped into two main categories: effects related to immune evasion and effects related to immune activation. Understanding lipoprotein-induced immunomodulation will aid in elucidating innate immunopathogenesis processes and subsequent adaptive mechanisms potentially relevant to spirochetal disease vaccine development and to inflammatory events associated with spirochetal diseases. PMID:25071771

  6. The Cross-Talk between Spirochetal Lipoproteins and Immunity.

    PubMed

    Kelesidis, Theodoros

    2014-01-01

    Spirochetal diseases such as syphilis, Lyme disease, and leptospirosis are major threats to public health. However, the immunopathogenesis of these diseases has not been fully elucidated. Spirochetes interact with the host through various structural components such as lipopolysaccharides (LPS), surface lipoproteins, and glycolipids. Although spirochetal antigens such as LPS and glycolipids may contribute to the inflammatory response during spirochetal infections, spirochetes such as Treponema pallidum and Borrelia burgdorferi lack LPS. Lipoproteins are most abundant proteins that are expressed in all spirochetes and often determine how spirochetes interact with their environment. Lipoproteins are pro-inflammatory, may regulate responses from both innate and adaptive immunity and enable the spirochetes to adhere to the host or the tick midgut or to evade the immune system. However, most of the spirochetal lipoproteins have unknown function. Herein, the immunomodulatory effects of spirochetal lipoproteins are reviewed and are grouped into two main categories: effects related to immune evasion and effects related to immune activation. Understanding lipoprotein-induced immunomodulation will aid in elucidating innate immunopathogenesis processes and subsequent adaptive mechanisms potentially relevant to spirochetal disease vaccine development and to inflammatory events associated with spirochetal diseases. PMID:25071771

  7. Effects of zinc and cholesterol/choleate on serum lipoproteins and the liver in rats

    SciTech Connect

    Cho, C.H.; Chen, S.M.; Ogle, C.W.; Young, T.K.

    1989-01-01

    The effects of short-term treatment with orally-administered zinc sulfate and/or a mixture of cholesterol/choleate on serum lipoprotein and hepatic enzyme levels were studied. Administration of graded doses of zinc sulfate for 5 days, dose-dependently increased serum and hepatic zinc levels but depressed the serum high-density lipoprotein-cholesterol (HDL-C) concentration and liver cytochrome P-450 activity. However, it did not affect hepatic concentrations of malondialdehyde and free {beta}-glucuronidase. Cholesterol/choleate treatment for 5 days markedly damaged the liver, as reflected by elevations of hepatic concentrations of malondialdehyde (both in the mitochondrial and microsomal fractions) and of free {beta}-glucuronidase; total cholesterol and low-density lipoprotein-cholesterol in the blood were increased, whereas HDL-C was decreased significantly. Concomitant administration of zinc sulfate with cholesterol/choleate further lowered HDL-C levels, but reversed the high hepatic concentrations of both malondialdehyde and free {beta}-glucuronidase. The present study indicates that both zinc ions and cholesterol can decrease circulatory HDL-C levels and that zinc protects against cholesterol-induced hepatic damage by reducing lysosomal enzyme release and preventing lipid peroxidation in the liver.

  8. Lipoprotein Particle Profiles by Nuclear Magnetic Resonance Spectroscopy in Medically-Underserved HIV-Infected Persons

    PubMed Central

    Swanson, Barbara; Sha, Beverly E.; Keithley, Joyce K.; Fogg, Louis; Nerad, Judith; Novak, Richard; Adeyemi, Oluwatoyin

    2009-01-01

    Background HIV infection is associated with dyslipidemia and increased risk for cardiovascular events. Few studies have described lipid status in medically-underserved, HIV-infected ethnic minorities, a group that is characterized by health disparities. Objective The objective was to characterize the lipid profile of a medically-underserved, largely ethnic minority sample of HIV-infected persons using standard lipid panels and nuclear magnetic resonance (NMR) -derived lipoprotein particle profiles. Methods Participants were recruited from a randomized controlled trial of a dietary supplement to manage HIV-related dyslipidemia (N=132). At the initial screening visit, sociodemographic, clinical, and behavioral data were collected, and fasting peripheral venous blood specimens were obtained and lipid status was analyzed using the standard lipid panel and the NMR-derived lipoprotein particle profile. Results Using NMR-derived LDL particle cutoffs, a higher percentage of participants was outside the target range (50%) than when standard LDL cholesterol NCEP cutoffs were used (24%). Antiretroviral therapy, especially protease inhibitor-containing regimens, was associated with higher LDL particle concentration. Conclusion Substantial numbers of medically-underserved, asymptomatic HIV-infected minorities may be at increased risk for CHD based on NMR-derived lipoprotein values. PMID:20161509

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

    PubMed Central

    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

  10. Absorption and transport of deuterium-substituted 2R,4'R,8'R-alpha-tocopherol in human lipoproteins

    SciTech Connect

    Traber, M.G.; Ingold, K.U.; Burton, G.W.; Kayden, H.J.

    1988-08-01

    Oral administration of a single dose of tri- or hexadeuterium substituted 2R,4'R,8'R-alpha-tocopheryl acetate (d3- or d6-alpha-T-Ac) to humans was used to follow the absorption and transport of vitamin E in plasma lipoproteins. Three hr after oral administration of d3-alpha-T-Ac (15 mg) to 2 subjects, plasma levels of d3-alpha-T were detectable; these increased up to 10 hr, reached a plateau at 24 hr, then decreased. Following administration of d6-alpha-T-Ac (15-16 mg) to 2 subjects, the percentage of deuterated tocopherol relative to the total tocopherol in chylomicrons increased more rapidly than the corresponding percentage in whole plasma. Chylomicrons and plasma lipoproteins were isolated from 2 additional subjects following administration of d3-alpha-T-Ac (140 or 60 mg). The percentage of deuterated tocopherol relative to the total tocopherol increased most rapidly in chylomicrons, then in very low density lipoproteins (VLDL), followed by essentially identical increases in low and high density lipoproteins (LDL and HDL, respectively) and lastly, in the red blood cells. This pattern of appearance of deuterated tocopherol is consistent with the concept that newly absorbed vitamin E is secreted by the intestine into chylomicrons; subsequently, chylomicron remnants are taken up by the liver from which the vitamin E is secreted in VLDL. The metabolism of VLDL in the circulation results in the simultaneous delivery of vitamin E into LDL and HDL.

  11. TRIGLYCERIDE-RICH LIPOPROTEIN LIPOLYSIS RELEASES NEUTRAL AND OXIDIZED FREE FATTY ACIDS THAT INDUCE ENDOTHELIAL CELL INFLAMMATION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective–Increased products of triglyceride-rich lipoprotein (TGRL) lipolysis provide a pro-inflammatory stimulus that may alter endothelial barrier function. To probe the mechanism of this lipolysis-induced dysfunction, we evaluated the pro-inflammatory potential of lipid classes derived from huma...

  12. Changes of very low-density lipoprotein concentration in hepatic blood from cows with fasting-induced hepatic lipidosis

    PubMed Central

    Oikawa, Shin; Mizunuma, Yuko; Iwasaki, Yukari; Tharwat, Mohamed

    2010-01-01

    The purpose of this study was to evaluate changes of very low-density lipoprotein (VLDL) components in hepatic blood (HB) from 5 nonlactating nonpregnant cows fasted from days 0 to 3 and subsequently refed to day 10 and, in addition, to assess those of other lipoproteins. Increased phospholipid concentrations in each lipoprotein after the start of fasting suggested their availability for the surface lipids of lipoproteins. Although the VLDL-triglyceride (TG) concentration in HB from all cows increased on day 1, the value on day 4 became similar to that on day 0. However, the concentration on day 10 was significantly increased. In all cows, the decreased ratio of the VLDL-TG concentration in HB to the non-esterified fatty acids (NEFA) concentration in portal blood (PB) on day 4 appeared to reflect relatively decreased secretion of TG as VLDL by NEFA excessively mobilized to the liver via PB. The markedly increased ratio on day 10 was considered to contribute to the improvement of hepatic lipidosis. PMID:21197233

  13. 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...

  14. Effects of angiopoietin-like protein 3 deficiency on postprandial lipid and lipoprotein metabolism.

    PubMed

    Minicocci, Ilenia; Tikka, Anna; Poggiogalle, Eleonora; Metso, Jari; Montali, Anna; Ceci, Fabrizio; Labbadia, Giancarlo; Fontana, Mario; Di Costanzo, Alessia; Maranghi, Marianna; Rosano, Aldo; Ehnholm, Christian; Donini, Lorenzo Maria; Jauhiainen, Matti; Arca, Marcello

    2016-06-01

    The consequences of angiopoietin-like protein 3 (ANGPTL3) deficiency on postprandial lipid and lipoprotein metabolism has not been investigated in humans. We studied 7 homozygous (undetectable circulating ANGPTL3 levels) and 31 heterozygous (50% of circulating ANGPTL3 levels) subjects with familial combined hypolipidemia (FHBL2) due to inactivating ANGPTL3 mutations in comparison with 35 controls. All subjects were evaluated at fasting and during 6 h after a high fat meal. Postprandial lipid and lipoprotein changes were quantified by calculating the areas under the curve (AUCs) using the 6 h concentration data. Plasma changes of β-hydroxybutyric acid (β-HBA) were measured as marker of hepatic oxidation of fatty acids. Compared with controls, homozygotes showed lower incremental AUCs (iAUCs) of total TG (-69%, P < 0.001), TG-rich lipoproteins (-90%, P < 0.001), apoB-48 (-78%, P = 0.032), and larger absolute increase of FFA (128%, P < 00.1). Also, heterozygotes displayed attenuated postprandial lipemia, but the difference was significant only for the iAUC of apoB-48 (-28%; P < 0.05). During the postprandial period, homozygotes, but not heterozygotes, showed a lower increase of β-HBA. Our findings demonstrate that complete ANGPTL3 deficiency associates with highly reduced postprandial lipemia probably due to faster catabolism of intestinally derived lipoproteins, larger expansion of the postprandial FFA pool, and decreased influx of dietary-derived fatty acids into the liver. These results add information on mechanisms underlying hypolipidemia in FHBL2. PMID:27040449

  15. Correlation analysis between serum lipoprotein (a) and the incidence of aortic valve sclerosis

    PubMed Central

    Yang, Ning; Zhang, Guogang; Li, Xiaogang; Zhou, Liping

    2015-01-01

    This clinical trial explores the correlation between serum lipoprotein and the severity of aortic valve sclerosis in patients diagnosed with aortic valve sclerosis (AVS). A total of 1260 subjects diagnosed with AVS were enrolled in this study between May 2005 and June 2013 and divided into the young-aged (30-59 years, n=217), middle-aged (60-74 years, n=561) and elderly groups (75-93 years, n=482). In each group, patients were sub-grouped into AVS and healthy controls according to angiography findings. Parameters including triglyceride (TG), serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), free fatty acid (FFA), lipoprotein (a) [Lp(a)], apolipoprotein A1 (ApoAl) and apolipoprotein B (ApoB) were accurately measured. Correlation between these parameters and the severity of AVS was statistically evaluated. In the middle-aged and elderly groups, serum Lp(a), TC and LDL-C were significantly higher in patients with AVS compared with healthy counterparts (both P<0.05). In the elderly group, serum HDL-C in AVS patients was significantly lower than healthy subjects (P<0.05). In the young-aged group, serum Lp(a) and ApoB were significantly increased compared with healthy counterparts (both P<0.05). Gemini score in the elderly group was significantly higher than the other groups (both P<0.01). No statistical significance was observed in Lp(a) levels among groups I, II and III. The number of coronary stenosis in group III was significantly increased than those in groups I and II (P<0.01). Lp(a), LDL-C and aging act as independent risk factors of AVS and promote the incidence and progress of AVS. PMID:26770570

  16. Lipoprotein (a) measurements for clinical application.

    PubMed

    Marcovina, Santica M; Albers, John J

    2016-04-01

    The high degree of size heterogeneity of apo(a), the distinct protein component of lipoprotein (a) [Lp(a)], renders the development and selection of specific antibodies directed to apo(a) more difficult and poses significant challenges to the development of immunoassays to measure its concentration in plasma or serum samples. Apo(a) is extremely variable in size not only between but also within individuals because of the presence of two different, genetically determined apo(a) isoform sizes. Therefore, the antigenic determinants per particle available to interact with the antibodies will vary in the samples and the calibrators, thus contributing to apo(a) size-dependent inaccuracy of different methods. The lack of rigorous validation of the immunoassays and common means of expressing Lp(a) concentrations hinder the harmonization of results obtained by different studies and contribute to the lack of common cut points for identification of individuals at risk for coronary artery disease or for interventions aimed at reducing Lp(a) levels. The aim of our review is to present and critically evaluate the issues surrounding the measurements of Lp(a), their impact on the clinical interpretation of the data, and the obstacles we need to overcome to achieve the standardization of Lp(a) measurements. PMID:26637278

  17. Lipoprotein(a) in Cardiovascular Diseases

    PubMed Central

    Malaguarnera, Michele; Vacante, Marco; Russo, Cristina; Malaguarnera, Giulia; Antic, Tijana; Malaguarnera, Lucia; Bella, Rita; Pennisi, Giovanni; Galvano, Fabio; Frigiola, Alessandro

    2013-01-01

    Lipoprotein(a) (Lp(a)) is an LDL-like molecule consisting of an apolipoprotein B-100 (apo(B-100)) particle attached by a disulphide bridge to apo(a). Many observations have pointed out that Lp(a) levels may be a risk factor for cardiovascular diseases. Lp(a) inhibits the activation of transforming growth factor (TGF) and contributes to the growth of arterial atherosclerotic lesions by promoting the proliferation of vascular smooth muscle cells and the migration of smooth muscle cells to endothelial cells. Moreover Lp(a) inhibits plasminogen binding to the surfaces of endothelial cells and decreases the activity of fibrin-dependent tissue-type plasminogen activator. Lp(a) may act as a proinflammatory mediator that augments the lesion formation in atherosclerotic plaques. Elevated serum Lp(a) is an independent predictor of coronary artery disease and myocardial infarction. Furthermore, Lp(a) levels should be a marker of restenosis after percutaneous transluminal coronary angioplasty, saphenous vein bypass graft atherosclerosis, and accelerated coronary atherosclerosis of cardiac transplantation. Finally, the possibility that Lp(a) may be a risk factor for ischemic stroke has been assessed in several studies. Recent findings suggest that Lp(a)-lowering therapy might be beneficial in patients with high Lp(a) levels. A future therapeutic approach could include apheresis in high-risk patients in order to reduce major coronary events. PMID:23484137

  18. Hemorheological abnormalities in lipoprotein lipase deficient mice with severe hypertriglyceridemia

    SciTech Connect

    Zhao Tieqiang; Guo Jun; Li Hui; Huang Wei; Xian Xunde; Ross, Colin J.D.; Hayden, Michael R.; Wen Zongyao . E-mail: rheol@bjmu.edu.cn; Liu George . E-mail: vangeorgeliu@gmail.com

    2006-03-24

    Severe hypertriglyceridemia (HTG) is a metabolic disturbance often seen in clinical practice. It is known to induce life-threatening acute pancreatitis, but its role in atherogenesis remains elusive. Hemorheological abnormality was thought to play an important role in pathogenesis of both pancreatitis and atherosclerosis. However, hemorheology in severe HTG was not well investigated. Recently, we established a severe HTG mouse model deficient in lipoprotein lipase (LPL) in which severe HTG was observed to cause a significant increase in plasma viscosity. Disturbances of erythrocytes were also documented, including decreased deformability, electrophoresis rate, and membrane fluidity, and increased osmotic fragility. Scanning electron microscopy demonstrated that most erythrocytes of LPL deficient mice deformed with protrusions, irregular appearances or indistinct concaves. Analysis of erythrocyte membrane lipids showed decreased cholesterol (Ch) and phospholipid (PL) contents but unaltered Ch/PL ratio. The changes of membrane lipids may be partially responsible for the hemorheological and morphologic abnormalities of erythrocytes. This study indicated that severe HTG could lead to significant impairment of hemorheology and this model may be useful in delineating the role of severe HTG in the pathogenesis of hyperlipidemic pancreatitis and atherosclerosis.

  19. TLR2-Modulating Lipoproteins of the Mycobacterium tuberculosis Complex Enhance the HIV Infectivity of CD4+ T Cells.

    PubMed

    Skerry, Ciaran; Klinkenberg, Lee G; Page, Kathleen R; Karakousis, Petros C

    2016-01-01

    Co-infection with Mycobacterium tuberculosis accelerates progression from HIV to AIDS. Our previous studies showed that M. tuberculosis complex, unlike M. smegmatis, enhances TLR2-dependent susceptibility of CD4+ T cells to HIV. The M. tuberculosis complex produces multiple TLR2-stimulating lipoproteins, which are absent in M. smegmatis. M. tuberculosis production of mature lipoproteins and TLR2 stimulation is dependent on cleavage by lipoprotein signal peptidase A (LspA). In order to determine the role of potential TLR2-stimulating lipoproteins on mycobacterial-mediated HIV infectivity of CD4+ T cells, we generated M. smegmatis recombinant strains overexpressing genes encoding various M. bovis BCG lipoproteins, as well as a Mycobacterium bovis BCG strain deficient in LspA (ΔlspA). Exposure of human peripheral blood mononuclear cells (PBMC) to M. smegmatis strains overexpressing the BCG lipoproteins, LprF (p<0.01), LprH (p<0.05), LprI (p<0.05), LprP (p<0.001), LprQ (p<0.005), MPT83 (p<0.005), or PhoS1 (p<0.05), resulted in increased HIV infectivity of CD4+ T cells isolated from these PBMC. Conversely, infection of PBMC with ΔlspA reduced HIV infectivity of CD4+ T cells by 40% relative to BCG-infected cells (p<0.05). These results may have important implications for TB vaccination programs in areas with high mother-to-child HIV transmission. PMID:26807859

  20. TLR2-Modulating Lipoproteins of the Mycobacterium tuberculosis Complex Enhance the HIV Infectivity of CD4+ T Cells

    PubMed Central

    Skerry, Ciaran; Klinkenberg, Lee G.; Page, Kathleen R.; Karakousis, Petros C.

    2016-01-01

    Co-infection with Mycobacterium tuberculosis accelerates progression from HIV to AIDS. Our previous studies showed that M. tuberculosis complex, unlike M. smegmatis, enhances TLR2-dependent susceptibility of CD4+ T cells to HIV. The M. tuberculosis complex produces multiple TLR2-stimulating lipoproteins, which are absent in M. smegmatis. M. tuberculosis production of mature lipoproteins and TLR2 stimulation is dependent on cleavage by lipoprotein signal peptidase A (LspA). In order to determine the role of potential TLR2-stimulating lipoproteins on mycobacterial-mediated HIV infectivity of CD4+ T cells, we generated M. smegmatis recombinant strains overexpressing genes encoding various M. bovis BCG lipoproteins, as well as a Mycobacterium bovis BCG strain deficient in LspA (ΔlspA). Exposure of human peripheral blood mononuclear cells (PBMC) to M. smegmatis strains overexpressing the BCG lipoproteins, LprF (p<0.01), LprH (p<0.05), LprI (p<0.05), LprP (p<0.001), LprQ (p<0.005), MPT83 (p<0.005), or PhoS1 (p<0.05), resulted in increased HIV infectivity of CD4+ T cells isolated from these PBMC. Conversely, infection of PBMC with ΔlspA reduced HIV infectivity of CD4+ T cells by 40% relative to BCG-infected cells (p<0.05). These results may have important implications for TB vaccination programs in areas with high mother-to-child HIV transmission. PMID:26807859

  1. [THE LIPOLYSIS IN PHYLOGENETICALLY EARLY LIPOPROTEINS OF LOW DENSITY AND MORE LATER LIPOPROTEINS OF VERY LOW DENSITY: FUNCTION AND DIAGNOSTIC VALUE OF APOE AND APOC-III].

    PubMed

    Rozhkova, T A; Titov, V N; Amelyushkina, V A; Kaba, S I; Kukhartchuk, V V

    2015-12-01

    According to phylogenetic theory of general pathology, the function of low density lipoproteins (LDL) and hydrolysis of triglycerides (TG) in them under the effect of hepatic glycerol hydrolase apoC-III (HGH) developed at much earlier stages of phylogenesis than functioning of insulin-dependent phylogenetically late very low density lipoproteins (VLDL). For millions ofyears, lipolysis and HGH+apoC-III have activated transfer of polyenic fatty acids (FA) in the form of cholesteryl polyesters (CLE) from high density lipoproteins (HDL) to linoleic and linolenic LDL under the effect of cholesteryl ester transfer protein. It is reasonable to suggest that hepatocytes physiologically secrete oleic and palmitic VLDL and linoleic and linolenic LDL. Cells uptake ligand oleic and palmitic VLVL by apoE/B-100 receptor-mediated endocytosis. Physiologically, VLDL are not converted to LDL. If hepatocytes secrete palmitic VLDL in greater amounts than oleic VLDL upon slow hydrolysis ofpalmitic TG and under the effect of postheparinic lipoprotein lipase+apoC-II, only some proportion of palmitic TG is uptaken by cells as VLDL, and the rest is converted in ligand-free palmitic LDL These LDL increase plasma contents of TG and LDL-cholesterol and form small dense palmitic LDL. Expression of HGH+apoC-III synthesis compensates TG hydrolysis in nonphysiological palmitic LDL. In vivo, apoC-III is neither physiological no pathological inhibitor of lipolysis. Increase in plasma apoC-III content is an indicator of accumulation of non-physiological palmitic LDL and atherosclerosis-atheromatosis risk factor ApoE content ofpalmitic LDL increases together with apoC-III, i.e., apoE in ligand VLDL is not internalized via apoE/B-100 endocytosis. An increase in apoC-III and apoE contents are reliable in vivo tests for the rise inpalmitic FA, palmitic TG and excessive secretion of palmitic VLDL by hepatocytes. ApoC-III and apoE contents in LDL are additional tests to evaluate the efficiency of

  2. Lipoprotein profiles in human heterozygote carriers of a functional mutation P297S in scavenger receptor class B1.

    PubMed

    Ljunggren, Stefan A; Levels, Johannes H M; Hovingh, Kees; Holleboom, Adriaan G; Vergeer, Menno; Argyri, Letta; Gkolfinopoulou, Christina; Chroni, Angeliki; Sierts, Jeroen A; Kastelein, John J; Kuivenhoven, Jan Albert; Lindahl, Mats; Karlsson, Helen

    2015-12-01

    The scavenger receptor class B type 1 (SR-B1) is an important HDL receptor involved in cholesterol uptake and efflux, but its physiological role in human lipoprotein metabolism is not fully understood. Heterozygous carriers of the SR-B1(P297S) mutation are characterized by increased HDL cholesterol levels, impaired cholesterol efflux from macrophages and attenuated adrenal function. Here, the composition and function of lipoproteins were studied in SR-B1(P297S) heterozygotes.Lipoproteins from six SR-B1(P297S) carriers and six family controls were investigated. HDL and LDL/VLDL were isolated by ultracentrifugation and proteins were separated by two-dimensional gel electrophoresis and identified by mass spectrometry. HDL antioxidant properties, paraoxonase 1 activities, apoA-I methionine oxidations and HDL cholesterol efflux capacity were assessed.Multivariate modeling separated carriers from controls based on lipoprotein composition. Protein analyses showed a significant enrichment of apoE in LDL/VLDL and of apoL-1 in HDL from heterozygotes compared to controls. The relative distribution of plasma apoE was increased in LDL and in lipid-free form. There were no significant differences in paraoxonase 1 activities, HDL antioxidant properties or HDL cholesterol efflux capacity but heterozygotes showed a significant increase of oxidized methionines in apoA-I.The SR-B1(P297S) mutation affects both HDL and LDL/VLDL protein compositions. The increase of apoE in carriers suggests a compensatory mechanism for attenuated SR-B1 mediated cholesterol uptake by HDL. Increased methionine oxidation may affect HDL function by reducing apoA-I binding to its targets. The results illustrate the complexity of lipoprotein metabolism that has to be taken into account in future therapeutic strategies aiming at targeting SR-B1. PMID:26454245

  3. microRNAs in lipoprotein metabolism and cardiometabolic disorders.

    PubMed

    Rotllan, Noemi; Price, Nathan; Pati, Paramita; Goedeke, Leigh; Fernández-Hernando, Carlos

    2016-03-01

    Circulating levels of low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) are two of the most important risk factors for the development of cardiovascular disease (CVD), the leading cause of death worldwide. Recently, miRNAs have emerged as critical regulators of cholesterol metabolism and promising therapeutic targets for the treatment of CVD. A great deal of work has established numerous miRNAs as important regulators of HDL metabolism. This includes miRNAs that target ABCA1, a critical factor for HDL biogenesis and reverse cholesterol transport (RCT), the process through which cells, including arterial macrophages, efflux cellular cholesterol for transport to and removal by the liver. The most well studied of these miRNAs, miR-33, has been demonstrated to target ABCA1, as well as numerous other genes involved in metabolic function and RCT, and therapeutic inhibition of miR-33 was found to increase HDL levels in mice and non-human primates. Moreover, numerous studies have demonstrated the beneficial effects of miR-33 inhibition or knockout on reducing atherosclerotic plaque burden. Even more recent work has identified miRNAs that regulate LDL cholesterol levels, including direct modulation of LDL uptake in the liver through targeting of the LDL receptor. Among these, inhibition of miR-128-1, miR-148a, or miR-185 was found to reduce plasma LDL levels, and inhibition of miR-185 was further demonstrated to reduce atherosclerotic plaque size in ApoE(-/-) mice. Due to their ability to target many different genes, miRNAs have the ability to mediate complex physiologic changes through simultaneous regulation of multiple interrelated pathways. Of particular importance for CVD, inhibition of miR-148a may prove an important therapeutic approach for combating dyslipidemia, as this has been demonstrated to both raise plasma HDL levels and lower LDL levels in mice by targeting both ABCA1 and LDLR, respectively. In this review we highlight

  4. The structure of human high density lipoprotein and the levels of apolipoprotein A-I in plasma as determined by radioimmunoassay.

    PubMed

    Schonfeld, G; Pfleger, B

    1974-08-01

    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 [(125)I]-ApoA-I was purified by gel filtration. > 85% of [(125)I]-ApoA-I was precipitated by antibody, and 90% of bound [(125)I]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

  5. Explaining Errors in Children's Questions

    ERIC Educational Resources Information Center

    Rowland, Caroline F.

    2007-01-01

    The ability to explain the occurrence of errors in children's speech is an essential component of successful theories of language acquisition. The present study tested some generativist and constructivist predictions about error on the questions produced by ten English-learning children between 2 and 5 years of age. The analyses demonstrated that,…

  6. Can Marxism Explain America's Racism?

    ERIC Educational Resources Information Center

    Willhelm, Sidney M.

    1980-01-01

    The Marxist interpretation of the Black experience in America has always had difficulty explaining various noneconomic aspects of racism. A perspective is needed that can blend racism as a variable in relationship with economic variables. To reach this perspective, the labor process within capitalism must be more fully understood. (Author/GC)

  7. Vitamin C protects low-density lipoprotein from homocysteine-mediated oxidation.

    PubMed

    Alul, Rushdi H; Wood, Michael; Longo, Joseph; Marcotte, Anthony L; Campione, Allan L; Moore, Michael K; Lynch, Sean M

    2003-04-01

    Homocysteine, an atherogenic amino acid, promotes iron-dependent oxidation of low-density lipoprotein (LDL). We investigated whether vitamin C, a physiological antioxidant, could protect LDL from homocysteine-mediated oxidation. LDL (0.2 mg of protein/ml) was incubated at 37 degrees C with homocysteine (1000 microM) and ferric iron (10-100 microM) in either the absence (control) or presence of vitamin C (5-250 microM). Under these conditions, vitamin C protected LDL from oxidation as evidenced by an increased lag time preceding lipid diene formation (> or = 5 vs. 2.5 h for control), decreased thiobarbituric acid-reactive substances accumulation (< or = 19 +/- 1 nmol/mg when vitamin C > or = 10 microM vs. 32 +/- 3 nmol/mg for control, p <.01), and decreased lipoprotein anodic electrophoretic mobility. Near-maximal protection was observed at vitamin C concentrations similar to those in human blood (50-100 microM); also, some protection was observed even at low concentrations (5-10 microM). This effect resulted neither from altered iron redox chemistry nor enhanced recycling of vitamin E in LDL. Instead, similar to previous reports for copper-dependent LDL oxidation, we found that vitamin C protected LDL from homocysteine-mediated oxidation through covalent lipoprotein modification involving dehydroascorbic acid. Protection of LDL from homocysteine-mediated oxidation by vitamin C may have implications for the prevention of cardiovascular disease. PMID:12654477

  8. Characterization of Lipoprotein Composition and Function in Pediatric Psoriasis Reveals a More Atherogenic Profile

    PubMed Central

    Tom, Wynnis L.; Playford, Martin P.; Admani, Shehla; Natarajan, Balaji; Joshi, Aditya A.; Eichenfield, Lawrence F.; Mehta, Nehal N.

    2015-01-01

    Psoriasis is associated with increased cardiovascular disease (CVD) in adults, but the risk profile of children with psoriasis remains to be fully characterized. We measured lipoprotein composition and function in 44 pediatric psoriasis patients and 44 age- and sex-matched healthy controls, using NMR spectroscopy and a validated ex vivo assay of high density lipoprotein (HDL) cholesterol efflux capacity (CEC). Mean age was 13.0 years and the population was ethnically diverse. Children with psoriasis had higher waist-hip ratios (0.85 vs. 0.80; p<0.002) and insulin resistance measures (log transformed HOMA-IR 0.65 vs. 0.41; p=0.07). Despite comparable traditional lipid values, having psoriasis was associated with higher apolipoprotein B concentrations (72.4 vs. 64.6; p=0.02), decreased large HDL particles (5.3 vs. 6.7; p<0.01), and reduced CEC after adjusting for age, sex, fasting glucose, HOMA-IR, systolic blood pressure, body mass index, apolipoprotein A-1, and HDL cholesterol concentration (beta -0.22, p=0.02). Pediatric psoriasis patients have a more atherogenic cardiometabolic risk profile, with evidence of insulin resistance and lipoprotein dysfunction by particle size, number, and functional assessment. These findings may provide a basis for the observed link later in life between psoriasis and CVD and support the need to screen and educate young patients to minimize later complications. PMID:26763425

  9. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection

    PubMed Central

    Sódar, Barbara W; Kittel, Ágnes; Pálóczi, Krisztina; Vukman, Krisztina V; Osteikoetxea, Xabier; Szabó-Taylor, Katalin; Németh, Andrea; Sperlágh, Beáta; Baranyai, Tamás; Giricz, Zoltán; Wiener, Zoltán; Turiák, Lilla; Drahos, László; Pállinger, Éva; Vékey, Károly; Ferdinandy, Péter; Falus, András; Buzás, Edit Irén

    2016-01-01

    Circulating extracellular vesicles have emerged as potential new biomarkers in a wide variety of diseases. Despite the increasing interest, their isolation and purification from body fluids remains challenging. Here we studied human pre-prandial and 4 hours postprandial platelet-free blood plasma samples as well as human platelet concentrates. Using flow cytometry, we found that the majority of circulating particles within the size range of extracellular vesicles lacked common vesicular markers. We identified most of these particles as lipoproteins (predominantly low-density lipoprotein, LDL) which mimicked the characteristics of extracellular vesicles and also co-purified with them. Based on biophysical properties of LDL this finding was highly unexpected. Current state-of-the-art extracellular vesicle isolation and purification methods did not result in lipoprotein-free vesicle preparations from blood plasma or from platelet concentrates. Furthermore, transmission electron microscopy showed an association of LDL with isolated vesicles upon in vitro mixing. This is the first study to show co-purification and in vitro association of LDL with extracellular vesicles and its interference with vesicle analysis. Our data point to the importance of careful study design and data interpretation in studies using blood-derived extracellular vesicles with special focus on potentially co-purified LDL. PMID:27087061

  10. Expression of microsomal triglyceride transfer protein in lipoprotein-synthesizing tissues of the developing chicken embryo☆

    PubMed Central

    Eresheim, Christine; Plieschnig, Julia; Ivessa, N. Erwin; Schneider, Wolfgang J.; Hermann, Marcela

    2014-01-01

    In contrast to mammals, in the chicken major sites of lipoprotein synthesis and secretion are not only the liver and intestine, but also the kidney and the embryonic yolk sac. Two key components in the assembly of triglyceride-rich lipoproteins are the microsomal triglyceride transfer protein (MTP) and apolipoprotein B (apoB). We have analyzed the expression of MTP in the embryonic liver, small intestine, and kidney, and have studied the expression of MTP in, and the secretion of apoB from, the developing yolk sac (YS). Transcript and protein levels of MTP increase during embryogenesis in YS, liver, kidney, and small intestine, and decrease in YS, embryonic liver, and kidney after hatching. In small intestine, the MTP mRNA level rises sharply during the last trimester of embryo development (after day 15), while MTP protein is detectable only after hatching (day 21). In the YS of 15- and 20-day old embryos, apoB secretion was detected by pulse-chase metabolic radiolabeling experiments and subsequent immunoprecipitation. Taken together, our data reveal the importance of coordinated production of MTP and apoB in chicken tissues capable of secreting triglyceride-rich lipoproteins even before hatching. PMID:24394625

  11. Ginsenoside Rf, a component of ginseng, regulates lipoprotein metabolism through peroxisome proliferator-activated receptor {alpha}

    SciTech Connect

    Lee, Hyunghee; Gonzalez, Frank J.; Yoon, Michung . E-mail: yoon60@mokwon.ac.kr

    2006-01-06

    We investigated whether ginseng regulates lipoprotein metabolism by altering peroxisome proliferator-activated receptor {alpha} (PPAR{alpha})-mediated pathways, using a PPAR{alpha}-null mouse model. Administration of ginseng extract, ginsenosides, and ginsenoside Rf (Rf) to wild-type mice not only significantly increased basal levels of hepatic apolipoprotein (apo) A-I and C-III mRNA compared with wild-type controls, but also substantially reversed the reductions in mRNA levels of apo A-I and C-III expected following treatment with the potent PPAR{alpha} ligand Wy14,643. In contrast, no effect was detected in the PPAR{alpha}-null mice. Testing of eight main ginsenosides on PPAR{alpha} reporter gene expression indicated that Rf was responsible for the effects of ginseng on lipoprotein metabolism. Furthermore, the inhibition of PPAR{alpha}-dependent transactivation by Rf seems to occur at the level of DNA binding. These results demonstrate that ginseng component Rf regulates apo A-I and C-III mRNA and the actions of Rf on lipoprotein metabolism are mediated via interactions with PPAR{alpha}.

  12. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection.

    PubMed

    Sódar, Barbara W; Kittel, Ágnes; Pálóczi, Krisztina; Vukman, Krisztina V; Osteikoetxea, Xabier; Szabó-Taylor, Katalin; Németh, Andrea; Sperlágh, Beáta; Baranyai, Tamás; Giricz, Zoltán; Wiener, Zoltán; Turiák, Lilla; Drahos, László; Pállinger, Éva; Vékey, Károly; Ferdinandy, Péter; Falus, András; Buzás, Edit Irén

    2016-01-01

    Circulating extracellular vesicles have emerged as potential new biomarkers in a wide variety of diseases. Despite the increasing interest, their isolation and purification from body fluids remains challenging. Here we studied human pre-prandial and 4 hours postprandial platelet-free blood plasma samples as well as human platelet concentrates. Using flow cytometry, we found that the majority of circulating particles within the size range of extracellular vesicles lacked common vesicular markers. We identified most of these particles as lipoproteins (predominantly low-density lipoprotein, LDL) which mimicked the characteristics of extracellular vesicles and also co-purified with them. Based on biophysical properties of LDL this finding was highly unexpected. Current state-of-the-art extracellular vesicle isolation and purification methods did not result in lipoprotein-free vesicle preparations from blood plasma or from platelet concentrates. Furthermore, transmission electron microscopy showed an association of LDL with isolated vesicles upon in vitro mixing. This is the first study to show co-purification and in vitro association of LDL with extracellular vesicles and its interference with vesicle analysis. Our data point to the importance of careful study design and data interpretation in studies using blood-derived extracellular vesicles with special focus on potentially co-purified LDL. PMID:27087061

  13. Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies

    PubMed Central

    Vanhamme, Luc; Roumeguère, Thierry; Zouaoui Boudjeltia, Karim

    2013-01-01

    Oxidation of low-density lipoprotein (LDL) has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO) is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNFα and IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis. PMID:23983406

  14. Persistent organic pollutants distribution in lipoprotein fractions in relation to cardiovascular disease and cancer.

    PubMed

    Ljunggren, Stefan A; Helmfrid, Ingela; Salihovic, Samira; van Bavel, Bert; Wingren, Gun; Lindahl, Mats; Karlsson, Helen

    2014-04-01

    Persistent organic pollutants (POPs) are lipophilic environmental toxins that have been associated with cardiovascular disease (CVD) and cancer. The aim of this study was to investigate the concentrations of POPs in human high and low/very low-density lipoproteins (HDL and LDL/VLDL) and the possible association with CVD and cancer occurrence in individuals living in a contaminated area. Lipoproteins from 28 individuals (7 healthy controls, 8 subjects with cancer, 13 subjects with CVD) were isolated and the fraction-specific concentration of 20 different POPs was analyzed by high resolution gas chromatography/high resolution mass spectrometry. The activity of Paraoxonase 1 (PON1), an anti-oxidant in HDL, was determined in plasma of these 28 subjects and additional 50 subjects from the same area excluding diseases other than cancer or CVD. Fourteen polychlorinated biphenyls (PCBs) and three organochlorine pesticides were detected, and especially highly chlorinated PCBs were enriched in lipoproteins. Significantly higher concentrations of POPs were found among individuals with CVD or cancer compared to controls. Principal component analyses showed that POP concentrations in HDL were more associated with CVD, while POP concentrations in LDL/VLDL were more associated with cancer. PON1 activity was negatively correlated to sumPCB and a co-variation between decreased arylesterase-activity, increased PCB concentrations and CVD was found. This study shows that POPs are present in lipoproteins and were more abundant in individuals with CVD or cancer compared to healthy controls. The results also indicate that PCB exposure is accompanied by reduced PON1 activity that could impair the HDL function to protect against oxidation. PMID:24472825

  15. The age dependency of gene expression for plasma lipids, lipoproteins, and apolipoproteins

    SciTech Connect

    Snieder, H.; Doornen, L.J.P. van; Boomsma, D.I.

    1997-03-01

    The aim of this study was to investigate and disentangle the genetic and nongenetic causes of stability and change in lipids and (apo)lipoproteins that occur during the lifespan. Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]) were measured in a group of 160 middle-aged parents and their twin offspring (first project) and in a group of 203 middle-aged twin pairs (second project). Combining the data of both projects enabled the estimation of the extent to which measured lipid parameters are influenced by different genes in adolescence and adulthood. To that end, an extended quantitative genetic model was specified, which allowed the estimation of heritabilities for each sex and generation separately. Heritabilities were similar for both sexes and both generations. Larger variances in the parental generation could be ascribed to proportional increases in both unique environmental and additive genetic variance from childhood to adulthood, which led to similar heritability estimates in adolescent and middle-aged twins. Although the magnitudes of heritabilities were similar across generations, results showed that, for total cholesterol, triglycerides, HDL, and LDL, partly different genes are expressed in adolescence compared to adulthood. For triglycerides, only 46% of the genetic variance was common to both age groups; for total cholesterol this was 80%. Intermediate values were found for HDL (66%) and LDL (76%). For ApoA1, ApoB, and Lp(a), the same genes seem to act in both generations. 56 refs., 2 figs., 5 tabs.

  16. Development and application of proton NMR methodology to lipoprotein analysis

    NASA Astrophysics Data System (ADS)

    Korhonen, Ari Juhani

    1998-11-01

    The present thesis describes the development of 1H NMR spectroscopy and its applications to lipoprotein analysis in vitro, utilizing biochemical prior knowledge and advanced lineshape fitting analysis in the frequency domain. A method for absolute quantification of lipoprotein lipids and proteins directly from the terminal methyl-CH3 resonance region of 1H NMR spectra of human blood plasma is described. Then the use of NMR methodology in time course studies of the oxidation process of LDL particles is presented. The function of the cholesteryl ester transfer protein (CETP) in lipoprotein mixtures was also assessed by 1H NMR, which allows for dynamic follow-up of the lipid transfer reactions between VLDL, LDL, and HDL particles. The results corroborated the suggestion that neutral lipid mass transfer among lipoproteins is not an equimolar heteroexchange. A novel method for studying lipoprotein particle fusion is also demonstrated. It is shown that the progression of proteolytically (α- chymotrypsin) induced fusion of LDL particles can be followed by 1H NMR spectroscopy and, moreover, that fusion can be distinguished from aggregation. In addition, NMR methodology was used to study the changes in HDL3 particles induced by phospholipid transfer protein (PLTP) in HDL3 + PLTP mixtures. The 1H NMR study revealed a gradual production of enlarged HDL particles, which demonstrated that PLTP-mediated remodeling of HDL involves fusion of the HDL particles. These applications demonstrated that the 1H NMR approach offers several advantages both in quantification and in time course studies of lipoprotein-lipoprotein interactions and of enzyme/lipid transfer protein function.

  17. Characterization of lipoproteins in human and canine cerebrospinal fluid (CSF)

    SciTech Connect

    Pitas, R.E.; Weisgraber, K.H.; Boyles, J.K.; Lee, S.; Mahley, R.W.

    1986-03-01

    Previously the authors demonstrated that rat brain astrocytes in vitro synthesize and secrete apo-E and possess apo-B,E(LDL) receptors. The apo-E secreted by astrocytes and apo-E in rat brain extracts differed from serum apo-E in two respects. Brain apo-E had a higher apparent molecular weight and a higher percentage of more acidic isoforms. To characterize further the apo-E within the central nervous system, apo-E in human and canine CSF was investigated. Compared to plasma apo-E, CSF apo-E had a higher apparent M/sub r/ and a higher percentage of acidic isoforms which were sialylated, as shown by neuraminidase digestion. The apo-E in human CSF was approx.5-10% of the plasma level. In CSF 60-80% of the apo-E was in lipoproteins with d = 1.09-1.15. The remainder of the apo-E was in the d > 1.21 fraction. Human CSF lipoproteins were primarily spherical (110-190 A) while canine CSF lipoproteins were a mixture of discs (205 x 65 A) while canine CSF lipoproteins were a mixture of discs (205 x 65 A) and spheres (100-150 A). The CSF also contained apo-AI in the d = 1.09-1.15 g/ml fraction. Human CSF lipoproteins containing both apo-E and apo-AI were isolated on an anti-apo-E affinity column, suggesting that apo-E and AI occurred in the same particles. The CSF apo-E-containing lipoproteins competed for binding of /sup 125/I-LDL to the apo-B,E(LDL) receptor. There was no detectable apo-B in CSF. These data suggest that CSF lipoproteins might transport lipid and regulate lipid homeostasis within the brain.

  18. Preparation and Characterization of Stable α-Synuclein Lipoprotein Particles.

    PubMed

    Eichmann, Cédric; Campioni, Silvia; Kowal, Julia; Maslennikov, Innokentiy; Gerez, Juan; Liu, Xiaoxia; Verasdonck, Joeri; Nespovitaya, Nadezhda; Choe, Senyon; Meier, Beat H; Picotti, Paola; Rizo, Josep; Stahlberg, Henning; Riek, Roland

    2016-04-15

    Multiple neurodegenerative diseases are caused by the aggregation of the human α-Synuclein (α-Syn) protein. α-Syn possesses high structural plasticity and the capability of interacting with membranes. Both features are not only essential for its physiological function but also play a role in the aggregation process. Recently it has been proposed that α-Syn is able to form lipid-protein particles reminiscent of high-density lipoproteins. Here, we present a method to obtain a stable and homogeneous population of nanometer-sized particles composed of α-Syn and anionic phospholipids. These particles are called α-Syn lipoprotein (nano)particles to indicate their relationship to high-density lipoproteins formed by human apolipoproteins in vivo and of in vitro self-assembling phospholipid bilayer nanodiscs. Structural investigations of the α-Syn lipoprotein particles by circular dichroism (CD) and magic angle solid-state nuclear magnetic resonance (MAS SS-NMR) spectroscopy establish that α-Syn adopts a helical secondary structure within these particles. Based on cryo-electron microscopy (cryo-EM) and dynamic light scattering (DLS) α-Syn lipoprotein particles have a defined size with a diameter of ∼23 nm. Chemical cross-linking in combination with solution-state NMR and multiangle static light scattering (MALS) of α-Syn particles reveal a high-order protein-lipid entity composed of ∼8-10 α-Syn molecules. The close resemblance in size between cross-linked in vitro-derived α-Syn lipoprotein particles and a cross-linked species of endogenous α-Syn from SH-SY5Y human neuroblastoma cells indicates a potential functional relevance of α-Syn lipoprotein nanoparticles. PMID:26846854

  19. Expression of the Serratia marcescens lipoproteins gene in Escherichia coli.

    PubMed Central

    Lee, N; Nakamura, K; Inouye, M

    1981-01-01

    The lipoprotein gene (lpp) of Serratia marcescens was cloned in a lambda phage vector (K. Nakamura and M. Inouye, Proc. Natl. Acad. Sci. U.S.A. 77: 1369-1373, 1980). This lpp gene was recloned in plasmid vectors pBR322 and pSC101. When a lipoprotein-deficient (lpp) mutant of Escherichia coli was transformed with pBR322 carrying the S. marcescens lpp gene, cells became nonleaky for ribonuclease, resistant to ethylenediaminetetraacetic acid, and sensitive to globomycin. The lipoprotein was found exclusively in the outer membrane fraction. These results indicate that the S. marcescens lipoprotein was normally secreted across the cytoplasmic membrane, modified, and assembled in the E. coli outer membrane. The amount of the free-form lipoprotein produced in this system was three times higher than that produced in lpp + C. coli cells, whereas there was no difference in the amount of the bound-form lipoprotein. On the other hand, lpp E. coli cells which harbored pSC101 carrying the S. marcescens lpp gene produced only one-third of the free-form lipoprotein produced in lpp E. coli cells which harbored pSC101 carrying the E. coli lpp gene. One of the major factors causing this difference in efficiency of gene expression between the lpp genes of S. marcescens and E. coli appears to be a deletion mutation at the transcription termination region found in the cloned S. marcescens lpp gene. The functional half-life of the S. marcescens lpp messenger ribonucleic acid in E. coli was found to be found half that of the E. coli lpp messenger ribonucleic acid. Images PMID:7016834

  20. Unidirectional transfer in vivo of high-density lipoprotein cholesteryl esters to lower-density lipoproteins in the pig, an animal species without plasma cholesteryl ester transfer activity.

    PubMed

    Terpstra, A H; Stucchi, A F; Foxall, T L; Shwaery, G T; Vespa, D B; Nicolosi, R J

    1993-12-01

    The metabolism of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesteryl esters (CE) was studied in the pig, an animal species without plasma cholesteryl ester transfer activity (CETA). In the first series of experiments, LDL and HDL from normocholesterolemic pigs were radiolabeled with cholesteryl (1-14C)oleate and intravenously administered to two groups of four normocholesterolemic pigs. Radioactive tracer in LDL remained associated with the LDL fraction, and there was no transfer of LDL-CE to HDL. The transport rate (which represents the production and disposal rate) of LDL-CE in normocholesterolemic pigs was 39 mumol CE/h/L. However, radiolabeled HDL-CE were transferred to LDL (25%), and 36% of the LDL-CE mass was derived from the HDL. The transport rate of HDL-CE was 54 mumol CE/h/L, and the flux of HDL-CE to LDL was 14 mumol CE/h/L. There was no accumulation of radiolabeled HDL-CE in very-low-density lipoprotein (VLDL), which suggests that there was no transfer to VLDL. However, this does not rule out the possibility that either the very low levels of VLDL-CE (< 0.09 mmol/L) or the rapid turnover rate of the VLDL pool might have prevented the accumulation of substantial amounts of tracer in VLDL. Therefore, in a second set of experiments, the kinetics of HDL-CE were studied in high-fat-and high-cholesterol-fed pigs with elevated VLDL-CE concentrations (1.92 mmol/L). Hypercholesterolemia was associated with increased transport rates of LDL-CE (165 mumol/h/L) and HDL-CE (78 mumol/h/L) and with an increased flux of HDL-CE to LDL (78 mumol/h/L).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8246765

  1. Heterogeneity of serum low density lipoproteins in normal human subjects

    SciTech Connect

    Shen, M.M.S.; Krauss, R.M.; Lindgren, F.T.; Forte, T.M.

    1981-01-01

    Equilibrium density gradient ultracentrifugation of serum low density lipoprotein (LDL) from twelve healthy human subjects was used to separate six subfractions with mean dinsity ranging from 1.0268 to 1.0597 g/ml. Mean corrected peak flotation rate (S/sup o//sub f/) measured by analytic ultracentrifugation, and mean particle diameter determined by negative staining electron microscopy, both declined significantly with increasing density of the subfractions. Major differences in chemical composition of the subfractions were noted, including a singnificantly lower triglyceride content and higher ratio of cholesteryl ester to triglyceride in the middle fractions compared with those of highest and lowest density. Concentration of fraction 2 correlated positively with HDL (P < 0.01) and negatively with VLDL (P < 0.001); concentration of fraction 4 correlated negatively with HDL (P < 0.05) and positively with VLDL (P < 0.001) and IDL (P < 0.01). LDL may thus include subspecies of differing structure and composition which might also have different metabolic and atherogenic roles.

  2. Cardiomyocyte-endothelial cell control of lipoprotein lipase.

    PubMed

    Chiu, Amy Pei-Ling; Wan, Andrea; Rodrigues, Brian

    2016-10-01

    In people with diabetes, inadequate pharmaceutical management predisposes the patient to heart failure, which is the leading cause of diabetes related death. One instigator for this cardiac dysfunction is change in fuel utilization by the heart. Thus, following diabetes, when cardiac glucose utilization is impaired, the heart undergoes metabolic transformation wherein it switches to using fats as an exclusive source of energy. Although this switching is geared to help the heart initially, in the long term, this has detrimental effects on cardiac function. These include the generation of noxious byproducts, which damage the cardiomyocytes, and ultimately result in increased morbidity and mortality. A key perpetrator that may be responsible for organizing this metabolic disequilibrium is lipoprotein lipase (LPL), the enzyme responsible for providing fat to the hearts. Either exaggeration or reduction in its activity following diabetes could lead to heart dysfunction. Given the disturbing news that diabetes is rampant across the globe, gaining more insight into the mechanism(s) by which cardiac LPL is regulated may assist other researchers in devising new therapeutic strategies to restore metabolic equilibrium, to help prevent or delay heart disease seen during diabetes. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26995461

  3. Lysosomal Cholesterol Accumulation Inhibits Subsequent Hydrolysis Of Lipoprotein Cholesteryl Ester

    PubMed Central

    Jerome, W. Gray; Cox, Brian E.; Griffin, Evelyn E.; Ullery, Jody C.

    2010-01-01

    Human macrophages incubated for prolonged periods with mildly oxidized LDL (oxLDL) or cholesteryl ester-rich lipid dispersions (DISP) accumulate free and esterified cholesterol within large, swollen lysosomes similar to those in foam cells of atherosclerosis. The cholesteryl ester (CE) accumulation is, in part, the result of inhibition of lysosomal hydrolysis due to increased lysosomal pH mediated by excessive lysosomal free cholesterol (FC). To determine if the inhibition of hydrolysis was long lived and further define the extent of the lysosomal defect, we incubated THP-1 macrophages with oxLDL or DISP to produce lysosome sterol engorgement and then chased with acetylated LDL (acLDL). Unlike oxLDL or DISP, CE from acLDL normally is hydrolyzed rapidly. Three days of incubation with oxLDL or DISP produced an excess of CE in lipid-engorged lysosomes, indicative of inhibition. After prolonged oxLDL or DISP pretreatment, subsequent hydrolysis of acLDL CE was inhibited. Coincident with the inhibition, the lipid-engorged lysosomes failed to maintain an acidic pH during both the initial pretreatment and subsequent acLDL incubation. This indicates that the alterations in lysosomes were general, long-lived and affected subsequent lipoprotein metabolism. This same phenomenon, occurring within atherosclerotic foam cells, could significantly affect lesion progression. PMID:18312718

  4. Parathyroid hormone is not an inhibitor of lipoprotein lipase activity.

    PubMed

    Arnadottir, M; Nilsson-Ehle, P

    1994-01-01

    The reduced lipoprotein lipase (LPL) activities in uraemia are reflected by increased serum triglyceride concentrations and reduced HDL cholesterol concentrations. Both hyperparathyroidism and circulating inhibitor(s) of LPL have been associated with the disturbances of lipid metabolism in uraemia. The aim of the present study was to investigate if parathyroid hormone (PTH) had an inhibitory effect on LPL activity. Plasma post-heparin LPL activities, plasma LPL inhibitory activities, serum PTHintact and serum PTHC-terminal concentrations were analysed in 20 patients on haemodialysis and 20 healthy controls. The effects of purified, human PTHintact and a carboxyterminal fragment of PTH (PTH39-84) on LPL activities in post-heparin plasma from healthy individuals and on the enzyme activity of purified, bovine milk LPL, activated with apolipoprotein CII, were studied. Patients had significantly higher plasma LPL inhibitory activities than controls, but there was no correlation between plasma LPL inhibitory activities and serum PTH concentrations. Neither PTHintact nor PTH39-84 had a significant effect on LPL activities in vitro. Thus there was no evidence of a direct inhibition of LPL activity by PTH under the present in-vivo or in-vitro conditions. PMID:7870347

  5. Alcohol alters low density lipoprotein composition and metabolism

    SciTech Connect

    Hoinacki, J.; Brown, J.; Dawson, M.; Deschenes, R.; Mulligan, J. )

    1991-03-11

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

  6. Lipoproteins are Major Targets of the Polyclonal Human T-cell Response to M. tuberculosis1

    PubMed Central

    Seshadri, Chetan; Turner, Marie T.; Lewinsohn, David M.; Moody, D. Branch; Van Rhijn, Ildiko

    2012-01-01

    Most vaccines and basic studies of T cell epitopes in M. tuberculosis emphasize water soluble proteins that are secreted into the extracellular space and presented in the context of MHC Class II. Much less is known about the role of antigens retained within the cell wall. We used polyclonal T cells from infected humans to probe for responses to immunodominant antigens in the M. tuberculosis cell wall. We found that the magnitude of response to secreted or cell wall intrinsic compounds was similar among healthy controls, patients with latent tuberculosis, and patients with active tuberculosis. Individual responses to secreted antigens and cell wall extract were strongly correlated (r2=0.495, p=0.001), suggesting that T cells responding to cell wall and secreted antigens are present at similar frequency. Surprisingly, T cell stimulatory factors intrinsic to the cell wall partition into organic solvents; however, these responses are not explained by CD1-mediated presentation of lipids. Instead, we find that molecules soluble in organic solvents are dependent upon MHC Class II and recognized by IFN-γ secreting CD4+ T cells. We reasoned that MHC Class II dependent antigens extracting into lipid mixtures might be found among triacylated lipoproteins present in mycobacteria. We used M. tuberculosis lacking prolipoprotein signal peptidase A (lspA), an enzyme required for lipoprotein synthesis, to demonstrate loss of polyclonal T cell responses. Our results demonstrate the use of bacterial genetics to identify lipoproteins as an unexpected and immunodominant class of cell wall-associated antigens targeted by the polyclonal human T cell response to M. tuberculosis. PMID:23197260

  7. Chlordecone, a mixed pregnane X receptor (PXR) and estrogen receptor alpha (ER{alpha}) agonist, alters cholesterol homeostasis and lipoprotein metabolism in C57BL/6 mice

    SciTech Connect

    Lee, Junga; Scheri, Richard C.; Zhang Yuan; Curtis, Lawrence R.

    2008-12-01

    Chlordecone (CD) is one of many banned organochlorine (OC) insecticides that are widespread persistent organic pollutants. OC insecticides alter lipid homeostasis in rodents at doses that are not neurotoxic or carcinogenic. Pretreatment of mice or rats with CD altered tissue distribution of a subsequent dose of [{sup 14}C]CD or [{sup 14}C]cholesterol (CH). Nuclear receptors regulate expression of genes important in the homeostasis of CH and other lipids. In this study, we report that CD suppresses in vitro reporter systems for human liver X receptors (LXRs) and activates those for human farnesoid X receptor (FXR), pregnane X receptor (PXR) and estrogen receptor {alpha} (ER{alpha}) in a concentration-dependent manner (0-50 {mu}M). Consistent with human PXR activation in vitro, three days after a single dose of CD (15 mg/kg) hepatic microsomal CYP3A11 protein increases in C57BL/6 mice. CD decreases hepatic CH ester content without altering total CH concentration. Apolipoprotein A-I (apoA-I) contents of hepatic lipoprotein-rich and microsomal fractions of CD-treated mice are higher than controls. There is a significant reduction in non-high density lipoprotein CH but not apolipoprotein B-48/100 (apoB-48/100) in plasma from CD-treated mice after a 4 h fast. At 14 days after 15 mg CD/kg apoA-I and apoB-100 proteins but not CYP3A11 protein in hepatic microsomes are similar to controls. This work indicates that altered CH homeostasis is a mode of OC insecticide action of relevance after a single dose. This at least partially explains altered CH tissue distribution in CD-pretreated mice.

  8. 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

  9. New and emerging regulators of intestinal lipoprotein secretion.

    PubMed

    Xiao, Changting; Dash, Satya; Morgantini, Cecilia; Lewis, Gary F

    2014-04-01

    Overproduction of hepatic apoB100-containing VLDL particles has been well documented in animal models and in humans with insulin resistance such as the metabolic syndrome and type 2 diabetes, and contributes to the typical dyslipidemia of these conditions. In addition, postprandial hyperlipidemia and elevated plasma concentrations of intestinal apoB48-containing chylomicron and chylomicron remnant particles have been demonstrated in insulin resistant states. Intestinal lipoprotein production is primarily determined by the amount of fat ingested and absorbed. Until approximately 10 years ago, however, relatively little attention was paid to the role of the intestine itself in regulating the production of triglyceride-rich lipoproteins (TRL) and its dysregulation in pathological states such as insulin resistance. We and others have shown that insulin resistant animal models and humans are characterized by overproduction of intestinal apoB48-containing lipoproteins. Whereas various factors are known to regulate hepatic lipoprotein particle production, less is known about factors that regulate the production of intestinal lipoprotein particles. Monosacharides, plasma free fatty acids (FFA), resveratrol, intestinal peptides (e.g. GLP-1 and GLP-2), and pancreatic hormones (e.g. insulin) have recently been shown to be important regulators of intestinal lipoprotein secretion. Available evidence in humans and animal models strongly supports the concept that the small intestine is not merely an absorptive organ but rather plays an active role in regulating the rate of production of chylomicrons in fed and fasting states. Metabolic signals in insulin resistance and type 2 diabetes and in some cases an aberrant intestinal response to these factors contribute to the enhanced formation and secretion of TRL. Understanding the regulation of intestinal lipoprotein production is imperative for the development of new therapeutic strategies for the prevention and treatment of

  10. Apolipoprotein B-containing lipoprotein particle assembly: Lipid capacity of the nascent lipoprotein particle

    SciTech Connect

    Manchekar, Medha; Forte, Trudy M.; Datta, Geeta; Richardson, Paul E.; Segrest, Jere P.; Dashti, Nassrin

    2003-12-01

    We previously proposed that the N-terminal 1000 residue {beta}{alpha}{sub 1} domain of apolipoprotein B (apoB) forms a bulk lipid pocket homologous to that of lamprey lipovitellin (LV). In support of this ''lipid pocket'' hypothesis, apoB:1000 (residues 1-1000) was shown to be secreted by a stable transformant of McA-RH7777 cells as a monodisperse particle with HDL{sub 3} density and Stokes diameter of 112 {angstrom}. In contrast, apoB:931 (residues 1-931), missing only 69 residues of the sequence homologous to LV, was secreted as a particle considerably more dense than HDL with Stokes diameter of 110 {angstrom}. The purpose of the present study was to determine the stoichiometry of the lipid component of the apoB:931 and apoB:1000 particles. This was accomplished by metabolic labeling of cells with either [{sup 14}C]oleic acid or [{sup 3}H]glycerol followed by immunoprecipitation (IP) or nondenaturing gradient gel electrophoresis (NDGGE) of secreted lipoproteins and by immunoaffinity chromatography of secreted unlabeled lipoproteins. The [{sup 3}H]-labeled apoB:1000-containing particles, isolated by NDGGE, contained 50 phospholipids (PL) and 11 triacylglycerols (TAG) molecules per particle. In contrast, apoB:931-containing particles contained only a few molecules of PL and were devoid of TAG. The unlabeled apoB:1000-containing particles isolated by immunoaffinity chromatography and analyzed for lipid mass, contained 56 PL, 8 TAG, and 7 cholesteryl ester molecules per particle. The surface:core lipid ratio of apoB:1000-containing particles was approximately 4:1 and was not affected by incubation of cells with oleate. Although small amounts of microsomal triglyceride transfer protein (MTP) were associated with apoB:1000-containing particles, it never approached a 1:1 molar ratio of MTP to apoB. These results support a model in which: (1) the first 1000 amino acid residues of apoB are competent to complete the ''lipid pocket'' without a structural requirement for MTP

  11. Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis.

    PubMed

    Hoeke, Geerte; Kooijman, Sander; Boon, Mariëtte R; Rensen, Patrick C N; Berbée, Jimmy F P

    2016-01-01

    Atherosclerosis, for which hyperlipidemia is a major risk factor, is the leading cause of morbidity and mortality in Western society, and new therapeutic strategies are highly warranted. Brown adipose tissue (BAT) is metabolically active in human adults. Although positron emission tomography-computed tomography using a glucose tracer is the golden standard to visualize and quantify the volume and activity of BAT, it has become clear that activated BAT combusts fatty acids rather than glucose. Here, we review the role of brown and beige adipocytes in lipoprotein metabolism and atherosclerosis, with evidence derived from both animal and human studies. On the basis of mainly data from animal models, we propose a model in which activated brown adipocytes use their intracellular triglyceride stores to generate fatty acids for combustion. BAT rapidly replenishes these stores by internalizing primarily lipoprotein triglyceride-derived fatty acids, generated by lipoprotein lipase-mediated hydrolysis of triglycerides, rather than by holoparticle uptake. As a consequence, BAT activation leads to the generation of lipoprotein remnants that are subsequently cleared via the liver provided that an intact apoE-low-density lipoprotein receptor pathway is present. Through these mechanisms, BAT activation reduces plasma triglyceride and cholesterol levels and attenuates diet-induced atherosclerosis development. Initial studies suggest that BAT activation in humans may also reduce triglyceride and cholesterol levels, but potential antiatherogenic effects should be assessed in future studies. PMID:26837747

  12. Learning from Biology: Synthetic Lipoproteins for Drug Delivery

    PubMed Central

    Huang, Huang; Cruz, William; Chen, Juan; Zheng, Gang

    2014-01-01

    Synthetic lipoproteins represent a relevant tool for targeted delivery of biological/chemical agents (chemotherapeutics, siRNAs, photosensitizers and imaging contrast agents) into various cell types. These nanoparticles offer a number of advantages on drugs delivery over their native counterparts while retaining their natural characteristics and biological functions. Their ultra-small size (<30nm), high biocompatibility, favorable circulation half-life and natural ability to bind specific lipoprotein receptors i.e. low-density lipoprotein receptor (LDLR) and Scavenger receptor class B member 1 (SRB1) that are found in a number of pathological conditions (e.g. cancer, atherosclerosis), make them superior delivery strategies when compared to other nanoparticle systems. We review the various approaches that have been developed for the generation of synthetic lipoproteins and their respective applications in vitro and in vivo. More specifically, we summarize the way to address the limitation on use of reconstituted lipoproteins by means of natural or recombinant apolipoproteins, as well as apolipoprotein mimetic molecules. Finally, we provide an overview of the advantages and disadvantages of these approaches and discuss future perspectives for clinical translation of these nanoparticles. PMID:25346461

  13. The Vascular Implications of Post-prandial Lipoprotein Metabolism

    PubMed Central

    Sullivan, David R; Celermajer, David S; Le Couteur, David G; Lam, Christopher W K

    2004-01-01

    Impaired lipoprotein metabolism is one of the major aetiological factors for the pathogenesis of atherosclerosis and cardiovascular disease (CVD). Assessment is usually made in the fasting state, and particular attention is directed towards the measurement of the cholesterol content of both the low and high-density lipoprotein fractions. By comparison, a massive amount of lipid fluxes through the intra-vascular compartment during the post-prandial period. This has led to the hypothesis that atherosclerosis could be partially, or even predominantly, due to the pathological effects of this flux of post-prandial lipoproteins on the vessel wall. This justifies efforts to systematically study the relationship between the lipoprotein responses to food (particularly fat) ingestion and cardiovascular disease or its surrogate markers. This review will consider the mechanisms by which post-prandial metabolism might affect the risk of CVD. It will examine the evidence for and against such an association. It will also consider the practical and methodological issues that are likely to determine the future utility of post-prandial lipoprotein assessment. PMID:18516208

  14. Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease

    PubMed Central

    Toth, Peter P

    2016-01-01

    Approximately 25% of US adults are estimated to have hypertriglyceridemia (triglyceride [TG] level ≥150 mg/dL [≥1.7 mmol/L]). Elevated TG levels are associated with increased cardiovascular disease (CVD) risk, and severe hypertriglyceridemia (TG levels ≥500 mg/dL [≥5.6 mmol/L]) is a well-established risk factor for acute pancreatitis. Plasma TG levels correspond to the sum of the TG content in TG-rich lipoproteins (TRLs; ie, very low-density lipoproteins plus chylomicrons) and their remnants. There remains some uncertainty regarding the direct causal role of TRLs in the progression of atherosclerosis and CVD, with cardiovascular outcome studies of TG-lowering agents, to date, having produced inconsistent results. Although low-density lipoprotein cholesterol (LDL-C) remains the primary treatment target to reduce CVD risk, a number of large-scale epidemiological studies have shown that elevated TG levels are independently associated with increased incidence of cardiovascular events, even in patients treated effectively with statins. Genetic studies have further clarified the causal association between TRLs and CVD. Variants in several key genes involved in TRL metabolism are strongly associated with CVD risk, with the strength of a variant’s effect on TG levels correlating with the magnitude of the variant’s effect on CVD. TRLs are thought to contribute to the progression of atherosclerosis and CVD via a number of direct and indirect mechanisms. They directly contribute to intimal cholesterol deposition and are also involved in the activation and enhancement of several proinflammatory, proapoptotic, and procoagulant pathways. Evidence suggests that non-high-density lipoprotein cholesterol, the sum of the total cholesterol carried by atherogenic lipoproteins (including LDL, TRL, and TRL remnants), provides a better indication of CVD risk than LDL-C, particularly in patients with hypertriglyceridemia. This article aims to provide an overview of the

  15. Regulation of apolipoprotein B-containing lipoproteins by dietary soluble fiber in guinea pigs.

    PubMed

    Fernandez, M L; Vergara-Jimenez, M; Conde, K; Behr, T; Abdel-Fattah, G

    1997-03-01

    Dietary soluble-fiber sources such as pectin, guar gum, or psyllium decrease plasma concentrations of low-density-lipoprotein (LDL) cholesterol in guinea pigs by distinct mechanisms, including increases in LDL apolipoprotein (apo) B turnover and/or decreases in LDL apo B flux (J Lipid Res 1995; 36:2394-404). The present studies were undertaken to test whether changes in the rates of very-low-density lipoprotein (VLDL) apo B secretion, VLDL conversion to LDL, and hepatic uptake of VLDL were related to the cholesterol-lowering actions of these soluble fibers. Guinea pigs were fed (by wt) 12.5% pectin, 12.5% guar gum, 7.5% psyllium, or a control diet containing cellulose as the fiber source. Plasma cholesterol concentrations were significantly lower in guinea pigs fed pectin, guar gum, and psyllium by 42%, 46%, and 35%, respectively (P < 0.001), compared with those animals fed the control diet, whereas plasma triacylglycerol concentrations were lower only with guar gum intake. The secretion rate of triacylglycerol, determined after Triton was injected to block VLDL catabolism, was not different among dietary treatment groups whereas the secretion rate of apo B was lower with pectin, guar gum, and psyllium intakes (P < 0.01). In addition, pectin, guar gum, and psyllium significantly altered the composition of newly secreted VLDLs by increasing the number of triacylglycerol and phospholipid molecules in the secreted lipoprotein, indicating the presence of larger nascent VLDLs. In contrast, the average particle diameter of mature VLDLs as determined by electron microscopy was smaller in the dietary soluble-fiber groups in the following order: pectin < psyllium < guar gum. Plasma lecithin-cholesteryl acyltransferase and cholesteryl ester transfer protein activities were lower with intake of pectin, guar gum, and psyllium (P < 0.01). Injection of radiolabeled lipoproteins indicated that pectin, guar gum, and psyllium intakes resulted in more rapid VLDL and LDL apo B

  16. Explaining the gender wealth gap.

    PubMed

    Ruel, Erin; Hauser, Robert M

    2013-08-01

    To assess and explain the United States' gender wealth gap, we use the Wisconsin Longitudinal Study to examine wealth accumulated by a single cohort over 50 years by gender, by marital status, and limited to the respondents who are their family's best financial reporters. We find large gender wealth gaps between currently married men and women, and between never-married men and women. The never-married accumulate less wealth than the currently married, and there is a marital disruption cost to wealth accumulation. The status-attainment model shows the most power in explaining gender wealth gaps between these groups explaining about one-third to one-half of the gap, followed by the human-capital explanation. In other words, a lifetime of lower earnings for women translates into greatly reduced wealth accumulation. After controlling for the full model, we find that a gender wealth gap remains between married men and women that we speculate may be related to gender differences in investment strategies and selection effects. PMID:23264038

  17. Explaining mirror-touch synesthesia.

    PubMed

    Ward, Jamie; Banissy, Michael J

    2015-01-01

    Mirror-touch synesthesia (MTS) is the conscious experience of tactile sensations induced by seeing someone else touched. This paper considers two different, although not mutually exclusive, theoretical explanations and, in the final section, considers the relation between MTS and other forms of synesthesia and also other kinds of vicarious perception (e.g., contagious yawning). The Threshold Theory explains MTS in terms of hyper-activity within a mirror system for touch and/or pain. This offers a good account for some of the evidence (e.g., from fMRI) but fails to explain the whole pattern (e.g., structural brain differences outside of this system; performance on some tests of social cognition). The Self-Other Theory explains MTS in terms of disturbances in the ability to distinguish the self from others. This can be construed in terms of over-extension of the bodily self in to others, or as difficulties in the control of body-based self-other representations. In this account, MTS is a symptom of a broader cognitive profile. We suggest this meets the criteria for synesthesia, despite the proximal causal mechanisms remaining largely unknown, and that the tendency to localize vicarious sensory experiences distinguishes it from other kinds of seemingly related phenomena (e.g., non-localized affective responses to observing pain). PMID:25893437

  18. Rosuvastatin Alters the Proteome of High Density Lipoproteins: Generation of alpha-1-antitrypsin Enriched Particles with Anti-inflammatory Properties.

    PubMed

    Gordon, Scott M; McKenzie, Benjamin; Kemeh, Georgina; Sampson, Maureen; Perl, Shira; Young, Neal S; Fessler, Michael B; Remaley, Alan T

    2015-12-01

    Statins lower plasma cholesterol by as much as 50%, thus reducing future cardiovascular events. However, the physiological effects of statins are diverse and not all are related to low density lipoprotein cholesterol (LDL-C) lowering. We performed a small clinical pilot study to assess the impact of statins on lipoprotein-associated proteins in healthy individuals (n = 10) with normal LDL-C (<130 mg/dL), who were treated with rosuvastatin (20 mg/day) for 28 days. Proteomic analysis of size-exclusion chromatography isolated LDL, large high density lipoprotein (HDL-L), and small HDL (HDL-S) fractions and spectral counting was used to compare relative protein detection before and after statin therapy. Significant protein changes were found in each lipoprotein pool and included both increases and decreases in several proteins involved in lipoprotein metabolism, complement regulation and acute phase response. The most dramatic effect of the rosuvastatin treatment was an increase in α-1-antirypsin (A1AT) spectral counts associated with HDL-L particles. Quantitative measurement by ELISA confirmed an average 5.7-fold increase in HDL-L associated A1AT. Molecular modeling predictions indicated that the hydrophobic reactive center loop of A1AT, the functional domain responsible for its protease inhibitor activity, is likely involved in lipid binding and association with HDL was found to protect A1AT against oxidative inactivation. Cell culture experiments, using J774 macrophages, demonstrated that the association of A1AT with HDL enhances its antiprotease activity, preventing elastase induced production of tumor necrosis factor α. In conclusion, we show that statins can significantly alter the protein composition of both LDL and HDL and our studies reveal a novel functional relationship between A1AT and HDL. The up-regulation of A1AT on HDL enhances its anti-inflammatory functionality, which may contribute to the non-lipid lowering beneficial effects of statins. PMID

  19. Heavy fermion behavior explained by bosons

    NASA Technical Reports Server (NTRS)

    Kallio, A.; Poykko, S.; Apaja, V.

    1995-01-01

    Conventional heavy fermion (HF) theories require existence of massive fermions. We show that heavy fermion phenomena can also be simply explained by existence of bosons with moderate mass but temperature dependent concentration below the formation temperature T(sub B), which in turn is close to room temperature. The bosons B(++) are proposed to be in chemical equilibrium with a system of holes h(+): B(++) = h(+) + h(+). This equilibrium is governed by a boson breaking function f(T), which determines the decreasing boson density and the increasing fermion density with increasing temperature. Since HF-compounds are hybridized from minimum two elements, we assume in addition existence of another fermion component h(sub s)(+) with temperature independent density. This spectator component is thought to be the main agent in binding the bosons in analogy with electronic or muonic molecules. Using a linear boson breaking function we can explain temperature dependence of the giant linear specific heat coefficient gamma(T) coming essentially from bosons. The maxima in resistivity, Hall coefficient, and susceptibility are explained by boson localization effects due to the Wigner crystallization. The antiferromagnetic transitions in turn are explained by similar localization of the pairing fermion system when their density n(sub h)(T(sub FL)) becomes lower than n(sub WC), the critical density of Wigner crystallization. The model applies irrespective whether a compound is superconducting or not. The same model explains the occurrence of low temperature antiferromagnetism also in high-T(sub c) superconductors. The double transition in UPt3 is proposed to be due to the transition of the pairing fermion liquid from spin polarized to unpolarized state.

  20. Characterization of human plasma apolipoprotein E-containing lipoproteins in the high density lipoprotein size range: focus on pre-beta1-LpE, pre-beta2-LpE, and alpha-LpE.

    PubMed

    Krimbou, L; Tremblay, M; Davignon, J; Cohn, J S

    1997-01-01

    We have used two-dimensional gel electrophoresis to separate and characterize human plasma apolipoprotein (apo) E-containing lipoproteins in the high density lipoprotein (HDL) size range. Lipoproteins were separated from whole plasma by electrophoresis (according to charge) in a 0.75% agarose gel, and then in the second dimension (according to size) in a 2-15% non-denaturing polyacrylamide gradient gel. ApoE-containing lipoproteins were detected by radiography after electrotransfer of lipoproteins to nitrocellulose membranes and incubation with 125I-labeled affinity-purified polyclonal apoE antibody. ApoE-containing lipoproteins in the HDL size range had a particle size ranging from 9 to 18.5 nm in diameter and could be characterized as having either gamma, pre-beta1-, pre-beta2- or alpha-electrophoretic mobility (designated gamma-LpE, pre-beta1-LpE, pre-beta2LpE, and alpha-LpE respectively). gamma-LpE and a substantial proportion of pre-beta1- and pre-beta2-LpE did not co-migrate with apoA-I, apoA-II, apoC-III, or apoB-100. Subsequent experiments focused on the pre-beta1-LpE, pre-beta2LpE, and alpha-LpE subfractions, which represented > 95% of apoE in HDL-sized lipoproteins. Storage of plasma at 4 degrees C or in vitro incubation of plasma at 37 degrees C caused a relative decrease in pre-beta1-LpE and increase in alpha-LpE. Normolipidemic patients with an apoE 2/2 phenotype tended to have increased levels of alpha-LpE, whereas apoE 4/4 subjects tended to have a greater proportion of HDL-apoE as pre-beta1-LpE. Decrease in plasma HDL apoE concentration after an oral fat load was associated with a reduction in the plasma concentration of all HDL-apoE subfractions. These results demonstrate that: 1) apoE-containing HDL are heterogeneous in size and charge; 2) pre-beta1-LpE is a relatively labile HDL subfraction; 3) HDL-apoE subfraction distribution is dependent on apoE phenotype; and 4) all apoE-containing HDL subfractions participate in the plasma transfer of apo

  1. The effects of chemically modifying serum apolipoproteins on their ability to activate lipoprotein lipase.

    PubMed Central

    Dodds, P F; Lopez-Johnston, A; Welch, V A; Gurr, M I

    1987-01-01

    Lipoprotein lipase activity was measured in an acetone-dried-powder preparation from rat epididymal adipose tissue using pig serum or pig serum lipoprotein, which had been chemically modified, as activator. Modification of acidic amino acids of lipoproteins with NN-dimethyl-1,3-diamine resulted in a complete loss of ability to activate lipoprotein lipase. Modification of 34% of lipoprotein arginine groups with cyclohexanedione resulted in the loss of 75% of the activation of lipoprotein lipase; approx. 42% of the original activity was recovered after reversal of the modification. This effect was dependent on the cyclohexanedione concentration. Modification of 48% of lipoprotein lysine groups with malonaldehyde decreased the maximum activation by 20%, but three times as much lipoprotein was required to achieve this. Non-enzymic glycosylation of lipoprotein with glucose, under a variety of conditions resulting in up to 28 nmol of glucose/mg of protein, had no effect upon the ability to activate lipoprotein lipase. In contrast non-enzymic sialylation resulted in a time-dependent loss of up to 60% of ability to activate lipoprotein lipase. Reductive methylation and acetoacetylation of serum did not affect the ability to activate lipoprotein lipase. The results are compared to the effects of similar modifications to low density lipoproteins on receptor-mediated endocytosis. PMID:3593262

  2. Extracellular Nucleotides Inhibit Insulin Receptor Signaling, Stimulate Autophagy and Control Lipoprotein Secretion

    PubMed Central

    Chatterjee, Cynthia; Sparks, Daniel L.

    2012-01-01

    Hyperglycemia is associated with abnormal plasma lipoprotein metabolism and with an elevation in circulating nucleotide levels. We evaluated how extracellular nucleotides may act to perturb hepatic lipoprotein secretion. Adenosine diphosphate (ADP) (>10 µM) acts like a proteasomal inhibitor to stimulate apoB100 secretion and inhibit apoA-I secretion from human liver cells at 4 h and 24 h. ADP blocks apoA-I secretion by stimulating autophagy. The nucleotide increases cellular levels of the autophagosome marker, LC3-II, and increases co-localization of LC3 with apoA-I in punctate autophagosomes. ADP affects autophagy and apoA-I secretion through P2Y13. Overexpression of P2Y13 increases cellular LC3-II levels by ∼50% and blocks induction of apoA-I secretion. Conversely, a siRNA-induced reduction in P2Y13 protein expression of 50% causes a similar reduction in cellular LC3-II levels and a 3-fold stimulation in apoA-I secretion. P2Y13 gene silencing blocks the effects of ADP on autophagy and apoA-I secretion. A reduction in P2Y13 expression suppresses ERK1/2 phosphorylation, increases the phosphorylation of IR-β and protein kinase B (Akt) >3-fold, and blocks the inhibition of Akt phosphorylation by TNFα and ADP. Conversely, increasing P2Y13 expression significantly inhibits insulin-induced phosphorylation of insulin receptor (IR-β) and Akt, similar to that observed after treatment with ADP. Nucleotides therefore act through P2Y13, ERK1/2 and insulin receptor signaling to stimulate autophagy and affect hepatic lipoprotein secretion. PMID:22590634

  3. The association between circulating lipoprotein(a) and type 2 diabetes: is it causal?

    PubMed

    Ye, Zheng; Haycock, Philip C; Gurdasani, Deepti; Pomilla, Cristina; Boekholdt, S Matthijs; Tsimikas, Sotirios; Khaw, Kay-Tee; Wareham, Nicholas J; Sandhu, Manjinder S; Forouhi, Nita G

    2014-01-01

    Epidemiological evidence supports a direct and causal association between lipoprotein(a) [Lp(a)] levels and coronary risk, but the nature of the association between Lp(a) levels and risk of type 2 diabetes (T2D) is unclear. In this study, we assessed the association of Lp(a) levels with risk of incident T2D and tested whether Lp(a) levels are causally linked to T2D. We analyzed data on 18,490 participants from the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort that included adults aged 40-79 years at baseline 1993-1997. During an average 10 years of follow-up, 593 participants developed incident T2D. Cox regression models were used to estimate the association between Lp(a) levels and T2D. In Mendelian randomization analyses, based on EPIC-Norfolk combined with DIAbetes Genetics Replication And Meta-analysis data involving a total of 10,088 diabetes case participants and 68,346 control participants, we used a genetic variant (rs10455872) as an instrument to test whether the association between Lp(a) levels and T2D is causal. In adjusted analyses, there was an inverse association between Lp(a) levels and T2D: hazard ratio was 0.63 (95% CI 0.49-0.81; P trend = 0.003) comparing the top versus bottom quintile of Lp(a). In EPIC-Norfolk, a 1-SD increase in logLp(a) was associated with a lower risk of T2D (odds ratio [OR] 0.88 [95% CI: 0.80-0.95]). However, in Mendelian randomization analyses, a 1-SD increase in logLp(a) due to rs10455872, which explained 26.8% of the variability in Lp(a) levels, was not associated with risk of T2D (OR 1.03 [0.96-1.10]; P = 0.41). These prospective findings demonstrate a strong inverse association of Lp(a) levels with risk of T2D. However, a genetic variant that elevated Lp(a) levels was not associated with risk of T2D, suggesting that elevated Lp(a) levels are not causally associated with a lower risk of T2D. PMID:24089516

  4. Serum lipid & lipoprotein profiles of obese Chinese children.

    PubMed

    Ho, T F; Paramsothy, S; Aw, T C; Yip, W C

    1996-03-01

    The serum lipid and lipoprotein levels of 59 obese Chinese children with a mean age of 13.0 years and mean relative weight of 164.2% were analysed. Between 40% to 54% of these children had elevated lipid and lipoprotein levels and about 78% had reduced high density lipoprotein (HDL) level when compared to healthy American and Japanese children. The obese children also had higher mean levels of total cholesterol (TC) and lower HDL compared to male adults in the local population. Those with elevated TC had higher mean relative weight (170% vs 159%, p < 0.05). In view of the close association between hyperlipidaemia and atherosclerosis, obese children should be carefully screened and managed to prevent long term morbidity and mortality of coronary artery disease. PMID:10967982

  5. Brucella outer membrane lipoprotein shares antigenic determinants with Escherichia coli Braun lipoprotein and is exposed on the cell surface.

    PubMed Central

    Gómez-Miguel, M J; Moriyón, I; López, J

    1987-01-01

    In an enzyme-linked immunosorbent assay (ELISA), purified Brucella abortus and Escherichia coli peptidoglycan-linked lipoproteins gave a strong cross-reaction with sera from rabbits hyperimmunized with the heterologous lipoprotein. When smooth E. coli cells were used as ELISA antigens, the immunological cross-reaction was not observed unless the cells were treated to remove lipopolysaccharide and other outer membrane components. In contrast, intact cells from smooth strains of B. abortus and Brucella melitensis bound anti-lipoprotein immunoglobulin G, and the controls performed by ELISA showed that this reaction was not due to antibodies to the lipopolysaccharide, group 3 outer membrane proteins, or porins. Electron microscopy of cells labeled with antilipoprotein serum and protein A-colloidal gold showed specific labeling of smooth cells from both B. abortus and B. melitensis, even though unspecific labeling by nonimmune serum was observed with rough B. abortus. These results confirm the close similarity between E. coli and Brucella peptidoglycan-linked lipoproteins and show that, in contrast to E. coli, the lipoprotein of B. abortus and B. melitensis is partially exposed on the surface of smooth cells. Images PMID:2432014

  6. 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

  7. Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative stress indices in male rats.

    PubMed

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Shabestari, Mahmoud M; Azad, Farahzad Jabbari; Farkhondeh, Tahereh; Bafandeh, Fereshteh

    2015-09-01

    Cadmium (Cd) is an environmental toxic metal implicated in lipid abnormalities. The present study was designed to elucidate the possible association between chronic exposure to Cd concentration and alterations in plasma lipid, lipoprotein, and oxidative stress indices in rats. Sixteen male rats were assigned to 2 groups of 8 rats each (test and control). The Cd-exposed group obtained drinking water containing cadmium chloride (CdCl2) in the concentration of 2.0 mg Cd/L in drinking water for 3 months. At the end of the experimental period, blood samples were obtained to determine the changes of serum triglycerides (TG), total cholesterol (TC), highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), reduced glutathione (GSH), malondialdehyde (MDA) and also serum Cd contents. The results of the present study indicated that Cd administration significantly increased the serum levels of TG, TC, LDL-C, MDA and Cd with reduction in the HDL-C and GSH levels. In conclusion, evidence is presented that chronic exposure to low Cd concentration can adversely affect the lipid and lipoprotein profile via lipid peroxidation. PMID:27486375

  8. Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative stress indices in male rats

    PubMed Central

    Azimi-Nezhad, Mohsen; Shabestari, Mahmoud M.; Azad, Farahzad Jabbari; Farkhondeh, Tahereh; Bafandeh, Fereshteh

    2015-01-01

    Cadmium (Cd) is an environmental toxic metal implicated in lipid abnormalities. The present study was designed to elucidate the possible association between chronic exposure to Cd concentration and alterations in plasma lipid, lipoprotein, and oxidative stress indices in rats. Sixteen male rats were assigned to 2 groups of 8 rats each (test and control). The Cd-exposed group obtained drinking water containing cadmium chloride (CdCl2) in the concentration of 2.0 mg Cd/L in drinking water for 3 months. At the end of the experimental period, blood samples were obtained to determine the changes of serum triglycerides (TG), total cholesterol (TC), highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), reduced glutathione (GSH), malondialdehyde (MDA) and also serum Cd contents. The results of the present study indicated that Cd administration significantly increased the serum levels of TG, TC, LDL-C, MDA and Cd with reduction in the HDL-C and GSH levels. In conclusion, evidence is presented that chronic exposure to low Cd concentration can adversely affect the lipid and lipoprotein profile via lipid peroxidation. PMID:27486375

  9. Changes in Lipids and Lipoprotein Indices in Relation to the Severity of Hypertension in Newly Diagnosed Hypertensive Nigerians

    PubMed Central

    Onwubuya, E. I.; Anisiuba, B. C.; Osuji, C. U.; Ahaneku, J. E.

    2012-01-01

    Hypertension and dyslipidaemia are important components of metabolic syndrome and both are known to complicate each other. Materials and Methods. A total of 149 subjects consisting of 107 hypertensive patients, grouped into 3 (of 37, 35, and 35 patients categorized based on the grade of hypertension as grade 1, grade 2, and grade 3, resp.) and 42 controls, were recruited for this study. Each subject had a recording of the bio- and anthropometric data comprising of the age, height, weight, body mass index (BMI), and abdominal circumference (AC). The blood pressure was also recorded. Fasting blood was collected and serum was used for the estimation of the lipids: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG), while low density lipoprotein cholesterol (LDL-C) and VLDL were estimated using Friedewald formula. Findings. Patients with hypertension had higher lipid and lipoprotein levels than the controls and the values became more significant with increasing severity of hypertension. The difference was statistically significant for TC, LDL-C, and VLDL-C (P < 0.05). Conclusion. This study showed that lipid and lipoprotein cholesterol abnormalities exist and even worsen with severity of hypertension. It is important that investigations in patients with hypertension should include a lipid profile. PMID:23304552

  10. Improving Assessment of Lipoprotein Profile in Type 1 Diabetes by 1H NMR Spectroscopy

    PubMed Central

    Brugnara, Laura; Mallol, Roger; Ribalta, Josep; Vinaixa, Maria; Murillo, Serafín; Casserras, Teresa; Guardiola, Montse; Vallvé, Joan Carles; Kalko, Susana G.; Correig, Xavier; Novials, Anna

    2015-01-01

    Patients with type 1 diabetes (T1D) present increased risk of cardiovascular disease (CVD). The aim of this study is to improve the assessment of lipoprotein profile in patients with T1D by using a robust developed method 1H nuclear magnetic resonance spectroscopy (1H NMR), for further correlation with clinical factors associated to CVD. Thirty patients with T1D and 30 non-diabetes control (CT) subjects, matched for gender, age, body composition (DXA, BMI, waist/hip ratio), regular physical activity levels and cardiorespiratory capacity (VO2peak), were analyzed. Dietary records and routine lipids were assessed. Serum lipoprotein particle subfractions, particle sizes, and cholesterol and triglycerides subfractions were analyzed by 1H NMR. It was evidenced that subjects with T1D presented lower concentrations of small LDL cholesterol, medium VLDL particles, large VLDL triglycerides, and total triglycerides as compared to CT subjects. Women with T1D presented a positive association with HDL size (p<0.005; R = 0.601) and large HDL triglycerides (p<0.005; R = 0.534) and negative (p<0.005; R = -0.586) to small HDL triglycerides. Body fat composition represented an important factor independently of normal BMI, with large LDL particles presenting a positive correlation to total body fat (p<0.005; R = 0.505), and total LDL cholesterol and small LDL cholesterol a positive correlation (p<0.005; R = 0.502 and R = 0.552, respectively) to abdominal fat in T1D subjects; meanwhile, in CT subjects, body fat composition was mainly associated to HDL subclasses. VO2peak was negatively associated (p<0.005; R = -0.520) to large LDL-particles only in the group of patients with T1D. In conclusion, patients with T1D with adequate glycemic control and BMI and without chronic complications presented a more favourable lipoprotein profile as compared to control counterparts. In addition, slight alterations in BMI and/or body fat composition showed to be relevant to provoking alterations in

  11. Merck Frosst award lecture 1995. La conference Merck Frosst 1995. Structural studies of lipoproteins and their apolipoprotein components.

    PubMed

    Ryan, R O

    1996-01-01

    Lipid transport processes via the circulatory system of animals are a vital function that utilizes highly specialized lipoprotein complexes. These complexes of protein and lipid impart solubility to otherwise insoluble lipids. The apoprotein components of lipoprotein complexes serve to stabilize the lipid components and modulate particle metabolism and function as ligands for receptor-mediated endocytosis of lipoproteins. We have used an insect (Manduca sexta) model system for studies of lipid transport. In this system, flight activity elicits a dramatic increase in the demand for glycerolipid fuel molecules by flight muscle tissue. These lipids are mobilized from a storage organ and transported through the hemolymph (blood) to the flight muscle by the lipoprotein, lipophorin. This system possesses the unique property that lipids are loaded onto pre-existing high density lipophorin through the action of a lipid transfer particle (LTP). LTP is a high molecular weight hemolymph component that facilitates net vectorial lipid transfer from fat body tissue to lipophorin. The increase in lipid content of the lipoprotein induces association of a low molecular weight amphipathic exchangeable apolipoprotein, apolipophorin III (apoLp-III). ApoLp-III is a 18 kDa protein that normally exists as a water-soluble monomeric hemolymph protein. The structural properties of apoLp-III have been investigated by X-ray crystallography. ApoLp-III from Locusta migratoria adopts a five helix bundle conformation wherein each of the amphipathic helices orients with its hydrophobic face directed toward the interior of the bundle. It has been hypothesized that lipid association requires a dramatic conformational change wherein the helix bundle opens about putative hinge domains located in the loops between helices. The data accumulated support the concept that apoLp-III is a member of the broad class of exchangeable apolipoproteins and structural information learned from this system is directly

  12. Structural changes of lipoprotein lipids by 1H NMR

    NASA Astrophysics Data System (ADS)

    Ala-Korpela, M.; Oja, J.; Lounila, J.; Jokisaari, J.; Savolainen, M. J.; Kesäniemi, Y. A.

    1995-08-01

    A new procedure for detecting structural changes of lipoprotein lipids is introduced and applied to study native low (LDL) and high density lipoprotein (HDL) particles. The method involves lineshape fitting analyses of specific resonances in proton nuclear magnetic resonance spectra together with numerical derivation of the obtained intensity curves with respect to temperature. In addition to the well-known phase transition of the LDL core cholesterol esters, a novel structural change was revealed in the phospholipid monolayer of both native LDL and HDL particles. The attributes of this phenomenon are discussed.

  13. The role of ANGPTL3 in controlling lipoprotein metabolism.

    PubMed

    Tikka, Anna; Jauhiainen, Matti

    2016-05-01

    Angiopoietin-like protein 3 (ANGPTL3) is a secretory protein regulating plasma lipid levels via affecting lipoprotein lipase- and endothelial lipase-mediated hydrolysis of triglycerides and phospholipids. ANGPTL3-deficiency due to loss-of-function mutations in the ANGPTL3 gene causes familial combined hypobetalipoproteinemia (FHBL2, OMIM # 605019), a phenotype characterized by low concentration of all major lipoprotein classes in circulation. ANGPTL3 is therefore a potential therapeutic target to treat combined hyperlipidemia, a major risk factor for atherosclerotic coronary heart disease. This review focuses on the mechanisms behind ANGPTL3-deficiency induced FHBL2. PMID:26754661

  14. JCL Roundtable: Hypertriglyceridemia due to defects in lipoprotein lipase function

    PubMed Central

    Brown, W. Virgil; Goldberg, Ira J.; Young, Stephen G.

    2015-01-01

    In this Roundtable, our intent is to discuss those rare genetic disorders that impair the function of lipoprotein lipase. These cause severe hypertriglyceridemia that appears in early childhood with Mendelian inheritance and usually with full penetrance in a recessive pattern. Dr Ira Goldberg from New York University School of Medicine and Dr Stephen Young from the University of California, Los Angeles have agreed to answer my questions about this topic. Both have done fundamental work in recent years that has markedly altered our views on lipoprotein lipase function. I am going to start by asking them to give us a brief history of this enzyme system as a clinical entity. PMID:26073384

  15. Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity.

    PubMed

    Kwiterovich, Peter O

    2002-10-17

    Traditional risk factors for coronary artery disease (CAD) predict about 50% of the risk of developing CAD. The Adult Treatment Panel (ATP) III has defined emerging risk factors for CAD, including small, dense low-density lipoprotein (LDL). Small, dense LDL is often accompanied by increased triglycerides (TGs) and low high-density lipoprotein (HDL). An increased number of small, dense LDL particles is often missed when the LDL cholesterol level is normal or borderline elevated. Small, dense LDL particles are present in families with premature CAD and hyperapobetalipoproteinemia, familial combined hyperlipidemia, LDL subclass pattern B, familial dyslipidemic hypertension, and syndrome X. The metabolic syndrome, as defined by ATP III, incorporates a number of the components of these syndromes, including insulin resistance and intra-abdominal fat. Subclinical inflammation and elevated procoagulants also appear to be part of this atherogenic syndrome. Overproduction of very low-density lipoproteins (VLDLs) by the liver and increased secretion of large, apolipoprotein (apo) B-100-containing VLDL is the primary metabolic characteristic of most of these patients. The TG in VLDL is hydrolyzed by lipoprotein lipase (LPL) which produces intermediate-density lipoprotein. The TG in intermediate-density lipoprotein is hydrolyzed further, resulting in the generation of LDL. The cholesterol esters in LDL are exchanged for TG in VLDL by the cholesterol ester tranfer proteins, followed by hydrolysis of TG in LDL by hepatic lipase which produces small, dense LDL. Cholesterol ester transfer protein mediates a similar lipid exchange between VLDL and HDL, producing a cholesterol ester-poor HDL. In adipocytes, reduced fatty acid trapping and retention by adipose tissue may result from a primary defect in the incorporation of free fatty acids into TGs. Alternatively, insulin resistance may promote reduced retention of free fatty acids by adipocytes. Both these abnormalities lead to

  16. Interactions between Phospholipids and Organic Phases: Insights into Lipoproteins and Nanoemulsions.

    PubMed

    Hildebrandt, Ellen; Dessy, Alberto; Sommerling, Jan-Hendrik; Guthausen, Gisela; Nirschl, Hermann; Leneweit, Gero

    2016-06-14

    The adsorption of phosphatidylcholines (PCs), dissolved in squalene or squalane as an organic phase, was studied at the interface with water. Using profile analysis tensiometry, the equilibrium adsorption isotherms, minimum molecular interfacial areas, and solubility limits were derived. For squalene, differences in PC solubility and interfacial adsorption were found, depending on PC saturation. Compared to saturated PCs, unsaturated PCs showed a 3-fold-lower interfacial density but up to a 28-fold-higher critical aggregation concentration (CAC). In addition, the solubility limit of unsaturated PC in squalene and in its saturated form squalane diverged by a factor of 739. These findings provided evidence for steric repulsion or π-π interactions of π bonds in both solvent and solute or both effects acting complementarily. In squalane, low solubilities but high interfacial densities were found for all investigated PCs. Changes in fatty acid chain lengths showed that the influence of the increases in entropy and enthalpy on solubility is much smaller than solvent/solute interactions. Oxidation products of squalene lowered the interfacial tension, but increasing concentrations of PC expelled them from the interface. The CAC of saturated PC was increased by oxidation products of squalene whereas that of unsaturated PCs was not. Our findings indicate that the oxidation of triglycerides in lipoprotein cores can lead to increased solubility of saturated phospholipids covering the lipoproteins, contributing to destabilization, coalescence, and terminally the formation of atherosclerotic plaques. The consideration of solvent/solute interactions in molecular modeling may contribute to the interfacial tension and the corresponding kinetic or thermodynamic stability of lipoproteins. Measured areas per molecule prove that PCs form monolayers of different interfacial densities at the squalene/water interface but multilayers at the squalane/water interface. These findings

  17. Intact human ceruloplasmin oxidatively modifies low density lipoprotein.

    PubMed Central

    Ehrenwald, E; Chisolm, G M; Fox, P L

    1994-01-01

    Ceruloplasmin is a plasma protein that carries most of the copper found in the blood. Although its elevation after inflammation and trauma has led to its classification as an acute phase protein, its physiological role is uncertain. A frequently reported activity of ceruloplasmin is its ability to suppress oxidation of lipids. In light of the intense recent interest in the oxidation of plasma LDL, we investigated the effects of ceruloplasmin on the oxidation of this lipoprotein. In contrast to our expectations, highly purified, undegraded human ceruloplasmin enhanced rather than suppressed copper ion-mediated oxidation of LDL. Ceruloplasmin increased the oxidative modification of LDL as measured by thiobarbituric acid-reacting substances by at least 25-fold in 20 h, and increased electrophoretic mobility, conjugated dienes, and total lipid peroxides. In contrast, ceruloplasmin that was degraded to a complex containing 115- and 19-kD fragments inhibited cupric ion oxidation of LDL, as did commercial preparations, which were also degraded. However, the antioxidant capability of degraded ceruloplasmin in this system was similar to that of other proteins, including albumin. The copper in ceruloplasmin responsible for oxidant activity was not removed by ultrafiltration, indicating a tight association. Treatment of ceruloplasmin with Chelex-100 removed one of seven copper atoms per molecule and completely blocked oxidant activity. Restoration of the copper to ceruloplasmin also restored oxidant activity. These data indicate that ceruloplasmin, depending on the integrity of its structure and its bound copper, can exert a potent oxidant rather than antioxidant action on LDL. Our results invite speculation that ceruloplasmin may be in part responsible for oxidation of LDL in blood or in the arterial wall and may thus have a physiological role that is quite distinct from what is commonly believed. Images PMID:8163654

  18. Speciated Human High Density Lipoprotein Protein Proximity Profiles†

    PubMed Central

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

    2010-01-01

    It is expected that the attendant structural heterogeneity of human high density lipoprotein (HDL) complexes is a determinant of its varied metabolic functions. To determine structural heterogeneity of HDL, major apolipoprotein stoichiometry profiles in human HDL were determined. First, HDL was separated into two main populations, with and without apolipoprotein (apo) A-II, LpA-I and LpA-I/A-II respectively. Each main population was further separated into six individual subfractions using size exclusion chromatography (SEC). Protein proximity profiles (PPP) of major apolipoproteins in each individual subfraction was determined by optimally cross-linking apolipoproteins within individual particles with bis(sulfosuccinimidyl)suberate (BS3), a bifunctional cross linker, followed by molecular weight determination by MALDI-MS. The PPPs of LpA-I subfractions indicated that the number of apoA-I molecules increased from two to three to four upon increase in the LpA-I particle size. On the other hand, the entire population of LpA-I/A-II demonstrated the presence of only two proximal apoA-I molecules per particle, while the number of apoA-II molecules varied from one dimeric apoA-II to two and then to three. For most of the above PPP profiles, an additional population that contained a single molecule of apoC-III in addition to apoA-I and/or apoA-II was detected. Upon composition analyses of individual subpopulations, LpA-I/A-II displayed comparable proportions for total protein (~58%), phospholipids (~21%) total cholesterol (~16%), triglycerides (~5%) and free cholesterol (~4%) across subfractions. LpA-I components, on the other hand, showed significant variability. This novel information on HDL subfractions will form a basis for better understanding particle specific functions of HDL. PMID:21073165

  19. The removal of partially metabolized very-low-density lipoproteins by the perfused rat liver.

    PubMed Central

    Suri, B S; Targ, M E; Robinson, D S

    1981-01-01

    1. Donor perfused rat livers were used to prepare VLD (very-low-density) lipoproteins, labelled in their triacylglycerol and protein components with [1-14C]oleic acid and L-[4,5-3H]leucine respectively. Partially metabolized VLD lipoproteins, similarly labelled, were obtained from supradiaphragmatic rats injected with the parent VLD lipoproteins. 2. The triacylglycerol and protein components of the partially metabolized VLD lipoproteins were removed by recipient perfused rat livers at rates much higher than those of the parent VLD lipoproteins. No degradation of the partially metabolized VLD lipoproteins to LD (low-density) lipoproteins occurred during the perfusions. 3. Removal of hepatic lipase from the livers did not significantly affect the rate of removal of the partially metabolized VLD lipoproteins. PMID:7317016

  20. Improving lipoprotein profiles by liver-directed gene transfer of low density lipoprotein receptor gene in hypercholesterolaemia mice.

    PubMed

    Ou, Hailong; Zhang, Qinghai; Zeng, Jia

    2016-06-01

    The defect of low density lipoprotein receptor disturbs cholesterol metabolism and causes familial hypercholesterolaemia (FH). In this study, we directly delivered exogenous Ldlr gene into the liver of FH model mice (Ldlr(-/-)) by lentiviral gene transfer system. The results showed that the Ldlr gene controlled by hepatocyte-specific human thyroxine-binding globulin (TBG) promoter successfully and exclusively expressed in livers.We found that, although, the content of high density lipoprotein in serum was not significantly affected by the Ldlr gene expression, the serum low density lipoprotein level was reduced by 46%, associated with a 30% and 28% decrease in triglyceride and total cholesterol, respectively, compared to uninjected Ldlr(-/-) mice. Moreover, the TBG directed expression of Ldlr significantly decreased the lipid accumulation in liver and reduced plaque burden in aorta (32%). Our results indicated that the hepatocyte-specific expression of Ldlr gene strikingly lowered serum lipid levels and resulted in amelioration of hypercholesterolaemia. PMID:27350674

  1. High-density lipoprotein proteome dynamics in human endotoxemia

    PubMed Central

    2011-01-01

    Background A large variety of proteins involved in inflammation, coagulation, lipid-oxidation and lipid metabolism have been associated with high-density lipoprotein (HDL) and it is anticipated that changes in the HDL proteome have implications for the multiple functions of HDL. Here, SELDI-TOF mass spectrometry (MS) was used to study the dynamic changes of HDL protein composition in a human experimental low-dose endotoxemia model. Ten healthy men with low HDL cholesterol (0.7+/-0.1 mmol/L) and 10 men with high HDL cholesterol levels (1.9+/-0.4 mmol/L) were challenged with endotoxin (LPS) intravenously (1 ng/kg bodyweight). We previously showed that subjects with low HDL cholesterol are more susceptible to an inflammatory challenge. The current study tested the hypothesis that this discrepancy may be related to differences in the HDL proteome. Results Plasma drawn at 7 time-points over a 24 hour time period after LPS challenge was used for direct capture of HDL using antibodies against apolipoprotein A-I followed by subsequent SELDI-TOF MS profiling. Upon LPS administration, profound changes in 21 markers (adjusted p-value < 0.05) were observed in the proteome in both study groups. These changes were observed 1 hour after LPS infusion and sustained up to 24 hours, but unexpectedly were not different between the 2 study groups. Hierarchical clustering of the protein spectra at all time points of all individuals revealed 3 distinct clusters, which were largely independent of baseline HDL cholesterol levels but correlated with paraoxonase 1 activity. The acute phase protein serum amyloid A-1/2 (SAA-1/2) was clearly upregulated after LPS infusion in both groups and comprised both native and N-terminal truncated variants that were identified by two-dimensional gel electrophoresis and mass spectrometry. Individuals of one of the clusters were distinguished by a lower SAA-1/2 response after LPS challenge and a delayed time-response of the truncated variants. Conclusions

  2. High-density lipoprotein cholesterol esterification and transfer rates to lighter density lipoproteins mediated by cholesteryl ester transfer protein in the fasting and postprandial periods are not altered in type 1 diabetes mellitus.

    PubMed

    Medina; Nunes; Carrilho; Shimabukuru; Lottenberg; Lottenberg; McPherson; Krauss; Quintão

    2000-10-01

    Background: Diabetes mellitus is associated with atherosclerosis that has, in part, been ascribed to abnormalities in the reverse cholesterol transport system. Methods: We determined, in the fasting and post-alimentary periods, rates of HDL cholesterol esterification and transfer to apoB-containing lipoproteins, cholesteryl ester transfer protein (CETP) concentration, and apoB lipoprotein size in 10 type 1 diabetics and 10 well-matched controls. Autologous HDL was labeled with [14C]cholesterol and incubated at 37 degrees C during a period of 30 min for measurement of the cholesterol esterification rate (CER), as well as for 24 h for measurement of the endogenous HDL [14C]cholesteryl ester ([14C]CE) transfer rate to apoB-containing lipoproteins after 2- and 4-h incubations with the subject's own plasma. Exogenous cholesteryl ester transfer activity (CETA) was estimated by incubation of the participant's plasma (CETP source) with [14C]CE-HDL and VLDL from a pool of plasma donors. ApoB lipoprotein size was determined using non-denaturing polyacrylamide gradient gel electrophoresis of whole plasma. Results: Contrary to previous studies, we showed that even not well-controlled type 1 diabetics did not differ from lipid-matched, non-diabetic subjects in HDL-[14C]cholesterol esterification rate, transfer rates, or CETP concentration. CETP concentration correlates with the exogenous method of [14C]CE transfer and with the endogenous method only when the latter is corrected for plasma triacylglycerol (TG) concentration. In addition, during the postprandial phase, diabetic patients' VLDL are smaller and IDL size increases less than in controls. Conclusion: In type 1 diabetes mellitus, CETA is not altered when the plasma levels of donor and/or acceptor lipoproteins are within the normal range. PMID:11025251

  3. Modified low-density lipoproteins and high-density lipoproteins. From investigation tools to real in vivo players.

    PubMed

    Koller, Elisabeth; Volf, Ivo; Gurvitz, Aner; Koller, Franz

    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 disputed, apoE-containing HDL(2) binds to LRP8. The nature of these interactions as well as the distinction between candidate receptor proteins was elucidated using covalently modified apolipoproteins, which pointed to the participation of apolipoproteins in high affinity binding. However, the platelet effects initiated by binding of native lipoproteins remain controversial. Some of this ambiguity can be traced to the fact that native LDL inevitably undergoes substantial oxidisation upon modification, including by radiolabelling. The platelet-activating effects provoked by oxidised LDL are irrefutable, but many details remain unknown. The role of CD36 in platelet binding by oxidised LDL is well established, although additional receptors may exist. Much less is known about the interaction of oxidised HDL with platelets, since platelet activation was observed in some, but not all studies. Various frequently applied in vitro oxidation methods produce modified lipoprotein species that may not be relevant in vivo. Based on the reported modifications obtained by in vitro oxidation of LDL, early investigations focused mainly on the formation and the eventual effects of oxidised lipids. More recently, alterations to lipoproteins performed using hypochloric acid and myeloperoxidase redirected the attention to the role of modified apoproteins in triggering platelet responses. PMID:16877881

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

    SciTech Connect

    Junker, L.H.; Davis, R.A. )

    1989-12-01

    The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, respectively. As a result of the uptake of LDL, the synthesis of (14C)cholesterol from (2-14C)acetate was decreased and cellular cholesteryl ester mass was increased. Further studies demonstrated that rat apoE-free LDL and apoE-rich high density lipoprotein (HDL) both stimulated bile acid synthesis 1.5-fold, as well as inhibited the formation of (14C)cholesterol from (2-14C)acetate. Reductive methylation of LDL blocked the inhibition of cholesterol synthesis, as well as the stimulation of bile acid synthesis, suggesting that these processes require receptor-mediated uptake. To identify the receptors responsible, competitive binding studies using 125I-labeled apoE-free LDL and 125I-labeled apoE-rich HDL were performed. Both apoE-free LDL and apoE-rich HDL displayed an equal ability to compete for binding of the other, suggesting that a receptor or a group of receptors that recognizes both apolipoproteins is involved. Additional studies show that hepatocytes from cholestyramine-treated rats displayed 2.2- and 3.4-fold increases in the binding of apoE-free LDL and apoE-rich HDL, respectively. These data show for the first time that receptor-mediated uptake of LDL by the liver is intimately linked to processes activating bile acid synthesis.

  5. Utilization of triacylglycerol-rich lipoproteins by the working rat heart: routes of uptake and metabolic fates

    PubMed Central

    Niu, You-Guo; Hauton, David; Evans, Rhys D

    2004-01-01

    Very-low-density lipoprotein (VLDL) and chylomicrons (CMs) transport triacylglycerol (TAG) to peripheral tissues. Lipoprotein-TAG may gain access to target cells by lipoprotein lipase (LPL) hydrolysis or via receptor-mediated uptake; the principal routes of entry of VLDL and CM into heart are unknown, and different routes of entry may result in different metabolic fates. To examine this, isolated working rat hearts were perfused with rat VLDL and CMs, dual-labelled with [3H]TAG and [14C]cholesterol. Uptake and utilization of CM-TAG were significantly greater than VLDL-TAG, but both were decreased significantly (more than halved) by tetrahydrolipstatin (THL, an inhibitor of lipoprotein lipase). By contrast, uptake of VLDL-cholesterol was much higher than CM-cholesterol (P < 0.01), and suramin (a lipoprotein receptor antagonist) decreased cholesterol uptake of both forms. CM-TAG oxidation rate was more than 4-fold higher than VLDL-TAG oxidation. However, suramin decreased TAG oxidation from both VLDL and CM without affecting TAG uptake or total utilization, suggesting that the TAG gaining access through receptor-mediated pathways is preferentially ‘channelled’ towards oxidation. Most (79%) CM-TAG was oxidized whilst the proportion of VLDL-TAG oxidized was only about half (49%). In the presence of suramin, there was a significant increase in esterification (incorporation of assimilated [3H]TAG into myocardial tissue [3H]lipids, mainly TAG) of assimilated TAG from both VLDL and CMs, again suggesting that receptor-mediated TAG uptake is directed towards oxidation rather than esterification. The importance of this relatively small pool of TAG is indicated by the fact that cardiac mechanical function declined markedly when lipoprotein receptors were inhibited. These results suggest that CMs, most fatty acids of which gain access into cardiomyocytes through LPL-mediated hydrolysis, are the major supplier of TAG for hearts to oxidize; however, the metabolic fate of VLDL

  6. [THE BECOMING IN PHYLOGENESIS OF TRANSFER IN INTERCELLULAR MEDIUM AND ACTIVE ABSORPTION OF POLYENOIC FATTY ACIDS BY CELLS SEQUENTIALLY OF HIGH DENSITY LIPOPROTEINS, LOW DENSITY LIPOPROTEINS AND HIGH DENSITY APOE-LIPOPROTEINS].

    PubMed

    Titov, V N

    2015-06-01

    After more than half-century of different conceptions, the theory of general pathology was used to substantiate that all lipoproteins are bi-layer:lipid by their structure. The main function of high density lipoproteins as of all lipoproteins is transfer of fatty acids to cells and only in second turn taking away of spirit cholesterol from cells. At the stages of phylogenesis high density lipoproteins, low density lipoproteins and very low density lipoproteins began to function in a subsequent way. The fatty acids were transferred by low density lipoproteins in polar lipids at passive absorption by cells. Later on, lipoproteins transfer fatty acids in non-polar ethers with spirits glycerin and spirit cholesterol. The cells absorb them by receptor endocytosis. The hepatocytes secret in blood palmitic, oleic, linoleic and linoleic very low density lipoproteins. The palmitic and oleic very low density lipoproteins absorb physiologically insulin-dependent cells apoE/B-100 = endocytosis. The linoleic and linoleic very low density lipoproteins after transition of polyethers cholesterol from high density lipoproteins turn into low density lipoproteins. The cells absorb them by apoB-100 = endocytosis. The formation of chylomicrons occurs in blood and hepatocytes absorb them by the way of apoB/E-48 = endocytosis. The absorption of poly-unsaturated fatty acids by cells with apoB-100 = endocytosis form sensitivity of animals to exogenous hyper spirit cholesterol and absorption of poly-unsaturated fatty acids by apoE/A-I = receptors form corresponding resistance. The ApoE in lipoproteins form cooperative ligands--apoE/B-48 for chylomicrons, apoE/B-100 for very low density lipoproteins and apoE/A-I for high density lipoproteins. The chylomicrons in blood form apoB-48 from complexes of triglycerides secreted by enterocytes. These views change conceptions of pathogenesis and prevention of atherosclerosis, metabolic syndrome and resistance to insulin whose pathogenesis is unified

  7. Towards Explaining the Water Siphon

    NASA Astrophysics Data System (ADS)

    Jumper, William D.; Stanchev, Boris

    2014-11-01

    Many high school and introductory college physics courses cover topics in fluidics through the Bernoulli and Poiseuille equations, and consequently one might think that siphons should present an excellent opportunity to engage students in various laboratory measurement exercises incorporating these fascinating devices. However, the flow rates (or average exit velocities) of simple water siphons have not been sufficiently explained,1 nor has an associated analytical model been developed demonstrating sufficient experimental correspondence to allow physics instructors to bring closure between theoretical concepts and laboratory experiences. We present such an explanation and analytical model for the flow rates of simple water tube siphons. Further, we report measurements that show the model gives good correspondence to flow rates of siphons over a wide range of tube lengths, inner diameters, and water heights (hydrostatic head), and for which the Reynolds numbers range from 102 to 105.

  8. Dark antiatoms can explain DAMA

    NASA Astrophysics Data System (ADS)

    Wallemacq, Quentin; Cudell, Jean-René

    2015-02-01

    We show that the existence of a sub-dominant form of dark matter, made of dark "antiatoms" of mass m~ 1 TeV and size dot a0~ 3 fm, can explain the results of direct detection experiments, with a positive signal in DAMA/NaI and DAMA/LIBRA and no signal in other experiments. The signal comes from the binding of the dark antiatoms to thallium, a dopant in DAMA, and is not present for the constituent atoms of other experiments. The dark antiatoms are made of two particles oppositely charged under a dark U(1) symmetry and can bind to terrestrial atoms because of a kinetic mixing between the photon and the massless dark photon, such that the dark particles acquire an electric millicharge ~ ± 5.10-4e. This millicharge enables them to bind to high-Z atoms via radiative capture, after they thermalize in terrestrial matter through elastic collisions.

  9. 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...

  10. 21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Lipoprotein X immunolog-ical test system. 866.5590 Section 866.5590 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-density lipoprotein) in serum and other body fluids. Measurement of lipoprotein X aids in the diagnosis...

  11. 21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Lipoprotein X immunolog-ical test system. 866.5590 Section 866.5590 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-density lipoprotein) in serum and other body fluids. Measurement of lipoprotein X aids in the diagnosis...

  12. 21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lipoprotein X immunolog-ical test system. 866.5590 Section 866.5590 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-density lipoprotein) in serum and other body fluids. Measurement of lipoprotein X aids in the diagnosis...

  13. 21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Lipoprotein X immunolog-ical test system. 866.5590 Section 866.5590 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-density lipoprotein) in serum and other body fluids. Measurement of lipoprotein X aids in the diagnosis...

  14. Lipoprotein cholesterol and triglyceride concentrations associated with dog body condition score; effect of recommended fasting duration on sample concentrations in Japanese private clinics

    PubMed Central

    USUI, Shiho; YASUDA, Hidemi; KOKETSU, Yuzo

    2015-01-01

    The objectives of this study were to survey clinics’ guidance about recommended fasting duration (FD) prior to lipoprotein analysis, and to characterize lipoprotein cholesterol and triglyceride concentrations in obese and overweight dogs categorized on the basis of the 5-point body condition score (BCS) scale. A dataset was created from lipoprotein analysis medical records of 1,538 dogs from 75 breeds in 354 clinics from 2012 to 2013. A phone survey was conducted to obtain the clinics’ FD. Two-level linear mixed-effects models were applied to the data. Over 50% of the clinics said they recommended fasting for 12 hr or more. Dogs in clinics with FD 12 hr or more had lower chylomicron triglyceride concentrations than those in clinics with FD less than 8 hr (P=0.05). Mean (± SEM) BCS at sampling was 3.7 ± 0.02. Obese and overweight dogs had higher very low density lipoprotein (VLDL) and high density lipoprotein (HDL) cholesterol and triglyceride concentrations than ideal dogs (P<0.05), but no such difference was found for low density lipoprotein cholesterol and triglyceride concentrations (P≥0.07). Across all BCS, as dog age rose from 0 to 8 years old, HDL cholesterol concentrations decreased by 13.5 mg/dl, whereas VLDL triglyceride concentrations increased by 81.7 mg/dl (P<0.05). In conclusion, FD of 8 hr or less may affect lipoprotein lipid concentrations. Obese and overweight dogs were characterized as having high VLDL and HDL cholesterol and triglyceride concentrations. PMID:25866404

  15. Apolipoprotein C-II deficiency syndrome. Clinical features, lipoprotein characterization, lipase activity, and correction of hypertriglyceridemia after apolipoprotein C-II administration in two affected patients.

    PubMed Central

    Baggio, G; Manzato, E; Gabelli, C; Fellin, R; Martini, S; Enzi, G B; Verlato, F; Baiocchi, M R; Sprecher, D L; Kashyap, M L

    1986-01-01

    Two patients (brother and sister, 41 and 39 yr of age, respectively) have been shown to have marked elevation of plasma triglycerides and chylomicrons, decreased low density lipoproteins (LDL) and high density lipoproteins (HDL), a type I lipoprotein phenotype, and a deficiency of plasma apolipoprotein C-II (apo C-II). The male patient had a history of recurrent bouts of abdominal pain often accompanied by eruptive xanthomas. The female subject, identified by family screening, was asymptomatic. Hepatosplenomegaly was present in both subjects. Analytical and zonal ultracentrifugation revealed a marked increase in triglyceride-rich lipoproteins including chylomicrons and very low density lipoproteins, a reduction in LDL, and the presence of virtually only the HDL3 subfraction. LDL were heterogeneous with the major subfraction of a higher hydrated density than that observed in plasma lipoproteins of normal subjects. Apo C-II levels, quantitated by radioimmunoassay, were 0.13 mg/dl and 0.12 mg/dl, in the male and female proband, respectively. A variant of apo C-II (apo C-IIPadova) with lower apparent molecular weight and more acidic isoelectric point was identified in both probands by two-dimensional gel electrophoresis. The marked hypertriglyceridemia and elevation of triglyceride-rich lipoproteins were corrected by the infusion of normal plasma or the injection of a biologically active synthesized 44-79 amino acid residue peptide fragment of apo C-II. The reduction in plasma triglycerides after the injection of the synthetic apo C-II peptide persisted for 13-20 d. These results definitively established that the dyslipoproteinemia in this syndrome is due to a deficiency of normal apo C-II. A possible therapeutic role for replacement therapy of apo C-II by synthetic or recombinant apo C-II in those patients with severe hypertriglyceridemia and recurrent pancreatitis may be possible in the future. Images PMID:3944267

  16. Serum lipid, lipoprotein and apolipoprotein changes in gestational diabetes mellitus: a cross-sectional and prospective study.

    PubMed Central

    Koukkou, E; Watts, G F; Lowy, C

    1996-01-01

    AIMS: To compare serum lipid, lipoprotein and apolipoprotein concentrations during and six to 12 months after pregnancy in control and diabetic women. METHODS: The serum lipid, lipoprotein and apolipoprotein concentrations were measured in 20 women with gestational diabetes mellitus (GDM) and 22 women with normal glucose tolerance (controls) during the third trimester of pregnancy and six to 12 months after delivery. RESULTS: During pregnancy the women with GDM had higher serum triglyceride (mean (95% confidence interval (CI)), 2.91 (2.22-3.51) v 2.1 (1.75-2.52)) but lower low density lipoprotein (LDL) cholesterol concentrations compared with controls (mean (SD), 3.08 (1.2) v 4.01 (1.1). Total cholesterol, high density lipoprotein (HDL) cholesterol and apolipoprotein concentrations were not significantly different between the two groups. After pregnancy, total cholesterol, HDL cholesterol, triglyceride, and apolipoprotein A1 and B decreased in a parallel manner, resulting in lower concentrations, comparable between the two groups. LDL cholesterol concentrations decreased after pregnancy in the controls (mean (SD), 4.01 (1.1) v 2.69 (0.6)) but not in those with GDM (3.08 (1.2) v 2.72 (0.7)). The change in lipid concentrations was not related to change in weight. CONCLUSION: Development of diabetes during pregnancy induces a state of dyslipidaemia characterised by elevated triglyceride concentrations, as seen in other insulin resistance states. However, GDM seems to blunt the increase in LDL cholesterol during pregnancy and this requires further investigation. Whether the changes in lipoprotein metabolism in GDM are significant for the health status of the mother and the foetus requires further study. PMID:8881912

  17. Bile salt-stimulated carboxyl ester lipase influences lipoprotein assembly and secretion in intestine: a process mediated via ceramide hydrolysis.

    PubMed

    Kirby, R Jason; Zheng, Shuqin; Tso, Patrick; Howles, Philip N; Hui, David Y

    2002-02-01

    Bile salt-stimulated carboxyl ester lipase (CEL), also called cholesterol esterase, is one of the major proteins secreted by the pancreas. The physiological role of CEL was originally thought to be its mediation of dietary cholesterol absorption. However, recent studies showed no difference between wild type and CEL knockout mice in the total amount of cholesterol absorbed in a single meal. The current study tests the hypothesis that CEL in the intestinal lumen may influence the type of lipoproteins produced. A lipid emulsion containing 4 mm phospholipid, 13.33 mm [(3)H]triolein, and 2.6 mm [(14)C]cholesterol in 19 mm taurocholate was infused into the duodenum of lymph fistula CEL(+/+) and CEL(-/-) mice at a rate of 0.3 ml/h. Results showed no difference between CEL(+/+) and CEL(-/-) mice in the rate of cholesterol and triglyceride transport from the intestinal lumen to the lymph. However, CEL(-/-) mice produced predominantly smaller lipoproteins, whereas the CEL(+/+) mice produced primarily large chylomicrons and very low density lipoprotein. The proximal intestine of CEL(-/-) mice was also found to possess significantly less ceramide hydrolytic activity than that present in CEL(+/+) mice. By using Caco2 cells grown on Transwell membranes as a model, sphingomyelinase treatment inhibited the secretion of larger chylomicron-like lipoproteins without affecting total cholesterol secretion. In contrast, the addition of CEL to the apical medium increased the amount of large lipoproteins produced and alleviated the inhibition induced by sphingomyelinase. Taken together, this study identified a novel and physiologically significant role for CEL, namely the promotion of large chylomicron production in the intestine. The mechanism appears to be mediated through CEL hydrolysis of ceramide generated during the lipid absorption process. PMID:11733511

  18. High-density lipoprotein, mitochondrial dysfunction and cell survival mechanisms.

    PubMed

    White, C Roger; Giordano, Samantha; Anantharamaiah, G M

    2016-09-01

    Ischemic injury is associated with acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting and open heart surgery. The timely re-establishment of blood flow is critical in order to minimize cardiac complications. Reperfusion after a prolonged ischemic period, however, can induce severe cardiomyocyte dysfunction with mitochondria serving as a major target of ischemia/reperfusion (I/R) injury. An increase in the formation of reactive oxygen species (ROS) induces damage to mitochondrial respiratory complexes leading to uncoupling of oxidative phosphorylation. Mitochondrial membrane perturbations also contribute to calcium overload, opening of the mitochondrial permeability transition pore (mPTP) and the release of apoptotic mediators into the cytoplasm. Clinical and experimental studies show that ischemic preconditioning (ICPRE) and postconditioning (ICPOST) attenuate mitochondrial injury and improve cardiac function in the context of I/R injury. This is achieved by the activation of two principal cell survival cascades: 1) the Reperfusion Injury Salvage Kinase (RISK) pathway; and 2) the Survivor Activating Factor Enhancement (SAFE) pathway. Recent data suggest that high density lipoprotein (HDL) mimics the effects of conditioning protocols and attenuates myocardial I/R injury via activation of the RISK and SAFE signaling cascades. In this review, we discuss the roles of apolipoproteinA-I (apoA-I), the major protein constituent of HDL, and sphingosine 1-phosphate (S1P), a lysosphingolipid associated with small, dense HDL particles as mediators of cardiomyocyte survival. Both apoA-I and S1P exert an infarct-sparing effect by preventing ROS-dependent injury and inhibiting the opening of the mPTP. PMID:27150975

  19. Lipid composition of circulating multiple-modified low density lipoprotein.

    PubMed

    Zakiev, E R; Sukhorukov, V N; Melnichenko, A A; Sobenin, I A; Ivanova, E A; Orekhov, A N

    2016-01-01

    Atherogenic modified low- density lipoprotein (LDL) induces pronounced accumulation of cholesterol and lipids in the arterial wall, while native LDL seems to lack such capability. Therefore, modified LDL appears to be a major causative agent in the pathogenesis of atherosclerosis. Possible modifications of LDL particles include changes in size and density, desialylation, oxidation and acquisition of negative charge. Total LDL isolated from pooled plasma of patients with coronary atherosclerosis, as well as from healthy subjects contains two distinct subfractions: normally sialylated LDL and desialylated LDL, which can be isolated by binding to a lectin affinity column. We called the desialylated LDL subfraction circulating modified LDL (cmLDL). In this study, we focused on lipid composition of LDL particles, analysing the total LDL preparation and two LDL subfractions: cmLDL and native LDL. The composition of LDL was studied using thin-layer chromatography. We found that cmLDL subfraction had decreased levels of free and esterified cholesterol, triglycerides, phospholipids (except for lysophosphatidylcholine) and sphingomyelin in comparison to native LDL. On the other hand, levels of mono-, and diglycerides, lysophosphatidylcholine and free fatty acids were higher in cmLDL than in native LDL. Our study demonstrated that lipid composition of cmLDL from atherosclerotic patients was altered in comparison to healthy subjects. In particular, phospholipid content was decreased, and free fatty acids levels were increased in cmLDL. This strengthens the hypothesis of multiple modification of LDL particles in the bloodstream and underscores the clinical importance of desialylated LDL as a possible marker of atherosclerosis progression. PMID:27558696

  20. Structure of human serum lipoproteins inferred from compositional analysis.

    PubMed Central

    Shen, B W; Scanu, A M; Kézdy, F J

    1977-01-01

    Analysis of the correlations between size and chemical composition of lipoproteins of normolipidemic human plasma shows that the structure of all circulating lipoproteins is consistent with a spherical model of radius r in which a spherical liquid core of cholesterol esters and triglycerides of radius = r --20.2 A is surrounded by a monolayer of cholesterol and phospholipids with closely hydrophobic ends on the surface of the core. The average molecular areas at this inner surface are Spl = 68.5 A2/molecule for phospholipids and Sc= 39.1 A2/molecule for cholesterol. The proteins are closely packed with the hydrophilic head groups of phospholipids at the outer surface of the particle, with S' pl = 62.7 A2/molecule for phospholipids and Saa = 15.6 A2/amino acid for proteins. The polar head group of free cholesterol does not participate in the packing of the outer layer and thus must be masked by proteins. Free cholesterol is distributed among the circulating lipoproteins--with the exception of very high density lipoprotein and perhaps chylomicrons--according to a thermodynamic equilibrium governed by the curvature of the surface of the particle. PMID:265578

  1. PCSK9 and triglyceride-rich lipoprotein metabolism

    PubMed Central

    Druce, Irena; Abujrad, Hussein; Ooi, Teik Chye

    2015-01-01

    Abstract Pro-protein convertase subtilisin-kexin 9 (PCSK9) is known to affect low-density lipoprotein (LDL) metabolism, but there are indications from several lines of research that it may also influence the metabolism of other lipoproteins, especially triglyceride-rich lipoproteins (TRL). This review summarizes the current data on this possible role of PCSK9. A link between PCSK9 and TRL has been suggested through the demonstration of (1) a correlation between plasma PCSK9 and triglyceride (TG) levels in health and disease, (2) a correlation between plasma PCSK9 and markers of carbohydrate metabolism, which is closely related to TG metabolism, (3) an effect of TG-lowering fibrate therapy on plasma PCSK9 levels, (4) an effect of PCSK9 on postprandial lipemia, (5) an effect of PCSK9 on adipose tissue biology, (6) an effect of PCSK9 on apolipoprotein B production from the liver and intestines, (7) an effect of PCSK9 on receptors other than low density lipoprotein receptor (LDLR) that are involved in TRL metabolism, and (8) an effect of anti-PCSK9 therapy on serum TG levels. The underlying mechanisms are unclear but starting to emerge. PMID:26320603

  2. Macrophage Infiltration into the Glomeruli in Lipoprotein Glomerulopathy

    PubMed Central

    Takasaki, Satoshi; Maeda, Kunihiko; Joh, Kensuke; Yamakage, Shu; Fukase, Sachiko; Takahashi, Toshiyuki; Suzuki, Masayuki; Matsunaga, Akira; Saito, Takao

    2015-01-01

    Lipoprotein glomerulopathy (LPG) is characterized by histopathological features showing intra-glomerular lipoprotein thrombi and type III hyperlipoproteinemia (HLP), with heterozygote mutation of apolipoprotein (apo) E gene. On the other hand, as another renal lipidosis with type III HLP, apoE2 homozygote-related glomerulopathy (apoE2-GN) showing foamy macrophages has been reported. The case of a 25-year-old man who had LPG by clinical behavior and gene analysis, but demonstrated atypical histopathological features with a substantial amount of foamy macrophage infiltration in the glomeruli, is presented. The combination of alleles for apoE Tokyo/Maebashi and classical apoE2 (Arg158Cys) was inferred to be the leading cause of the unique renal pathology with lipoprotein thrombi and foamy macrophages. In addition, foamy macrophages infiltrated some part of the apoE-positive region within the glomerulus, but did not exist in lipoprotein thrombi despite apoE positivity, suggesting that properties of apoE are crucial in the development of LPG rather than macrophage function. This case provides important information related to the pathogenesis of LPG and apoE2-GN. PMID:26955632

  3. Lifecycle of a Lipoprotein from a Biophysical Perspective

    NASA Astrophysics Data System (ADS)

    Rutledge, John C.; Huser, Thomas; Voss, John; Chan, James; Parikh, Atul

    The goal of our project was to understand how lipids and lipoproteins interact with cell membranes. This chapter will present the five major areas in which we have focused our attention on understanding how lipids and lipoproteins interact with cell membranes (Fig. 11.1): (1) triglycerides and vascular injury, (2) single lipoprotein analysis, (3) apolipoprotein E (apoE) conformation changes in the postprandial state, (4) triglyceride-rich lipoproteins (TGRLs) and endothelial cell inflammation, and (5) TGRL lipolysis products and monocyte activation. For over a hundred years, Western civilization has questioned how the food we eat translates into disease, and specifically atherosclerotic cardiovascular disease. Although most information indicates that this basic pathophysiological process is mediated through consumption of excess saturated fats, much remains unknown. After humans eat a meal, there is an elevation of triglycerides in the blood in the postprandial state. In normal individuals, triglycerides can rise after a meal by 50 to 100%. This has been documented many times in the past, including a paper by Hyson et al, (1998) [1]. In that study, normal healthy individuals were given a 40%-fat meal. Plasma triglycerides, which were modestly elevated initially, rose about 60% higher three to four hours after ingestion of the meal. Subsequently plasma triglycerides fell to baseline levels six hours after the meal. Even in these healthy individuals, a significant elevation of triglycerides was noted after ingestion of a moder ately high-fat meal.

  4. Inhibition of endothelial lipase activity by sphingomyelin in the lipoproteins.

    PubMed

    Yang, Peng; Belikova, Natalia A; Billheimer, Jeff; Rader, Daniel J; Hill, John S; Subbaiah, Papasani V

    2014-10-01

    Endothelial lipase (EL) is a major determinant of plasma HDL concentration, its activity being inversely proportional to HDL levels. Although it is known that it preferentially acts on HDL compared to LDL and VLDL, the basis for this specificity is not known. Here we tested the hypothesis that sphingomyelin, a major phospholipid in lipoproteins is a physiological inhibitor of EL, and that the preference of the enzyme for HDL may be due to low sphingomyelin/phosphatidylcholine (PtdCho) ratio in HDL, compared to other lipoproteins. Using recombinant human EL, we showed that sphingomyelin inhibits the hydrolysis of PtdCho in the liposomes in a concentration-dependent manner. While the enzyme showed lower hydrolysis of LDL PtdCho, compared to HDL PtdCho, this difference disappeared after the degradation of lipoprotein sphingomyelin by bacterial sphingomyelinase. Analysis of molecular species of PtdCho hydrolyzed by EL in the lipoproteins showed that the enzyme preferentially hydrolyzed PtdCho containing polyunsaturated fatty acids (PUFA) such as 22:6, 20:5, 20:4 at the sn-2 position, generating the corresponding PUFA-lyso PtdCho. This specificity for PUFA-PtdCho species was not observed after depletion of sphingomyelin by sphingomyelinase. These results show that sphingomyelin not only plays a role in regulating EL activity, but also influences its specificity towards PtdCho species. PMID:25167836

  5. A Novel Anti-Inflammatory Effect for High Density Lipoprotein

    PubMed Central

    Cameron, Scott J.; Morrell, Craig N.; Bao, Clare; Swaim, AnneMarie F.; Rodriguez, Annabelle; Lowenstein, Charles J.

    2015-01-01

    High density lipoprotein has anti-inflammatory effects in addition to mediating reverse cholesterol transport. While many of the chronic anti-inflammatory effects of high density lipoprotein (HDL) are attributed to changes in cell adhesion molecules, little is known about acute signal transduction events elicited by HDL in endothelial cells. We now show that high density lipoprotein decreases endothelial cell exocytosis, the first step in leukocyte trafficking. ApoA-I, a major apolipoprotein of HDL, mediates inhibition of endothelial cell exocytosis by interacting with endothelial scavenger receptor-BI which triggers an intracellular protective signaling cascade involving protein kinase C (PKC). Other apolipoproteins within the HDL particle have only modest effects upon endothelial exocytosis. Using a human primary culture of endothelial cells and murine apo-AI knockout mice, we show that apo-AI prevents endothelial cell exocytosis which limits leukocyte recruitment. These data suggest that high density lipoprotein may inhibit diseases associated with vascular inflammation in part by blocking endothelial exocytosis. PMID:26680360

  6. [Residual risk: The roles of triglycerides and high density lipoproteins].