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Sample records for cholesterol high-density lipoprotein

  1. High-density lipoprotein cholesterol: How High

    Directory of Open Access Journals (Sweden)

    G Rajagopal

    2012-01-01

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

  2. A relation between high-density-lipoprotein cholesterol and bile cholesterol saturation.

    OpenAIRE

    Thornton, J R; Heaton, K. W.; Macfarlane, D G

    1981-01-01

    The association of cholesterol gall stones with coronary artery disease is controversial. To investigate this possible relation at the biochemical level, bile cholesterol saturation and the plasma concentrations of triglycerides, total cholesterol, and high-density-lipoprotein cholesterol (HDL cholesterol) were measured in 25 healthy, middle-aged women. Bile cholesterol saturation index was negatively correlated with HDL cholesterol. It was positively correlated with plasma triglycerides and ...

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

    NARCIS (Netherlands)

    J.S. Rana; S.M. Boekholdt

    2010-01-01

    Purpose of review Despite aggressive low-density lipoprotein cholesterol lowering, patients continue to be at significant risk of cardiovascular events. Assessment of non-high-density lipoprotein cholesterol (non-HDL-C) provides a measure of cholesterol contained in all atherogenic particles. In the

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

    Science.gov (United States)

    ... National Technical Information Service NCHS Total and High-density Lipoprotein Cholesterol in Adults: National Health and Nutrition ... less than 10% of women) had low high-density lipoprotein (HDL) cholesterol during 2011–2012. The percentage ...

  5. High-density lipoprotein cholesterol on a roller coaster: where will the ride end?

    Science.gov (United States)

    Kronenberg, Florian

    2016-04-01

    Bowe et al. report an association between low high-density lipoprotein cholesterol concentrations and various incident chronic kidney disease end points in a cohort of almost 2 million US veterans followed for 9 years. These impressive data should be a starting point for further investigations including genetic epidemiologic investigations as well as post hoc analyses of interventional trials that target high-density lipoprotein cholesterol and, finally, studies that focus on the functionality of high-density lipoprotein particles. PMID:26994572

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

    Science.gov (United States)

    Rimmer, James H.; Kelly, Luke E.

    1990-01-01

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

  7. Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol

    NARCIS (Netherlands)

    R.P.F. Dullaart (Robin); A. Groen (Albert); G.M. Dallinga-Thie (Geesje); R. de Vries (Rindert); W. Sluiter (Wim); A. van Tol (Arie)

    2008-01-01

    textabstractObjective: We tested whether in metabolic syndrome (MetS) subjects the ability of plasma to stimulate cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport pathway, is maintained despite low high-density lipoprotein (HDL) cholesterol. Design: In

  8. Triglycerides and high-density lipoprotein cholesterol are associated with insulinemia in adolescents

    Directory of Open Access Journals (Sweden)

    Ramírez-López Guadalupe

    2006-01-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the association between lipids and insulin concentration in adolescents. MATERIAL AND METHODS: A cross-sectional study of 350 adolescents aged 14-19 years old from a public high school in Guadalajara, in the state of Jalisco, Mexico, was conducted. Fasting insulin concentration was determined using microparticle enzyme immunoassay; total cholesterol and triglycerides were detected by standard enzymatic procedures; and low- and high-density lipoproteins were found using standard precipitation methods. Statistical analysis included linear multivariate regression. RESULTS: Serum triglycerides were associated positively with insulin fasting (beta= 0.003, p= 0.0001 and high-density lipoprotein cholesterol was negatively associated with insulin fasting in male adolescents 18-19 years old (beta= -0.03, p= 0.012. CONCLUSIONS: The relationships between triglycerides and insulin and between high-density lipoprotein cholesterol and insulin are already present in adolescence.

  9. Genetic analysis of long-lived families reveals novel variants influencing high density-lipoprotein cholesterol

    DEFF Research Database (Denmark)

    Feitosa, Mary F; Wojczynski, Mary K; Straka, Robert;

    2014-01-01

    The plasma levels of high-density lipoprotein cholesterol (HDL) have an inverse relationship to the risks of atherosclerosis and cardiovascular disease (CVD), and have also been associated with longevity. We sought to identify novel loci for HDL that could potentially provide new insights...

  10. Nevirapine Increases High-Density Lipoprotein Cholesterol Concentration by Stimulation of Apolipoprotein A-I Production

    NARCIS (Netherlands)

    R. Franssen; R.R. Sankatsing; E. Hassink; B. Hutten; M.T. Ackermans; K. Brinkman; R. Oesterholt; A. Arenas-Pinto; S.P. Storfer; J.J. Kastelein; H.P. Sauerwein; P. Reiss; E.S. Stroes

    2009-01-01

    Objective-The purpose of this study was to investigate the mechanism by which the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine (NVP) increases high-density lipoprotein cholesterol (HDLc) in treatment-experienced human immunodeficiency virus-1 (HIV-1)-infected patients. Methods an

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

    OpenAIRE

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

    2011-01-01

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

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

    OpenAIRE

    Heffernan, Kevin S; Karas, Richard H.; Kuvin, Jeffrey T.; Jae, Sae Young; Vieira, Victoria J.; Fernhall, Bo

    2009-01-01

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

  13. Drugs targeting high-density lipoprotein cholesterol for coronary artery disease management.

    Science.gov (United States)

    Katz, Pamela M; Leiter, Lawrence A

    2012-01-01

    Many patients remain at high risk for future cardiovascular events despite levels of low-density lipoprotein cholesterol (LDL-C) at, or below, target while taking statin therapy. Much effort is therefore being focused on strategies to reduce this residual risk. High-density lipoprotein cholesterol (HDL-C) is a strong, independent, inverse predictor of coronary heart disease risk and is therefore an attractive therapeutic target. Currently available agents that raise HDL-C have only modest effects and there is limited evidence of additional cardiovascular risk reduction on top of background statin therapy associated with their use. It was hoped that the use of cholesteryl ester transfer protein (CETP) inhibitors would provide additional benefit, but the results of clinical outcome studies to date have been disappointing. The results of ongoing trials with other CETP inhibitors that raise HDL-C to a greater degree and also lower LDL-C, as well as with other emerging therapies are awaited.

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

    Directory of Open Access Journals (Sweden)

    Subedi BH

    2014-04-01

    Full Text Available Bishnu H Subedi,1,2 Parag H Joshi,1 Steven R Jones,1 Seth S Martin,1 Michael J Blaha,1 Erin D Michos1 1Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 2Greater Baltimore Medical Center, Baltimore, MD, USA Abstract: 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. Keywords: high-density lipoprotein, lipids, cholesterol, atherosclerosis, cardiovascular disease, therapy

  15. Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol levels, and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Lundegaard, Christiane; Tybjærg-Hansen, Anne; Grande, Peer;

    2010-01-01

    Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD)....

  16. Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol levels, and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Lundegaard, Christiane; Tybjærg-Hansen, Anne; Grande, Peer;

    2010-01-01

    Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD).......Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD)....

  17. A Possible Mechanism Linking Hyperglycemia and Reduced High-density Lipoprotein Cholesterol Levels in Diabetes

    Institute of Scientific and Technical Information of China (English)

    高峰; 严同; 赵艳; 尹凡; 胡翠宁

    2010-01-01

    This study investigated the role of glucose in the biogenesis of high-density lipoprotein cholesterol(HDL-C).Mouse primary peritoneal macrophages were harvested and maintained in Dulbecco's modified Eagle's medium(DMEM) containing glucose of various concentrations.The cells were divided into 3 groups in terms of different glucose concentrations in the cultures:Control group(5.6 mmol/L glucose),high glucose concentration groups(16.7 mmol/L and 30 mmol/L glucose).ATP-binding cassette transporter A1(ABCA1) mRN...

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

    OpenAIRE

    Subedi BH; Joshi PH; Jones SR; Martin SS; Blaha MJ; Michos ED

    2014-01-01

    Bishnu H Subedi,1,2 Parag H Joshi,1 Steven R Jones,1 Seth S Martin,1 Michael J Blaha,1 Erin D Michos1 1Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 2Greater Baltimore Medical Center, Baltimore, MD, USA Abstract: 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...

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

    Science.gov (United States)

    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

  20. Treating patients with low high-density lipoprotein cholesterol: choices, issues and opportunities

    Directory of Open Access Journals (Sweden)

    Watts Gerald F

    2001-05-01

    Full Text Available Abstract Three clinical trials have recently focused on the benefits of lipid-regulating therapy in populations with normocholesterolaemia and low high-density lipoprotein (HDL-cholesterol. Two secondary prevention studies (Veterans Affairs HDL-Cholesterol Intervention Trial [VA-HIT] and Bezafibrate Infarction Prevention [BIP] trial testified to the efficacy of fibrates in decreasing cardiovascular events, particularly in patients with coexisting risk factors, including hypertriglyceridaemia. The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS demonstrated that a statin could decrease acute coronary events in patients with isolated low HDL-cholesterol in a primary prevention setting. The absolute risk reduction in coronary events in the VA-HIT study compares favourably with those reported from the statin-based Cholesterol and Recurrent Events (CARE and Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID trials. The absolute risk reduction in AFCAPS-TexCAPS is similar to that in West of Scotland Coronary Pravastatin Study (WOSCOPS. Recommendations are given concerning lifestyle and pharmacological management of low HDL-cholesterol. Optimal management also requires review of current treatment targets for HDL-cholesterol and triglycerides levels.

  1. A Splice Region Variant in LDLR Lowers Non-high Density Lipoprotein Cholesterol and Protects against Coronary Artery Disease

    NARCIS (Netherlands)

    Gretarsdottir, S.; Helgason, H.; Helgadottir, A.; Sigurdsson, A.; Thorleifsson, G.; Magnusdottir, A.; Oddsson, A.; Steinthorsdottir, V.; Rafnar, T.; Graaf, J. de; Daneshpour, M.S.; Hedayati, M.; Azizi, F.; Grarup, N.; Jorgensen, T.; Vestergaard, H.; Hansen, T.; Eyjolfsson, G.; Sigurdardottir, O.; Olafsson, I.; Kiemeney, B.; Pedersen, O.; Sulem, P.; Thorgeirsson, G.; Gudbjartsson, D.F.; Holm, H.; Thorsteinsdottir, U.; Stefansson, K.

    2015-01-01

    Through high coverage whole-genome sequencing and imputation of the identified variants into a large fraction of the Icelandic population, we found four independent signals in the low density lipoprotein receptor gene (LDLR) that associate with levels of non-high density lipoprotein cholesterol (non

  2. Role of Hepatic Lipase and Endothelial Lipase in High-Density Lipoprotein-Mediated Reverse Cholesterol Transport

    NARCIS (Netherlands)

    Annema, Wijtske; Tietge, Uwe J. F.

    2011-01-01

    Reverse cholesterol transport (RCT) constitutes a key part of the atheroprotective properties of high-density lipoproteins (HDL). Hepatic lipase (HL) and endothelial lipase (EL) are negative regulators of plasma HDL cholesterol levels. Although overexpression of EL decreases overall macrophage-to-fe

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

    Science.gov (United States)

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

  4. Effects of lifestyle interventions on high-density lipoprotein cholesterol levels.

    Science.gov (United States)

    Roussell, Michael A; Kris-Etherton, Penny

    2007-03-01

    This review summarizes intervention studies that evaluated the effects of lifestyle behaviors on high-density lipoprotein-cholesterol (HDL-C) levels. Current diet and lifestyle recommendations beneficially affect HDL-C. Individual lifestyle interventions that increase HDL-C include: a healthful diet that is low (7-10% of calories) in saturated fat and sufficient in unsaturated fat (15-20% of calories), regular physical activity, attaining a healthy weight, with moderate alcohol consumption, and cessation of cigarette smoking. Combining a healthy diet with weight loss and physical activity can increase HDL-C 10% to 13%. When combined with interventions that beneficially affect other cardiovascular disease risk factors, this increase in HDL-C is expected to contribute to a overall reduction in cardiovascular disease risk.

  5. High-density lipoprotein-cholesterol levels and risk of cancer in HIV-infected subjects

    Science.gov (United States)

    Squillace, Nicola; Galli, Laura; Bandera, Alessandra; Castagna, Antonella; Madeddu, Giordano; Caramello, Pietro; Antinori, Andrea; Cattelan, Annamaria; Maggiolo, Franco; Cingolani, Antonella; Gori, Andrea; Monforte, Antonella d’Arminio

    2016-01-01

    Abstract Investigation of the relationship between high-density lipoprotein-cholesterol (HDL-c) and the risk of developing cancer in a prospective cohort of human immunodeficiency virus (HIV)-infected patients. The Italian Cohort of Antiretroviral-naïve Patients Foundation Cohort is an Italian multicenter observational study recruiting HIV-positive patients while still antiretroviral treatment-naïve, regardless of the reason since 1997. Patients with at least 1 HDL-c value per year since enrollment and one such value before antiretroviral treatment initiation were included. HDL-c values were categorized as either low (HIV-ribonucleic acid. The multivariate model confirmed an association between HDL-c (AHR 2.61, 95% CI 1.40–4.89, P = 0.003) and risk of NADM. Low HDL-c is an independent predictor of cancer in HIV-1-infected subjects. PMID:27603338

  6. High-density lipoprotein-cholesterol and diet in a healthy elderly population.

    Science.gov (United States)

    Hooper, P L; Garry, P J; Goodwin, J S; Hooper, E M; Leonard, A G

    1982-01-01

    This study examined how high-density lipoprotein-cholesterol (HDL-C) correlated with a 3-day food record of fat, protein, carbohydrate, and alcohol consumption in a group of 270 healthy subjects over age 60. HDL-C concentrations correlated with alcohol consumption (expressed as grams/day) (r = + .25, P less than .001), and inversely with total carbohydrate (r = - .18, P less than .01) and refined carbohydrate (r = - .17, P less than .01) ingestion (expressed as a percent of total caloric intake). Subjects consuming diets low in either total carbohydrate or refined carbohydrate had 10 to 20% higher HDL-C levels than did those consuming diets high in these food substances. The relationships between HDL-C levels and alcohol and carbohydrate ingestion were independent of other variables which correlated with HDL-C levels. Dietary fat (total fat, saturated fat, unsaturated fat, and cholesterol) did not correlate with HDL-C. LDL-cholesterol and triglyceride levels did not correlate with any dietary variable measured.

  7. Influence of contraceptive pill and menstrual cycle on serum lipids and high-density lipoprotein cholesterol concentrations.

    OpenAIRE

    Demacker, P N; Schade, R W; Stalenhoef, A F; Stuyt, P M; Van 't Laar, A

    1982-01-01

    The fluctuations of serum lipid and lipoprotein concentrations within one cycle were studied both in women using and not using oral contraceptives. High-density lipoprotein cholesterol decreased significantly from 1.47 mmol/l (57 mg/100 ml) to 1.30 mmol/l (50 mg/100 ml) during one contraceptive cycle in eight women and rose again to the initial value during the pill-free days. The mean concentration of total cholesterol also fell significantly as a result of the decrease of high-density lipop...

  8. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    DEFF Research Database (Denmark)

    Chapman, M John; Ginsberg, Henry N; Amarenco, Pierre;

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipop...

  9. High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies

    DEFF Research Database (Denmark)

    van der Steeg, Wim A; Holme, Ingar; Boekholdt, S Matthijs;

    2008-01-01

    OBJECTIVES: This study was designed to assess the relationship of high-density-lipoprotein cholesterol (HDL-C), HDL particle size, and apolipoprotein A-I (apoA-I) with the occurrence of coronary artery disease (CAD), with a focus on the effect of very high values of these parameters. BACKGROUND......: High plasma levels of HDL-C and apoA-I are inversely related to the risk of CAD. However, recent data suggest that this relationship does not hold true for very high HDL-C levels, particularly when a preponderance of large HDL particles is observed. METHODS: We conducted a post-hoc analysis of 2...... prospective studies: the IDEAL (Incremental Decrease in End Points through Aggressive Lipid Lowering; n = 8,888) trial comparing the efficacy of high-dose to usual-dose statin treatment for the secondary prevention of cardiovascular events, and the EPIC (European Prospective Investigation into Cancer and...

  10. Physical inactivity interacts with an endothelial lipase polymorphism to modulate high density lipoprotein cholesterol in the GOLDN study

    Science.gov (United States)

    BACKGROUND: Plasma high density lipoprotein (HDL) cholesterol (HDL-C) concentration is highly heritable but is also modifiable by environmental factors including physical activity. HDL-C response to exercise varies among individuals, and this variability may be associated with genetic polymorphism...

  11. Alpinia zerumbet potentially elevates high-density lipoprotein cholesterol level in hamsters.

    Science.gov (United States)

    Lin, Li-Yun; Peng, Chiung-Chi; Liang, Yu-Jing; Yeh, Wan-Ting; Wang, Hui-Er; Yu, Tung-Hsi; Peng, Robert Y

    2008-06-25

    In folkloric plant medicines, Alpinia zerumbet (AZ) has been popularly recognized as an exellent hepatoprotector. To search for a good high-density lipoprotein cholesterol (HDL-C) elevating herbal preparation, we examined AZ for its antioxidant and hypolipidaemic bioactivities, especially its HDL-C elevating activity. AZ seeds contain 0.51% essential oils (SO), which are comprised of monoterpenoids, oxygenated monoterpenoids, sesquiterpenoids, oxygenated sesquiterpenoids, aldehydes, acid, and esters. Gas chromatography/mass spectrometry analysis indicated that most of the monoterpenes and sesquiterpenes were recoverable in pentane eluent, whilst the oxygenated monoterpenoids and sesquiterpenoids remained in ether eluent. The high contents of rutin, quercetin, and polyphenolics in ethanolic extract of AZ seeds exhibit moderate antilipoperoxidative but potent DPPH free radical scavenging bioactivities. Conclusively, both seed powder (SP) and SO are effective hypolipidaemics with amazingly potent HDL-C elevating capabilities. On the basis of hepatoprotectivity, SP is a more feasible hypolipidemic agent as well as a promising HDL-C elevating plant medicine.

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

    Directory of Open Access Journals (Sweden)

    Xu Yanhua

    2011-04-01

    Full Text Available Abstract Background To investigate alteration of high density lipoproteins (HDL subclasses distribution in different total cholesterol (TC levels, mainly the characteristics of HDL subclasses distribution in desirable TC levels and analyze the related mechanisms. Methods ApoA-I contents of plasma HDL subclasses were determined by 2-dimensional gel electrophoresis coupled with immunodetection. 486 Chinese Adults subjects were assigned to different TC groups according to the third Report of NCEP (ATP- III guidelines. Results The increase in contents of small preβ1-HDL, HDL3c, HDL3b, and HDL3a particles clustered and reduce in HDL2b with increased of TC. The distribution of HDL subclasses have shown abnormality characterized by the lower HDL2b (324.2 mg/L contents and the higher preβ1-HDL (90.4 mg/L contents for desirable TC Chinese subjects. Among 176 desirable TC subjects, 58.6% subjects with triglyceride (TG Conclusions The particles size of HDL subclasses shifted towards smaller with increased TC levels. The TC was liner with HDL2b contents and those can be reduced 17 mg/L for 0.5 mmol/L increment in TC levels. The HDL subclasses distribution phenotype was not expectation for Chinese Population with desirable TC levels. Thus, from the HDL subclasses distribution point, when assessing the coronary heart disease(CHD risk not only rely on the TC levels, but also the concentrations of TG, HDL-C and LDL-C must considered in case the potential risk for desirable TC subjects with other plasma lipids metabolism disorders.

  13. Elevated high-density lipoprotein cholesterol and age-related macular degeneration: the Alienor study.

    Directory of Open Access Journals (Sweden)

    Audrey Cougnard-Grégoire

    Full Text Available BACKGROUND: Lipid metabolism and particularly high-density lipoprotein (HDL may be involved in the pathogenic mechanism of age-related macular degeneration (AMD. However, conflicting results have been reported in the associations of AMD with plasma HDL and other lipids, which may be confounded by the recently reported associations of AMD with HDL-related genes. We explored the association of AMD with plasma lipid levels and lipid-lowering medication use, taking into account most of HDL-related genes associated with AMD. METHODS: The Alienor study is a population-based study on age-related eye diseases performed in 963 elderly residents of Bordeaux (France. AMD was graded from non mydriatic color retinal photographs in three exclusive stages: no AMD (n = 430 subjects, 938 eyes; large soft distinct drusen and/or large soft indistinct drusen and/or reticular drusen and/or pigmentary abnormalities (early AMD, n = 176, 247; late AMD (n = 40, 61. Associations of AMD with plasma lipids (HDL, total cholesterol (TC, Low-density lipoprotein (LDL, and triglycerides (TG were estimated using Generalized Estimating Equation logistic regressions. Statistical analyses included 646 subjects with complete data. RESULTS: After multivariate adjustment for age, sex, educational level, smoking, BMI, lipid-lowering medication use, cardiovascular disease and diabetes, and for all relevant genetic polymorphisms (ApoE2, ApoE4, CFH Y402H, ARMS2 A69S, LIPC rs10468017, LIPC rs493258, LPL rs12678919, ABCA1 rs1883025 and CETP rs3764261, higher HDL was significantly associated with an increased risk of early (OR = 2.45, 95%CI: 1.54-3.90; P = 0.0002 and any AMD (OR = 2.29, 95%CI: 1.46-3.59; P = 0.0003. Association with late AMD was far from statistical significance (OR = 1.58, 95%CI: 0.48-5.17; p = 0.45. No associations were found for any stage of AMD with TC, LDL and TG levels, statin or fibrate drug use. CONCLUSIONS: This study suggests that elderly patients with high HDL

  14. Mechanism of the hepatic lipase induced accumulation of high-density lipoprotein cholesterol by cells in culture

    International Nuclear Information System (INIS)

    Hepatic lipase can enhance the delivery of high-density lipoprotein (HDL) cholesterol to cells by a process which does not involve apoprotein catabolism. The incorporation of HDL-free (unesterified) cholesterol, phospholipid, and cholesteryl ester by cells has been compared to establish the mechanism of this delivery process. Human HDL was reconstituted with 3H-free cholesterol and [14C]sphingomyelin, treated with hepatic lipase in the presence of albumin to remove the products of lipolysis, reisolated, and then incubated with cultured rat hepatoma cells. Relative to control HDL, modification of HDL with hepatic lipase stimulated both the amount of HDL-free cholesterol taken up by the cell and the esterification of HDL-free cholesterol but did not affect the delivery of sphingomyelin. Experiments utilizing HDL reconstituted with 14C-free cholesterol and [3H]cholesteryl oleoyl ether suggest that hepatic lipase enhances the incorporation of HDL-esterified cholesterol. However, the amount of free cholesterol delivered as a result of treatment with hepatic lipase was 4-fold that of esterified cholesterol. On the basis of HDL composition, the cellular incorporation of free cholesterol was about 10 times that which would occur by the uptake and degradation of intact particles. The preferential incorporation of HDL-free cholesterol did not require the presence of lysophosphatidylcholine. To correlate the events observed at the cellular level with alterations in lipoprotein structure, high-resolution, proton-decoupled 13C nuclear magnetic resonance spectroscopy (90.55 MHz) was performed on HDL3 in which the cholesterol molecules were replaced with [4-13C]cholesterol by particle reconstitution

  15. The effects of apolipoprotein F deficiency on high density lipoprotein cholesterol metabolism in mice.

    Directory of Open Access Journals (Sweden)

    William R Lagor

    Full Text Available Apolipoprotein F (apoF is 29 kilodalton secreted sialoglycoprotein that resides on the HDL and LDL fractions of human plasma. Human ApoF is also known as Lipid Transfer Inhibitor protein (LTIP based on its ability to inhibit cholesteryl ester transfer protein (CETP-mediated transfer events between lipoproteins. In contrast to other apolipoproteins, ApoF is predicted to lack strong amphipathic alpha helices and its true physiological function remains unknown. We previously showed that overexpression of Apolipoprotein F in mice reduced HDL cholesterol levels by 20-25% by accelerating clearance from the circulation. In order to investigate the effect of physiological levels of ApoF expression on HDL cholesterol metabolism, we generated ApoF deficient mice. Unexpectedly, deletion of ApoF had no substantial impact on plasma lipid concentrations, HDL size, lipid or protein composition. Sex-specific differences were observed in hepatic cholesterol content as well as serum cholesterol efflux capacity. Female ApoF KO mice had increased liver cholesteryl ester content relative to wild type controls on a chow diet (KO: 3.4+/-0.9 mg/dl vs. WT: 1.2+/-0.3 mg/dl, p<0.05. No differences were observed in ABCG1-mediated cholesterol efflux capacity in either sex. Interestingly, ApoB-depleted serum from male KO mice was less effective at promoting ABCA1-mediated cholesterol efflux from J774 macrophages relative to WT controls.

  16. Higher high density lipoprotein cholesterol associated with moderate alcohol consumption is not related to altered plasma lecithin : cholesterol acyltransferase and lipid transfer protein activity levels

    NARCIS (Netherlands)

    Riemens, SC; vanTol, A; Hoogenberg, K; vanGent, T; Scheek, LM; Sluiter, WJ; Dullaart, RPF

    1997-01-01

    Lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are important factors involved in HDL metabolism. Altered plasma activity levels of these factors could play a role in the increase in high density lipoprotein (HDL) choles

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

    Directory of Open Access Journals (Sweden)

    Nader - Rahnama

    2009-11-01

    Full Text Available

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

    • Association of High Density Lipoprotein Cholesterol with Renal Function in Type 2 Diabetic Subjects in a Bangladeshi Population

      Directory of Open Access Journals (Sweden)

      Shoma Hayat

      2012-07-01

      Full Text Available Background: Abnormalities in lipid metabolism are associated with renal diseases. Association of serum lipid parameters with renal function is less studied in subjects with type 2 diabetes in Bangladeshi population. Objective: To assess the correlation of high density lipoprotein cholesterol with glomerular filtration rate (GFR in type 2 diabetic subjects. Materials and Methods: One thousand three hundred thirty confirmed diabetic subjects advised for HbA1c, serum creatinine, serum total cholesterol, serum triglycerides, serum HDL cholesterol and LDL cholesterol were included in the study. Serum total cholesterol, HDL cholesterol, triglyceride, serum creatinine, HbA1c were measured by standard methods and serum LDL cholesterol was calculated by Friedewald’s formula. GFR was calculated by MDRD4 variables prediction equation. Total subjects were grouped according to sex; both males and females were subdivided into three subgroups depending on GFR values. Results of lipid parameters were compared by one-way ANOVA among different groups and correlation of lipid parameters with GFR were expressed by Pearson r. Results: HDL cholesterol was significantly different among different GFR groups (p0.05 in males. Total cholesterol, HDL cholesterol, LDL cholesterol, non-HDL cholesterol and LDLC/HDL-C were significantly different among three different GFR groups (p<0.01 and only HDL cholesterol and LDL-C/HDL-C showed weak correlation with GFR (r = 0.0770, p<0.05 for HDL cholesterol and r = -0.0803, p<0.05 for LDL-C/HDL-C in females. Conclusion: The study revealed that HDL cholesterol was significantly and positively correlated with glomerular filtration rate in both male and female diabetic subjects and assessment of lipid parameters might be a helpful tool to prevent or delay the progression of renal insufficiency.

    • On-treatment non-high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipid ratios in relation to residual vascular risk after treatment with potent statin therapy

      DEFF Research Database (Denmark)

      Mora, Samia; Glynn, Robert J; Boekholdt, S Matthijs;

      2012-01-01

      The goal of this study was to determine whether residual risk after high-dose statin therapy for primary prevention individuals with reduced levels of low-density lipoprotein cholesterol (LDL-C) is related to on-treatment apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), tri...

    • Levels of high-density lipoprotein cholesterol (HDL-C among children with steady-state sickle cell disease

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      Seixas Magda O

      2010-08-01

      Full Text Available Abstract Background The search for sickle cell disease (SCD prognosis biomarkers is a challenge. These markers identification can help to establish further therapy, later severe clinical complications and with patients follow-up. We attempted to study a possible involvement of levels of high-density lipoprotein cholesterol (HDL-C in steady-state children with SCD, once that this lipid marker has been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities, important aspects to be considered in sickle cell disease pathogenesis. Methods We prospectively analyzed biochemical, inflammatory and hematological biomarkers of 152 steady-state infants with SCD and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records. Results Of the 152 infants investigated had a significant positive association of high-density lipoprotein cholesterol with hemoglobin (P Conclusions We hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by low HDL-C with hypertriglyceridemia and high VLDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. Additional studies are warranted to test this hypothesis and the probably mechanisms involved in this complex network of markers and their role in SCD pathogenesis.

  1. Fasting serum triglyceride and high-density lipoprotein cholesterol levels in patients intended to be treated for dyslipidemia

    Directory of Open Access Journals (Sweden)

    Genovefa D Kolovou

    2005-07-01

    Full Text Available Genovefa D Kolovou1, Katherine Anagnostopoulou1, Nektarios D Pilatis1, Klelia D Salpea1, Ioannis S Hoursalas1, Ilias Petropoulos1, Helen I Bilianou2, Dennis V Cokkinos11Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece; 2Cardiology Department, Tzanio State Hospital, Piraeus, GreeceObjective: The aim of the present investigation was to evaluate the influence of serum triglycerides (TG on other plasma lipids in patients to be treated for dyslipidemia.Methodology: Lipid profiles of a cohort of 801 patients (487 males and 314 females aged 57 ± 9 years (mean ± SD were evaluated. Patients were stratified according to their plasma lipid levels. They were divided into various groups on the basis of serum TG (≥ 150 or < 150 mg/dL and high-density lipoprotein cholesterol (HDL-C (≥ 40 or < 40 mg/dL.Results: Patients with TG ≥ 150 mg/dL had a higher total cholesterol and lower HDL-C levels compared with those with TG < 150 mg/dL, (p < 0.001. Patients with HDL-C < 40 mg/dL had a lower serum total cholesterol and higher TG compared with those with HDL-C ≥ 40 mg/dL (p = 0.011 and p < 0.0001, respectively. In all patients as well as in the subgroups, an inverse correlation between TG and HDL-C was found (r = –0.377, p < 0.001.Conclusions: Although, the metabolic pathway for TG and HDL-C is closely linked, an inverse correlation between TG and HDL-C levels seems to exist in the entire sampled population. This correlation also appears to persist in fasting patients with low levels of TG.Keywords: triglycerides, high-density lipoprotein cholesterol, dyslipidemia

  2. Trans-intestinal cholesterol effl ux is not mediated through high density lipoprotein

    NARCIS (Netherlands)

    Vrins, C.L.; Ottenhoff, R.; Oever, K. van den; Waart, D.R. de; Kruyt, J.K.; Zhao, Y.; Berkel, T.J. van; Havekes, L.M.; Aerts, J.M.; Eck, M. van; Rensen, P.C.; Groen, A.K.

    2012-01-01

    Transintestinal cholesterol efflux (TICE) provides an attractive target to increase body cholesterol excretion. At present, the cholesterol donor responsible for direct delivery of plasma cholesterol to the intestine is unknown. In this study, we investigated the role of HDL in TICE. ATP-binding cas

  3. Roles of High-Density Lipoprotein Cholesterol in Patients With Acute Myocardial Infarction.

    Science.gov (United States)

    Lee, Cheol Hyun; Woo, Jong Shin; Park, Chang Bum; Cho, Jin Man; Ahn, Young Keun; Kim, Chong Jin; Jeong, Myung Ho; Kim, Weon

    2016-05-01

    Many observational studies showed hogh-density lipoprotein cholesterol (HDL-C) is a strong inverse predictor of cardiovascular (CV) outcome. However, recent large clinical trials evaluating therapies to raise HDL-C level in those already on statin therapy have been discouraging. This complexity is not well-known.A total of 28,357 acute myocardial infarction (AMI) patients were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR), which was a prospective, multicenter, nationwide, web-based database of AMI in Korea. From this registry, we evaluated 3574 patients with AMI who have follow-up HDL-C level to investigate its association with clinical outcomes. The primary endpoint was the relationship between follow-up change in HDL-C and a 12-month composite of major adverse cardiac events (MACEs).Patients with initial HDL-C ≥ 40 mg/dL showed significantly lower rates of 12-month MACEs, especially cardiac and all-cause mortalities (P < 0.001). When patients were stratified into 4 groups according to the change of HDL-C, patients with decreasing HDL-C showed significantly higher rates of 12-month MACEs as comparable with patients with increasing HLD-C. A multivariate analysis indicated that HDL-C level was a significant predictor of CV events (hazard ratio, 1.38; 95% confidence interval, 1.12-1.71) after correcting for confounding variables.The follow-up change in HDL-C level was significantly related with CV outcomes in patients with AMI. PMID:27149442

  4. Role of phospholipid transfer protein and pre beta-high density lipoproteins in maintaining cholesterol efflux from Fu5AH cells to plasma from insulin-resistant subjects

    NARCIS (Netherlands)

    Dullaart, RPF; Van Tol, A

    2001-01-01

    Plasma phospholipid transfer protein (PLTP) enhances the generation of pre beta -high density lipoproteins (HDL) that may act as initial accepters of cellular cholesterol, and are likely to play an important role in the antiatherogenic process of reverse cholesterol transport. We: examined the inter

  5. Effect of monounsaturated fatty acids on high-density and low-density lipoprotein cholesterol levels and blood pressure in healthy men and women.

    NARCIS (Netherlands)

    Mensink, R.P.

    1990-01-01

    The purpose of the studies described in this thesis was to examine the effect of monounsaturated fatty acids on the distribution of serum cholesterol over high-density and low-density lipoproteins (HDL and LDL) and on blood pressure in healthy men and women. High levels of LDL cholesterol and bl

  6. Low-Density Lipoprotein Cholesterol, Non-High-Density Lipoprotein Cholesterol, Triglycerides, and Apolipoprotein B and Cardiovascular Risk in Patients With Manifest Arterial Disease.

    Science.gov (United States)

    van den Berg, M Johanneke; van der Graaf, Yolanda; de Borst, Gert Jan; Kappelle, L Jaap; Nathoe, Hendrik M; Visseren, Frank L J

    2016-09-15

    Low-density lipoprotein cholesterol (LDL-C) only partly represents the atherogenic lipid burden, and a growing body of evidence suggests that non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and apolipoprotein B (apoB) are more accurate in estimating lipid-related cardiovascular disease risk. Our objective was to compare the relation among LDL-C, non-HDL-C, triglycerides, and apoB and the occurrence of future vascular events and mortality in patients with manifest arterial disease. This is a prospective cohort study of 7,216 patients with clinically manifest arterial disease in the Secondary Manifestations of Arterial Disease Study. Cox proportional hazard models were used to quantify the risk of major cardiovascular events (MACE; i.e., stroke, myocardial infarction, and vascular mortality) and all-cause mortality. Interaction was tested for type of vascular disease at inclusion. MACE occurred in 1,185 subjects during a median follow-up of 6.5 years (interquartile range 3.4 to 9.9 years). Adjusted hazard ratios (HRs) of MACE per 1 SD higher were for LDL-C (HR 1.15, 95% confidence interval [CI] 1.09 to 1.22), for non-HDL-C (HR 1.17, 95% CI 1.11 to 1.23), for log(triglycerides) (HR 1.12, 95% CI 1.06 to 1.19), and for apoB HR (1.12, 95% CI 0.99 to 1.28). The relation among LDL-C, non-HDL-C, and cardiovascular events was comparable in patients with cerebrovascular disease, coronary artery disease, or polyvascular disease and absent in those with aneurysm of abdominal aorta or peripheral artery disease. In conclusion, in patients with a history of cerebrovascular, coronary artery, or polyvascular disease, but not aneurysm of abdominal aorta or peripheral artery disease, higher levels of LDL-C and non-HDL-C are related to increased risk of future MACE and of comparable magnitude. PMID:27471056

  7. Accelerated decline in renal function after acute myocardial infarction in patients with high low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol ratio.

    Science.gov (United States)

    Okumura, Satoshi; Sakakibara, Masaki; Hayashida, Ryo; Jinno, Yasushi; Tanaka, Akihito; Okada, Koji; Hayashi, Mutsuharu; Ishii, Hideki; Murohara, Toyoaki

    2014-01-01

    High low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol (L/H) ratio is associated with progressions of coronary arteriosclerosis and chronic kidney disease. On the other hand, renal function markedly declined after acute myocardial infarction (AMI). The aims of the present study were (1) to identify what type of patients with AMI would have high L/H ratio at follow-up and (2) to evaluate whether decline in renal function after AMI had accelerated or not in patients with high L/H ratio. The 190 eligible AMI patients who underwent primary percutaneous coronary intervention (PCI) and received atorvastatin (10 mg) were divided into one of two groups according to the L/H ratio at 6-month follow-up: L/H >2 group (n = 81) or L/H ≤2 group (n = 109). The characteristics on admission in the two groups were examined. Furthermore, changes in serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) during 1- and 6-month follow-up were compared between the two groups. L/H >2 group were significantly younger and had greater body mass index (BMI) and worse lipid profile on admission compared with L/H ≤2 group. Percentage increase in sCr and percentage decrease in eGFR during 1-month follow-up in L/H >2 group tended to be greater than in L/H ≤2 group, and those during 6-month follow-up were significantly greater (16.5 ± 2.77 vs. 9.79 ± 2.23 %, p = 0.03 and 11.8 ± 1.93 vs. 2.75 ± 3.85 %, p = 0.04, respectively). In AMI patients undergoing primary PCI, those who were young and had large BMI and poor lipid profile on admission were likely to have a high L/H ratio at follow-up despite statin therapy. In addition, the decline in renal function after AMI had significantly accelerated in patients with high L/H ratio.

  8. Low-Density Lipoprotein Cholesterol, Non-High-Density Lipoprotein Cholesterol, Triglycerides, and Apolipoprotein B and Cardiovascular Risk in Patients With Manifest Arterial Disease.

    Science.gov (United States)

    van den Berg, M Johanneke; van der Graaf, Yolanda; de Borst, Gert Jan; Kappelle, L Jaap; Nathoe, Hendrik M; Visseren, Frank L J

    2016-09-15

    Low-density lipoprotein cholesterol (LDL-C) only partly represents the atherogenic lipid burden, and a growing body of evidence suggests that non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and apolipoprotein B (apoB) are more accurate in estimating lipid-related cardiovascular disease risk. Our objective was to compare the relation among LDL-C, non-HDL-C, triglycerides, and apoB and the occurrence of future vascular events and mortality in patients with manifest arterial disease. This is a prospective cohort study of 7,216 patients with clinically manifest arterial disease in the Secondary Manifestations of Arterial Disease Study. Cox proportional hazard models were used to quantify the risk of major cardiovascular events (MACE; i.e., stroke, myocardial infarction, and vascular mortality) and all-cause mortality. Interaction was tested for type of vascular disease at inclusion. MACE occurred in 1,185 subjects during a median follow-up of 6.5 years (interquartile range 3.4 to 9.9 years). Adjusted hazard ratios (HRs) of MACE per 1 SD higher were for LDL-C (HR 1.15, 95% confidence interval [CI] 1.09 to 1.22), for non-HDL-C (HR 1.17, 95% CI 1.11 to 1.23), for log(triglycerides) (HR 1.12, 95% CI 1.06 to 1.19), and for apoB HR (1.12, 95% CI 0.99 to 1.28). The relation among LDL-C, non-HDL-C, and cardiovascular events was comparable in patients with cerebrovascular disease, coronary artery disease, or polyvascular disease and absent in those with aneurysm of abdominal aorta or peripheral artery disease. In conclusion, in patients with a history of cerebrovascular, coronary artery, or polyvascular disease, but not aneurysm of abdominal aorta or peripheral artery disease, higher levels of LDL-C and non-HDL-C are related to increased risk of future MACE and of comparable magnitude.

  9. Sphingomyelin phosphodiesterase-1 (SMPD1 coding variants do not contribute to low levels of high-density lipoprotein cholesterol

    Directory of Open Access Journals (Sweden)

    Genest Jacques

    2007-12-01

    Full Text Available Abstract Background Niemann-Pick disease type A and B is caused by a deficiency of acid sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase-1 (SMPD1 gene. In Niemann-Pick patients, SMPD1 gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL cholesterol. Methods Two common coding polymorphisms in the SMPD1 gene, the G1522A (G508R and a hexanucleotide repeat sequence within the signal peptide region, were investigated in 118 unrelated subjects of French Canadian descent with low plasma levels of HDL-cholesterol (th percentile for age and gender-matched subjects. Control subjects (n = 230 had an HDL-cholesterol level > the 25th percentile. Results For G1522A the frequency of the G and A alleles were 75.2% and 24.8% respectively in controls, compared to 78.6% and 21.4% in subjects with low HDL-cholesterol (p = 0.317. The frequency of 6 and 7 hexanucleotide repeats was 46.2% and 46.6% respectively in controls, compared to 45.6% and 49.1% in subjects with low HDL-cholesterol (p = 0.619. Ten different haplotypes were observed in cases and controls. Overall haplotype frequencies in cases and controls were not significantly different. Conclusion These results suggest that the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population.

  10. High density lipoprotein 3 inhibits oxidized low density lipoprotein-induced apoptosis via promoting cholesterol efflux in RAW264.7 cells

    Institute of Scientific and Technical Information of China (English)

    Pei JIANG; Peng-ke YAN; Jian-xiong CHEN; Bing-yang ZHU; Xiao-yong LEI; Wei-dong YIN; Duan-fang LIAO

    2006-01-01

    Aim: To investigate the protective effect of high density lipoprotein 3 (HDL3) on oxidized low density lipoprotein (ox-LDL)-induced apoptosis in RAW264.7 cells.Methods: RAW264.7 cells were exposed to 50 mg/L ox-LDL for various durations up to 48 h, and apoptosis was detected using Hoechst 33258 staining and flow cytometric analysis. Total cholesterol levels were detected by high performance liquid chromatography, cholesterol efflux was determined by Tritium labeling, and the cellular lipid droplets were assayed by oil red O staining. Results: Treatment with 50 mg/L ox-LDL for 12, 24, and 48 h increased the apoptotic rate of RAW264.7 cells in a time-dependent manner. The peak apoptotic rate (47.7%) was observed after 48 h incubation. HDL3 at various concentrations (50 mg/L, 100 mg/L, and 200mg/L) inhibited the ox-LDL (50 mg/L for 48 h)-mediated apoptosis that was accompanied by an increased rate of intracellular cholesterol efflux, and decreased total cholesterol levels in cells in a concentration-dependent manner. Blockage of cholesterol efflux by brefeldin decreased the protective effect of HDL3 on ox-LDL-induced apoptosis. Increase of the cholesterol efflux effected by another cholesterol acceptor, β-cyclodextrin, led to a dramatic decrease in the apoptotic rate of cells. Conclusion: HDL3 antagonizes ox-LDL-induced apoptosis in RAW264.7cells, through reducing the accumulation of toxic cholesterol.

  11. Add-on rosiglitazone therapy improves plasminogen activity and high-density lipoprotein cholesterol in type 2 diabetes mellitus.

    Science.gov (United States)

    Mustaffa, Nazri; Ibrahim, Suhairi; Abdullah, Wan Zaidah; Yusof, Zurkurnai

    2011-09-01

    Rosiglitazone is an oral hypoglycaemic agent of the thiazolidinedione group. This study aimed to assess changes in the diabetic prothrombotic state via plasminogen activity and changes in surrogate markers of atherosclerotic burden via ankle-brachial pressure index (ABPI) measurements after rosiglitazone was added to a pre-existing type 2 diabetes mellitus treatment regime. A nonblinded interventional study was designed. Fifty-nine patients were enrolled. Rosiglitazone-naïve patients were prescribed oral rosiglitazone 4 mg daily for 10 weeks. ABPI, plasminogen activity, glycosylated haemoglobin (HbA1c) and fasting lipid profile were measured pretreatment and post-treatment. Forty-eight patients completed the study. At the end of this study, mean plasminogen activity improvement was nearly 16% (PABPI improvement was 0.01 (P=0.439), mean HbA1c reduction was 0.51% (P<0.05), mean total cholesterol (TC) increase was 0.36 mmol/l (P<0.05), mean high-density lipoprotein cholesterol (HDL-C) increase was 0.15 mmol/l (P<0.05) and mean low-density lipoprotein cholesterol increased by 0.19 mmol/l (P=0.098). Rosiglitazone significantly improved plasminogen activity. There was also significant HbA1c reduction, and rise in both TC and HDL-C. Thus, rosiglitazone potentially improves the atherosclerotic burden and prothrombotic state. In future, more studies are needed to confirm the relationship between rosiglitazone, fibrinolytic system and atheromatous reduction in type 2 diabetes mellitus. PMID:21537159

  12. A Splice Region Variant in LDLR Lowers Non-high Density Lipoprotein Cholesterol and Protects against Coronary Artery Disease

    DEFF Research Database (Denmark)

    Gretarsdottir, Solveig; Helgason, Hannes; Helgadottir, Anna;

    2015-01-01

    Through high coverage whole-genome sequencing and imputation of the identified variants into a large fraction of the Icelandic population, we found four independent signals in the low density lipoprotein receptor gene (LDLR) that associate with levels of non-high density lipoprotein cholesterol...... associations were replicated in three additional populations. Both variants lower non-HDL-C levels (rs72658867-A, non-HDL-C effect = -0.44 mmol/l, Padj = 1.1 × 10⁻⁸⁰ and rs17248748-T, non-HDL-C effect = -0.13 mmol/l, Padj = 1.3 × 10⁻¹²) and confer protection against CAD (rs72658867-A, OR = 0.76 and Padj = 2.......7 × 10⁻⁸ and rs17248748-T, OR = 0.92 and Padj = 0.022). The LDLR splice region variant, rs72658867-A, located at position +5 in intron 14 (NM_000527:c.2140+5G>A), causes retention of intron 14 during transcription and is expected to produce a truncated LDL receptor lacking domains essential for function...

  13. Skeletal muscle insulin resistance associated with cholesterol-induced activation of macrophages is prevented by high density lipoprotein.

    Directory of Open Access Journals (Sweden)

    Andrew L Carey

    Full Text Available BACKGROUND: Emerging evidence suggests that high density lipoprotein (HDL may modulate glucose metabolism through multiple mechanisms including pancreatic insulin secretion as well as insulin-independent glucose uptake into muscle. We hypothesized that HDL may also increase skeletal muscle insulin sensitivity via cholesterol removal and anti-inflammatory actions in macrophages associated with excess adiposity and ectopic lipid deposition. METHODS: Human primary and THP-1 macrophages were treated with vehicle (PBS or acetylated low density lipoprotein (acLDL with or without HDL for 18 hours. Treatments were then removed, and macrophages were incubated with fresh media for 4 hours. This conditioned media was then applied to primary human skeletal myotubes derived from vastus lateralis biopsies taken from patients with type 2 diabetes to examine insulin-stimulated glucose uptake. RESULTS: Conditioned media from acLDL-treated primary and THP-1 macrophages reduced insulin-stimulated glucose uptake in primary human skeletal myotubes compared with vehicle (primary macrophages, 168±21% of basal uptake to 104±19%; THP-1 macrophages, 142±8% of basal uptake to 108±6%; P<0.05. This was restored by co-treatment of macrophages with HDL. While acLDL increased total intracellular cholesterol content, phosphorylation of c-jun N-terminal kinase and secretion of pro- and anti-inflammatory cytokines from macrophages, none were altered by co-incubation with HDL. Insulin-stimulated Akt phosphorylation in human skeletal myotubes exposed to conditioned media was unaltered by either treatment condition. CONCLUSION: Inhibition of insulin-stimulated glucose uptake in primary human skeletal myotubes by conditioned media from macrophages pre-incubated with acLDL was restored by co-treatment with HDL. However, these actions were not linked to modulation of common pro- or anti-inflammatory mediators or insulin signaling via Akt.

  14. The Effect of Aerobic Exercise on Total Cholesterol, High-Density Lipoprotein, Apolipoprotein B, Apolipoprotein A-I, and Percent Body Fat in Adolescent Females.

    Science.gov (United States)

    Lungo, Diane; And Others

    The effect of aerobic exercise on total cholesterol (TC), high-density lipoprotein (HDL), apolipoprotein B (Apo B), apolioprotein A-I (Apo A-I), and percent body fat in adolescent females was studied. The control subjects (n=86) were volunteers who had completed a physical education class at least six months prior to the commencement of the study,…

  15. Alcohol consumption, TaqIB polymorphism of cholesteryl ester transfer protein, high-density lipoprotein cholesterol, and risk of coronary heart disease in men and women

    DEFF Research Database (Denmark)

    Jensen, Majken K; Mukamal, Kenneth J; Overvad, Kim;

    2008-01-01

    AIMS: To investigate whether a common polymorphism in the cholesteryl ester transfer protein (CETP) gene modifies the relationship of alcohol intake with high-density lipoprotein cholesterol (HDL-C) and risk of coronary heart disease (CHD). METHODS AND RESULTS: Parallel nested case-control studies...

  16. Znf202 affects high density lipoprotein cholesterol levels and promotes hepatosteatosis in hyperlipidemic mice.

    Directory of Open Access Journals (Sweden)

    Carlos L J Vrins

    Full Text Available BACKGROUND: The zinc finger protein Znf202 is a transcriptional suppressor of lipid related genes and has been linked to hypoalphalipoproteinemia. A functional role of Znf202 in lipid metabolism in vivo still remains to be established. METHODOLOGY AND PRINCIPAL FINDINGS: We generated mouse Znf202 expression vectors, the functionality of which was established in several in vitro systems. Next, effects of adenoviral znf202 overexpression in vivo were determined in normo- as well as hyperlipidemic mouse models. Znf202 overexpression in mouse hepatoma cells mhAT3F2 resulted in downregulation of members of the Apoe/c1/c2 and Apoa1/c3/a4 gene cluster. The repressive activity of Znf202 was firmly confirmed in an apoE reporter assay and Znf202 responsive elements within the ApoE promoter were identified. Adenoviral Znf202 transfer to Ldlr-/- mice resulted in downregulation of apoe, apoc1, apoa1, and apoc3 within 24 h after gene transfer. Interestingly, key genes in bile flux (abcg5/8 and bsep and in bile acid synthesis (cyp7a1 were also downregulated. At 5 days post-infection, the expression of the aforementioned genes was normalized, but mice had developed severe hepatosteatosis accompanied by hypercholesterolemia and hypoalphalipoproteinemia. A much milder phenotype was observed in wildtype mice after 5 days of hepatic Znf202 overexpression. Interestingly and similar to Ldl-/- mice, HDL-cholesterol levels in wildtype mice were lowered after hepatic Znf202 overexpression. CONCLUSION/SIGNIFICANCE: Znf202 overexpression in vivo reveals an important role of this transcriptional regulator in liver lipid homeostasis, while firmly establishing the proposed key role in the control of HDL levels.

  17. A Splice Region Variant in LDLR Lowers Non-high Density Lipoprotein Cholesterol and Protects against Coronary Artery Disease.

    Directory of Open Access Journals (Sweden)

    Solveig Gretarsdottir

    2015-09-01

    Full Text Available Through high coverage whole-genome sequencing and imputation of the identified variants into a large fraction of the Icelandic population, we found four independent signals in the low density lipoprotein receptor gene (LDLR that associate with levels of non-high density lipoprotein cholesterol (non-HDL-C and coronary artery disease (CAD. Two signals are novel with respect to association with non-HDL-C and are represented by non-coding low frequency variants (between 2-4% frequency, the splice region variant rs72658867-A in intron 14 and rs17248748-T in intron one. These two novel associations were replicated in three additional populations. Both variants lower non-HDL-C levels (rs72658867-A, non-HDL-C effect = -0.44 mmol/l, Padj = 1.1 × 10⁻⁸⁰ and rs17248748-T, non-HDL-C effect = -0.13 mmol/l, Padj = 1.3 × 10⁻¹² and confer protection against CAD (rs72658867-A, OR = 0.76 and Padj = 2.7 × 10⁻⁸ and rs17248748-T, OR = 0.92 and Padj = 0.022. The LDLR splice region variant, rs72658867-A, located at position +5 in intron 14 (NM_000527:c.2140+5G>A, causes retention of intron 14 during transcription and is expected to produce a truncated LDL receptor lacking domains essential for function of the receptor. About half of the transcripts generated from chromosomes carrying rs72658867-A are characterized by this retention of the intron. The same variant also increases LDLR mRNA expression, however, the wild type transcripts do not exceed levels in non-carriers. This demonstrates that sequence variants that disrupt the LDL receptor can lower non-HDL-C and protect against CAD.

  18. Vitamin C may have similar beneficial effects to Gemfibrozil on serum high-density lipoprotein-cholesterol in type 2 diabetic patients

    OpenAIRE

    Siavash, Mansour; Amini, Masoud

    2014-01-01

    Objective: Type 2 diabetes mellitus (DM-T2) is commonly associated with increased triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) levels. Fibrates like gemfibrozil are frequently used in diabetic patients to decrease TG and increase HDL-C levels. We compared the efficacy of Vitamin C, an antioxidant vitamin, with gemfibrozil on serum HDL-C in diabetic patients. Methods: Type 2 diabetic patients, referred to our out-patient c...

  19. High-density lipoprotein cholesterol strongly discriminates between healthy free-living and disabled octo-nonagenarians: a cross sectional study. Associazione Medica Sabin.

    Science.gov (United States)

    Zuliani, G; Palmieri, E; Volpato, S; Bader, G; Mezzetti, A; Costantini, F; Sforza, G R; Imbastaro, T; Romagnoni, F; Fellin, R

    1997-10-01

    Aging is frequently associated with a deterioration in health and functional status, which often induces important modifications in several biological parameters, including plasma lipids; as a consequence, the real "meaning" of lipoprotein parameters in old individuals is complex. A cross sectional study was carried out in order to investigate the lipoprotein profile in very old individuals with or without disability, and evaluate the possible influence of other biological variables on plasma lipids. One hundred selected healthy free-living (FL) and 62 disabled (DIS) subjects aged over 80 were enrolled; 91 healthy adults matched for origin were included as controls. Lipoprotein profile [total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, apoprotein A-I and B], anthropometric parameters, and ADL were measured. The FL octo-nonagenarians featured higher HDL-cholesterol levels than adult controls. DIS octo-nonagenarians showed lower total and HDL-C levels than FL. Discriminant analysis indicated that HDL-cholesterol and apoprotein A-I, but not total cholesterol, strongly discriminated between FL and DIS octo-nonagenarians. Multivariate analysis demonstrated that the waist/hip ratio, an index of visceral adiposity, was negatively associated with HDL-C levels in FL, but not in DIS elderly. We conclude that: 1) in very old individuals, the absence or presence of disability is strongly associated with high or low HDL-cholesterol values, respectively; 2) HDL-C and apo A-I are the parameters which better discriminate between FL and DIS octo-nonagenarians; and 3) the differences in HDL-C levels between FL and DIS are not due to modifications in anthropometric parameters. Prospective studies are needed to better understand the relationship between high-density lipoprotein levels, disability and aging. PMID:9458994

  20. Effect of tomato consumption on high-density lipoprotein cholesterol level: a randomized, single-blinded, controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Cuevas-Ramos D

    2013-07-01

    Full Text Available Daniel Cuevas-Ramos,1 Paloma Almeda-Valdés,1 Emma Chávez-Manzanera,1 Clara Elena Meza-Arana,2 Griselda Brito-Córdova,1 Roopa Mehta,1 Oscar Pérez-Méndez,3 Francisco J Gómez-Pérez1 1Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 2Department of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 3Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico Introduction: Epidemiologic evidence suggests that tomato-based products could reduce the risk of cardiovascular diseases. One of the main cardiovascular risk factors is low levels of high-density lipoprotein cholesterol (HDL-C. This study aimed to prospectively evaluate the effect of tomato consumption on HDL-C levels. Subject and methods: We conducted a randomized, single-blinded, controlled clinical trial. We screened 432 subjects with a complete lipid profile. Those individuals with low HDL-C (men 40 mg/dL. A linear regression model that adjusted for those parameters that impact HDL-C levels (age, gender, waist-to-hip ratio, body mass index, fasting triglyceride concentration, simple sugars, alcohol, physical activity, and omega-3 consumption showed an independent association between tomato consumption and the increase in HDL-C (r2 = 0.69; P > 0.0001. Conclusion: Raw tomato consumption produced a favorable effect on HDL-C levels in overweight women. Keywords: lycopene, hypoalphalipoproteinemia, dyslipidemia, overweight, cardiovascular diseases

  1. Pathways-driven sparse regression identifies pathways and genes associated with high-density lipoprotein cholesterol in two Asian cohorts.

    Directory of Open Access Journals (Sweden)

    Matt Silver

    2013-11-01

    Full Text Available Standard approaches to data analysis in genome-wide association studies (GWAS ignore any potential functional relationships between gene variants. In contrast gene pathways analysis uses prior information on functional structure within the genome to identify pathways associated with a trait of interest. In a second step, important single nucleotide polymorphisms (SNPs or genes may be identified within associated pathways. The pathways approach is motivated by the fact that genes do not act alone, but instead have effects that are likely to be mediated through their interaction in gene pathways. Where this is the case, pathways approaches may reveal aspects of a trait's genetic architecture that would otherwise be missed when considering SNPs in isolation. Most pathways methods begin by testing SNPs one at a time, and so fail to capitalise on the potential advantages inherent in a multi-SNP, joint modelling approach. Here, we describe a dual-level, sparse regression model for the simultaneous identification of pathways and genes associated with a quantitative trait. Our method takes account of various factors specific to the joint modelling of pathways with genome-wide data, including widespread correlation between genetic predictors, and the fact that variants may overlap multiple pathways. We use a resampling strategy that exploits finite sample variability to provide robust rankings for pathways and genes. We test our method through simulation, and use it to perform pathways-driven gene selection in a search for pathways and genes associated with variation in serum high-density lipoprotein cholesterol levels in two separate GWAS cohorts of Asian adults. By comparing results from both cohorts we identify a number of candidate pathways including those associated with cardiomyopathy, and T cell receptor and PPAR signalling. Highlighted genes include those associated with the L-type calcium channel, adenylate cyclase, integrin, laminin, MAPK

  2. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    DEFF Research Database (Denmark)

    Chapman, M John; Ginsberg, Henry N; Amarenco, Pierre;

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high...

  3. Coexistence of High Fibrinogen and Low High-density Lipoprotein Cholesterol Levels Predicts Recurrent Cerebral Venous Thrombosis

    Institute of Scientific and Technical Information of China (English)

    Xin Ma; Xun-Ming Ji; Paul Fu; Yu-Chuan Ding; Qiang Xue; Yue Huang

    2015-01-01

    Background:Cerebral venous thrombosis (CVT) may lead to serious neurological disorders;however,little is known about the risk factors for recurrent CVT.Our aim was to determine the association between elevated fibrinogen and decreased high-density lipoprotein cholesterol (HDL-C) levels with recurrent CVT.Methods:This retrospective cohort study included participants if they had a first episode of objectively defined CVT and were admitted to Xuan Wu Hospital,Capital Medical University from August 2005 to September 2009.Demographic and clinical variables were collected,as well as laboratory parameters,including plasma fibrinogen and HDL-C.Patients with CVT were followed for recurrent symptomatic CVT.Follow-up was through the end of September 2010.Potential predictors of recurrence were analyzed using Cox survival analysis.Results:At the end of the follow-up,95 patients were eligible for the study.Twelve of 95 patients (12.6%) had recurred CVT.The median time of recurrence was 7 months (range:1-39 months).Eight of these 12 (66.7%) experienced recurrence within the first 12 months after their initial CVT.The recurrence rate of CVT was 2.76 per 100 patient-years.Multivariate Cox regression analysis demonstrated that the coexistence of high fibrinogen (>4.00 g/L) and low HDL-C (<1.08 mmol/L) levels at baseline was the only independent predictor for recurrent CVT (hazard ratio:4.69;95% confidence interval:1.10-20.11;P < 0.05).Of the twelve patients with recurrent CVT in our study,7 (58.3%) had high fibrinogen plus low HDL-C levels.All 7 of these patients took warfarin for 3-12 months,and 6 of 7 had recurrent CVT after the discontinuation of anticoagulant treatment.Conclusions:Concomitant high fibrinogen and low HDL-C levels may be associated with recurrence of CVT.The effect of potential risk factors related to atherothrombosis on recurrent CVT should be closely monitored.

  4. Abnormal high density lipoproteins in cerebrotendinous xanthomatosis

    Energy Technology Data Exchange (ETDEWEB)

    Shore, V. (Lawrence Livermore Lab., CA); 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.

  5. High density lipoproteins and atherosclerosis: emerging aspects

    Institute of Scientific and Technical Information of China (English)

    Federica Sala; Alberico Luigi Catapano; Giuseppe Danilo Norata

    2012-01-01

    High density lipoproteins (HDL) promote the efflux of excess cholesterol from peripheral tissues to the liver for excretion. This ability is responsible for the most relevant anti-atherogenic effect of HDL. The ability of HDL to promote cholesterol efflux results also in the modulation of a series of responses in the immune cells involved in atherosclerosis, including monocyte-macrophages, B and T lymphocytes.Furthermore, during inflammation, the composition of this class of lipoproteins varies to a large extent, thus promoting the formation of dysfunctional HDL. The aim of this review is to discuss the emerging role of HDL in modulating the activity of immune cells and immune-inflammatory mediators during atherogenesis.

  6. A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol

    DEFF Research Database (Denmark)

    Surakka, Ida; Whitfield, John B; Perola, Markus;

    2012-01-01

    in serum lipid and apolipoprotein levels. We report data for 1,720 monozygotic female twin-pairs from GenomEUtwin project with 2.5 million SNPs, imputed or genotyped, and measured serum lipid fractions for both twins. We found one locus associated with intra-pair differences in high-density lipoprotein...... cholesterol, rs2483058 in an intron of SRGAP2, where twins carrying the C allele are more sensitive to environmental factors(P=3.98 x 10-8). We followed up the association in further genotyped monozygotic twins (N= 1,261),which showed a moderate association for the variant (P= 0.200, same direction...

  7. Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans : a meta-analysis

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Katan, M.B.

    2001-01-01

    Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. Objective: The objective was to review the effect of dietary cholesterol o

  8. Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Frikke-Schmidt, R.; Nordestgaard, B.G.; Stene, M.C.A.;

    2008-01-01

    Context Low levels of high- density lipoprotein ( HDL) cholesterol are inversely related to cardiovascular risk. Whether this is a causal effect is unclear. Objective To determine whether genetically reduced HDL cholesterol due to heterozygosity for 4 loss- of- function mutations in ABCA1 cause...... increased risk of ischemic heart disease ( IHD). Design, Setting, and Participants Three studies of white individuals from Copenhagen, Denmark, were used: the Copenhagen City Heart Study ( CCHS), a 31-year prospective general population study ( n= 9022; 28 heterozygotes); the Copenhagen General Population...... Study ( CGPS), a cross- sectional general population study ( n= 31 241; 76 heterozygotes); and the Copenhagen Ischemic Heart Disease Study ( CIHDS), a case- control study ( n= 16 623; 44 heterozygotes). End points in all 3 studies were recorded during the period of January 1, 1976, through July 9, 2007...

  9. Low high-density lipoprotein cholesterol is a residual risk factor associated with long-term clinical outcomes in diabetic patients with stable coronary artery disease who achieve optimal control of low-density lipoprotein cholesterol.

    Science.gov (United States)

    Ogita, Manabu; Miyauchi, Katsumi; Miyazaki, Tadashi; Naito, Ryo; Konishi, Hirokazu; Tsuboi, Shuta; Dohi, Tomotaka; Kasai, Takatoshi; Yokoyama, Takayuki; Okazaki, Shinya; Kurata, Takeshi; Daida, Hiroyuki

    2014-01-01

    Diabetes mellitus is recognized an independent risk factor for coronary artery disease (CAD) and mortality. Clinical trials have shown that statins significantly reduce cardiovascular events in diabetic patients. However, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein cholesterol (LDL-C) levels with statin. High-density lipoprotein cholesterol (HDL-C) is an established coronary risk factor that is independent of LDL-C levels. We evaluated the impact of HDL-C on long-term mortality in diabetic patients with stable CAD who achieved optimal LDL-C. We enrolled 438 consecutive diabetic patients who were scheduled for percutaneous coronary intervention between 2004 and 2007 at our institution. We identified 165 patients who achieved target LDL-C coronary syndrome, and target lesion revascularization were evaluated between the two groups. The median follow-up period was 946 days. The rate of MACE was significantly higher in diabetic patients with low-HDL-C who achieved optimal LDL-C (6.9 vs 17.9 %, log-rank P = 0.030). Multivariate Cox regression analysis showed that HDL-C is significantly associated with clinical outcomes (adjusted hazard ratio for MACE 1.33, 95 % confidence interval 1.01-1.75, P = 0.042). Low HDL-C is a residual risk factor that is significantly associated with long-term clinical outcomes among diabetic patients with stable CAD who achieve optimal LDL-C levels.

  10. Recombinant high-density lipoprotein nanoparticles containing gadolinium-labeled cholesterol for morphologic and functional magnetic resonance imaging of the liver

    Directory of Open Access Journals (Sweden)

    Rui M

    2012-07-01

    Full Text Available Mengjie Rui,1 Wei Guo,2 Qian Ding,2 Xiaohui Wei,2 Jianrong Xu,3 Yuhong Xu21School of Life Science and Biotechnology, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China; 3Department of Radiology, Renji Hospital Affiliation with Medical School of Shanghai Jiao Tong University, Shanghai, People's Republic of ChinaBackground: Natural high-density lipoproteins (HDL possess important physiological functions to the transport of cholesterol from the peripheral tissues to the liver for metabolic degradation and excretion in the bile.Methods and results: In this work, we took advantage of this pathway and prepared two different gadolinium (Gd-DTPA-labeled cholesterol-containing recombinant HDL nanoparticles (Gd-chol-HDL and Gd-(chol2-HDL as liver-specific magnetic resonance imaging (MRI contrast agents. The reconstituted HDL nanoparticles had structural similarity to native HDL, and could be taken up by HepG2 cells via interaction with HDL receptors in vitro. In vivo MRI studies in rats after intravenous injections of 10 µmol gadolinium per kg of recombinant HDL nanoparticles indicated that both nanoparticles could provide signal enhancement in the liver and related organs. However, different T1-weighted image details suggested that they participated in different cholesterol metabolism and excretion pathways in the liver.Conclusion: Such information could be highly useful to differentiate functional changes as well as anatomic differences in the liver. These cholesterol-derived contrast agents and their recombinant HDL preparations may warrant further development as a new class of contrast agents for MRI of the liver and related organs.Keywords: magnetic resonance imaging, apolipoprotein, high-density lipoprotein, contrast agent, gadolinium, liver

  11. Primary Low Level of High-Density Lipoprotein Cholesterol and Risks of Coronary Heart Disease, Cardiovascular Disease, and Death: Results From the Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Ahmed, Haitham M; Miller, Michael; Nasir, Khurram; McEvoy, John W; Herrington, David; Blumenthal, Roger S; Blaha, Michael J

    2016-05-15

    Prior studies observing associations between low levels of high-density lipoprotein (HDL) cholesterol and cardiovascular disease (CVD) have often been conducted among persons with metabolic or other lipid abnormalities. In this study, we investigated the association between primary low HDL cholesterol and coronary heart disease (CHD), CVD, and all-cause death after adjustment for confounders in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants who were free of clinical CVD were recruited from 6 US research centers from 2000 to 2002 and followed for a median duration of 10.2 years. We defined "primary low HDL cholesterol" as HDL cholesterol level death were 2.25 (95% confidence interval (CI): 1.20, 4.21; P = 0.011), 1.93 (95% CI: 1.11, 3.34; P = 0.020), and 1.11 (95% CI: 0.67, 1.84; P = 0.69), respectively. Participants with primary low HDL cholesterol had higher risks of CHD and CVD than participants with optimal lipid profiles but no difference in survival after a median 10.2 years of follow-up. PMID:27189327

  12. High-density lipoprotein cholesterol is related to the TaqIB cholesteryl ester transfer protein gene polymorphism and smoking, but not to moderate alcohol consumption in insulin-dependent diabetic men

    NARCIS (Netherlands)

    Dullaart, RPF; Beusekamp, BJ; Riemens, SC; Hoogenberg, K; Stulp, BK; Van Tol, A; Sluiter, WJ

    1998-01-01

    In non-diabetic subjects, the high-density lipoprotein (HDL) cholesterol level is increased by alcohol and decreased by smoking. The biallelic B1B2 polymorphism of the cholesteryl ester transfer protein (CETP) gene is a genetic determinant of HDL cholesterol. We evaluated the effect of moderate alco

  13. An increased coronary risk is paradoxically associated with common cholesteryl ester transfer protein gene variations that relate to higher high-density lipoprotein cholesterol: A population-based study

    NARCIS (Netherlands)

    S.E. Borggreve (Susanna); H.L. Hillege (Hans); B.H.R. Wolffenbuttel (Bruce); P. de Jong (Paul); M.W. Zuurman (Mike); G. van der Steege (Gerrit); A. van Tol (Arie); R.P.F. Dullaart (Robin)

    2006-01-01

    textabstractBackground: Several cholesteryl ester transfer protein (CETP) polymorphisms affect high-density lipoprotein (HDL) cholesterol, but the impact of CETP gene variants on incident coronary disease in the general population is uncertain after correction for their effect on HDL cholesterol. De

  14. Higher testosterone levels are associated with increased high-density lipoprotein cholesterol in men with cardiovascular disease: results from the Massachusetts Male Aging Study

    Institute of Scientific and Technical Information of China (English)

    Stephanie T.Page; Beth A.Mohr; Carol L.Link; Amy B.O' Donnell; William J.Bremner; John B.McKinlay

    2008-01-01

    Aim: To study the relationship between circulating androgens (total testosterone [TT], free testosterone [fT] and dihydrotestosterone [DHT]) and high-density lipoprotein cholesterol (HDL-C) in men with and without cardiovascular disease (CVD). Methods: Cross-sectional analyses included 1 661 baseline samples from the Massachusetts Male Aging Study (MMAS), a population-based cohort of men ages 40-70 years. Serum hormones were measured by radioimmunoassay and HDL-C was determined following precipitation of the lower density lipoproteins. CVD was determined by self-report. Analyses were performed using multiple linear regression. Results: TT and HDL-C were positively correlated in the entire sample (r = 0.11, P = 0.0001). After adjusting for confounders, we found this relationship was mostly limited to the 209 men with CVD. Among men with CVD, TT (P = 0.0004), fT (P = 0.0172)and DHT (P = 0.0128) were all positively correlated with HDL-C, whereas in men without CVD only TT correlatedwith HDL-C (P = 0.0099). Conclusion: Our results suggest that if androgens contribute to CVD in middle-aged men, the effect is not related to a suppressive effect of endogenous T on HDL-C.

  15. Implications of Total to High-Density Lipoprotein Cholesterol Ratio Discordance With Alternative Lipid Parameters for Coronary Atheroma Progression and Cardiovascular Events.

    Science.gov (United States)

    Elshazly, Mohamed B; Nicholls, Stephen J; Nissen, Steven E; St John, Julie; Martin, Seth S; Jones, Steven R; Quispe, Renato; Stegman, Brian; Kapadia, Samir R; Tuzcu, E Murat; Puri, Rishi

    2016-09-01

    The total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio may quantify atherogenic lipoproteins beyond low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apolipoprotein B (apoB). We analyzed pooled data from 9 trials involving 4,957 patients with coronary artery disease undergoing serial intravascular ultrasonography to assess changes in percent atheroma volume (ΔPAV) and 2-year major adverse cardiovascular event (MACE) rates when TC/HDL-C levels were discordant with LDL-C, non-HDL-C, and apoB. Discordance was investigated when lipid levels were stratified by

  16. Alterations of serum cholesterol and serum lipoprotein in breast cancer of women

    OpenAIRE

    Hasija, Kiran; Bagga, Hardeep K.

    2005-01-01

    Fasting blood sample of 50 normal subjects (control) and 100 patients of breast cancer were investigated for serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein, high density lipoprotein cholesterol:low density lipoprotein cholesterol ratio and total cholesterol:high density lipoprotein cholesterol ratio during breast cancer of women. Five cancer stages, types, age groups, parity and menopausal status were undertaken...

  17. Obesity and high-density lipoprotein cholesterol in black and white 9- and 10-year-old girls : The National Heart, Lung, and Blood Institute Growth and Health Study

    NARCIS (Netherlands)

    Morrison, JA; Sprecher, D; McMahon, RP; Schreiber, GB; Khoury, PR

    1996-01-01

    It has been hypothesized that the role of obesity in the pathogenesis of coronary heart disease (CHD) may be mediated in part through its inverse relationship with high-density lipoprotein cholesterol (HDL-C). Obesity is inversely correlated with HDL-C, and HDL-C has been shown to be protective agai

  18. Plasma cholesteryl ester transfer and hepatic lipase activity are related to high-density lipoprotein cholesterol in association with insulin resistance in type 2 diabetic and non-diabetic subjects

    NARCIS (Netherlands)

    Riemens, SC; Van Tol, A; Scheek, LM; Dullaart, RPF

    2001-01-01

    We evaluated the: hypothesis that plasma cholesteryl ester transfer (CET) and lipase activities are influenced by insulin sensitivity and contribute to the low high-density lipoprotein (HDL) cholesterol observed in type 2 diabetic patients and insulin-resistant non-diabetic subjects. Sixteen type 2

  19. Effects of red grape juice consumption on high density lipoprotein-cholesterol, apolipoprotein AI, apolipoprotein B and homocysteine in healthy human volunteers.

    Science.gov (United States)

    Khadem-Ansari, Mohammad H; Rasmi, Yousef; Ramezani, Fatemeh

    2010-01-01

    It has suggested that grape juice consumption has lipid- lowering effect and it is associated with a decreased risk of heart disease. We aimed to evaluate the effects of red grape juice (RGj) consumption on high density lipoprotein-cholesterol (HDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB) and homocysteine (Hcy) levels in healthy human volunteers. Twenty six healthy and nonsmoking males, aged between 25-60 years, who were under no medication asked to consume 150 ml of RGj twice per day for one month. Serum HDL-C, apoAI, apoB and plasma Hcy levels were measured before and after one month RGj consumption. HDL-C levels after RGj consumption were significantly higher than the corresponding levels before the RGj consumption (41.44 ± 4.50 and 44.37 ± 4.30 mg/dl; P0.05). Hcy levels were decreased after RGj consumption (7.70 ± 2.80 and 6.20 ± 2.30 µmol/l; P<0.001). The present study demonstrates that RGj consumption can significantly increase serum HDL-C levels and decrease Hcy levels. These findings may have important implications for the prevention of atherosclerosis in healthy individuals. PMID:21633724

  20. High-density lipoprotein-cholesterol levels and risk of cancer in HIV-infected subjects: Data from the ICONA Foundation Cohort.

    Science.gov (United States)

    Squillace, Nicola; Galli, Laura; Bandera, Alessandra; Castagna, Antonella; Madeddu, Giordano; Caramello, Pietro; Antinori, Andrea; Cattelan, Annamaria; Maggiolo, Franco; Cingolani, Antonella; Gori, Andrea; Monforte, Antonella d'Arminio

    2016-09-01

    Investigation of the relationship between high-density lipoprotein-cholesterol (HDL-c) and the risk of developing cancer in a prospective cohort of human immunodeficiency virus (HIV)-infected patients.The Italian Cohort of Antiretroviral-naïve Patients Foundation Cohort is an Italian multicenter observational study recruiting HIV-positive patients while still antiretroviral treatment-naïve, regardless of the reason since 1997.Patients with at least 1 HDL-c value per year since enrollment and one such value before antiretroviral treatment initiation were included. HDL-c values were categorized as either low (AHR] 1.87, 95% CI 1.18-2.95, P = 0.007) in older patients, those patients more recently enrolled, and in those with low current cluster of differentiation 4+ levels, and/or high current HIV-ribonucleic acid.The multivariate model confirmed an association between HDL-c (AHR 2.61, 95% CI 1.40-4.89, P = 0.003) and risk of NADM.Low HDL-c is an independent predictor of cancer in HIV-1-infected subjects. PMID:27603338

  1. Understanding Lipoproteins as Transporters of Cholesterol and Other Lipids

    Science.gov (United States)

    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…

  2. Exercise raises high-density lipoprotein cholesterol in men after consumption of ground beef with a high but not low monounsaturated fatty acid-saturated fatty acid ratio.

    Science.gov (United States)

    Crouse, Stephen F; Green, John S; Meade, Thomas H; Smith, Dana R; Smith, Stephen B

    2016-09-01

    Exercise and diets with higher monounsaturated fatty acid (MUFA):saturated fatty acid (SFA) ratios are independently linked to improved blood lipid profiles, yet interactive effects in men have not been studied. We hypothesized that dietary ground beef with a high MUFA:SFA ratio (HR = 1.1) would augment the beneficial changes in the lipid profile induced by exercise compared to dietary ground beef with a lower MUFA:SFA ratio (LR = 0.71). Untrained men (n = 13, age = 35 ± 12 y, weight = 91.4 ± 14.2 kg, body mass index = 27.8 ± 3.3kg/m(2)) consumed 5 HR or LR 114 g ground beef patties weekly for 5 weeks (random order) interspersed with a 4-week self-selected (SS) washout diet. One session of exercise (70% VO2max, 1675 kJ) was completed at the end of HR and LR diets, and again after a 5-week SS diet. Diets and physical activity were otherwise not controlled. Fasting blood samples for lipid and lipoprotein analyses were obtained 30 min before and 24 h after exercise. Subjects reported no other changes in diets or physical activity patterns, and body weight and body mass index did not change over the study duration. Diet (3) × Exercise Time (2) repeated measures analysis of variance (α = .05) and follow-up analyses revealed that blood concentrations (mmol/L ± SD) of total cholesterol (5.07 ± 1.16 to 5.73 ± 1.36), high-density lipoprotein cholesterol (HDL-C) (1.19 ± 0.20 to 1.36 ± 0.29), HDL2-C (0.24 ± 0.08 to 0.28 ± 0.11), HDL3-C (0.94 ± 0.14 to 1.08 ± 0.20), and non-HDL-C (3.88 ± 1.24 to 4.37 ± 1.38) were significantly elevated with exercise after the HR beef diet, but not after LR and SS diets. Thus, in healthy, untrained men the dietary beef MUFA:SFA ratio affects the blood lipid response to a single session of aerobic exercise. PMID:27632917

  3. Monitoring of high-density lipoprotein cholesterol level is predictive of EGFR mutation and efficacy of EGFR-TKI in patients with advanced lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Lv Y

    2016-01-01

    Full Text Available Yang Lv,1,2 Li-Yun Miao,2 Qiu-Fang Chen,1 Yan Li,2 Zhi-Xiang Shi,1 Xuan-Sheng Ding1 1Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China; 2Division of Respiratory Medicine, Department of Respiration, The Affiliated Drum Tower Hospital of Nanjing University Medical College, Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China Abstract: High-density lipoprotein cholesterol (HDL-C has an inverse association with the incidence of lung cancer. However, whether it can be used as a predictive factor in advanced lung adenocarcinoma patients treated with epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKI still remains undefined. This research aimed at studying the relationship of serum HDL-C baseline level and HDL-C kinetics to EGFR mutation, the efficacy of EGFR-TKI, and the predictive value of PFS. The presence of mutation rate in the 192 patients with lung adenocarcinoma was compared within stratified groups. Levels of baseline HDL-C and kinetics of HDL-C were analyzed retrospectively in patients treated with EGFR-TKI harboring EGFR mutation. Univariate and multivariate analyses were performed to investigate the prognostic value of HDL-C. EGFR mutation rate of HDL-C high-level group was significantly higher than that of low-level group (59.0% vs 35.6%, P=0.001. Multivariate logistic analysis showed that high-level HDL-C was an independent predictive factor for EGFR gene mutation (P=0.005; odds ratio =0.417; 95% confidence interval [CI], 0.227–0.768. Patients with a low level of HDL-C before therapy showed a progression of disease in most cases (P<0.001. According to HDL-C kinetics, patients who received EGFR-TKI treatment harboring EGFR mutation were divided into four groups. Univariate analysis showed that patients in nondecreased group had longer progression-free survival (P<0.001; hazard ratio =0.003; 95% CI, 0.001–0.018. Multivariate

  4. 血清总胆固醇与高密度脂蛋白胆固醇比值作为冠心病危险标志的意义%Significance of serum total cholesterol to high density lipoprotein cholesterol ratio as a risk marker for coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    李璐; 纪玲

    2015-01-01

    目的:分析冠心病(CHD)患者的血脂水平,探讨血清总胆固醇(TC)与高密度脂蛋白胆固醇(HDL‐C)比值作为CHD危险标志的临床意义。方法测定295例CHD患者的血清 TC、三酰甘油(TG)、HDL‐C及低密度脂蛋白胆固醇(LDL‐C)水平,并计算TC/HDL‐C比值。结果依据《中国成人血脂异常防治指南》颁布的血脂水平合适范围,CHD患者血清 TC、TG及LDL‐C高于合适范围百分率分别为32.20%、34.24%及37.63%,血清 HDL‐C低于合适范围百分率为39.32%。血清TC/HDL‐C比值高于合适范围百分率为57.29%。血清TC/HDL‐C比值异常率显著高于血清TC、TG、HDL‐C及LDL‐C(χ2=37.540、31.576、19.066、22.866,P<0.01)。结论与任一单项血脂检测相比,血清 TC/HDL‐C比值作为CHD危险标志可能更有临床意义,临床血脂检测报告单应增加TC/HDL‐C比值。%Objective To analyze blood lipid levels in patients with coronary heart disease ,and to explore clinical significance of serum total cholesterol to high density lipoprotein cholesterol ratio as a risk marker for coronary heart disease .Methods Serum lev‐els of total cholesterol ,triglycerides ,high density lipoprotein cholesterol ,and low density lipoprotein cholesterol were measured for 295 patients with coronary heart disease .Ratio of total cholesterol to high density lipoprotein cholesterol was calculated based on the lipid tests .Results The percentages of abnormal total cholesterol ,triglycerides ,high density lipoprotein cholesterol ,and low density lipoprotein cholesterol were 32 .20% 、34 .24% ,39 .32% ,and 37 .63% ,respectively ,for patients with coronary heart disease according to normal ranges issued by Guidelines on Prevention and Treatment of Dyslipidemia in Adults in Chinese Population .The abnormal percentage of total cholesterol to high density lipoprotein cholesterol ratio was 57 .29% .The

  5. The characteristics of high density lipoprotein cholesterol and the relationship between high density lipoprotein cholesterol and the severity of coronary artery lesions in young men with acute myocardial infarction%青年男性心肌梗死的高密度脂蛋白胆固醇特点及其与冠状动脉病变的关系

    Institute of Scientific and Technical Information of China (English)

    李昭; 陶英; 黄觊; 王茜; 张冬花; 吴翔宇

    2013-01-01

    .784)、高血压(OR =7.782)、早发冠心病家族史(OR =4.613)、LDL-C(OR=2.496)、吸烟(OR=2.241)、Hb(OR=1.042)及UA(OR=1.005)是心梗的独立危险因素(均P<0.05),HDL-C(OR=0.147,P<0.05)是心梗的保护性因素;在青年男性心梗人群中,LDL-C(OR=2.095)及高血压(OR=1.042)(均P<0.05)是冠脉多支病变的独立危险因素,HDL-C(OR=0.071,P<0.05)是冠脉多支病变的保护性因素.结论 高密度脂蛋白胆固醇是青年男性急性心梗和冠脉多支病变的保护性因素.%Objective To investigate the characteristics of high density lipoprotein cholesterol and the relationship between high density lipoprotein cholesterol and the severity of coronary artery lesions in young men with acute myocardial infarction (AMI).Methods We retrospectively studied 278 young men with acute myocardial infarction and compared with 208 non-CHD young men,137 old men with AMI.All patients were admitted to hospital from Jan 2009 to Dec 2011 and undergone coronary angiography,and the clinic and coronary angiographic features were assessed.According to the result of coronary angiography,the patients were divided into three groups:the single,double and triple vessel lesions.The relation between systolic body mass index (BMI),hemoglobin (Hb),serum uric acid (UA),total cholesterol (TC),triglyceride (TG),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDLC),smoking history,essential hypertension,type 2 diabetes mellitus,familial history of early coronary artery disease with acute myocardial infarction and severity of coronary artery disease are observed.And observe the characteristics of HDL-C in the obesity group and the smoking group in young men based on body mass index and smoking history.Results (1) In young men with AMI group,the HDL-C levels was significantly lower than those in non-CHD young men group ((1.00 ± 0.28) mmol/L vs (1.05 ± 0.23)mmol/L,P < 0.05).In young men with AMI group,the HDL-C levels was

  6. The Predictive Role of Serum Triglyceride to High-Density Lipoprotein Cholesterol Ratio According to Renal Function in Patients with Acute Myocardial Infarction

    Science.gov (United States)

    Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyoon; Moon, Joo Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

    2016-01-01

    Objective A high serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been reported as an independent predictor for cardiovascular events in the general population. However, the prognostic value of this ratio in patients with renal dysfunction is unclear. We examined the association of the TG/HDL-C ratio with major adverse cardiovascular events (MACEs) according to renal function in patients with acute myocardial infarction (AMI). Method This study was based on the Korea Acute Myocardial Infarction Registry database. Of 13,897 patients who were diagnosed with AMI, the study population included the 7,016 patients with available TG/HDL-C ratio data. Patients were stratified into three groups according to their estimated glomerular filtration rate (eGFR), and the TG/HDL-C ratio was categorized into tertiles. We investigated 12-month MACEs, which included cardiac death, myocardial infarction, and repeated percutaneous coronary intervention or coronary artery bypass grafting. Results During the 12-month follow up period, 593 patients experienced MACEs. There was a significant association between the TG/HDL-C ratio and MACEs (p<0.001) in the entire study cohort. Having a TG/HDL-C ratio value in the highest tertile of TG/HDL-C ratio was an independent factor associated with increased risk of MACEs (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.26–1.93; p<0.001). Then we performed subgroup analyses according to renal function. In patients with normal renal function (eGFR ≥ 90 ml/min/1.73m2) and mild renal dysfunction (eGFR ≥ 60 to < 90ml/min/1.73m2), a higher TG/HDL-C ratio was significantly associated with increased risk of MACEs (HR, 1.64; 95% CI, 1.04–2.60; p = 0.035; and HR, 1.56; 95% CI, 1.14–2.12; p = 0.005, respectively). However, in patients with moderate renal dysfunction (eGFR < 60 ml/min/1.73m2), TG/HDL-C ratio lost its predictive value on the risk of MACEs (HR, 1.23; 95% CI, 0.82–1.83; p = 0.317). Conclusions In

  7. A Novel Anti-Inflammatory Effect for High Density Lipoprotein.

    Directory of Open Access Journals (Sweden)

    Scott J Cameron

    Full Text Available 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.

  8. Baseline blood pressure, low- and high-density lipoproteins, and triglycerides and the risk of vascular events in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

    DEFF Research Database (Denmark)

    Amarenco, Pierre; Goldstein, Larry B; Callahan, Alfred;

    2009-01-01

    cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and triglyceride levels. After 4.9 years of follow-up, there were 575 primary end points (fatal and nonfatal stroke), including 491 ischemic strokes, and 740 MCVEs (stroke plus myocardial infarction and vascular death). Cox regression...... AND RESULTS: The SPARCL trial randomized 4731 patients with recent stroke or transient ischemic attack (TIA) and no known coronary heart disease and LDL-C between 100 and 190 mg/dL to either atorvastatin 80 mg/d or placebo. Baseline assessment included SBP, DBP and measurements of low-density lipoprotein...... models analysis showed a trend (P>0.05 and PLDL/HDL ratio were each associated with MCVEs...

  9. [Residual risk: The roles of triglycerides and high density lipoproteins].

    Science.gov (United States)

    Grammer, Tanja; Kleber, Marcus; Silbernagel, Günther; Scharnagl, Hubert; März, Winfried

    2016-06-01

    In clinical trials, the reduction of LDL-cholesterol (LDL-C) with statins reduces the incidence rate of cardiovascular events by approximately one third. This means, that a sizeable "residual risk" remains. Besides high lipoprotein (a), disorders in the metabolism of triglyceride-rich lipoproteins and high density liproteins have been implicated as effectors of the residual risk. Both lipoprotein parameters correlate inversely with each other. Therefore, the etiological contributions of triglycerides and / or of HDL for developing cardiovascular disease can hardly be estimated from either observational studies or from intervention studies. The largely disappointing results of intervention studies with inhibitors of the cholesteryl ester transfer protein and in particular the available set of genetically-epidemiological studies suggest that in the last decade, the importance of HDL cholesterol has been overvalued, while the importance of triglycerides has been underestimated. High triglycerides not always atherogenic, but only if they are associated with the accumulation relatively cholesterol-enriched, incompletely catabolized remnants of chylomicrons and very low density lipoproteins (familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus). The normalization of the concentration of triglycerides and remnants by inhibiting the expression of apolipoprotein C3 is hence a new, promising therapeutic target. PMID:27305303

  10. Cholesterol in serum lipoprotein fractions after spaceflight

    Science.gov (United States)

    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.

  11. High-density lipoprotein and atherosclerosis: Roles of lipid transporters

    Institute of Scientific and Technical Information of China (English)

    Yoshinari; Uehara; Keijiro; Saku

    2014-01-01

    Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases.

  12. Triglycerides and high-density lipoprotein cholesterol are associated with insulinemia in adolescents Triglicéridos y colesterol de lipóproteína de alta densidad asociados con insulina en adolescentes

    Directory of Open Access Journals (Sweden)

    Guadalupe Ramírez-López

    2006-08-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the association between lipids and insulin concentration in adolescents. MATERIAL AND METHODS: A cross-sectional study of 350 adolescents aged 14-19 years old from a public high school in Guadalajara, in the state of Jalisco, Mexico, was conducted. Fasting insulin concentration was determined using microparticle enzyme immunoassay; total cholesterol and triglycerides were detected by standard enzymatic procedures; and low- and high-density lipoproteins were found using standard precipitation methods. Statistical analysis included linear multivariate regression. RESULTS: Serum triglycerides were associated positively with insulin fasting (beta= 0.003, p= 0.0001 and high-density lipoprotein cholesterol was negatively associated with insulin fasting in male adolescents 18-19 years old (beta= -0.03, p= 0.012. CONCLUSIONS: The relationships between triglycerides and insulin and between high-density lipoprotein cholesterol and insulin are already present in adolescence.OBJETIVO: Evaluar la relación entre lípidos e insulina en adolescentes. MATERIAL Y MÉTODOS: Estudio transversal en 350 adolescentes de 14 a 19 años de preparatoria pública en Guadalajara, Jal., México. La insulina se midió por inmunoensayo enzimático de micropartícula, el colesterol total y triglicéridos por pruebas enzimáticas estándares, y las lipoproteínas de baja y alta densidad por métodos de precipitación. Se utilizó análisis de regresión lineal multivariada. RESULTADOS: Los triglicéridos se asociaron en forma positiva con insulina (beta= 0.003, p= 0.0001 y la lipoproteína de alta densidad se asoció en forma negativa con insulina en varones de 18-19 años de edad (beta= -0.03, p= 0.012. CONCLUSIONES: En los adolescentes, los triglicéridos y las lipoproteínas de alta densidad están asociados con la insulinemia.

  13. Metabolism of high density lipoproteins in liver cancer

    Institute of Scientific and Technical Information of China (English)

    Jing-Ting Jiang; Ning Xu; Chang-Ping Wu

    2007-01-01

    Liver plays a vital role in the production and catabolism of plasma lipoproteins. It depends on the integrity of cellular function of liver, which ensures homeostasis of lipid and lipoprotein metabolism. When liver cancer occurs these processes are impaired and high-density lipoproteins are changed.

  14. Low fasting low high-density lipoprotein and postprandial lipemia

    Directory of Open Access Journals (Sweden)

    Sorodila Konstandina

    2004-07-01

    Full Text Available Abstract Background Low levels of high density lipoprotein (HDL cholesterol and disturbed postprandial lipemia are associated with coronary heart disease. In the present study, we evaluated the variation of triglyceride (TG postprandially in respect to serum HDL cholesterol levels. Results Fifty two Greek men were divided into 2 main groups: a the low HDL group (HDL p = 0.002. The low HDL group had significantly higher TG at 4, 6 and 8 h postprandially compared to the controls (p = 0.006, p = 0.002, and p p = 0.017 compared to the matched-control group. ROC analysis showed that fasting TG ≥ 121 mg/dl have 100% sensitivity and 81% specificity for an abnormal TG response (auc = 0.962, p Conclusions The delayed TG clearance postprandially seems to result in low HDL cholesterol even in subjects with low fasting TG. The fasting TG > 121 mg/dl are predictable for abnormal response to fatty meal.

  15. The association between the apolipoprotein A1/ high density lipoprotein -cholesterol and diabetes in Taiwan — a cross-sectional study

    OpenAIRE

    Jian, Zhi-Hong; Lung, Chia-Chi; Ko, Pei-Chieh; Sun, Yi-Hua; Huang, Jing-Yang; Ho, Chien-Chang; Ho, Chia-Yo; Chiang, Yi-Chen; Chen, Chien-Jen; Liaw, Yung-Po

    2013-01-01

    Background Traditional lipid indices have been associated with type 2 diabetes, but it remains uncertain which lipid index is the best discriminator for diabetes. In this study, we aimed to assess lipoproteins, traditional lipid variables, and other variables to discover their association with diabetes in the Taiwanese population. Methods Data from a nationwide cross-sectional population-based survey of 3087 men and 3373 women in 2002 were analyzed in this study. All participants were assesse...

  16. EFFECT OF ADIPOSITY ON PLASMA-LIPID TRANSFER PROTEIN ACTIVITIES - A POSSIBLE LINK BETWEEN INSULIN-RESISTANCE AND HIGH-DENSITY-LIPOPROTEIN METABOLISM

    NARCIS (Netherlands)

    DULLAART, RPF; SLUITER, WJ; DIKKESCHEI, LD; HOOGENBERG, K; VANTOL, A

    1994-01-01

    The mechanisms responsible for the decreased high density lipoprotein (HDL) cholesterol levels associated with obesity and insulin resistance are not well understood. Lecithin: cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) are key factors in the esterification of c

  17. The effect of cholesteryl ester transfer protein-629C -> A promoter polymorphism on high-density lipoprotein cholesterol is dependent on serum triglycerides

    NARCIS (Netherlands)

    Borggreve, SE; Hillege, HL; Wolffenbuttel, BHR; de Jong, PE; Bakker, SJL; van der Steege, G; van Tol, A; Dullaart, RPF

    2005-01-01

    Context: The -629C -> A cholesteryl ester transfer protein (CETP) promoter polymorphism is a determinant of HDL cholesterol (HDL-C). The effect of the closely linked CETP TaqIB polymorphism on HDL-C has been suggested to be modified by obesity and hyperinsulinemia. Objective: Because the CETP-mediat

  18. Enhancement of High-Density Lipoprotein Cholesterol Functions by Encapsulation of Policosanol Exerts Anti-Senescence and Tissue Regeneration Effects Via Improvement of Anti-Glycation, Anti-Apoptosis, and Cholesteryl Ester Transfer Inhibition.

    Science.gov (United States)

    Lim, So-Mang; Yoo, Jeong-Ah; Lee, Eun-Young; Cho, Kyung-Hyun

    2016-02-01

    Consumption of policosanol (PCO), a refined mixture of sugar cane wax alcohols, can elevate serum levels of high-density lipoprotein cholesterol (HDL-C), although the molecular mechanism is still unknown. To investigate the mechanism of action responsible for the anti-senescence effects of PCO on lipoprotein metabolism and HDL functionality, we synthesized reconstituted HDL (rHDL) containing PCO. Encapsulation of PCO by rHDL (PCO-rHDL) enhanced anti-oxidant activity against cupric ion-mediated low-density lipoprotein (LDL) oxidation. PCO-rHDL (final concentration, 9 μM PCO) showed more potent anti-oxidant activity than vitamin C treatment (final concentration, 100 μM). PCO-rHDL inhibited fructose-mediated glycation, which is a major pathological mechanism of diabetic complications, in a dose-dependent manner. PCO also showed cytoprotective effects in monocytes and macrophages with less triggering of apoptotic processes and reactive oxygen species (ROS) production in the presence of hydrogen peroxide (H2O2). PCO-rHDL strongly inhibited uptake of acetylated LDL into macrophages, which is an initial atherosclerotic process. Surprisingly, PCO-rHDL inhibited human serum cholesteryl ester transfer protein (CETP) activity by up to 47% (final concentration, 10 μM PCO). Subcutaneous injection of PCO-rHDL dose-dependently enhanced tissue regeneration activity by 2.4-fold and 3.6-fold compared to that of the phosphate-buffered saline (PBS) control. In conclusion, PCO in HDL showed potent anti-oxidant, anti-glycation, and CETP inhibitory activities along with tissue regenerative activity, especially upon incorporation into HDL. These results suggest that PCO can enhance functionality of HDL in serum to exert anti-senescence and longevity effects. PMID:26161621

  19. High-density lipoprotein functionality in coronary artery disease.

    Science.gov (United States)

    Kosmas, Constantine E; Christodoulidis, Georgios; Cheng, Jeh-wei; Vittorio, Timothy J; Lerakis, Stamatios

    2014-06-01

    The role of high-density lipoprotein (HDL) in cardiovascular atheroprotection is well established. Epidemiological data have clearly demonstrated an inverse relationship between HDL levels and the risk for coronary artery disease, which is independent of the low-density lipoprotein levels. However, more recent data provide evidence that high HDL levels are not always protective and that under certain conditions may even confer an increased risk. Thus, a new concept has arisen, which stresses the importance of HDL functionality, rather than HDL concentration per se, in the assessment of cardiovascular risk. HDL functionality is genetically defined but can also be modified by several environmental and lifestyle factors, such as diet, smoking or certain pharmacologic interventions. Furthermore, HDL is consisted of a heterogeneous group of particles with major differences in their structural, biological and functional properties. Recently, the cholesterol efflux capacity from macrophages was proven to be an excellent metric of HDL functionality, because it was shown to have a strong inverse relationship with the risk of angiographically documented coronary artery disease, independent of the HDL and apolipoprotein A-1 levels, although it may not actually predict the prospective risk for cardiovascular events. Thus, improving the quality of HDL may represent a better therapeutic target than simply raising the HDL level, and assessment of HDL function may prove informative in refining our understanding of HDL-mediated atheroprotection.

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

    Science.gov (United States)

    Luthi, Andrea Jane

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

  1. Mendelian Disorders of High-Density Lipoprotein Metabolism

    NARCIS (Netherlands)

    Oldoni, Federico; Sinke, Richard J.; Kuivenhoven, Jan Albert

    2014-01-01

    High-density lipoproteins (HDLs) are a highly heterogeneous and dynamic group of the smallest and densest lipoproteins present in the circulation. This review provides the current molecular insight into HDL metabolism led by articles describing mutations in genes that have a large affect on HDL chol

  2. Pistachio intake increases high density lipoprotein levels and inhibits low-density lipoprotein oxidation in rats.

    Science.gov (United States)

    Aksoy, Nur; Aksoy, Mehmet; Bagci, Cahit; Gergerlioglu, H Serdar; Celik, Hakim; Herken, Emine; Yaman, Abdullah; Tarakcioglu, Mehmet; Soydinc, Serdar; Sari, Ibrahim; Davutoglu, Vedat

    2007-05-01

    There is increasing evidence that nuts have protective effects against coronary artery disease by improving lipid profile and inhibiting lipid oxidation. However, data about pistachio nuts are limited, and to our knowledge, there is no study investigating the effects of pistachio intake on lipid oxidation and serum antioxidant levels. This study, therefore, sought to determine the effects of pistachio intake on serum lipids and determine whether consumption of pistachio would alter serum antioxidant levels. Rats were randomly divided into three groups (n=12 for each): control group fed basic diet for 10 weeks and treated groups fed basic diet plus pistachio which constituted 20% and 40% of daily caloric intake, respectively. Consumption of pistachio as 20% of daily caloric intake increased high-density lipoprotein (HDL) levels and decreased total cholesterol (TC)/HDL ratio, compared with those not taking pistachio. However, TC, low-density lipoprotein (LDL) cholesterol and triglyceride levels were unaffected by pistachio consumption. Consumption of pistachio as 20% of daily caloric intake increased serum paraoxonase activity by 35% and arylesterase activity by 60%, which are known to inhibit LDL cholesterol oxidation, compared with the control group. However, increased antioxidant activity was blunted when pistachio intake was increased to 40% of daily caloric intake. In conclusion, the present results show that consumption of pistachio as 20% of daily caloric intake leads to significant improvement in HDL and TC/HDL ratio and inhibits LDL cholesterol oxidation. These results suggest that pistachio may be beneficial for both prevention and treatment of coronary artery disease.

  3. High-density lipoprotein endocytosis in endothelial cells

    Institute of Scientific and Technical Information of China (English)

    Stefanie; Fruhwürth; Margit; Pavelka; Robert; Bittman; Werner; J; Kovacs; Katharina; M; Walter; Clemens; Rhrl; Herbert; Stangl

    2013-01-01

    AIM: To describe the way stations of high-density lipoprotein(HDL) uptake and its lipid exchange in endothelial cells in vitro and in vivo. METHODS: A combination of fluorescence microscopy using novel fluorescent cholesterol surrogates and electron microscopy was used to analyze HDL endocytosis in great detail in primary human endothelial cells. Further, HDL uptake was quantified using radio-labeled HDL particles. To validate the in vitro findings mice were injected with fluorescently labeled HDL and particle uptake in the liver was analyzed using fluorescencemicroscopy. RESULTS: HDL uptake occurred via clathrin-coated pits, tubular endosomes and multivesicular bodies in human umbilical vein endothelial cells. During uptake and resecretion, HDL-derived cholesterol was exchanged at a faster rate than cholesteryl oleate, resembling the HDL particle pathway seen in hepatic cells. In addition, lysosomes were not involved in this process and thus HDL degradation was not detectable. In vivo, we found HDL mainly localized in mouse hepatic endothelial cells. HDL was not detected in parenchymal liver cells, indicating that lipid transfer from HDL to hepatocytes occurs primarily via scavenger receptor, class B, type Ⅰ mediated selective uptake without concomitant HDL endocytosis. CONCLUSION: HDL endocytosis occurs via clathrincoated pits, tubular endosomes and multivesicular bodies in human endothelial cells. Mouse endothelial cells showed a similar HDL uptake pattern in vivo indicating that the endothelium is one major site of HDL endocytosis and transcytosis.

  4. Consistency of genetic inheritance mode and heritability patterns of triglyceride vs. high density lipoprotein cholesterol ratio in two Taiwanese family samples

    Directory of Open Access Journals (Sweden)

    Yang Chi-Yu

    2003-04-01

    Full Text Available Abstract Background Triglyceride/HDL cholesterol ratio (TG/HDL-C is considered as a risk factor for cardiovascular events. Genetic components were important in controlling the variation in western countries. But the mode of inheritance and family aggregation patterns were still unknown among Asian-Pacific countries. This study, based on families recruited from community and hospital, is aimed to investigate the mode of inheritance, heritability and shared environmental factors in controlling TG/HDL-C. Results Two populations, one from community-based families (n = 988, 894 parent-offspring and 453 sibling pairs and the other from hospital-based families (n = 1313, 76 parent-offspring and 52 sibling pairs were sampled. The population in hospital-based families had higher mean age values than community-based families (54.7 vs. 34.0. Logarithmic transformed TG/ HDL-C values, after adjusted by age, gender and body mass index, were for genetic analyses. Significant parent-offspring and sibling correlations were also found in both samples. The parent-offspring correlation coefficient was higher in the hospital-based families than in the community-based families. Genetic heritability was higher in community-based families (0.338 ± 0.114, p = 0.002, but the common shared environmental factor was higher in hospital-based families (0.203 ± 0.042, p Conclusion Variations of TG/HDL-C in the normal ranges were likely to be influenced by multiple factors, including environmental and genetic components. Higher genetic factors were proved in younger community-based families than in older hospital-based families.

  5. Human endothelial progenitor cells internalize high-density lipoprotein.

    Science.gov (United States)

    Srisen, Kaemisa; Röhrl, Clemens; Meisslitzer-Ruppitsch, Claudia; Ranftler, Carmen; Ellinger, Adolf; Pavelka, Margit; Neumüller, Josef

    2013-01-01

    Endothelial progenitor cells (EPCs) originate either directly from hematopoietic stem cells or from a subpopulation of monocytes. Controversial views about intracellular lipid traffic prompted us to analyze the uptake of human high density lipoprotein (HDL), and HDL-cholesterol in human monocytic EPCs. Fluorescence and electron microscopy were used to investigate distribution and intracellular trafficking of HDL and its associated cholesterol using fluorescent surrogates (bodipy-cholesterol and bodipy-cholesteryl oleate), cytochemical labels and fluorochromes including horseradish peroxidase and Alexa Fluor® 568. Uptake and intracellular transport of HDL were demonstrated after internalization periods from 0.5 to 4 hours. In case of HDL-Alexa Fluor® 568, bodipy-cholesterol and bodipy-cholesteryl oleate, a photooxidation method was carried out. HDL-specific reaction products were present in invaginations of the plasma membrane at each time of treatment within endocytic vesicles, in multivesicular bodies and at longer periods of uptake, also in lysosomes. Some HDL-positive endosomes were arranged in form of "strings of pearl"- like structures. HDL-positive multivesicular bodies exhibited intensive staining of limiting and vesicular membranes. Multivesicular bodies of HDL-Alexa Fluor® 568-treated EPCs showed multilamellar intra-vacuolar membranes. At all periods of treatment, labeled endocytic vesicles and organelles were apparent close to the cell surface and in perinuclear areas around the Golgi apparatus. No HDL-related particles could be demonstrated close to its cisterns. Electron tomographic reconstructions showed an accumulation of HDL-containing endosomes close to the trans-Golgi-network. HDL-derived bodipy-cholesterol was localized in endosomal vesicles, multivesicular bodies, lysosomes and in many of the stacked Golgi cisternae and the trans-Golgi-network Internalized HDL-derived bodipy-cholesteryl oleate was channeled into the lysosomal intraellular

  6. Human endothelial progenitor cells internalize high-density lipoprotein.

    Directory of Open Access Journals (Sweden)

    Kaemisa Srisen

    Full Text Available Endothelial progenitor cells (EPCs originate either directly from hematopoietic stem cells or from a subpopulation of monocytes. Controversial views about intracellular lipid traffic prompted us to analyze the uptake of human high density lipoprotein (HDL, and HDL-cholesterol in human monocytic EPCs. Fluorescence and electron microscopy were used to investigate distribution and intracellular trafficking of HDL and its associated cholesterol using fluorescent surrogates (bodipy-cholesterol and bodipy-cholesteryl oleate, cytochemical labels and fluorochromes including horseradish peroxidase and Alexa Fluor® 568. Uptake and intracellular transport of HDL were demonstrated after internalization periods from 0.5 to 4 hours. In case of HDL-Alexa Fluor® 568, bodipy-cholesterol and bodipy-cholesteryl oleate, a photooxidation method was carried out. HDL-specific reaction products were present in invaginations of the plasma membrane at each time of treatment within endocytic vesicles, in multivesicular bodies and at longer periods of uptake, also in lysosomes. Some HDL-positive endosomes were arranged in form of "strings of pearl"- like structures. HDL-positive multivesicular bodies exhibited intensive staining of limiting and vesicular membranes. Multivesicular bodies of HDL-Alexa Fluor® 568-treated EPCs showed multilamellar intra-vacuolar membranes. At all periods of treatment, labeled endocytic vesicles and organelles were apparent close to the cell surface and in perinuclear areas around the Golgi apparatus. No HDL-related particles could be demonstrated close to its cisterns. Electron tomographic reconstructions showed an accumulation of HDL-containing endosomes close to the trans-Golgi-network. HDL-derived bodipy-cholesterol was localized in endosomal vesicles, multivesicular bodies, lysosomes and in many of the stacked Golgi cisternae and the trans-Golgi-network Internalized HDL-derived bodipy-cholesteryl oleate was channeled into the lysosomal

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

    NARCIS (Netherlands)

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

    2010-01-01

    There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for

  8. Study On Multiple Risk Factors Of High Density Lipoprotein Cholesterol Disorder%高密度脂蛋白胆固醇(HDL-CH)异常的危险因素研究

    Institute of Scientific and Technical Information of China (English)

    谢娟; 来则民; 黄国伟; 木村美惠子

    2000-01-01

    用病例对照研究方法调查211名自愿者的高密度脂 蛋白胆固醇(HDL-CH)异常的危险因素进行初步研究。结果 显示:调查者HDL-CH异常患病率为42.18%,男性为 34.55%,女性为50.50%。吸烟、肥胖、缺少体力活动、舒张压 升高、脂肪、肉类摄入过多及蔬菜摄入少均为HDL-CH异常 的危险因素。%In order to find out the multiple risk factors of high density lipoprotein cholesterol disorder, we have undertaken case- control study of 211 volunteers with questionnaire, diet survey and labo- ratory examination to get the information. It was found that the prevalence of HDL - CH disorder was 42. 18 %, 34. 55 % in male and 50. 50 % in female. Smoking, obesity, poor labour and motion, high diastolic pressure, high level intake of fat and meat, and low level intake of vegetables were risk factors of HDL - CH disorder.

  9. Bile Acids Reduce Endocytosis of High-Density Lipoprotein (HDL) in HepG2 Cells

    OpenAIRE

    Clemens Röhrl; Karin Eigner; Stefanie Fruhwürth; Herbert Stangl

    2014-01-01

    High-density lipoprotein (HDL) transports lipids to hepatic cells and the majority of HDL-associated cholesterol is destined for biliary excretion. Cholesterol is excreted into the bile directly or after conversion to bile acids, which are also present in the plasma as they are effectively reabsorbed through the enterohepatic cycle. Here, we provide evidence that bile acids affect HDL endocytosis. Using fluorescent and radiolabeled HDL, we show that HDL endocytosis was reduced in the presence...

  10. Emerging Roles for Cholesterol and Lipoproteins in Lung Disease

    OpenAIRE

    Gowdy, Kymberly M; Fessler, Michael B.

    2012-01-01

    Dyslipidemia, the condition of elevated serum triglycerides, elevated low-density lipoprotein cholesterol, and/or low high-density lipoprotein cholesterol, is a public health problem of growing concern. Dyslipidemia clusters with other disorders of the metabolic syndrome that together influence, and may derive from, chronic inflammation. While best recognized as a risk factor for atherosclerotic cardiovascular disease, lipid dysregulation has recently been shown to influence a variety of dise...

  11. Serum Non-high-density lipoprotein cholesterol concentration and risk of death from cardiovascular diseases among U.S. adults with diagnosed diabetes: the Third National Health and Nutrition Examination Survey linked mortality study

    Directory of Open Access Journals (Sweden)

    Balluz Lina S

    2011-05-01

    Full Text Available Abstract Background Non-high-density lipoprotein cholesterol (non-HDL-C measures all atherogenic apolipoprotein B-containing lipoproteins and predicts risk of cardiovascular diseases (CVD. The association of non-HDL-C with risk of death from CVD in diabetes is not well understood. This study assessed the hypothesis that, among adults with diabetes, non-HDL-C may be related to the risk of death from CVD. Methods We analyzed data from 1,122 adults aged 20 years and older with diagnosed diabetes who participated in the Third National Health and Nutrition Examination Survey linked mortality study (299 deaths from CVD according to underlying cause of death; median follow-up length, 12.4 years. Results Compared to participants with serum non-HDL-C concentrations of 35 to 129 mg/dL, those with higher serum levels had a higher risk of death from total CVD: the RRs were 1.34 (95% CI: 0.75-2.39 and 2.25 (95% CI: 1.30-3.91 for non-HDL-C concentrations of 130-189 mg/dL and 190-403 mg/dL, respectively (P = 0.003 for linear trend after adjustment for demographic characteristics and selected risk factors. In subgroup analyses, significant linear trends were identified for the risk of death from ischemic heart disease: the RRs were 1.59 (95% CI: 0.76-3.32 and 2.50 (95% CI: 1.28-4.89 (P = 0.006 for linear trend, and stroke: the RRs were 3.37 (95% CI: 0.95-11.90 and 5.81 (95% CI: 1.96-17.25 (P = 0.001 for linear trend. Conclusions In diabetics, higher serum non-HDL-C concentrations were significantly associated with increased risk of death from CVD. Our prospective data support the notion that reducing serum non-HDL-C concentrations may be beneficial in the prevention of excess death from CVD among affected adults.

  12. Impact of Combined C-Reactive Protein and High-Density Lipoprotein Cholesterol Levels on Long-Term Outcomes in Patients With Coronary Artery Disease After a First Percutaneous Coronary Intervention.

    Science.gov (United States)

    Ogita, Manabu; Miyauchi, Katsumi; Tsuboi, Shuta; Shitara, Jun; Endo, Hirohisa; Wada, Hideki; Doi, Shinichiro; Naito, Ryo; Konishi, Hirokazu; Dohi, Tomotaka; Kasai, Takatoshi; Tamura, Hiroshi; Okazaki, Shinya; Suwa, Satoru; Daida, Hiroyuki

    2015-10-01

    Cardiovascular risk persists despite intensive low-density lipoprotein cholesterol (LDL-C) reduction using statins. High-density lipoprotein (HDL-C) is inversely associated with coronary artery disease (CAD) that is independent of LDL-C levels. C-reactive protein (CRP) is an established marker of inflammation that can impair the protective function of HDL-C: however, the impact of inflammation on the association between HDL-C and long-term outcomes in patients with CAD under statin therapy remains uncertain. We prospectively enrolled 3,507 consecutive patients with CAD who underwent a first percutaneous coronary intervention (PCI) from 1997 to 2011 at our institution. We stratified 1,682 patients (48%) who had been treated with statin at the time of PCI into 4 groups according to HDL-C levels (cutoffs of 40 and 50 mg/dl for men and women, respectively) and a CRP cutoff of 2 mg/dl: (1) high HDL-C/low CRP, (2) high HDL-C/high CRP, (3) low HDL-C/low CRP, and (4) low HDL-C/high CRP comparing the rates of all-cause death among them. The median follow-up period was 1,985 days (interquartile range 916 to 3,183 days). During this period, 197 patients (11.7%) died because of cardiac death (n = 58), carcinoma (n = 61), stroke (n = 10), and other causes (n = 69). The rates of all-cause death significantly differed among the groups (log-rank test, p <0.0001). In multivariate Cox hazard regression analyses, low HDL-C with high CRP levels remained significantly associated with a higher rate of all-cause death even after adjustment for other co-variates (hazard ratio 2.38, 1.59 to 3.61, p <0.0001). Low HDL-C together with elevated CRP levels is significantly associated with long-term outcomes in patients who received statin therapy after PCI.

  13. Alterations in high-density lipoprotein metabolism and reverse cholesterol transport in insulin resistance and type 2 diabetes mellitus : role of lipolytic enzymes, lecithin : cholesterol acyltransferase and lipid transfer proteins

    NARCIS (Netherlands)

    Borggreve, SE; de Vries, R; Dullaart, RPF

    2003-01-01

    Insulin resistance and type 2 diabetes mellitus are generally accompanied by low HDL cholesterol and high plasma triglycerides, which are major cardiovascular risk factors. This review describes abnormalities in HDL metabolism and reverse cholesterol transport, i.e. the transport of cholesterol from

  14. High density lipoproteins as indicators of endothelial dysfunction in children with diadetes type I

    Directory of Open Access Journals (Sweden)

    Lobanova S.M.

    2011-12-01

    Full Text Available The aim of the investigation was to study the level of blood high density lipoproteins (HDL in the groups of children with different course of diadetes type I in order to find out the dependence of course and complications of diabetes on that level. Materials and methods: Blood high density lipoprotein (HDL levels were investigated in children and adolescents with diadetes type I, depending on the duration of diadetes type I, age, stage of sexual development, the stage of diabetic nephropathy and levels of plasma endothelin-1 (E-1. Results: Decrease in HDL level with increasing duration of diadetes type I in prepubertate patients, higher indices of HDL cholesterol were determined in girls, especially with impaired puberty. HDL cholesterol was higher in diabetic nephropathy at the stage of proteinuria and high level of blood endothelin-1. Conclusion: The revealed changes were considered to cause deregulation of vascular endothelium as a manifestation of the initial stages of endothelial dysfunction

  15. Atorvastatin affects low density lipoprotein and non-high density lipoprotein cholesterol relations with apolipoprotein B in type 2 diabetes mellitus: modification by triglycerides and cholesteryl ester transfer protein

    NARCIS (Netherlands)

    P.J.W.H. Kappelle; L. Zwang; M.V. Huisman; J.D. Banga; W.J. Sluiter; G.M. Dallinga-Thie; R.P.F. Dullaart

    2009-01-01

    Objectives: Non-HDL-cholesterol (non-HDL-C) and apolipoprotein (apo) B are proposed as treatment targets. The extent to which statin therapy affects relationships of LDL-C and non-HDL-C with apoB was examined in type 2 diabetes. Methods: Analyses were performed in 217 hypertriglyceridaemic type 2 di

  16. Atorvastatin affects low density lipoprotein and non-high density lipoprotein cholesterol relations with apolipoprotein B in type 2 diabetes mellitus : modification by triglycerides and cholesteryl ester transfer protein

    NARCIS (Netherlands)

    Kappelle, Paul J. W. H.; Zwang, Louwerens; Huisman, Menno V.; Banga, Jan Dirk; Sluiter, Wim. J.; Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.

    2009-01-01

    Objectives: Non-HDL-cholesterol (non-HDL-C) and apolipoprotein (apo) B are proposed as treatment targets. The extent to which statin therapy affects relationships of LDL-C and non-HDL-C with apoB was examined in type 2 diabetes. Methods: Analyses were performed in 217 hypertriglyceridaemic type 2 di

  17. Triglycerides and ratio of triglycerides to high-density lipoprotein cholesterol are better than liver enzymes to identify insulin resistance in urban middle-aged and older non-obese Chinese without diabetes

    Institute of Scientific and Technical Information of China (English)

    Sun Yu; Li Wenjuan; Hou Xinguo; Wang Chuan; Li Chengqiao; Zhang Xiuping; Yang Weifang

    2014-01-01

    Background Insulin resistance (IR) plays an important pathophysiological role in the development of diabetes,dyslipidemia,hypertension,and cardiovascular disease.Moreover,IR can occur even in non-obese people without diabetes.However,direct detection of IR is complicated.In order to find a simple surrogate marker of IR early in nonobese people,we investigate the association of commonly-used biochemical markers (liver enzymes and lipid profiles) with IR in urban middle-aged and older non-obese Chinese without diabetes.Methods This cross-sectional study included 1 987 subjects (1 473 women).Fasting blood samples were collected for measurement of glucose,insulin,liver enzymes,lipid profiles and creatinine.Subjects whose homeostasis model of assessment-IR (HOMA-IR) index values exceeded the 75th percentile (2.67 for women and 2.48 for men) of the population were considered to have IR.The area under the receiver operating characteristic curve (ROC) was used to compare the power of potential markers in identifying IR.Results Triglycerides (TG) and ratio of TG to high-density lipoprotein cholesterol (TG/HDL-C) discriminated IR better than other indexes for both sexes; areas under the receiver operating characteristic (ROC) curves (AUC) values were 0.770 (95% confidence interval 0.733-0.807) and 0.772 (0.736-0.809),respectively,for women and 0.754 (0.664-0.844)and 0.756 (0.672-0.840),respectively,for men.To identify IR,the optimal cut-offs for TG and TG/HDL-C ratio were 1.315 mmol/L (sensitivity 74.3%,specificity 71.0%) and 0.873 (sensitivity 70.1%,specificity 73.4%),respectively,for women,and 1.275 mmol/L (sensitivity 66.7%,specificity 74.4%) and 0.812 (sensitivity 75.8%,specificity 69.2%),respectively,for men.Conclusion TG and TG/HDL-C ratio could be used to identify IR in urban middle-aged and older non-obese Chinese without diabetes.

  18. Role of lipids in spheroidal high density lipoproteins

    OpenAIRE

    Timo Vuorela; Andrea Catte; Niemelä, Perttu S.; Anette Hall; Marja T Hyvönen; Siewert-Jan Marrink; Mikko Karttunen; Ilpo Vattulainen

    2010-01-01

    We study the structure and dynamics of spherical high density lipoprotein (HDL) particles through coarse-grained multi-microsecond molecular dynamics simulations. We simulate both a lipid droplet without the apolipoprotein A-I (apoA-I) and the full HDL particle including two apoA-I molecules surrounding the lipid compartment. The present models are the first ones among computational studies where the size and lipid composition of HDL are realistic, corresponding to human serum HDL. We focus o...

  19. Role of Lipids in Spheroidal High Density Lipoproteins

    OpenAIRE

    Vuorela, Timo; Catte, Andrea; Niemela, Perttu S.; Hall, Anette; Hyvonen, Marja T.; Marrink, Siewert-Jan; Karttunen, Mikko; Vattulainen, Ilpo; Niemelä, Perttu S.; Marja T Hyvönen

    2010-01-01

    We study the structure and dynamics of spherical high density lipoprotein (HDL) particles through coarse-grained multi-microsecond molecular dynamics simulations. We simulate both a lipid droplet without the apolipoprotein A-I (apoA-I) and the full HDL particle including two apoA-I molecules surrounding the lipid compartment. The present models are the first ones among computational studies where the size and lipid composition of HDL are realistic, corresponding to human serum HDL. We focus o...

  20. High-density lipoproteincholesterol, reverse cholesterol transport, and cardiovascular risk: a tale of genetics?

    Directory of Open Access Journals (Sweden)

    Giovanni Cimmino

    2013-10-01

    Full Text Available Cholesterol deposition plays a central role in atherogenesis. The accumulation of lipid material is the result of an imbalance between the influx and efflux of cholesterol within the arterial wall. High levels of plasma low-density lipoprotein-cholesterol are considered the major mechanism responsible for the influx and accumulation of cholesterol in the arterial wall, while high-density lipoprotein (HDL- cholesterol seems responsible for its efflux. The mechanism by which cholesterol is removed from extra-hepatic organs and delivered to the liver for its catabolism and excretion is called reverse cholesterol transport (RCT. Epidemiological evidence has associated high levels of HDL-cholesterol/ApoA-I with protection against atherosclerotic disease, but the ultimate mechanism(s responsible for the beneficial effect is not well established. HDLs are synthesized by the liver and small intestine and released to the circulation as a lipid-poor HDL (nascent HDL, mostly formed by ApoA-I and phospholipids. Through their metabolic maturation, HDLs interact with the ABCA1 receptor in the macrophage surface increasing their lipid content by taking phospholipids and cholesterol from macrophages becoming mature HDL. The cholesterol of the HDLs is transported to the liver, via the scavenger receptor class B, type I, for further metabolization and excretion to the intestines in the form of bile acids and cholesterol, completing the process of RCT. It is clear that an inherited mutation or acquired abnormality in any of the key players in RCT mat affect the atherosclerotic process.

  1. Ciprofibrate therapy in patients with hypertriglyceridemia and low high density lipoprotein (HDL-cholesterol: greater reduction of non-HDL cholesterol in subjects with excess body weight (The CIPROAMLAT study

    Directory of Open Access Journals (Sweden)

    Medel Octavio

    2004-07-01

    Full Text Available Abstract Background Hypertriglyceridemia in combination with low HDL cholesterol levels is a risk factor for cardiovascular disease. Our objective was to evaluate the efficacy of ciprofibrate for the treatment of this form of dyslipidemia and to identify factors associated with better treatment response. Methods Multicenter, international, open-label study. Four hundred and thirty seven patients were included. The plasma lipid levels at inclusion were fasting triglyceride concentrations between 1.6–3.9 mM/l and HDL cholesterol ≤ 1.05 mM/l for women and ≤ 0.9 mM/l for men. The LDL cholesterol was below 4.2 mM/l. All patients received ciprofibrate 100 mg/d. Efficacy and safety parameters were assessed at baseline and at the end of the treatment. The primary efficacy parameter of the study was percentage change in triglycerides from baseline. Results After 4 months, plasma triglyceride concentrations were decreased by 44% (p 2 compared to the rest of the population (8.2 vs 19.7%, p Conclusions Ciprofibrate is efficacious for the correction of hypertriglyceridemia / low HDL cholesterol. A greater decrease in non-HDL cholesterol was found among cases with excess body weight. The mechanism of action of ciprofibrate may be influenced by the pathophysiology of the disorder being treated.

  2. Lipoprotein distribution and serum concentrations of 7α-hydroxy-4-cholesten-3-one and bile acids: effects of monogenic disturbances in high-density lipoprotein metabolism

    DEFF Research Database (Denmark)

    Steiner, Carine; Holleboom, Adriaan G; Karuna, Ratna;

    2012-01-01

    BA (bile acid) formation is considered an important final step in RCT (reverse cholesterol transport). HDL (high-density lipoprotein) has been reported to transport BAs. We therefore investigated the effects of monogenic disturbances in human HDL metabolism on serum concentrations and lipoprotein...... distributions of the major 15 BA species and their precursor C4 (7a-hydroxy-4-cholesten-3-one). In normolipidaemic plasma, approximately 84%, 11% and 5% of BAs were recovered in the LPDS (lipoprotein-depleted serum), HDL and the combined LDL (low-density lipoprotein)/VLDL (very-low-density lipoproteins...

  3. Health benefits of high-density lipoproteins in preventing cardiovascular diseases.

    Science.gov (United States)

    Berrougui, Hicham; Momo, Claudia N; Khalil, Abdelouahed

    2012-01-01

    Plasma levels of high-density lipoprotein (HDL) are strongly and inversely correlated with atherosclerotic cardiovascular diseases. However, it is becoming clear that a functional HDL is a more desirable target than simply increasing HDL-cholesterol levels. The best known antiatherogenic function of HDL particles relates to their ability to promote reverse cholesterol transport from peripheral cells. However, HDL also possesses antioxidant, anti-inflammatory, and antithrombotic effects. This review focuses on the state of knowledge regarding assays of HDL heterogeneity and function and their relationship to cardiovascular diseases.

  4. Combined analysis of six lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease

    DEFF Research Database (Denmark)

    Wittrup, Hans H; Andersen, Rolf V; Tybjaerg-Hansen, Anne;

    2006-01-01

    Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD).......Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD)....

  5. Saturated fatty acid (SFA) status and SFA intake exhibit different relations with serum total cholesterol and lipoprotein cholesterol : a mechanistic explanation centered around lifestyle-induced low-grade inflammation

    NARCIS (Netherlands)

    Ruiz Nunez, Begona; Kuipers, Remko S.; Luxwolda, Martine F.; De Graaf, Deti J.; Breeuwsma, Benjamin B.; Dijck-Brouwer, Janneke; Muskiet, Frits A. J.

    2014-01-01

    We investigated the relations between fatty acid status and serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol and total cholesterol/HDL cholesterol ratio in five Tanzanian ethnic groups and one Dutch group. Total cholesterol/HDL cholesterol rati

  6. 高密度脂蛋白胆固醇水平相关的遗传学研究最新进展%New Research Advances in Genetics Associated With High-density Lipoprotein Cholesterol

    Institute of Scientific and Technical Information of China (English)

    刘晓艳; 路倩; 陈五军; 唐朝克

    2012-01-01

    Since the inverse relationship between plasma high-density lipoprotein cholesterol (HDL-C) levels and the risk of coronary artery disease (CAD) have been well-established, it has always been a hot spot on how to regulate HDL-C levels for the treatment of CAD-related disease. High and low HDL levels are closely related to its own production and metabolism, which are primarily determined by corresponding regulatory genes. It has been suggested that plasma HDL-C levels have a strong inherited basis with heritability estimates of 40% ~60%, showing the great significance in discussing variants causes associated with HDL-C levels. Candidate gene, genome-wide linkage, and most recently genome-wide association (GWA) studies have identified several genetic variations for plasma HDL-C levels. However, the functional role of some variants remains unknown, and they do not always have relation to the risk of CAD. This review will be summarized on the structure of HDL, its metabolism and production, as well as the genetic causes of high and low HDL-C. Notably, recent genetic findings from candidate gene and the GWA studies will be the focus of this text aiming at elucidating the important genetic factors affecting HDL-C concentrations. Comprehensive study on genetics conferring to high and low HDL-C levels using integrative approaches is essential to reveal their relationships with CAD and explore novel pathways on the treatment of CAD.%研究已经证实血浆高密度脂蛋白胆固醇(HDL-C)水平与冠状动脉疾病(CAD)的发生呈负相关,因此,HDL-C水平的调控成为CAD治疗的研究热点.HDL水平高低与其自身的产生和代谢密切相关,而HDL的产生和代谢主要由相应的调控基因决定,有研究表明,血浆HDL-C水平具有显著的遗传基础,遗传率达到40%~60%,提示研究影响HDL-C水平的遗传性因素具有重要意义.候选基因、全基因组连锁以及近来的全基因组关联(GWA)研究已鉴定出影响血浆HDL-C

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

    Science.gov (United States)

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

    2004-05-01

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

  8. Progress of cardioprotective effects of high density lipoprotein: function and mechanism

    Directory of Open Access Journals (Sweden)

    Hai-ge SUN

    2015-01-01

    Full Text Available The high density lipoprotein (HDL in human plasma is a heterogeneous lipoprotein consisting of roughly equal contents of lipid and protein in roughly equal content, and it consists of several subtypes. HDL possesses several well-documented functions, including anti-atherosclerosis by promoting reverse cholesterol transport, inhibiting the oxidative modification of low density lipoproteins (LDLs, inhibiting vascular inflammation, preventing thrombosis and apoptosis, and promoting endothelial repair. Recently, more cardiovascular protective functions of HDL have been found, mainly including the ability of suppressing immune inflammatory reaction, inhibiting the proliferation of hematopoietic stem cells, and regulating the plasma glucose level. It is of great importance to understand how different HDL subtypes contribute to the potentially cardioprotective functions. DOI: 10.11855/j.issn.0577-7402.2014.11.13

  9. 非高密度脂蛋白胆固醇是评价血脂异常患者心血管风险的指标%Non-high density lipoprotein-cholesterol is an indicator to assess cardiovascular risk for subjects with dyslipidemia

    Institute of Scientific and Technical Information of China (English)

    张鹏睿; 徐援; 王广; 杨金奎

    2014-01-01

    目的 证实无论患者是否有血糖升高,非高密度脂蛋白胆固醇(non-high density lipoprotein-cholesterol,non-HDL-C)都是不弱于低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)的评估血脂异常患者患者心血管病风险和降脂治疗疗效的有效临床指标.方法 选取2007年首都医科大学附属北京同仁医院内分泌科大规模临床调查患者6 341例,检测总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,LDL-C)、三酰甘油(triglyceride,TG),并且计算non-HDL-C(non-HDL -C等于TC-HDL-C).根据空腹血糖高低分为血糖正常组和血糖升高组,比较两组中血脂异常患者的各项血脂指标;以non-HDL-C为纵轴,分别以LDL-C和TG为横轴作散点图.结果 血糖升高组的TC、LDL-C、HDL-C、TG、non-HDL-C较血糖正常组均明显升高.作non-HDL-C与LDL-C和TG相关性的散点图并作趋势拟合线后,发现non-HDL-C与LDL-C、TG均呈线性正相关.结论 non-HDL-C是一项评估血脂异常患者心血管病风险和降脂治疗疗效的有效临床指标.

  10. High density lipoprotein – a hero, a mirage or a witness?

    Directory of Open Access Journals (Sweden)

    Dmitri eSviridov

    2014-11-01

    Full Text Available Negative relationship between plasma High Density Lipoprotein (HDL levels and risk of cardiovascular disease is a firmly established medical fact, but attempts to reproduce protective properties of HDL by pharmacologically elevating HDL levels were mostly unsuccessful. This conundrum presents a fundamental question: were the approaches used to raise HDL flawed or the protective effects of HDL are an epiphenomenon. Recent attempts to elevate plasma HDL were universally based on reducing HDL catabolism by blocking reverse cholesterol transport. Here we argue that this mode of HDL elevation may be mechanistically different to natural mechanisms and thus be counterproductive. We further argue that independently of whether HDL is a driving force or a surrogate measure of the rate of reverse cholesterol transport, approaches aimed at increasing HDL supply, rather than reducing its catabolism, would be most beneficial for speeding up reverse cholesterol transport and improving protection against cardiovascular disease.

  11. Biominetic High Density Lipoproteins for the Delivery of Therapeutic Oligonucleotides

    Science.gov (United States)

    Tripathy, Sushant

    Advances in nanotechnology have brought about novel inorganic and hybrid nanoparticles with unique physico-chemical properties that make them suitable for a broad range of applications---from nano-circuitry to drug delivery. A significant part of those advancements have led to ground-breaking discoveries that have changed the approaches to formulation of therapeutics against diseases, such as cancer. Now-a-days the focus does not lie solely on finding a candidate small-molecule therapeutic with minimal adverse effects, but researchers are looking up to nanoparticles to improve biodistribution and biocompatibility profile of clinically proven therapeutics. The plethora of conjugation chemistries offered by currently extant inorganic nanoparticles have, in recent years, led to great leaps in the field of biomimicry---a modality that promises high biocompatibility. Further, in the pursuit of highly specific therapeutic molecules, researchers have turned to silencing oligonucleotides and some have already brought together the strengths of nanoparticles and silencing oligonucleotides in search of an efficacious therapy for cancer with minimal adverse effects. This dissertation work focuses on such a biomimetic platform---a gold nanoparticle based high density lipoprotein biomimetic (HDL NP), for the delivery of therapeutic oligonucleotides. The first chapter of this body of work introduces the molecular target of the silencing oligonucleotides---VEGFR2, and its role in the progression of solid tumor cancers. The background information also covers important aspects of natural high density lipoproteins (HDL), especially their innate capacity to bind and deliver exogenous and endogenous silencing oligonucleotides to tissues that express their high affinity receptor SRB1. We subsequently describe the synthesis of the biomimetic HDL NP and its oligonucleotide conjugates, and establish their biocompatibility. Further on, experimental data demonstrate the efficacy of silencing

  12. Hepatic lipase, genetically elevated high-density lipoprotein, and risk of ischemic cardiovascular disease

    DEFF Research Database (Denmark)

    Johannsen, Trine Holm; Kamstrup, Pia R; Andersen, Rolf V;

    2008-01-01

    CONTEXT: Hepatic lipase influences metabolism of high-density lipoprotein (HDL), a risk factor for ischemic cardiovascular disease (ICD: ischemic heart disease and ischemic cerebrovascular disease). OBJECTIVE: We tested the hypothesis that genetic variation in the hepatic lipase genetic variants V...... of whom had incident ICD during 28 yr of follow-up. For the case-control studies, 2110 ischemic heart disease patients vs. 4899 controls and 769 ischemic cerebrovascular disease patients vs. 2836 controls, respectively, were genotyped. Follow-up was 100% complete. RESULTS: HDL cholesterol was higher by 0......73M, N193S, S267F, L334F, T383M, and -480c>t influence levels of lipids, lipoproteins, and apolipoproteins and risk of ICD. DESIGN: For the cross-sectional study, we genotyped 9003 individuals from the Copenhagen City Heart Study; hereof were 8971 individuals included in the prospective study, 1747...

  13. Folded functional lipid-poor apolipoprotein A-I obtained by heating of high-density lipoproteins: relevance to high-density lipoprotein biogenesis.

    Science.gov (United States)

    Jayaraman, Shobini; Cavigiolio, Giorgio; Gursky, Olga

    2012-03-15

    HDL (high-density lipoproteins) remove cell cholesterol and protect from atherosclerosis. The major HDL protein is apoA-I (apolipoprotein A-I). Most plasma apoA-I circulates in lipoproteins, yet ~5% forms monomeric lipid-poor/free species. This metabolically active species is a primary cholesterol acceptor and is central to HDL biogenesis. Structural properties of lipid-poor apoA-I are unclear due to difficulties in isolating this transient species. We used thermal denaturation of human HDL to produce lipid-poor apoA-I. Analysis of the isolated lipid-poor fraction showed a protein/lipid weight ratio of 3:1, with apoA-I, PC (phosphatidylcholine) and CE (cholesterol ester) at approximate molar ratios of 1:8:1. Compared with lipid-free apoA-I, lipid-poor apoA-I showed slightly altered secondary structure and aromatic packing, reduced thermodynamic stability, lower self-associating propensity, increased adsorption to phospholipid surface and comparable ability to remodel phospholipids and form reconstituted HDL. Lipid-poor apoA-I can be formed by heating of either plasma or reconstituted HDL. We propose the first structural model of lipid-poor apoA-I which corroborates its distinct biophysical properties and postulates the lipid-induced ordering of the labile C-terminal region. In summary, HDL heating produces folded functional monomolecular lipid-poor apoA-I that is distinct from lipid-free apoA-I. Increased adsorption to phospholipid surface and reduced C-terminal disorder may help direct lipid-poor apoA-I towards HDL biogenesis. PMID:22150513

  14. Single step reconstitution of multifunctional high-density lipoprotein-derived nanomaterials using microfluidics.

    Science.gov (United States)

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

    2013-11-26

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

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

    Directory of Open Access Journals (Sweden)

    Shinji Yokoyama

    2015-04-01

    Full Text Available 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.

  16. The value and distribution of high-density lipoprotein subclass in patients with acute coronary syndrome.

    Directory of Open Access Journals (Sweden)

    Li Tian

    Full Text Available BACKGROUND: High-density lipoprotein (HDL enhances cholesterol efflux from the arterial wall and exhibits potent anti-inflammatory and anti-atherosclerosis (AS properties. Whether raised HDL levels will clinically benefit patients with acute coronary syndrome (ACS and the value at which these effects will be apparent, however, is debatable. This study examined the HDL subclass distribution profile in patients with ACS. METHODS: Plasma HDL subclasses were measured in 158 patients with established ACS and quantified by two-dimensional gel electrophoresis and immunoblotting. ACS diagnosis was based on symptoms of cardiac ischemia, electrocardiogram (ECG abnormalities, speciality cardiac enzyme change along with presence of coronary heart disease (CHD on coronary angiography. RESULTS: The small-sized preβ1-HDL, HDL3b, and HDL3a levels were significantly higher, and the large-sized HDL2a and HDL2b levels were significantly lower in patients with ACS than in those with stable angina pectoris (SAP and in normal control subjects. Meanwhile, with an elevation in the low-density lipoprotein cholesterol (LDL-C, fasting plasma glucose (FPG, body mass index (BMI, and blood pressure (BP, and the reduction in the high density lipoprotein cholesterol (HDL-C levels, the HDL2b contents significantly decreased and the preβ1-HDL contents significantly increased in patients with ACS. The correlation analysis revealed that the apolipoprotein (apoA-I levels were positively and significantly with all HDL subclasses contents; plasma total cholesterol (TC and fasting plasma glucose (FPG levels were inversely associated with HDL2a, and HDL2b. Moreover, the FPG levels were positively related to HDL3c, HDL3b, and HDL3a in ACS patients. CONCLUSION: The HDL subclass distribution profile remodeling was noted in the patients with ACS. Plasma lipoprotein and FPG levels, BP, and BMI play an important role in the HDL subclass metabolism disorder for patients with ACS. The HDL

  17. Reconstituted high-density lipoprotein modulates activation of human leukocytes.

    Directory of Open Access Journals (Sweden)

    Rolf Spirig

    Full Text Available An anti-inflammatory effect of reconstituted High Density Lipoprotein (rHDL has been demonstrated in atherosclerosis and in sepsis models. An increase of adhesion molecules as well as tissue factor expression on endothelial cells in response to inflammatory or danger signals are attenuated by the treatment with rHDL. Here we show the inhibitory effect of rHDL on the activation of human leukocytes in a whole blood assay as well as on monocyte-derived human dendritic cells (DC. Multiplex analysis of human whole blood showed that phytohaemagglutinin (PHA-induced secretion of the cytokines IL-1β, IL-1RA, IL-2R, IL-6, IL-7, IL-12(p40, IL-15 and IFN-α was inhibited. Furthermore, an inhibitory effect on the production of the chemokines CCL-2, CCL-4, CCL-5, CXCL-9 and CXCL-10 was observed. Activation of granulocytes and CD14+ monocytes by PHA is inhibited dose-dependently by rHDL shown as decreased up-regulation of ICAM-1 surface expression. In addition, we found a strong inhibitory effect of rHDL on toll-like receptor 2 (TLR2- and TLR4-mediated maturation of DC. Treatment of DC with rHDL prevented the up-regulation of cell surface molecules CD80, CD83 and CD86 and it inhibited the TLR-driven activation of inflammatory transcription factor NF-κB. These findings suggest that rHDL prevents activation of crucial cellular players of cellular immunity and could therefore be a useful reagent to impede inflammation as well as the link between innate and adaptive immunity.

  18. High-density lipoprotein, mitochondrial dysfunction and cell survival mechanisms.

    Science.gov (United States)

    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. Measurement of cholesterol and other lipoprotein constituents in the clinical laboratory.

    Science.gov (United States)

    Warnick, G R

    2000-04-01

    Measurements of lipids and lipoproteins in the clinical laboratory have become increasingly important because of their predictive association with cardiovascular diseases, especially coronary artery disease. The US National Institutes of Health-sponsored National Cholesterol Education Program and counterparts in other countries have developed national consensus guidelines for diagnosis and treatment of coronary artery disease which provide risk cut-points and define use of the lipid/lipoprotein analytes in case finding and therapy. Total and low density lipoprotein cholesterol and triglycerides are measured as positive risk factors and high density lipoprotein cholesterol as an inverse risk factor for coronary artery disease. A National Cholesterol Education Program-sponsored expert laboratory panel has developed guidelines for measurements with requisite analytical performance targets for total error and corresponding precision and bias. The US Centers for Disease Control and Prevention have established reference methods for total and high density lipoprotein cholesterol and for triglycerides, with a method for low density lipoprotein cholesterol in development. Standardization programs for research laboratories and a Cholesterol Reference Method Laboratory Network for diagnostic manufacturers and clinical laboratories provide reliable access and documentation of traceability to accepted reference methods. Methods for the lipid/lipoprotein analytes have improved dramatically in recent years and, coupled with improved chemistry analyzer systems and more attention to standardization by manufacturers, offer considerable improvement in analytical performance. Fully automated homogeneous assays for high density lipoprotein cholesterol and newer similar assays for low-density lipoprotein cholesterol have potential for better precision as well as more convenient and cost-effective measurements. Attention to pre-analytical sources of variation is also important in making

  20. Effect of apolipoprotein M on high density lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knock-out mice

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Jauhiainen, Matti; Moser, Markus;

    2008-01-01

    To investigate the role of apoM in high density lipoprotein (HDL) metabolism and atherogenesis, we generated human apoM transgenic (apoM-Tg) and apoM-deficient (apoM(-/-)) mice. Plasma apoM was predominantly associated with 10-12-nm alpha-migrating HDL particles. Human apoM overexpression (11-fold......) increased plasma cholesterol concentration by 13-22%, whereas apoM deficiency decreased it by 17-21%. The size and charge of apoA-I-containing HDL in plasma were not changed in apoM-Tg or apoM(-/-) mice. However, in plasma incubated at 37 degrees C, lecithin:cholesterol acyltransferase-dependent conversion...... of alpha- to pre-alpha-migrating HDL was delayed in apoM-Tg mice. Moreover, lecithin: cholesterol acyltransferase-independent generation of pre-beta-migrating apoA-I-containing particles in plasma was increased in apoM-Tg mice (4.2 +/- 1.1%, p = 0.06) and decreased in apoM(-/-) mice (0.5 +/- 0.3%, p = 0...

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

    DEFF Research Database (Denmark)

    Ollila, O. H. S.; Lamberg, A.; Lehtivaara, M.;

    2012-01-01

    Lipid droplets play a central role in energy storage and metabolism on a cellular scale. Their core is comprised of hydrophobic lipids covered by a surface region consisting of amphiphilic lipids and proteins. For example, high and low density lipoproteins (HDL and LDL, respectively......) are essentially lipid droplets surrounded by specific proteins, their main function being to transport cholesterol. Interfacial tension and surface pressure of these particles are of great interest because they are related to the shape and the stability of the droplets and to protein adsorption at the interface...

  2. Liver disease alters high-density lipoprotein composition, metabolism and function.

    Science.gov (United States)

    Trieb, Markus; Horvath, Angela; Birner-Gruenberger, Ruth; Spindelboeck, Walter; Stadlbauer, Vanessa; Taschler, Ulrike; Curcic, Sanja; Stauber, Rudolf E; Holzer, Michael; Pasterk, Lisa; Heinemann, Akos; Marsche, Gunther

    2016-07-01

    High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk.

  3. Liver disease alters high-density lipoprotein composition, metabolism and function.

    Science.gov (United States)

    Trieb, Markus; Horvath, Angela; Birner-Gruenberger, Ruth; Spindelboeck, Walter; Stadlbauer, Vanessa; Taschler, Ulrike; Curcic, Sanja; Stauber, Rudolf E; Holzer, Michael; Pasterk, Lisa; Heinemann, Akos; Marsche, Gunther

    2016-07-01

    High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk. PMID:27106140

  4. Lipoproteins, cholesterol homeostasis and cardiac health

    Directory of Open Access Journals (Sweden)

    Tyler F. Daniels, Karen M. Killinger, Jennifer J. Michal, Raymond W. Wright Jr., Zhihua Jiang

    2009-01-01

    Full Text Available Cholesterol is an essential substance involved in many functions, such as maintaining cell membranes, manufacturing vitamin D on surface of the skin, producing hormones, and possibly helping cell connections in the brain. When cholesterol levels rise in the blood, they can, however, have dangerous consequences. In particular, cholesterol has generated considerable notoriety for its causative role in atherosclerosis, the leading cause of death in developed countries around the world. Homeostasis of cholesterol is centered on the metabolism of lipoproteins, which mediate transport of the lipid to and from tissues. As a synopsis of the major events and proteins that manage lipoprotein homeostasis, this review contributes to the substantial attention that has recently been directed to this area. Despite intense scrutiny, the majority of phenotypic variation in total cholesterol and related traits eludes explanation by current genetic knowledge. This is somewhat disappointing considering heritability estimates have established these traits as highly genetic. Thus, the continued search for candidate genes, mutations, and mechanisms is vital to our understanding of heart disease at the molecular level. Furthermore, as marker development continues to predict risk of vascular illness, this knowledge has the potential to revolutionize treatment of this leading human disease.

  5. Synthesis and Characterization of Biomimetic High Density Lipoprotein Nanoparticles To Treat Lymphoma

    Science.gov (United States)

    Damiano, Marina Giacoma

    High density lipoproteins (HDLs), natural nanoparticles that function as vehicles for cholesterol transport, have enhanced uptake by several human cancers. This uptake is mediated, in part, by the high affinity HDL receptor, scavenger receptor B-1 (SR-B1). More specifically, studies show that the rate of cellular proliferation of lymphoma, a cancer of the lymphocytes, is directly proportional to the amount of HDL-cholesterol available. Thus, targeting of HDL-cholesterol uptake by these cells could be an effective therapeutic approach that may have lower toxicity to healthy cells compared to conventional therapies. Biomimetic HDL can be synthesized using a gold nanoparticle template (HDL-AuNPs), which provides control over size, shape, and surface chemistry. Like their natural counterparts, HDL-AuNPs sequester cholesterol. However, since the gold nanoparticle replaces the cholesterol core of natural HDL, HDL-AuNPs inherently deliver less cholesterol. We show that HDL-AuNPs are able to induce dose dependent apoptosis in B cell lymphoma cell lines and reduce tumor volume following systemic administration to mice bearing B cell lymphoma tumors. Furthermore, HDL-AuNPs are neither toxic to healthy human lymphocytes (SR-B1-), nor to hepatocytes and macrophages (SR-B1+), which are cells naturally encountered by HDLs. Manipulation of cholesterol flux and targeting of SR-B1 are responsible for the efficacy of HDL-AuNPs against B cell lymphoma. HDL-AuNPs could be used to treat B cell lymphomas and other diseases that involve pathologic accumulation of cholesterol. Titanium dioxide nanoparticle (TiO2 NP) core HDLs (HDL-TiO 2 NPs) have been synthesized for high resolution cellular localization studies and for future use as a therapeutic and imaging agent. In initial studies, HDL-TiO(2 NPs display maximum uptake in B cell lymphoma cell lines. X-ray fluorescence microscopy studies show interaction between HDL-TiO2 NPs and cells 10 minutes after treatment and internalization after

  6. Flow-cytometric determination of high-density-lipoprotein binding sites on human leukocytes

    International Nuclear Information System (INIS)

    In this method, leukocytes were isolated from 6 mL of EDTA-blood by density-gradient centrifugation and subsequently incubated with rhodamine isothiocyanate (RITC)-conjugated high-density lipoproteins (HDL). The receptor-bound conjugate particles were determined by fluorescent flow cytometry and compared with 125I-labeled HDL binding data for the same cells. Human granulocytes express the highest number of HDL binding sites (9.4 x 10(4)/cell), followed by monocytes (7.3 x 10(4)/cell) and lymphocytes (4.0 x 10(4)/cell). Compared with conventional analysis of binding of 125I-labeled HDL in tissue-culture dishes, the present determination revealed significantly lower values for nonspecific binding. In competition studies, the conjugate competes for the same binding sites as 125I-labeled HDL. With the use of tetranitromethane-treated HDL3, which fails to compete for the HDL receptor sites while nonspecific binding is not affected, we could clearly distinguish between 37 degrees C surface binding and specific 37 degrees C uptake of RITC-HDL3, confirming that the HDL receptor leads bound HDL particles into an intracellular pathway rather than acting as a docking type of receptor. Patients with familial dysbetalipoproteinemia showed a significantly higher number of HDL binding sites in the granulocyte population but normal in lymphocytes and monocytes, indicating increased uptake of cholesterol-containing lipoproteins. In patients with familial hypercholesterolemia, HDL binding was increased in all three cell types, indicating increased cholesterol uptake and increased cholesterol synthesis. The present method allows rapid determination of HDL binding sites in leukocytes from patients with various forms of hyper- and dyslipoproteinemias

  7. Alimentary lipemia: plasma high-density lipoproteins and apolipoproteins CII and CIII in healthy subjects.

    Science.gov (United States)

    Kashyap, M L; Barnhart, R L; Srivastava, L S; Perisutti, G; Allen, C; Hogg, E; Glueck, C J; Jackson, R L

    1983-02-01

    Three healthy male and three female inpatient volunteers consumed isocaloric diets for 4 wk. At weekly intervals, a fatty meal (100 g fat) was consumed by each fasting subject and blood drawn at 2 h intervals for 12 h. Of the four oral fat loads, two contained saturated fat (polyunsaturated/saturated fat ratio = 0.34) and two contained unsaturated fat (polyunsaturated/saturated fat = 2.21). The magnitude of alimentary lipemia, expressed as area under the plasma triglyceride curve, was 3- to 4-fold higher in males than females. Alimentary lipemia was inversely related to the subjects' fasting plasma high-density lipoprotein (HDL)-cholesterol, HDL apolipoprotein (apo) CIII and directly related to plasma triglycerides. The P/S ratios of the daily diet or the fat meal did not significantly influence the plasma triglyceride curve. After fat intake, mean (+/- SEM) plasma total apoCII and CIII fell to 54 +/- 20% and 73 +/- 5% of base-line, respectively, at 12 h in five of six subjects. After oral fat, an initial fall and a subsequent rise in apoCII and CIII in HDL was associated with reciprocal changes in apoC concentrations in very low-density lipoproteins. We speculate from the data that 1) plasma HDL and their apoC concentrations are important determinants of chylomicron clearance and 2) transfer of apoCs from HDL to triglyceride-rich lipoproteins in the early phase of fat absorption does not result in the total recycling of apoCs from these lipoproteins to HDL during the late phase of alimentary lipemia.

  8. Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment : individual patient meta-analysis of 13,677 subjects

    NARCIS (Netherlands)

    Boekholdt, S M; Sacks, F M; Jukema, J W; Shepherd, J; Freeman, D J; McMahon, A D; Cambien, F; Nicaud, V; de Grooth, G J; Talmud, P J; Humphries, S E; Miller, G J; Eiriksdottir, G; Gudnason, V; Kauma, H; Kakko, S; Savolainen, M J; Arca, M; Montali, A; Liu, S; Lanz, H J; Zwinderman, A H; Kuivenhoven, J A; Kastelein, J J P

    2005-01-01

    BACKGROUND: Several studies have reported that the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism is associated with HDL cholesterol (HDL-C) levels and the risk of coronary artery disease (CAD), but the results are inconsistent. In addition, an interaction has been implicated betw

  9. Modulation of low-density lipoprotein-induced inhibition of intercellular communication by antioxidants and high-density lipoproteins

    NARCIS (Netherlands)

    Zwijsen, R M; de Haan, L H; Kuivenhoven, J A; Nusselder, I C

    1991-01-01

    In order to study the capacity of antioxidants and high-density lipoproteins (HDL) to modulate the effects of low-density lipoprotein (LDL) on intercellular communication, arterial smooth muscle cells and a dye transfer method were used. LDL, in contrast to HDL, inhibited the communication between a

  10. 低密度脂蛋白胆固醇与高密度脂蛋白胆固醇的比值与脑梗死的关系研究%The relationship of low density lipoprotein-cholesterol/high density lipopro-tein-cholesterol ratio to cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    刘辉; 张之福; 陈炜; 高亚丽; 杨伏肖; 宋西方

    2014-01-01

    目的:探讨低密度脂蛋白胆固醇(LDL-C)与高密度脂蛋白胆固醇(HDL-C)的比值(LDL-C/HDL-C)与脑梗死发生的关系。方法将本院2013年2月~2014年3月接收的136例确诊为脑梗死的患者作为试验组,对照组为110例同期检查的健康体检者,测定并比较两组LDL-C、HDL-C、总胆固醇(TC)、三酰甘油(TG)的含量,计算LDL-C/HDL-C。结果试验组的LDL-C、TC及LDL-C/HDL-C显著高于对照组,HDL-C明显低于对照组,差异有统计学意义(P0.05)。脑梗死与LDL-C、TC及LDL-C/HDL-C呈正相关(r=0.148、0.106、0.162,P0.05)。结论 LDL-C/HDL-C明显增高与脑梗死发生具有重要的相关性,其可以作为一项生化指标对脑梗死的发生进行预测判断,相对于单一的LDL-C或HDL-C指标具有更高的敏感性和独立性,该比值具有较高的临床价值。%Objective To observe the relationship of low density lipoprotein-cholesterol (LDL-C)/high density lipopro-tein-cholesterol (HDL-C) ratio (LDL-C/HDL-C) to acute cerebral infarction. Methods 136 patients diagnosed as cere-bral infarction in our hospital from February 2013 to March 2014 were selected as test group,and 110 healthy people examined at the same time were selected as the control group,LDL-C,HDL-C,TC,TG and LDL-C/HDL-C were detected and compared. Results The level of LDL-C,TC and LDL-C/HDL-C in test group were higher than those of control group,while the level of HDL-C was lower than that of control group,the differences were significant (P0.05).Cerebral infarction was positively correlated to LDL-C, TC and LDL-C/HDL-C (r=0.148,0.106,0.162,P0.05). Conclusion The increasing of LDL-C/HDL is closely related to cerebral infarction, can be used as a biochemical indicator to predict the occurrence of cerebral infarction,compared with LDL-C or HDL-C,the ratio of LDL-C/HDL-C is more sensitive and independent,so it’s of great clinical value.

  11. Dysfunctional High-Density Lipoprotein: An Innovative Target for Proteomics and Lipidomics

    Directory of Open Access Journals (Sweden)

    Juan Salazar

    2015-01-01

    Full Text Available High-Density Lipoprotein-Cholesterol (HDL-C is regarded as an important protective factor against cardiovascular disease, with abundant evidence of an inverse relationship between its serum levels and risk of cardiovascular disease, as well as various antiatherogenic, antioxidant, and anti-inflammatory properties. Nevertheless, observations of hereditary syndromes featuring scant HDL-C concentration in absence of premature atherosclerotic disease suggest HDL-C levels may not be the best predictor of cardiovascular disease. Indeed, the beneficial effects of HDL may not depend solely on their concentration, but also on their quality. Distinct subfractions of this lipoprotein appear to be constituted by specific protein-lipid conglomerates necessary for different physiologic and pathophysiologic functions. However, in a chronic inflammatory microenvironment, diverse components of the HDL proteome and lipid core suffer alterations, which propel a shift towards a dysfunctional state, where HDL-C becomes proatherogenic, prooxidant, and proinflammatory. This heterogeneity highlights the need for further specialized molecular studies in this aspect, in order to achieve a better understanding of this dysfunctional state; with an emphasis on the potential role for proteomics and lipidomics as valuable methods in the search of novel therapeutic approaches for cardiovascular disease.

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

    Science.gov (United States)

    Deitrick, Russell; Gibson, Emily; Razzaghi, Hamid

    2009-10-01

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

  13. Bile acids reduce endocytosis of high-density lipoprotein (HDL in HepG2 cells.

    Directory of Open Access Journals (Sweden)

    Clemens Röhrl

    Full Text Available High-density lipoprotein (HDL transports lipids to hepatic cells and the majority of HDL-associated cholesterol is destined for biliary excretion. Cholesterol is excreted into the bile directly or after conversion to bile acids, which are also present in the plasma as they are effectively reabsorbed through the enterohepatic cycle. Here, we provide evidence that bile acids affect HDL endocytosis. Using fluorescent and radiolabeled HDL, we show that HDL endocytosis was reduced in the presence of high concentrations of taurocholate, a natural non-cell-permeable bile acid, in human hepatic HepG2 and HuH7 cells. In contrast, selective cholesteryl-ester (CE uptake was increased. Taurocholate exerted these effects extracellularly and independently of HDL modification, cell membrane perturbation or blocking of endocytic trafficking. Instead, this reduction of endocytosis and increase in selective uptake was dependent on SR-BI. In addition, cell-permeable bile acids reduced HDL endocytosis by farnesoid X receptor (FXR activation: chenodeoxycholate and the non-steroidal FXR agonist GW4064 reduced HDL endocytosis, whereas selective CE uptake was unaltered. Reduced HDL endocytosis by FXR activation was independent of SR-BI and was likely mediated by impaired expression of the scavenger receptor cluster of differentiation 36 (CD36. Taken together we have shown that bile acids reduce HDL endocytosis by transcriptional and non-transcriptional mechanisms. Further, we suggest that HDL endocytosis and selective lipid uptake are not necessarily tightly linked to each other.

  14. Sphingomyelin in High-Density Lipoproteins: Structural Role and Biological Function

    Directory of Open Access Journals (Sweden)

    Jesús Osada

    2013-04-01

    Full Text Available High-density lipoprotein (HDL levels are an inverse risk factor for cardiovascular diseases, and sphingomyelin (SM is the second most abundant phospholipid component and the major sphingolipid in HDL. Considering the marked presence of SM, the present review has focused on the current knowledge about this phospholipid by addressing its variable distribution among HDL lipoparticles, how they acquire this phospholipid, and the important role that SM plays in regulating their fluidity and cholesterol efflux from different cells. In addition, plasma enzymes involved in HDL metabolism such as lecithin–cholesterol acyltransferase or phospholipid transfer protein are inhibited by HDL SM content. Likewise, HDL SM levels are influenced by dietary maneuvers (source of protein or fat, drugs (statins or diuretics and modified in diseases such as diabetes, renal failure or Niemann–Pick disease. Furthermore, increased levels of HDL SM have been shown to be an inverse risk factor for coronary heart disease. The complexity of SM species, described using new lipidomic methodologies, and their distribution in different HDL particles under many experimental conditions are promising avenues for further research in the future.

  15. Sphingomyelin in High-Density Lipoproteins: Structural Role and Biological Function

    Science.gov (United States)

    Martínez-Beamonte, Roberto; Lou-Bonafonte, Jose M.; Martínez-Gracia, María V.; Osada, Jesús

    2013-01-01

    High-density lipoprotein (HDL) levels are an inverse risk factor for cardiovascular diseases, and sphingomyelin (SM) is the second most abundant phospholipid component and the major sphingolipid in HDL. Considering the marked presence of SM, the present review has focused on the current knowledge about this phospholipid by addressing its variable distribution among HDL lipoparticles, how they acquire this phospholipid, and the important role that SM plays in regulating their fluidity and cholesterol efflux from different cells. In addition, plasma enzymes involved in HDL metabolism such as lecithin–cholesterol acyltransferase or phospholipid transfer protein are inhibited by HDL SM content. Likewise, HDL SM levels are influenced by dietary maneuvers (source of protein or fat), drugs (statins or diuretics) and modified in diseases such as diabetes, renal failure or Niemann–Pick disease. Furthermore, increased levels of HDL SM have been shown to be an inverse risk factor for coronary heart disease. The complexity of SM species, described using new lipidomic methodologies, and their distribution in different HDL particles under many experimental conditions are promising avenues for further research in the future. PMID:23571495

  16. The effects of physical exercise on plasma prebeta-1 high-density lipoprotein.

    Science.gov (United States)

    Jafari, Mahtab; Leaf, David Alexander; Macrae, Holden; Kasem, Julie; O'conner, Patricia; Pullinger, Clive; Malloy, Marry; Kane, John P

    2003-04-01

    The impact of physical exercise on high-density lipoprotein (HDL) metabolism is recognized as a major mechanism of coronary artery disease (CAD) risk reduction. Prebeta-1 HDL subparticle species play a pivotal role in initiating reverse cholesterol transport (RCT). We examined the effect of acute physical exercise on plasma prebeta-1 HDL levels. Nineteen nonsmoking, healthy men (n = 11) and women (n = 8) not receiving lipid-altering medications completed dietary surveys, and had percent body fat determinations, and fasting blood drawn for measurements of plasma lipids, lipoproteins, apolipoprotein A-I (Apo A-I), and absolute and percent prebeta-1 HDL. Each subject completed cardiopulmonary exercise stress testing to Vo(2max) followed by a 4-km course of run-jogging. Laboratory measurements were repeated from blood drawn immediately after exercise. Mean +/- SD values were determined for age, percent body fat, dietary calories, dietary cholesterol, dietary fat, and plasma lipids, lipoproteins, Apo A-I, and absolute and percent prebeta-1 HDL using 1-way analysis of variance (ANOVA). One-way ANOVA comparisons were made for measurements of plasma lipids, lipoproteins, Apo A-I, and absolute and percent prebeta HDL measurements taken before and after exercise for all subjects combined. Entry characteristics showed the following (mean +/-SD): age, 24 +/- 5.8 years; body mass index (BMI), 22.4 +/- 2.6; percent body fat, 13 +/- 5.7; and Vo(2max), 49.1 +/- 7.9 mL O(2)/kg/min. Exercise significantly increased absolute plasma prebeta HDL (0.10 +/- 0.05 to 0.130 +/- 0.07 microg/mL, P =.039) and decreased plasma HDL-triglycerides (23.3 +/- 10.8 to 12.5 +/- 5.6 mg/dL, P =.012). Our findings indicate that prebeta-1 HDL and HDL-triglyceride metabolism are significant components of the effect of acute exercise on RCT. These findings have important relevance for studies pertaining to exercise-related effects on HDL metabolism as pertains to CAD risk reduction. PMID:12701055

  17. Retroendocytosis of high density lipoproteins by the human hepatoma cell line, HepG2

    Energy Technology Data Exchange (ETDEWEB)

    Kambouris, A.M.; Roach, P.D.; Calvert, G.D.; Nestel, P.J. (CSIRO, Division of Human Nutrition, Adelaide (Australia))

    1990-07-01

    When human HepG2 hepatoma cells were pulsed with 125I-labeled high density lipoproteins (HDL) and chased in fresh medium, up to 65% of the radioactivity released was precipitable with trichloroacetic acid. Cell-internalized 125I-HDL contributed to the release of acid-precipitable material; when cells were treated with trypsin before the chase to remove 125I-HDL bound to the outer cell membrane, 50% of the released material was still acid-precipitable. Characterization of the radioactive material resecreted by trypsinized cells revealed the presence of particles that were similar in size and density to mature HDL and contained intact apolipoproteins (apo) A-I and A-II. The release of internalized label occurred at 37 degrees C but not at 4 degrees C. Monensin, which inhibits endosomal recycling of receptors, decreased the binding of 125I-HDL to cells by 75%, inhibited the release of internalized radioactivity as acid-precipitable material by 80%, and increased the release of acid-soluble material by 90%. In contrast, the lysosomal inhibitor chloroquine increased the association of 125I-HDL to cells by 25%, inhibited the release of precipitable material by 10%, and inhibited the release of acid-soluble radioactivity by 80%. Pre-incubation with cholesterol caused a 50% increase in the specific binding, internalization, and resecretion of HDL label. Cholesterol affected the release of acid-precipitable label much more (+90%) than that of acid-soluble material (+20%). Taken together, these findings suggest that HepG2 cells can bind, internalize, and resecrete HDL by a retroendocytotic process. Furthermore, the results with cholesterol and monensin indicate that a regulated, recycling, receptor-like molecule is involved in the binding and intracellular routing of HDL.

  18. Loss of Function of GALNT2 Lowers High-Density Lipoproteins in Humans, Nonhuman Primates, and Rodents

    DEFF Research Database (Denmark)

    Khetarpal, Sumeet A; Schjoldager, Katrine T; Christoffersen, Christina;

    2016-01-01

    Human genetics studies have implicated GALNT2, encoding GalNAc-T2, as a regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, but the mechanisms relating GALNT2 to HDL-C remain unclear. We investigated the impact of homozygous GALNT2 deficiency on HDL-C in humans and mammalian......C-III as GalNAc-T2 targets. Additional glycoproteomics in rodents identified targets influencing HDL-C, including phospholipid transfer protein (PLTP). GALNT2 deficiency reduced plasma PLTP activity in humans and rodents, and in mice this was rescued by reconstitution of hepatic Galnt2. We also found...

  19. High-density lipoprotein is a potential growth factor for adrenocortical cells

    International Nuclear Information System (INIS)

    The entry of cholesterol contained within high-density lipoprotein (HDL) into adrenocortical cells is mediated by a human homologue of SR-BI, CD36, and LIMPII Analogous-1 (CLA-1) and thus augmenting their growth. To address the role of CLA-1, we created a mutant mCLA that lacked the C-terminal tail. HDL CE selective uptake by cells carrying the mCLA-1 receptor was fully active and equivalent to those transfected with full-length CLA-1 (fCLA-1). Expression of mCLA inhibited the proliferation of an adrenocortical cell line and the incorporation of [3H]thymidine into the cells. This effect was sensitive to wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). Our transcriptional studies revealed that the inhibitory action of mCLA required the transcriptional factor AP-1 and the effect of HDL on AP-1 activation was also abrogated by wortmannin. These findings raise the possibility that the inhibitors of the effects of HDL may be of therapeutic value for adrenocortical tumor

  20. Folded Functional Lipid-Poor Apolipoprotein A-I Obtained by Heating of High-Density Lipoproteins: Relevance to HDL Biogenesis

    OpenAIRE

    Jayaraman, Shobini; Cavigiolio, Giorgio; Gursky, Olga

    2012-01-01

    High-density lipoproteins (HDL) remove cell cholesterol and protect from atherosclerosis. The major HDL protein is apolipoprotein A-I (apoA-I). Most plasma apoA-I circulates in lipoproteins, yet ~5% forms monomeric lipid-poor/free species. This metabolically active species is a primary cholesterol acceptor and is central to HDL biogenesis. Structural properties of lipid-poor apoA-I are unclear due to difficulties in isolating this transient species. We used thermal denaturation of human HDL t...

  1. Predictive value of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio on the cardiovascular events in patients undergoing percutaneous coronary intervention%LDL-C/HDL-C比值对经皮冠脉介入术后患者心血管事件的预测价值

    Institute of Scientific and Technical Information of China (English)

    师姗姗; 刘幼文; 金光临; 潘楚梅; 王涓; 曾繁芳

    2013-01-01

    目的 评估低密度脂蛋白胆固醇(LDL-C)/高密度脂蛋白胆固醇(HDL-C)比值对经皮冠脉介入(PCI)术后患者心血管事件的预测价值.方法 选择急性冠脉综合征(ACS)并予前降支置入支架的患者119例,依据血浆LDL-C/HDL-C比值将患者分为3组,随访1年,评估三组患者心血管事件发生率,以及各危险因素与心血管事件发生率的关系.结果 ①与LDL-C/HDL-C比值较低的两组相比,比值较高组患者体重指数、女性患者百分率、吸烟人数及糖化血红蛋白、高敏C反应蛋(hs-CRP)、总胆固醇和LDL-C水平均明显升高,而HDL-C水平和他汀类药物使用率则较低(P<0.05).②第1组风险比(HR)1.04,95%可信区间(CI)0.98~1.08,第2组HR 1.16,95%CI 1.08~1.20,第3组HR 1.27,95%CI 1.19~1.36(P<0.05).随着LDL-C/HDL-C比值的升高,PCI术后1年患者心血管事件发生率也逐渐升高(P<0.05).③Cox比例风险回归模型提示,LDL-C/HDL-C比值对PCI术后心血管事件风险的预测价值优于其他危险因素.结论 LDL-C/HDL-C比值对PCI术后患者1年内心血管事件再发具有一定的预测价值.%Objective To investigate the predictive value of LDL-C/HDL-C ratio on the cardiovascular events in patients with PCI treatment. Methods One hundred and nineteen patients defined as acute coronary syndrome treating with stent implantation in anterior descending artery were enrolled. According to the category of LDL-C/HDL-C ratio, patients were assigned into 3 groups and were followed up for one year to evaluate the occurrence of cardiovascular events and the relationship of cardiovascular events with risk factors. Results (1)Compared to the two low categories of LDL-C/HDL-C ratio groups, body mass index, percentage of female, number of smoker, levels of GHBA1C, hs-CRP, total cholesterol and LDL-C were higher, while level of HDL-C and usage of statin were lower (P<0.05). (2)In line with the escalation of LDL-C/HDL-C ratio, the rate of

  2. Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels

    Science.gov (United States)

    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...

  3. 脑血流低灌注老龄大鼠中脑皮质血流的改变与血清总胆固醇和高密度脂蛋白的动态变化%Dynamic changes of cortical blood flow and serum total cholesterol and high density lipoprotein in brains of aging rat during cerebral hypoperfusion

    Institute of Scientific and Technical Information of China (English)

    王林辉; 田茗源; 滕志朋; 王晨; 李昱

    2012-01-01

    目的:通过建立脑血流低灌注模型,观察老龄大鼠脑血流的变化以及在脑血流低灌注下血清中总胆固醇(Total cholesterol,TC)和高密度脂蛋白(High density lipoprotein,HDL)的动态变化.方法:采用持久性双侧颈总动脉结扎法(2Vo)致老龄大鼠脑血流灌注不足,测定术后7、14、21、28d大鼠脑皮质血流;检测、比较术后不同时间段大鼠血清中TC和HDL浓度差异.结果:术后第14天大鼠脑颞区血流出现明显减少;术后21、28d大鼠脑局部皮质血管有再生侧支形成,大鼠脑颞区血流仍未恢复;术后第14天血清中HDL、TC含量明显高于假手术组(P<0.05),随着缺血时间延长,又逐渐降低.结论:血清TC和HDL浓度在脑缺血灌注不足的不同时间段经历了先增强后减弱的动态变化,提示脑血流低灌注老龄大鼠因大脑血流灌注不足可出现体内胆固醇代谢失衡并出现应激调节现象.%Objective: To investigate the change of cortical blood flow and the dynamic changes of serum total cholesterol(TC ) and high density lipoprotein(HDL) in brains of aging rat during cerebral ischemic injury. Methods:The model of aging rats with cerebral hy-poperfusion was successfully constructed by persistent bilateral common carotid artery ligation(2V0). The cortical blood flow and the concentration of serum TC and HDL at different time points were determined and compared. Results: Compared with the sham-operated group,the temporal blood flow was significantly decreased in 14 d group. But the collateral vessels were gradually regenerated and formed in local brain,while the temporal blood flow was restored in 21 d and 28 d group. The concentration of HDL and TC was significantly higher in 14 d group than in the sham-operated group (P<0.05), and both of them were decreased with the extention of ischemia time. Conclusions:The serum TC and HDL concentration undergo dynamic changes-increasing first and then decreasing during the process

  4. Role of sphingosine 1-phosphate in anti-atherogenic actions of high-density lipoprotein

    Institute of Scientific and Technical Information of China (English)

    Koichi; Sato; Fumikazu; Okajima

    2010-01-01

    The reverse cholesterol transport mediated by highdensity lipoprotein(HDL)is an important mechanism for maintaining body cholesterol,and hence,the crucial anti-atherogenic action of the lipoprotein.Recent studies,however,have shown that HDL exerts a variety of anti-inflammatory and anti-atherogenic actions independently of cholesterol metabolism.The present review provides an overview of the roles of sphingosine 1-phosphate(S1P)/S1P receptor and apolipoprotein A-I/ scavenger receptor class B typeⅠsystems in the antiatherogenic HDL actions.In addition,the physiological significance of the existence of S1P in the HDL particles is discussed.

  5. HDL Cholesterol Test

    Science.gov (United States)

    ... limited. Home Visit Global Sites Search Help? HDL Cholesterol Share this page: Was this page helpful? Also ... HDL; HDL-C Formal name: High-density Lipoprotein Cholesterol Related tests: Cholesterol ; LDL Cholesterol ; Triglycerides ; Lipid Profile ; ...

  6. Psyllium husk. I: Effect on plasma lipoproteins, cholesterol metabolism, and atherosclerosis in African green monkeys.

    Science.gov (United States)

    McCall, M R; Mehta, T; Leathers, C W; Foster, D M

    1992-08-01

    Psyllium's effects on plasma and lipoprotein cholesterol concentrations, cholesterol metabolism, and diet-induced atherosclerosis were studied in adult male African green monkeys (Cercopithecus aethiops). Animals were fed for 3.5 y one of three experimental diets: low-cholesterol cellulose (LCC), high-cholesterol cellulose (HCC), or high-cholesterol psyllium (HCP). The LCC and HCP groups had significantly (P less than 0.05) lower plasma cholesterol concentrations (39% lower) at 1 mo than did the HCC group. These responses persisted throughout the study. Plasma cholesterol changes were due to a reduction in intermediate-density and low-density lipoproteins; very-low and high-density-lipoprotein concentrations were similar among groups. Aortic atherosclerosis, evaluated as percent sudanophilia at 3.5 y, was lowest in the LCC group, intermediate in the HCP group, and highest in the HCC group. Cholesterol absorption, neutral steroid and fat excretion, HMGCoA reductase activity (in intestine and liver), and body weight were unrelated to psyllium's hypocholesterolemic effects. PMID:1322032

  7. Relationship between insulin resistance and non-high density lipoprotein cholesterol in essential hypertensives%原发性高血压患者胰岛素抵抗与非高密度脂蛋白胆固醇的关系

    Institute of Scientific and Technical Information of China (English)

    王若琦; 段国凤; 刘忠仁; 蓝景生; 陆克兴; 黄照河; 潘兴寿

    2011-01-01

    目的 探讨壮族原发性高血压患者胰岛素抵抗(IR)与非HDL-C的关系,为壮族高血压综合治疗提供参考.方法 选取壮族高血压患者200例,以是否合并糖尿病分为合并组80例和未合并组120例;另选健康体检者60例为对照组.各组均测定TC、TG、LDL-C、HDL-C、空腹血糖和空腹胰岛素,计算IR指数(HOMA-IR)和非HDL-C,分析非HDL-C与1R等指标的关系.以非HDL-C水平进行四分位,分为上四分位组51例和下四分位组48例,并分析HOMA-IR等指标间的关系.结果 与对照组比较,合并组和未合并组患者空腹血糖、空腹胰岛素、TC、TG、LDL-C、非HDL-C和HOMA-IR明显升高,HDL-C明显降低(P<0.05,P<0.01);与未合并组比较,合并组患者空腹胰岛素、非HDL-C和HOMA-IR明显升高,HDL-C明显降低(P<0.05).与下四分位组比较,上四分位组患者收缩压、舒张压、空腹血糖、TC、TG、LDL-C和HOMA-IR明显升高,HDL-C明显降低(P<0.05,P<0.01).结论 不同糖代谢状态下壮族高血压患者均存在脂代谢紊乱和IR.非HDL-C与IR密切相关,是临床上评估糖、脂代谢异常的良好指标.%Objective To investigate the relationship between the level of non-high density lipoprotein cholesterol(non-HDL-C) and insulin resistance(IR)in essential hypertensive people. Methods 200 hypertensive patients were randomly divided into hypertension group, hypertension with diabetes mellitus group and other 60 healthy persons served as control group. TC, TG, HDL-C,LDL-C,fasting plasma glucose(FPG) and insulin(FINS) were determined. Non-HDL-C and insulin resistance(HOMA-IR) were calculated and the relation between non-high density lipoprotein and HOMA-IR was analyzed. Results In hypertensive patients with or without diabetes mellitus,FPG,FINS, TC, TG, LDL-C, non-HDL-C and HOMA-IR were higher than those in control group,while HDL-C-was lower. The level of IR and non-HDL-C in hypertensive patients with diabetes mellitus were higher than

  8. [Lipoprotein metabolic characteristics in the liver and intestinal wall of rabbits after a single exposure to sunflower oil and cholesterol].

    Science.gov (United States)

    Leskova, G F

    1982-04-01

    Lipoprotein metabolism in the rabbit liver and intestinal wall was studied by an alimentary action on the cholesterol blood content. The data obtained indicated that the diet including cholesterol intensifies the release of chylomicrons into the lymph of the intestinal lymphatic trunk. Single addition of sunflower-seed oil to the diet leads to the increased deposition of high, low and very low density lipoproteins in the intestinal wall. Upon adding cholesterol to the rabbit diet the retention of low and very low density lipids in the intestine is followed by the increased release of high density lipoproteins into the blood of the portal vein. Single addition of sunflower-seed oil stimulates the synthesis of high density lipoproteins by the rabbit liver.

  9. Nanocrystal core high-density lipoproteins: A multimodality contrast agent platform

    OpenAIRE

    Cormode, David P.; Skajaa, Torjus; van Schooneveld, Matti M.; Koole, Rolf; Jarzyna, Peter; Lobatto, Mark E.; Calcagno, Claudia; Barazza, Alessandra; Gordon, Ronald E.; Zanzonico, Pat; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2008-01-01

    High density lipoprotein (HDL), is an important natural nanoparticle that may be modified for biomedical imaging purposes. Here we developed a novel technique to create unique multimodality HDL mimicking nanoparticles by inclusion of gold, iron oxide or quantum dot nanocrystals for computed tomography, magnetic resonance and fluorescence imaging, respectively. By including additional labels in the corona of the particles, they were made multi-functional. The characterization of these nanopart...

  10. TaqI B1/B2 and -629A/C cholesteryl ester transfer protein (CETP gene polymorphisms and their association with CETP activity and high-density lipoprotein cholesterol levels in a Tehranian population. Part of the Tehran Lipid and Glucose Study (TLGS

    Directory of Open Access Journals (Sweden)

    Maryam S Daneshpour

    2007-01-01

    Full Text Available We examined the cholesteryl ester transfer protein (CETP gene TaqI intron 1 B1/B2 polymorphism and the -629A/C CETP promoter polymorphism in respect to high-density lipoprotein cholesterol (HDL-C in a healthy Iranian population taken from the Tehran Lipid and Glucose Study (TLGS. The relationship between CETP activity and HDL-C level was also determined along with body mass index, blood pressure and tobacco smoking status. PCR-RFLP used to amplify a segment of the CETP intron 1 TaqI (B2/B1 polymorphism from 1021 individuals and we selected 345 individuals from the lowest, middle and highest HDL-C deciles and investigated the -629A/C polymorphism. We also evaluated the CETP activity of 103 of these individuals, each with at least one homozygous allele. The presence of the TaqI B2 and -629A/C A alleles were significantly associated with increased HDL-C levels (B2B2 = 1.19 ± 0.31 mmolL-1 vs. B1B1 = 1.01 ± 0.2 mmol L-1 for p < 0.001; AA = 1.15 ± 0.41 mmol L-1 vs. CC = 0.95 ± 0.28 mmol L-1 for p < 0.001 and decreased the CETP activity (B1B1 = 67.8 ± 8.9 pmol L-1 vs. B2B2 = 62.6 ± 9.6 pmol L-1 for p < 0.01; CC = 68.6 ± 8.4 pmol L-1 vs. AA = 62.7 ± 9.7 pmol L-1 for p < 0.002. The frequencies were 0.382 for the TaqI B2 allele and 0.462 for the -629A/C A allele, with linkage disequilibrium analysis giving D = 0.0965 and D' = 0.4695. We demonstrated that the TaqI B1 and B2 alleles and the -629A/C A and C alleles were in linkage disequilibrium in our population and that there was a significant association between the B2 and A alleles and high HDL-C levels and low CETP activity. Linkage disequilibrium between the TaqI A and B2 alleles also detected.

  11. Apparent protective effect of high density lipoprotein against coronary heart disease in the elderly

    Institute of Scientific and Technical Information of China (English)

    李健斋; 陈曼丽; 王抒; 董军; 曾平; 侯鲁维

    2004-01-01

    Background This study was designed to evaluate the relationship between high-density lipoprotein cholesterol (HDL-C) level and acute myocardial infarction (AMI) and coronary heart disease (CHD)death and to explore the protective effect of HDL against CHD in the elderly Chinese.Methods Started from 1986, 1211 retirees (92% males) were enrolled consecutively and studied prospectively. The average starting age was 70 ±9 years, and that at the end of the study was 80 ±9years. During the follow-up study, all the participants received yearly physical examination and blood chemistry survey from 1986 -2000. The average duration of the follow up study was 11.2 years. The end point of this study was either attacks of AMI or death due to CHD and other causes. CHD risk factors were screened by logistic regression analysis. According to their HDL-C levels, cases were divided into Iow (<1.03 mmol/L), medium (or normal, 1.03 - 1.56 mmol/L) and high(>1.56mmol/L) level groups, the differences in incidence of AMI and CHD death in each group were analyzed.Results The cumulative attacks of acute coronary syndrome (mostly AMI) were 214 cases,including 89 cases of coronary death and 308 death caused by other diseases during the follow up study. AMI occurrence and CHD death in normal HDL-C group were lower than those in the low HDLC group by 40% and 53%; and those in the high HDL-C group were lower than in the normal group by 56% and 50%, respectively. Statistical analysis on normal lipid cases (411 cases, total cholesterol<5. 17mmol/L, triglyceride<1.69 mmol/L) revealed that the cases at low HDL-C level had similar rates of AMI events and CHD mortality as those of the entire group (including hyperlipidemia);however, AMI attacks and CHD deaths decreased significantly at the normal and high HDL-C levels.The results demonstrated that the protective effect of HDL against coronary artery disease is more prominent in people with low lipid level.Conclusion Low HDL is an important

  12. High-density lipoproteins: a novel therapeutic target for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    TS Mohamed Saleem

    2011-01-01

    Full Text Available TS Mohamed Saleem1, PV Sandhya Rani1, K Gauthaman21Department of Pharmacology, Annamacharya College of Pharmacy, New Boyanapalli, Andhrapradesh, India; 2Department of Drug Technology, Faculty of Medical Technology, Derna, LibyaAbstract: Cardiovascular disease has a high rate of mortality in both Western and developing countries. Atherosclerosis and generation of reactive oxygen species through oxidative stress is the major risk factor for cardiovascular disease. Atherothrombosis with low levels of high-density lipoprotein (HDL and high levels of low-density lipoprotein is a major risk factor for atherosclerosis-induced cardiovascular disease. Lipid-lowering drugs like statins, niacin, fibrates, and some newer agents, ie, the apolipoprotein A-I mimetics and the cholesteryl ester transfer protein inhibitors, not only increase HDL levels but are also effective in reducing key atherogenic lipid components, including triglyceride-rich lipoproteins. The aim of this review is to discuss the accumulating evidence suggesting that HDL possesses a diverse range of biological actions, and that increasing HDL levels by drug treatment may be beneficial in the prevention of cardiovascular disease.Keywords: cardiovascular disease, lipoproteins, statins, apolipoprotein, atherosclerosis

  13. Association between moderately oxidized low-density lipoprotein and high-density lipoprotein particle subclass distribution in hemodialyzed and post-renal transplant patients

    Institute of Scientific and Technical Information of China (English)

    El(z)bieta KIMAK; Magdalena HA(L)ABI(S); Iwona BARANOWICZ-GA SZCZYK; Janusz SOLSKI; Andrzej KSIA(Z)EK

    2011-01-01

    Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed (HD) and post-renal transplant (Tx) patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein (HDL) reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle,oxidized low-density lipoprotein (ox-LDL) and anti-ox-LDL, and paraoxonase-1 (PON-1) activity in HD (n=33) and Tx (n=71) patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy.HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-Ⅰ (apoA-Ⅰ) and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios (total cholesterol (TC)/HDL-C, LDL-C/HDL-C, triglyceride (TG)/HDL-C, HDL-C/non-HDL-C,apoA-Ⅰ/apoB, HDL-C/apoA-Ⅰ, TG/HDL) were atherogenic. The Spearman's rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level (R=0.363, P=0.004), and negatively with TC (R=-0.306, P=0.012), LDL-C (R=-0.283, P=0.020), and non-HDL-C (R=-0.263, P=0.030) levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and decreased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre

  14. Interactions of Apolipoprotein A-I with High-Density Lipoprotein Particles

    OpenAIRE

    Nguyen, David; Nickel, Margaret; Mizuguchi, Chiharu; Saito, Hiroyuki; Lund-Katz, Sissel; Phillips, Michael C.

    2013-01-01

    Although the partitioning of apolipoprotein A-I (apoA-I) molecules in plasma between high-density lipoprotein (HDL)-bound and -unbound states is an integral part of HDL metabolism, the factors that control binding of apoA-I to HDL particles are poorly understood. To address this gap in knowledge, we investigated how the properties of the apoA-I tertiary structure domains and surface characteristics of spherical HDL particles influence apoA-I binding. The abilities of 14C-labeled human and mou...

  15. Practical technique to quantify small, dense low-density lipoprotein cholesterol using dynamic light scattering

    Science.gov (United States)

    Trirongjitmoah, Suchin; Iinaga, Kazuya; Sakurai, Toshihiro; Chiba, Hitoshi; Sriyudthsak, Mana; Shimizu, Koichi

    2016-04-01

    Quantification of small, dense low-density lipoprotein (sdLDL) cholesterol is clinically significant. We propose a practical technique to estimate the amount of sdLDL cholesterol using dynamic light scattering (DLS). An analytical solution in a closed form has newly been obtained to estimate the weight fraction of one species of scatterers in the DLS measurement of two species of scatterers. Using this solution, we can quantify the sdLDL cholesterol amount from the amounts of the low-density lipoprotein cholesterol and the high-density lipoprotein (HDL) cholesterol, which are commonly obtained through clinical tests. The accuracy of the proposed technique was confirmed experimentally using latex spheres with known size distributions. The applicability of the proposed technique was examined using samples of human blood serum. The possibility of estimating the sdLDL amount using the HDL data was demonstrated. These results suggest that the quantitative estimation of sdLDL amounts using DLS is feasible for point-of-care testing in clinical practice.

  16. New micromethod for measuring cholesterol in plasma lipoprotein fractions.

    Science.gov (United States)

    Bronzert, T J; Brewer, H B

    1977-11-01

    A method is described for the reliable, fast, and relatively inexpensive fractionation of plasma lipoproteins and quantitation of their cholesterol content. This procedure requires 350 microliter of plasma and can be completed within 3 h. Plasma lipoproteins (175 microliter of plasma) were prestained with Fat Red 7B and centrifuged (Beckman Airfuge) at plasma density (d = 1.006 kg/liter) and at a solvent density of 1.060 kg/liter, adjusted by adding solid KBr. Prestained centrifuged samples demonstrated the characteristic elevation of chylomicrons in phenotypes I and V, low-density lipoproteins of phenotype II, very-low-density lipoproteins in phenotype IV and V, and continuum of pink color throughout the centrifuge tube, diagnostic of the floating beta lipoprotein of type III. Centrifuged samples were separated into top and bottom fractions by aspiration. Cholesterol was quantitated with an enzymic oxygen-electrode analyzer (Beckman Cholesterol Analyzer). Correlation coefficients between cholesterol values for plasma from normal hyperlipidemic individuals obtained with the Beckman Analyzer vs. the Technicon AutoAnalyzer II and SMAC systems were 0.977 and 0.973, respectively.

  17. High Density Lipoprotein Phospholipids as a Marker of Coronary Heart Disease of Shen-Yang Deficiency Syndrome

    Institute of Scientific and Technical Information of China (English)

    GUO Ping-qing (郭平清); LIN Qiu-cheng (林求诚); GUO Yin-geng (郭银庚); SHEN Zong-guo (沈宗国)

    2003-01-01

    Objective: To seek a new biochemical index for diagnosis of coronary heart disease (CHD)of shen-Yang deficiency syndrom (CHD-SYD). Methods: Sixty-one patients with CHD were divided into 3 groups according to their TCM Syndrome type, 10 patients in the group without Xin-Qi deficiency (Group A), 25 in the group with Xin-Qi deficiency but without Shen-Yang deficiency (Group B) and 26 in the group both with Xin-Qi deficiency and Shen-Yang deficiency (Group C). Levels of 17-hydroxy-corticosteroid in urine (urinary 17-OHCS) per 24 hrs, and serum level of high density lipoprotein cholesterol (HDL-C) and high density lipoprotein phospholipid (HDL-PL) in them were determined in synchrostep and compared with those in the control group of 23 healthy aged persons. urinary 17-OHCS per 24 hrs was taken as the diagnostic standard to screen a new index for diagnosis of Shen-Yang deficiency Syndrome, and preliminary appraisal to the index was made. Results: Serum HDL-PL in the CHD-SYD patients( Group C) was 616±157 mg/L, which was obviously lower than that in the patients of Group A and B. With low HDL-PL (<650 mg/L) used as the index to diagnose CHD-SYD, the sensitivity was 73%, the specificity 86% and the accuracy 80%. Conclusion: HDL-PL <650 mg/L could be adopted as an index for CHD-SYD diagnosis, which is simple and practical.

  18. High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease

    Science.gov (United States)

    Gordon, Elizabeth M.; Figueroa, Debbie M.; Barochia, Amisha V.; Yao, Xianglan; Levine, Stewart J.

    2016-01-01

    Apolipoprotein A-I (apoA-I) and high-density lipoproteins (HDL) mediate reverse cholesterol transport out of cells. Furthermore, HDL has additional protective functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and vasoprotective effects. In contrast, HDL can become dysfunctional with a reduction in both cholesterol efflux and anti-inflammatory properties in the setting of disease or the acute phase response. These paradigms are increasingly being recognized to be active in the pulmonary system, where apoA-I and HDL have protective effects in normal lung health, as well as in a variety of disease states, including acute lung injury (ALI), asthma, chronic obstructive pulmonary disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and viral pneumonia. Similar to observations in cardiovascular disease, however, HDL may become dysfunctional and contribute to disease pathogenesis in respiratory disorders. Furthermore, synthetic apoA-I mimetic peptides have been shown to have protective effects in animal models of ALI, asthma, pulmonary hypertension, and influenza pneumonia. These findings provide evidence to support the concept that apoA-I mimetic peptides might be developed into a new treatment that can either prevent or attenuate the manifestations of lung diseases, such as asthma. Thus, the lung is positioned to take a page from the cardiovascular disease playbook and utilize the protective properties of HDL and apoA-I as a novel therapeutic approach.

  19. Concentração plasmática de colesterol total e lipoproteína de alta densidade em novilhas mestiças doadoras de embriões tratadas com somatotropina bovina recombinante Total plasma cholesterol and high-density lipoprotein levels in crossbred heifer embryo donors treated with bovine recombinant somatotropin

    Directory of Open Access Journals (Sweden)

    Á.M. Borges

    2001-10-01

    Full Text Available O objetivo do experimento foi o de estudar as concentrações plasmáticas de colesterol total e lipoproteína de alta densidade (HDL em novilhas mestiças tratadas com somatotropina bovina recombinante (rbST. Coletas de sangue foram feitas durante dois ciclos estrais, normal e superovulado, em 26 fêmeas distribuídas em dois tratamentos: T1 = aplicação de 500mg de rbST no terceiro dia do ciclo estral utilizado para a superovulação e T2 = controle. Análises dos metabólitos sangüíneos foram feitas utilizando-se o método enzimático, cujas concentrações médias plasmáticas de colesterol total e de HDL durante o ciclo estral normal não foram diferentes (P>0,05 entre os dois tratamentos: 87,9 e 25,8mg/dl e 85,9 e 26,7mg/dl para T1 e T2, respectivamente. O ciclo estral utilizado para a superovulação foi dividido em três períodos: P1 = do estro à inseminação artificial (0 ao15º dia, P2 = da inseminação artificial até a coleta de embriões (15º ao 21º dia e P3 = da coleta até o final do período experimental (21º ao 27º dia. As concentrações plasmáticas de colesterol total e HDL no P1 não diferiram entre os tratamentos (P>0,05. Em P2 e P3 houve diferença nas concentrações de HDL e colesterol total entre os dois tratamentos: 29,0 e 88,5mg/dl (T1 e 27,1 e 81,8mg/dl (T2 no P2; e 30,4 e 88,0mg/dl (T1 e 26,6 e 80,5mg/dl (T2 no P3, respectivamente (PThe objective of the experiment was to study the total cholesterol and high-density lipoprotein (HDL levels in crossbred heifers treated with bovine recombinant somatotropina (rbST. Blood samples were collected for two estrous cycles, normal and superovulated, from 26 animals randomly distributed into two treatments: T1 - injected with 500mg rbST on day 3 of estrous cycle and T2 - control. The lipidic metabolite levels were determined by an enzymatic method, and plasma levels of total cholesterol and HDL in normal estrous cycle did not differ (P>0.05 between treatments: 87

  20. Paraoxonase-1 L55M Polymorphism with Fatty Acid Composition of Phospholipids in High-Density Lipoproteins

    Directory of Open Access Journals (Sweden)

    M Hashemzadeh Chaleshtory

    2012-04-01

    Full Text Available Background: Paraoxonase-1 (PON1 moves with high-density lipoprotein (HDL particles in blood and prevents low-density lipoprotein (LDL particles from oxidation. The aims of this study were to investigate the correlation between fatty acid composition of HDL phospholipids with pon-1 polymorphisms and response to lovastatin treatment in people with high blood cholesterol. Methods: In this descriptive study, 265 patients were selected and divided into two groups based on LDL-C concentrations; 131 patients with LDL-C greater than 130 mg/dl (cases and 134 patients with LDL-C lower than 130 mg/dl (controls. Fatty acids of HDL phospholipids were measured with gas chromatography and lipid profile (cholesterol, triglyceride, LDL-C, HDL-C, apolipoprotein A1 and apolipoprotein B were measured by relevant commercial kits. Oxidized LDL was measured by ELISA method and activity of paraoxonase was determined by a relevant standard manual method. Genotypes of L55M polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphism procedure. Results: Prevalence of L allele from L55M polymorphism was 0.65 and 0.53 in the case and control groups, respectively (P=0.04. PON1 paraoxonase activity in LL homozygote genotype was higher than other genotypes upon treatment with lovastatin. Concentrations of oleic, linoleic and eicosapentaenoic acids in LL genotype were increased by lovastatin administration. Conclusion: Allele (L from L55M polymorphism had a higher frequency in patients with higher LDL-C concentrations. PON1 genotypes seemed to have a modifying role on paraoxonase-1 activity after lovastatin therapy.

  1. Correlation between the High Density Lipoprotein and its Subtypes in Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Fen Gao

    2016-05-01

    Full Text Available Background/Aims: To detect the changes of high density lipoprotein (HDL and its subtypes in serum of patients with coronary heart disease (CHD. Methods: 337 hospitalized patients were selected from our hospital during August, 2014 - January, 2015, and divided into CHD group (n = 190 and control group (n = 127. Lipoprint lipoprotein analyzer was used to classify low density lipoprotein (LDL particle size and its sub-components, as well as HDL particle size and its sub-components. The changes of the subtypes in patients with CHD were statistically analyzed. The possible mechanism was explored. Results: (1 Compared with the control group, the concentration of HDL in CHD patients reduced, HDLL significantly decreased (P S increased (P L had the most significant decreased; (3 HDL and all HDL subtypes were positively correlated with apolipoprotein A-I (apoA-I, of which, HDLL had the biggest correlation with apoA-I (P M had a maximum correlation with HDL (P Conclusion: HDL maturation disorders existed in the serum of CHD patients, HDLL may be protected factor for CHD, whose decrease was closely related wit the risk increase of CHD. The cardiovascular protection function of HDLL may be related with apoA-I content.

  2. Carbohydrate composition of serum low and high density lipoproteins of nonhuman primate species.

    Science.gov (United States)

    Pargaonkar, P S; Radhakrishnamurthy, B; Srinivasan, S R; Berenson, G S

    1977-01-01

    1. Carbohydrate composition of serum low and high density lipoproteins obtained from 5 nonhuman primate species (chimpanzee, patas, baboon, rhesus, and spider) and humans was studied. 2. Individual lipoproteins were isolated from pooled sera of each species by ultracentrifugal flotation between the densities 1.019-1.063 for LDL-2; 1.063-1.12 for HDL-2; and 1.12-1.21 for HDL-3. After delipidation, sialic acid, fucose, glucosamine, mannose, galactose, and glucose were determined on apo LDL-2, apo HDL-2, and apo HDL-3. 3. Glucosamine, galactose, and mannose constituted a major component of the sugars in apo LDL-2, with similar relative proportions in all species. Sialic acid, fucose, and glucose formed a minor component, the proportions of which varied greatly among the species. 4. Unlike apo LDL-2, sialic acid, fucose, and glucosamine constituted the bulk of the sugars in apo HDL-2 and apo HDL-3. Mannose, galactose, and glucose were minor components, with galactose predominating. 5. Qualitative differences were observed in electrophoretic mobilities of apo HDL-2 and apo HDL-3 on polyacrylamide gel. One faster moving band was unique to chimpanzee. 6. Intraspecies differences in the content of sialic acid and fucose of apolipoproteins may be related to lipoprotein metabolism and species susceptibility (or resistance) to either spontaneous or diet-induced atherosclerosis. PMID:233783

  3. Transport of cholesterol autoxidation products in rabbit lipoproteins

    International Nuclear Information System (INIS)

    Radiolabeled pure [4-14C] cholesterol was kept at 600C under air to autoxidize for 5 weeks, after which approximately 12% cholesterol oxidation products were formed. The mixture, suspended in gelatin, was given to rabbits by gastric gavage. Rabbits were killed 4, 24 and 48 h after treatment. Cholesterol and its autoxidation products were separated by thin-layer chromatography into 5 fractions and radioactivities of each fraction were measured. Percentages of each fraction of cholesterol oxidation products and cholesterol in the original mixture before administration and in the rabbit sera after administration were similar, suggesting that the rates of absorption of cholesterol oxidation products are not significantly different from that of cholesterol. Lipoproteins were fractioned by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each fraction in lipoproteins separated by thin layer chromatography showed that fractions containing cholestane-3β, 5α, 6β-triol, 7α- and 7β-hydroxycholesterol and 7-ketocholesterol were more selectively transported in VLDL, whereas most of the 25-hydroxycholesterol was present in LDL. HDL contained only minute amounts of cholesterol oxidation products. 22 refs

  4. The role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in comparison with whole egg yolk for sperm cryopreservation in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Qiao-Xiang Dong; Sarah E Rodenburg; Dana Hill; Catherine A VandeVoort

    2011-01-01

    Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein (HDL) in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant (glycerol) on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in post-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.

  5. Low-density lipoprotein cholesterol and risk of gallstone disease

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, Ruth; Benn, Marianne;

    2013-01-01

    Drugs which reduce plasma low-density lipoprotein cholesterol (LDL-C) may protect against gallstone disease. Whether plasma levels of LDL-C per se predict risk of gallstone disease remains unclear. We tested the hypothesis that elevated LDL-C is a causal risk factor for symptomatic gallstone...

  6. Oxidative modification of high density lipoprotein induced by cultured human arterial smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    江渝; 刘红; 彭家和; 叶治家; 何凤田; 董燕麟; 刘秉文

    2003-01-01

    Objective: To observe the oxidative modification of high density lipoprotein (HDL) induced by cultured human arterial smooth muscle cells (SMCs). Methods: HDL cocultured with SMCs at 37℃ in 48 h was subjected, and native HDL (N-HDL) served as control. Oxidative modification of HDL was identified by using agarose gel electrophoresis. Absorbances of conjugated diene (CD) and lipid hydroperoxide (LOOH) were measured with ultraviolet spectrophotometry at 234 and 560 nm respectively, and fluorescence intensity of thiobarbuturic acid reaction substance (TBARS) with fluorescence spectrophotometry at 550 nm emission wavelength with excitation at 515 nm. Results: In comparison with N-HDL, the electrophoretic mobility of SMCs-cocultured HDL was increased, and the contents of CD, LOOH and TBARS HDL were very significantly higher than those of the control HDL (P<0.01). Conclusion: Oxidative modification of HDL can be induced by human arterial SMCs.

  7. A disposable electrochemical sensor based on protein G for High-Density Lipoprotein (HDL) detection.

    Science.gov (United States)

    Chammem, H; Hafaid, I; Bohli, N; Garcia, A; Meilhac, O; Abdelghani, A; Mora, L

    2015-11-01

    In this work, two biosensors were developed for the detection of High-Density Lipoproteins (HDL) particles, which are biomarkers inversely correlated with cardiovascular risk and which represent therapeutic targets for atherosclerosis. The electrochemical properties of the grafted antibody on interdigitated gold electrode were achieved by Impedance Spectroscopy (IS). The used deposition method was based on oriented antibody Anti-ApoA1 with an intermediate thin layer of protein G. The developed biosensor was able to detect both native plasma HDL and reconstituted HDL (rHDL) particles respectively with the detection limit of 50n g/mL and 1 ng/mL, respectively. Dynamic contact angle and atomic force microscopy were used. The developed biosensors are able to differentiate the HDL particles according to their differences in size and interactions with the immobilized antibody. PMID:26452849

  8. Glycation of high-density lipoprotein in type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    SUN Jia-teng; SHEN Ying; L(U) An-kang; LU Lin; SHEN Wei-feng

    2013-01-01

    Objective To evaluate whether glycation of high-density lipoprotein (HDL) increases cardiovascular risk in patients with type 2 diabetes mellitus by altering its anti-atherogenic property.Data sources Data cited in this review were obtained mainly from Pubmed and Medline in English from 2000 to 2013,with keywords "glycation","HDL",and "atherosclerosis".Study selection Articles regarding glycation of HDL and its role in atherogenesis in both humans and experimental animal models were identified,retrieved and reviewed.Results Glycation alters the structure of HDL and its associated enzymes,resulting in an impairment of atheroprotective functionality and increased risks for cardiovascular events in type 2 diabetic patients.Conclusion Glycation of HDL exerts a deleterious effect on the development of cardiovascular complications in diabetes.

  9. Lipoprotein composition and serum cholesterol ester fatty acids in nonwesternized Melanesians.

    Science.gov (United States)

    Lindeberg, S; Nilsson-Ehle, P; Vessby, B

    1996-02-01

    In this study, the relationships between dietary fat [as measured by serum cholesterol ester fatty acids (CE-FA)], age, smoking, body mass index, and serum lipids were analyzed in 151 subsistence horticulturalists, aged 20-86 yr, from Kitava, Trobriand Islands, Papua New Guinea. Their diet consists of tubers, fruit, coconut, fish, and vegetables with a negligible influence of western food and alcohol. Total fat intake is low [21% of energy (en%)], while saturated fat intake from coconuts is high (17 en%, mainly lauric and myristic acid). In multivariate analysis, 11-43% of the variation of the serum lipoprotein composition was explained by CE-FA, age, and smoking habits. The proportion of CE20:5n-3 explained much of the variation of triglycerides (TG, negative relation) and high density lipoprotein-cholesterol (HDL-C, positive) in both sexes and serum apolipoprotein A1 (ApoA1, positive) in the males. CE16:0 was positively related to TG and negatively related to HDL-C and ApoA1 in both sexes, and in males it related negatively to total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). In males, negative relationships were present between CE18:2n-6 and TC and between CE14:0 and serum lipoprotein(a). Smoking was independently associated with lower ApoA1 in both sexes and with lower HDL-C and higher TG, TC, LDL-C, and apolipoprotein B in males. In conclusion, marine n-3 fatty acids and linoleic acid showed the same potentially beneficial relationships with lipoproteins and apolipoproteins as in western populations. The relations of palmitic acid to serum lipids may be explained in terms of endogenous fat synthesis at a low-fat intake, rather than reflecting its relative intake.

  10. Trypanosome lytic factor, an antimicrobial high-density lipoprotein, ameliorates Leishmania infection.

    Directory of Open Access Journals (Sweden)

    Marie Samanovic

    2009-01-01

    Full Text Available Innate immunity is the first line of defense against invading microorganisms. Trypanosome Lytic Factor (TLF is a minor sub-fraction of human high-density lipoprotein that provides innate immunity by completely protecting humans from infection by most species of African trypanosomes, which belong to the Kinetoplastida order. Herein, we demonstrate the broader protective effects of human TLF, which inhibits intracellular infection by Leishmania, a kinetoplastid that replicates in phagolysosomes of macrophages. We show that TLF accumulates within the parasitophorous vacuole of macrophages in vitro and reduces the number of Leishmania metacyclic promastigotes, but not amastigotes. We do not detect any activation of the macrophages by TLF in the presence or absence of Leishmania, and therefore propose that TLF directly damages the parasite in the acidic parasitophorous vacuole. To investigate the physiological relevance of this observation, we have reconstituted lytic activity in vivo by generating mice that express the two main protein components of TLFs: human apolipoprotein L-I and haptoglobin-related protein. Both proteins are expressed in mice at levels equivalent to those found in humans and circulate within high-density lipoproteins. We find that TLF mice can ameliorate an infection with Leishmania by significantly reducing the pathogen burden. In contrast, TLF mice were not protected against infection by the kinetoplastid Trypanosoma cruzi, which infects many cell types and transiently passes through a phagolysosome. We conclude that TLF not only determines species specificity for African trypanosomes, but can also ameliorate an infection with Leishmania, while having no effect on T. cruzi. We propose that TLFs are a component of the innate immune system that can limit infections by their ability to selectively damage pathogens in phagolysosomes within the reticuloendothelial system.

  11. Combined analysis of six lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease: cross-sectional, prospective, and case-control studies from the Copenhagen City Heart Study

    DEFF Research Database (Denmark)

    Wittrup, HH; Andersen, RV; Tybjærg-Hansen, A;

    2006-01-01

    CONTEXT: Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD). OBJECTIVE: The objective of this study was to investigate the influence of T(-93)G, G(-53)C, Asp9Asn, Gly188Glu, Asn291Ser, and Ser447Ter lipoprotein....... SETTING: The study was performed in the Danish general population (the Copenhagen City Heart Study). PARTICIPANTS: IHD was angina pectoris or myocardial infarction. MAIN OUTCOME MEASURES: Triglycerides, HDL, and IHD were the main outcome measures. RESULTS: Cross-sectionally, triglycerides varied...... by genotype with 1.27 mmol/liter in women and 1.22 mmol/liter in men. HDL cholesterol varied by genotype with 0.49 mmol/liter in women and 0.60 mmol/liter in men. Prospectively, 9Asn (with -93G) heterozygotes and homozygotes combined vs. noncarriers had a hazard ratio for IHD of 1.6 [95% confidence interval...

  12. TOTAL CHOLESTEROL, HIGH DENSITY LIPOPROTEINS (HDL AND CORTISOL PLASMA LEVELS, AND THEIR BIORHYTMICITY, IN 24 HOURS, THROUGHOUT YEAR, IN IDEAL-POLWARTH RAMS NÍVEIS PLASMÁTICOS DE COLESTEROL TOTAL, LIPOPROTEÍNAS DE ALTA DENSIDADE (HDL E CORTISOL, E SUA BIORRITMICIDADE, EM CARNEIROS IDEAL-POLWARTH

    Directory of Open Access Journals (Sweden)

    Alcides de Amorim Ramos

    2006-12-01

    Full Text Available To evaluate the mean plasma concentrations of total cholesterol (TC, high density lipoproteins (HDL and cortisol, blood samples were collected of five Ideal-Polwarth rams, maintained at 22?53’S latitude, in semi-confinement, every two months throughout the year, by 24h period, with 2-hour intervals between colects. The TC, changed 40.70?1,11mg/dL (April and 61.48?1,11mg/dL (December, between months, while HDL changed 22.16?0.23mg/dL (December as 33.40?0.23mg/dL (February, but not make evident a circannual rhythm in this levels. The TC presented the lowest value at 16:30h (50.40?1.57mg/dL and the highest value at 8:30h collect (54.67?1.57mg/dL; the HDL lowest level was at 10:30h (27.04?0.33mg/dL and the highest level also at 8:30h collect (28.49?0.33mg/dL, however without permit circadian rhythm determination in your plasma concentrations. Similarly, the cortisol plasma concentrations, between collect months, presents variable, however without demonstrate circadian rhythm in this hormone secretion. In relation to different collection’s moments, throughout months, it wasn’t possible to define, by statistical analysis, a circadian rhythm of cortisol secretion. KEY WORDS: Ovine, adrenal hormone, biochemistry metabolites, circadian rhythm. Visando avaliar as concentrações médias de colesterol total (CT, lipoproteínas de alta densidade (HDL e cortisol plasmáticos, foram colhidas amostras de sangue de cinco carneiros Ideal-Polwarth, alocados em latitude 22°53’S, em regime de semiconfinamento, a cada dois meses, ao longo de um ano, com as colheitas em um período de 24 horas, e intervalos de duas horas entre elas. O CT oscilou entre 40,70±1,11mg/dL (abril e 61,48±1,11mg/dL (dezembro, entre os meses, enquanto HDL variou de 22,16±0,23mg/dL (dezembro a 33,40±0,23mg/dL (fevereiro, mas não evidenciando um ritmo circanual em seus níveis. O CT apresentou seu valor mínimo na colheita das 16h30min (50,40±1,57mg/dL e o máximo às 8h30min

  13. Association of High Density Lipoprotein with Platelet to Lymphocyte and Neutrophil to Lymphocyte Ratios in Coronary Artery Disease Patients

    Directory of Open Access Journals (Sweden)

    Jayesh H. Prajapati

    2014-01-01

    Full Text Available Background. We aimed to evaluate a relationship between platelet-lymphocyte ratio (PLR and neutrophil-lymphocyte ratio (NLR with high density lipoprotein (HDL cholesterol levels in coronary artery disease (CAD patients. Methods. A total of 354 patients with angiographically confirmed coronary blockages were enrolled in the study. Hematological indices and lipid profiling data of all the patients were collected. Results. We have observed significant association between HDL and PLR (P=0.008 and NLR (P=0.009; however no significant relationship was obtained with HDL and isolated platelet (P=0.488, neutrophil (P=0.407, and lymphocyte (P=0.952 counts in CAD patients. The association was subjected to gender specific variation as in males PLR (P=0.024 and NLR (P=0.03 were highly elevated in low HDL patients, whereas in females the elevation could not reach the statistically significant level. The PLR (217.47 versus 190.3; P=0.01 and NLR (6.33 versus 5.10; P=0.01 were significantly higher among the patients with acute coronary syndrome. In young patients the PLR (P=0.007 and NLR (P=0.001 were inversely associated with HDL, whereas in older population only NLR (P=0.05 had showed a significant association. Conclusion. We conclude that PLR and NLR are significantly elevated in CAD patients having low HDL levels.

  14. Cholesterol transfer from normal and atherogenic low density lipoproteins to Mycoplasma membranes

    International Nuclear Information System (INIS)

    The purpose of this study was to determine whether the free cholesterol of hypercholesterolemic low density lipoprotein from cholesterol-fed nonhuman primates has a greater potential for surface transfer to cell membranes than does the free cholesterol of normal low density lipoprotein. The low density lipoproteins were isolated from normal and hypercholesterolemic rhesus and cynomolgus monkeys, incubated with membranes from Acholeplasma laidlawii, a mycoplasma species devoid of cholesterol in its membranes, and the mass transfer of free cholesterol determined by measuring membrane cholesterol content. Since these membranes neither synthesize nor esterify cholesterol, nor degrade the protein or cholesterol ester moieties of low density lipoprotein, they are an ideal model with which to study differences in the cholesterol transfer potential of low density lipoprotein independent of the uptake of the intact low density lipoprotein particle. These studies indicate that, even though there are marked differences in the cholesterol composition of normal and hypercholesterolemic low density lipoproteins, this does not result in a greater chemical potential for surface transfer of free cholesterol. Consequently, if a difference in the surface transfer of free cholesterol is responsible for the enhanced ability of hypercholesterolemic low density lipoprotein to promote cellular cholesterol accumulation and, perhaps, also atherosclerosis, it must be the result of differences in the interaction to the hypercholesterolemic low density lipoprotein with the more complicated mammalian cell membranes, rather than differences in the chemical potential for cholesterol transfer

  15. Clinical significance of high-density lipoproteins and the development of atherosclerosis: focus on the role of the adenosine triphosphate-binding cassette protein A1 transporter.

    Science.gov (United States)

    Brewer, H Bryan; Santamarina-Fojo, Silvia

    2003-08-21

    Low levels of high-density lipoprotein (HDL) cholesterol constitute a risk factor for coronary artery disease, and there is evidence that increasing HDL cholesterol levels reduces cardiovascular risk. The phenotype of low HDL cholesterol with or without elevated triglycerides is at least as common in patients hospitalized for cardiovascular disease as is hypercholesterolemia, and it is characteristic of diabetes and the metabolic syndrome, conditions associated with increased cardiovascular risk. Recent studies have elucidated mechanisms by which HDL acts to reduce cardiovascular risk, bolstering the rationale for targeting of HDL in lipid-modifying therapy. In particular, HDL (1) carries excess cholesterol from peripheral cells to the liver for removal in the process termed reverse cholesterol transport, (2) reduces oxidative modification of low-density lipoproteins (LDL), and (3) inhibits cytokine-induced expression of cellular adhesion molecules on endothelial cells. Studies of the newly described adenosine triphosphate-binding cassette protein A1 (ABCA1) transporter have established a crucial role for this transporter in modulating the levels of plasma HDL and intracellular cholesterol in the liver as well as in peripheral cells. Elevated levels of intracellular cholesterol stimulate the liver X receptor pathway, enhancing the expression of ABCA1, which increases intracellular trafficking of excess cholesterol to the cell surface for interaction with lipid-poor apolipoprotein A-I to form nascent HDL. Nascent HDL facilitates the removal of additional excess cellular cholesterol, which is esterified by lecithin-cholesterol acyltransferase with conversion of the nascent HDL to mature spherical HDL. Overexpression of ABCA1 in mice on a regular chow or Western diet results in a marked increase in plasma HDL, increased LDL, and increased transport of cholesterol to the liver. On a high cholesterol/cholate diet, transgenic mice overexpressing ABCA1 have increased HDL

  16. High density lipoprotein (HDL) metabolism in noninsulin-dependent diabetes mellitus: measurement of HDL turnover using tritiated HDL

    Energy Technology Data Exchange (ETDEWEB)

    Golay, A.; Zech, L.; Shi, M.Z.; Chiou, Y.A.; Reaven, G.M.; Chen, Y.D.

    1987-09-01

    High density lipoprotein (HDL) kinetics were studied by injecting (/sup 3/H)apoprotein A-I (apoA-I)/HDL into 12 subjects with normal glucose tolerance and 12 patients with noninsulin-dependent diabetes mellitus (NIDDM). The results indicate that the mean fractional catabolic rate (FCR) of apoA-I/HDL was significantly faster (0.63 +/- 0.07 (+/- SEM) vs. 0.39 +/- 0.02 1/day; P less than 0.001) and the apoA-I/HDL synthetic rate greater (29.4 +/- 2.9 vs. 22.9 +/- 1.3 mg/kg X day; P less than 0.02) in patients with NIDDM than in normal subjects. Furthermore, there were statistically significant inverse relationships between apoA-I/HDL FCR and plasma levels of both HDL cholesterol (r = -0.71; P less than 0.001) and apoA-I (r = -0.63; P less than 0.001). In addition, the increase in apoA-I/HDL FCR was directly related to fasting plasma glucose (r = 0.78; P less than 0.001) and insulin (r = 0.76; P less than 0.001) concentrations. These data support the view that the decrease in plasma HDL cholesterol and apoA-I levels commonly found in patients with noninsulin-dependent diabetes is due to an increase in the catabolic rate of apoA-I/HDL secondary to the defects in carbohydrate metabolism present in these patients.

  17. Multidrug resistance P-glycoprotein dampens SR-BI cholesteryl ester uptake from high density lipoproteins in human leukemia cells.

    Science.gov (United States)

    Spolitu, Stefano; Uda, Sabrina; Deligia, Stefania; Frau, Alessandra; Collu, Maria; Angius, Fabrizio; Batetta, Barbara

    2016-01-01

    Tumor cells are characterised by a high content of cholesterol esters (CEs), while tumor-bearing patients show low levels of high-density lipoproteins (HDLs). The origin and significance of high CE levels in cancer cell biology has not been completely clarified. Recent evidence that lymphoblastic cells selectively acquire exogenous CE from HDL via the scavenger receptor SR-BI has drawn attention to the additional membrane proteins involved in this pathway. P-glycopotein-MDR1 (P-gp) is a product of the MDR1 gene and confers resistance to antitumor drugs. Its possible role in plasma membrane cholesterol trafficking and CE metabolism has been suggested. In the present study this aspect was investigated in a lymphoblastic cell line selected for MDR1 resistance. CEM were made resistant by stepwise exposure to low (LR) and high (HR) doses of vincristine (VCR). P-gp activity ((3)H-vinblastine), CE content, CE and triglycerides (TG) synthesis ((14)C-oleate), neutral lipids and Dil-HDL uptake (fluorescence), SR-BI, ABCA1 and P-gp protein expression (western blotting) were determined. To better evaluate the relationship between CE metabolism and P-gp activity, the ACAT inhibitor Sandoz-58035 and the P-gp inhibitors progesterone, cyclosporine and verapamil were used. CE content and synthesis were similar in the parental and resistant cells. However, in the latter population, SR-BI protein expression increased, whereas CE-HDL uptake decreased. These changes correlated with the degree of VCR-resistance. As well as reverting MDR1-resistance, the inhibitors of P-gp activity induced the CE-HDL/SR-BI pathway by reactivating membrane cholesterol trafficking. Indeed, CE-HDL uptake, SRBI expression and CE content increased, whereas there was a decrease in cholesterol esterification. These results demonstrated that P-gp overexpression impairs anticancer drug uptake as well as the SR-BI mediated selective CE-HDL uptake. This suggests that these membrane proteins act in an opposite

  18. High-Density and Very-Low-Density Lipoprotein Have Opposing Roles in Regulating Tumor-Initiating Cells and Sensitivity to Radiation in Inflammatory Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, Adam R. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Atkinson, Rachel L. [Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reddy, Jay P. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Debeb, Bisrat G.; Larson, Richard; Li, Li [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Masuda, Hiroko; Brewer, Takae [Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Atkinson, Bradley J. [Department of Clinical Pharmacy Services, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Brewster, Abeena [Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ueno, Naoto T. [Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Woodward, Wendy A., E-mail: wwoodward@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-04-01

    Purpose: We previously demonstrated that cholesterol-lowering agents regulate radiation sensitivity of inflammatory breast cancer (IBC) cell lines in vitro and are associated with less radiation resistance among IBC patients who undergo postmastectomy radiation. We hypothesized that decreasing IBC cellular cholesterol induced by treatment with lipoproteins would increase radiation sensitivity. Here, we examined the impact of specific transporters of cholesterol (ie lipoproteins) on the responses of IBC cells to self-renewal and to radiation in vitro and on clinical outcomes in IBC patients. Methods and Materials: Two patient-derived IBC cell lines, SUM 149 and KPL4, were incubated with low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), or high-density lipoproteins (HDL) for 24 hours prior to irradiation (0-6 Gy) and mammosphere formation assay. Cholesterol panels were examined in a cohort of patients with primary IBC diagnosed between 1995 and 2011 at MD Anderson Cancer Center. Lipoprotein levels were then correlated to patient outcome, using the log rank statistical model, and examined in multivariate analysis using Cox regression. Results: VLDL increased and HDL decreased mammosphere formation compared to untreated SUM 149 and KPL4 cells. Survival curves showed enhancement of survival in both of the IBC cell lines when pretreated with VLDL and, conversely, radiation sensitization in all cell lines when pretreated with HDL. In IBC patients, higher VLDL values (>30 mg/dL) predicted a lower 5-year overall survival rate than normal values (hazard ratio [HR] = 1.9 [95% confidence interval [CI]: 1.05-3.45], P=.035). Lower-than-normal patient HDL values (<60 mg/dL) predicted a lower 5-year overall survival rate than values higher than 60 mg/dL (HR = 3.21 [95% CI: 1.25-8.27], P=.015). Conclusions: This study discovered a relationship among the plasma levels of lipoproteins, overall patient response, and radiation resistance in IBC patients

  19. High-Density and Very-Low-Density Lipoprotein Have Opposing Roles in Regulating Tumor-Initiating Cells and Sensitivity to Radiation in Inflammatory Breast Cancer

    International Nuclear Information System (INIS)

    Purpose: We previously demonstrated that cholesterol-lowering agents regulate radiation sensitivity of inflammatory breast cancer (IBC) cell lines in vitro and are associated with less radiation resistance among IBC patients who undergo postmastectomy radiation. We hypothesized that decreasing IBC cellular cholesterol induced by treatment with lipoproteins would increase radiation sensitivity. Here, we examined the impact of specific transporters of cholesterol (ie lipoproteins) on the responses of IBC cells to self-renewal and to radiation in vitro and on clinical outcomes in IBC patients. Methods and Materials: Two patient-derived IBC cell lines, SUM 149 and KPL4, were incubated with low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), or high-density lipoproteins (HDL) for 24 hours prior to irradiation (0-6 Gy) and mammosphere formation assay. Cholesterol panels were examined in a cohort of patients with primary IBC diagnosed between 1995 and 2011 at MD Anderson Cancer Center. Lipoprotein levels were then correlated to patient outcome, using the log rank statistical model, and examined in multivariate analysis using Cox regression. Results: VLDL increased and HDL decreased mammosphere formation compared to untreated SUM 149 and KPL4 cells. Survival curves showed enhancement of survival in both of the IBC cell lines when pretreated with VLDL and, conversely, radiation sensitization in all cell lines when pretreated with HDL. In IBC patients, higher VLDL values (>30 mg/dL) predicted a lower 5-year overall survival rate than normal values (hazard ratio [HR] = 1.9 [95% confidence interval [CI]: 1.05-3.45], P=.035). Lower-than-normal patient HDL values (<60 mg/dL) predicted a lower 5-year overall survival rate than values higher than 60 mg/dL (HR = 3.21 [95% CI: 1.25-8.27], P=.015). Conclusions: This study discovered a relationship among the plasma levels of lipoproteins, overall patient response, and radiation resistance in IBC patients

  20. SR-BI: Linking Cholesterol and Lipoprotein Metabolism with Breast and Prostate Cancer

    Science.gov (United States)

    Gutierrez-Pajares, Jorge L.; Ben Hassen, Céline; Chevalier, Stéphan; Frank, Philippe G.

    2016-01-01

    Studies have demonstrated the significant role of cholesterol and lipoprotein metabolism in the progression of cancer. The SCARB1 gene encodes the scavenger receptor class B type I (SR-BI), which is an 82-kDa glycoprotein with two transmembrane domains separated by a large extracellular loop. SR-BI plays an important role in the regulation of cholesterol exchange between cells and high-density lipoproteins. Accordingly, hepatic SR-BI has been shown to play an essential role in the regulation of the reverse cholesterol transport pathway, which promotes the removal and excretion of excess body cholesterol. In the context of atherosclerosis, SR-BI has been implicated in the regulation of intracellular signaling, lipid accumulation, foam cell formation, and cellular apoptosis. Furthermore, since lipid metabolism is a relevant target for cancer treatment, recent studies have focused on examining the role of SR-BI in this pathology. While signaling pathways have initially been explored in non-tumoral cells, studies with cancer cells have now demonstrated SR-BI's function in tumor progression. In this review, we will discuss the role of SR-BI during tumor development and malignant progression. In addition, we will provide insights into the transcriptional and post-transcriptional regulation of the SCARB1 gene. Overall, studying the role of SR-BI in tumor development and progression should allow us to gain useful information for the development of new therapeutic strategies.

  1. Lipoprotein Lipase and PPAR Alpha Gene Polymorphisms, Increased Very-Low-Density Lipoprotein Levels, and Decreased High-Density Lipoprotein Levels as Risk Markers for the Development of Visceral Leishmaniasis by Leishmania infantum

    Directory of Open Access Journals (Sweden)

    Márcia Dias Teixeira Carvalho

    2014-01-01

    Full Text Available In visceral leishmaniasis (VL endemic areas, a minority of infected individuals progress to disease since most of them develop protective immunity. Therefore, we investigated the risk markers of VL within nonimmune sector. Analyzing infected symptomatic and, asymptomatic, and noninfected individuals, VL patients presented with reduced high-density lipoprotein cholesterol (HDL-C, elevated triacylglycerol (TAG, and elevated very-low-density lipoprotein cholesterol (VLDL-C levels. A polymorphism analysis of the lipoprotein lipase (LPL gene using HindIII restriction digestion (N = 156 samples (H+ = the presence and H− = the absence of mutation revealed an increased adjusted odds ratio (OR of VL versus noninfected individuals when the H+/H+ was compared with the H−/H− genotype (OR = 21.3; 95% CI = 2.32–3335.3; P = 0.003. The H+/H+ genotype and the H+ allele were associated with elevated VLDL-C and TAG levels (P < 0.05 and reduced HDL-C levels (P < 0.05. An analysis of the L162V polymorphism in the peroxisome proliferator-activated receptor alpha (PPARα gene (n = 248 revealed an increased adjusted OR when the Leu/Val was compared with the Leu/Leu genotype (OR = 8.77; 95% CI = 1.41–78.70; P = 0.014. High TAG (P = 0.021 and VLDL-C (P = 0.023 levels were associated with susceptibility to VL, whereas low HDL (P = 0.006 levels with resistance to infection. The mutated LPL and the PPARα Leu/Val genotypes may be considered risk markers for the development of VL.

  2. High-density lipoprotein loses its anti-inflammatory capacity by accumulation of pro-inflammatory-serum amyloid A

    NARCIS (Netherlands)

    Toelle, Markus; Huang, Tao; Schuchardt, Mirjam; Jankowski, Vera; Pruefer, Nicole; Jankowski, Joachim; Tietge, Uwe J. F.; Zidek, Walter; van der Giet, Markus

    2012-01-01

    Aims High-density lipoprotein (HDL) is known to have potent anti-inflammatory properties. Monocyte chemoattractant protein-1 is an important pro-inflammatory cytokine in early atherogenesis. There is evidence that HDL can lose its protective function during inflammatory disease. In patients with end

  3. Pitavastatin versus Pravastatin in Reduction of Remnant Lipoprotein Cholesterol in Patients with Dyslipidemias.

    Science.gov (United States)

    Roever, Leonardo

    2016-05-01

    Remnant lipoproteins cholesterol are products of partially catabolized chylomicrons and very-low-density lipoprotein, from which some triglycerides have been removed. These particles are smaller and are believed to be strongly atherogenic. Elevated Remnant lipoproteins cholesterol levels were reported to be associated with endothelial dysfunction and atherosclerotic disease.

  4. Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles

    Directory of Open Access Journals (Sweden)

    Mian M.K. Shahzad

    2011-04-01

    Full Text Available RNA interference holds tremendous potential as a therapeutic approach, especially in the treatment of malignant tumors. However, efficient and biocompatible delivery methods are needed for systemic delivery of small interfering RNA (siRNA. To maintain a high level of growth, tumor cells scavenge high-density lipoprotein (HDL particles by overexpressing its receptor: scavenger receptor type B1 (SR-B1. In this study, we exploited this cellular characteristic to achieve efficient siRNA delivery and established a novel formulation of siRNA by incorporating it into reconstituted HDL (rHDL nanoparticles. Here, we demonstrate that rHDL nanoparticles facilitate highly efficient systemic delivery of siRNA in vivo, mediated by the SR-B1. Moreover, in therapeutic proof-of-concept studies, these nanoparticles were effective in silencing the expression of two proteins that are key to cancer growth and metastasis (signal transducer and activator of transcription 3 and focal adhesion kinase in orthotopic mouse models of ovarian and colorectal cancer. These data indicate that an rHDL nanoparticle is a novel and highly efficient siRNA carrier, and therefore, this novel technology could serve as the foundation for new cancer therapeutic approaches.

  5. Long term stability of paraoxonase-1 and high-density lipoprotein in human serum

    Directory of Open Access Journals (Sweden)

    Beekhof Piet K

    2012-05-01

    Full Text Available Abstract Background Paraoxonase-1 (PON1 is an enzyme with numerous functions and receives an increasing interest in clinical and epidemiological studies. Sometimes samples are stored for longer periods at a certain temperature. Therefore the stability of PON1 activity must be checked and retained upon storage for longer periods. Results In this study the stability of PON1 activity has been tested in human serum samples during storage up to 12 months at 3 commonly used temperatures, -20°C, -70°C and −196°C. It was found that the stability of the PON1 activity is constant during 12 months of storage at −70°C and −196°C. Storage at −20°C resulted in a small but statistically significant decrease after 6 months to about 94% of its original value. Nonetheless, the rank order between the samples at T = 0 and 12 months remained the same. The same temperature dependence was found for the associated high-density lipoprotein. Conclusions It can be concluded that −70°C is the right temperature for storage to maintain the PON1 activity for at least one year. Storage at a lower temperature in liquid nitrogen (−196°C is not necessary.

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

    Science.gov (United States)

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

    2014-01-01

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

  7. A Biomimic Reconstituted High Density Lipoprotein Nanosystem for Enhanced VEGF Gene Therapy of Myocardial Ischemia

    Directory of Open Access Journals (Sweden)

    Xiaotian Sun

    2015-01-01

    Full Text Available A biomimic reconstituted high density lipoprotein (rHDL based system, rHDL/Stearic-PEI/VEGF complexes, was fabricated as an advanced nanovector for delivering VEGF plasmid. Here, Stearic-PEI was utilized to effectively condense VEGF plasmid and to incorporate the plasmid into rHDL. The rHDL/Stearic-PEI/VEGF complexes with diameter under 100 nm and neutral surface charge demonstrated enhanced stability under the presence of bovine serum albumin. Moreover, in vitro cytotoxicity and transfection assays on H9C2 cells further revealed their superiority, as they displayed lower cytotoxicity with much higher transfection efficiency when compared to PEI 10K/VEGF and Lipos/Stearic-PEI/VEGF complexes. In addition, in vivo investigation on ischemia/reperfusion rat model implied that rHDL/Stearic-PEI/VEGF complexes possessed high transgene capacity and strong therapeutic activity. These findings indicated that rHDL/Stearic-PEI/VEGF complexes could be an ideal gene delivery system for enhanced VEGF gene therapy of myocardial ischemia, which might be a new promising strategy for effective myocardial ischemia treatment.

  8. Bone and high-density lipoprotein: The beginning of a beautiful friendship.

    Science.gov (United States)

    Papachristou, Dionysios J; Blair, Harry C

    2016-02-18

    There is a tight link between bone and lipid metabolic pathways. In this vein, several studies focused on the exploration of high-density lipoprotein (HDL) in the pathobiology of bone diseases, with emphasis to the osteoarthritis (OA) and osteoporosis, the most common bone pathologies. Indeed, epidemiological and in vitro data have connected reduced HDL levels or dysfunctional HDL with cartilage destruction and OA development. Recent studies uncovered functional links between HDL and OA fueling the interesting hypothesis that OA could be a chronic element of the metabolic syndrome. Other studies have linked HDL to bone mineral density. Even though at epidemiological levels the results are conflicting, studies in animals as well as in vitro experiments have shown that HDL facilitates osteoblastogensis and bone synthesis and most probably affects osteoclastogenesis and osteoclast bone resorption. Notably, reduced HDL levels result in increased bone marrow adiposity affecting bone cells function. Unveiling the mechanisms that connect HDL and bone/cartilage homeostasis may contribute to the design of novel therapeutic agents for the improvement of bone and cartilage quality and thus for the treatment of related pathological conditions. PMID:26925377

  9. Modulation of Lipoprotein Cholesterol Levels in Plasmodium berghei Malarial Infection by Crude Aqueous Extract of Ganoderma lucidum

    Directory of Open Access Journals (Sweden)

    Olarewaju M. Oluba

    2012-01-01

    Full Text Available In this study, attempt is made to establish changes in serum and liver lipoprotein cholesterols accompanying Plasmodium berghei malarial infection in mice treated with aqueous extract of Ganoderma lucidum at 100, 250, and 500 mg/kg body weight in comparison with 15 mg/kg chloroquine (CQ. Significant increases in all the lipoprotein fractions were observed in infected untreated mice compared with normal control mice. Treatment with 100 and 250 mg/kg G. lucidum extract produced significant reduction in serum total cholesterol (TC and low-density cholesterol (LDL-C contents compared with 500 mg/kg G. lucidum and CQ. Treatment with CQ, however, produced significant reduction in hepatic TC and LDL-C compared with the extract. A dose-dependent significant increase in serum high-density lipoprotein cholesterol (HDL-C was observed in the G. lucidum treated mice compared with normal control but significantly lower compared with CQ-treated mice. Liver HDL-C level was significantly higher in CQ-treated mice compared with normal control and significantly lower compared with G. lucidum-treated and infected untreated mice. A dose-dependent effect of the extract was observed in both serum and liver very-low density lipoprotein cholesterol (VLDL-C. The implication of these results is discussed with respect to the parasite survival and proliferation in the serum and liver.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-04-01

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

  11. Liver gene transfer of interkeukin-15 constructs that become part of circulating high density lipoproteins for immunotherapy.

    Directory of Open Access Journals (Sweden)

    Maria C Ochoa

    Full Text Available Apolipoprotein A-I (Apo A-I is a major component of high density lipoproteins (HDL that transport cholesterol in circulation. We have constructed an expression plasmid encoding a chimeric molecule encompassing interleukin-15 (IL-15 and Apo A-I (pApo-hIL15 that was tested by hydrodynamic injections into mice and was co-administered with a plasmid encoding the sushi domain of IL-15Rα (pSushi in order to enhance IL-15 trans-presentation and thereby bioactivity. The pharmacokinetics of the Apo A-I chimeric protein were much longer than non-stabilized IL-15 and its bioactivity was enhanced in combination with IL-15Rα Sushi. Importantly, the APO-IL-15 fusion protein was incorporated in part into circulating HDL. Liver gene transfer of these constructs increased NK and memory-phenotype CD8 lymphocyte numbers in peripheral blood, spleen and liver as a result of proliferation documented by CFSE dilution and BrdU incorporation. Moreover, the gene transfer procedure partly rescued the NK and memory T-cell deficiency observed in IL-15Rα(-/- mice. pApo-hIL15+ pSushi gene transfer to the liver showed a modest therapeutic activity against subcutaneously transplanted MC38 colon carcinoma tumors, that was more evident when tumors were set up as liver metastases. The improved pharmacokinetic profile and the strong biological activity of APO-IL-15 fusion protein holds promise for further development in combination with other immunotherapies.

  12. Biophysical characterization of the interaction of high-density lipoprotein (HDL) with endotoxins.

    Science.gov (United States)

    Brandenburg, Klaus; Jürgens, Gudrun; Andrä, Jörg; Lindner, Buko; Koch, Michel H J; Blume, Alfred; Garidel, Patrick

    2002-12-01

    The interaction of bacterial endotoxins [lipopolysaccharide (LPS) and the 'endotoxic principle' lipid A], with high-density lipoprotein (HDL) from serum was investigated with a variety of physical techniques and biological assays. HDL exhibited an increase in the gel to liquid crystalline phase transition temperature Tc and a rigidification of the acyl chains of the endotoxins as measured by Fourier-transform infrared spectroscopy and differential scanning calorimetry. The functional groups of the endotoxins interacting with HDL are the phosphates and the diglucosamine backbone. The finding of phosphates as target groups is in accordance to measurements of the electrophoretic mobility showing that the zeta potential decreases from -50 to -60 mV to -20 mV at binding saturation. The importance of the sugar backbone as further target structure is in accordance with the remaining negative potential and competition experiments with polymyxin B (PMB) and phase transition data of the system PMB/dephosphorylated LPS. Furthermore, endotoxin binding to HDL influences the secondary structure of the latter manifesting in a change from a mixed alpha-helical/beta-sheet structure to a predominantly alpha-helical structure. The aggregate structure of the lipid A moiety of the endotoxins as determined by small-angle X-ray scattering shows a change of a unilamellar/inverted cubic into a multilamellar structure in the presence of HDL. Fluorescence resonance energy transfer data indicate an intercalation of pure HDL, and of [LPS]-[HDL] complexes into phospholipid liposomes. Furthermore, HDL may enhance the lipopolysaccharide-binding protein-induced intercalation of LPS into phospholipid liposomes. Parallel to these observations, the LPS-induced cytokine production of human mononuclear cells and the reactivity in the Limulus test are strongly reduced by the addition of HDL. These data allow to develop a model of the [endotoxin]/[HDL] interaction. PMID:12444987

  13. High density lipoprotein (HDL promotes glucose uptake in adipocytes and glycogen synthesis in muscle cells.

    Directory of Open Access Journals (Sweden)

    Qichun Zhang

    Full Text Available BACKGROUND: High density lipoprotein (HDL was reported to decrease plasma glucose and promote insulin secretion in type 2 diabetes patients. This investigation was designed to determine the effects and mechanisms of HDL on glucose uptake in adipocytes and glycogen synthesis in muscle cells. METHODS AND RESULTS: Actions of HDL on glucose uptake and GLUT4 translocation were assessed with 1-[(3H]-2-deoxyglucose and plasma membrane lawn, respectively, in 3T3-L1 adipocytes. Glycogen analysis was performed with amyloglucosidase and glucose oxidase-peroxidase methods in normal and palmitate-treated L6 cells. Small interfering RNA was used to observe role of scavenger receptor type I (SR-BI in glucose uptake of HDL. Corresponding signaling molecules were detected by immunoblotting. HDL stimulated glucose uptake in a time- and concentration-dependent manner in 3T3-L1 adipocytes. GLUT4 translocation was significantly increased by HDL. Glycogen deposition got enhanced in L6 muscle cells paralleling with elevated glycogen synthase kinase3 (GSK3 phosphorylation. Meanwhile, increased phosphorylations of Akt-Ser473 and AMP activated protein kinase (AMPK α were detected in 3T3-L1 adipocytes. Glucose uptake and Akt-Ser473 activation but not AMPK-α were diminished in SR-BI knock-down 3T3-L1 cells. CONCLUSIONS: HDL stimulates glucose uptake in 3T3-L1 adipocytes through enhancing GLUT4 translocation by mechanisms involving PI3K/Akt via SR-BI and AMPK signaling pathways, and increases glycogen deposition in L6 muscle cells through promoting GSK3 phosphorylation.

  14. Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

    DEFF Research Database (Denmark)

    Varbo, Anette; Tybjærg-Hansen, Anne; Nordestgaard, Børge G;

    2013-01-01

    Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown....

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

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M.; Brown, Robert J., E-mail: rbrown@mun.ca

    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.

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

    International Nuclear Information System (INIS)

    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

  17. Association of dietary fiber intake with serum total cholesterol and low density lipoprotein cholesterol levels in Urban Asian-Indian adults with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Shreya Narayan

    2014-01-01

    Full Text Available Context: There is little data correlating dietary fibre (DF intake and cardiovascular risk in Asian Indians with diabetes. Aim: To assess the DF intake and its association with lipid profile (total serum cholesterol and low density lipoprotein [LDL] - cholesterol levels in urban Asian Indians with diabetes. Subjects and Methods: Dietary assessment using validated Food Frequency Questionnaire was conducted in 1191 free-living adults with known diabetes in the Chennai Urban Rural Epidemiology Study. Subjects taking medication for dyslipidemia, and those with cardiovascular disease and implausible energy intake (n = 262 were excluded, leaving 929 participants. Anthropometric and relevant biochemical parameters were measured using standardized techniques. Results: Diabetic individuals who consumed DF median intake of DF group. The risk of hypercholesterolemia (odds ratio [OR] =1.38 [95% confidence interval [CI]: 1.02-1.85], P = 0.04, and high LDL cholesterol (OR: 1.43 [95% CI: 1.06-1.94], P = 0.02 was higher among those whose DF intake was less than the median. Serum triglycerides and high density lipoprotein cholesterol were not associated with DF intake. The main sources of DF were vegetables and legumes. Conclusion: In urban Asian Indians with diabetes, lower DF intake is positively related to total cholesterol and LDL cholesterol levels.

  18. Effects of curcumin on serum total cholesterol and high-density lipoprotein contents and expression of ABCA1 and apoA1 in CA1 region of hippocampus in APP/PS1 double transgenic mice%姜黄素对APP/PS1双转基因鼠海马ABCA1、apoA1的表达和血清TC、HDL含量的影响

    Institute of Scientific and Technical Information of China (English)

    滕志朋; 王晨; 张雄; 李昱

    2014-01-01

    目的:探讨姜黄素对APP/PS1双转基因鼠海马组织中三磷酸腺苷结合盒转运子A1 (ATP binding cassette transport proteinA1,ABCA1)和载脂蛋白A1(apolipoprotein A1,apoA1)的表达及血清中总胆固醇(total cholesterol,TC)和高密度脂蛋白(high-density lipoprotein,HDL)含量的影响.方法:用APP/PS1双转基因鼠建立阿尔茨海默病(Alzheimer's disease,AD)模型,不同浓度姜黄素饲料喂养6个月.免疫组化SP法检测转基因鼠的海马组织CA1区ABCA1和apoA1的表达变化.胆固醇酶法比色法检测血清中TC和HDL的含量.结果:经过不同浓度姜黄素饲喂转基因鼠后,其海马组织CA1区ABCA1和apoA1的表达增加(P=o.005和0.003; P=0.025和0.001),且血清中HDL的含量也随之增加,TC的含量逐渐减少,其差异均有统计学意义(P=0.041和0.010;P=0.046和0.002).结论:ABCA1在AD的发生发展中起着重要的作用,姜黄素可能是通过增加ABCA1表达和升高apoA1和HDL含量降低胆固醇水平.

  19. The high-density lipoprotein-adjusted SCORE model worsens SCORE-based risk classification in a contemporary population of 30,824 Europeans

    DEFF Research Database (Denmark)

    Mortensen, Martin B; Afzal, Shoaib; Nordestgaard, Børge G;

    2015-01-01

    AIMS: Recent European guidelines recommend to include high-density lipoprotein (HDL) cholesterol in risk assessment for primary prevention of cardiovascular disease (CVD), using a SCORE-based risk model (SCORE-HDL). We compared the predictive performance of SCORE-HDL with SCORE in an independent.......8 years of follow-up, 339 individuals died of CVD. In the SCORE target population (age 40-65; n = 30,824), fewer individuals were at baseline categorized as high risk (≥5% 10-year risk of fatal CVD) using SCORE-HDL compared with SCORE (10 vs. 17% in men, 1 vs. 3% in women). SCORE-HDL did not improve...... discrimination of future fatal CVD, compared with SCORE, but decreased the detection rate (sensitivity) of the 5% high-risk threshold from 42 to 26%, yielding a negative net reclassification index (NRI) of -12%. Importantly, using SCORE-HDL, the sensitivity was zero among women. Both SCORE and SCORE...

  20. Changes in chemical composition and physico-chemical properties of chick low- and high-density lipoproteins induced by supplementation of coconut oil to the diet.

    Science.gov (United States)

    Talavera, E M; Zafra, M F; Gil-Villarino, A; Pérez, M I; Alvarez-Pez, J M; García-Peregrín, E

    1997-06-01

    Supplementation of coconut oil to the diet for 1-2 weeks produced a significant hypercholesterolemia in 14-day-old chicks. Changes in plasma fatty acid composition correlated positively with those of diets. In this study, we have shown a different response of low- and high-density lipoprotein (LDL and HDL) fractions to dietary saturated fat (coconut oil) rich in lauric and myristic acids. Although all the components of these particles seemed to increase, the percentages of increases found in total (TC), free (FC) and esterified cholesterol (EC) were higher in LDL than in HDL. TC/phospholipid (PL) ratio, considered as an inverse index of membrane fluidity, also increased with the dietary regimen in LDL, while no significant differences were found in HDL. These results suggest that supplementation of coconut oil to the diet decreased the fluidity of LDL. The EC/triglycerides (TG) ratio was also significantly increased in LDL, corroborating the main atherogenic function of this lipoprotein fraction in response to lauric and myristic acids. We have also estimated the lipidic order parameter, S, from the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH)-labelled low- and high-density lipoproteins. In LDL, temperature dependence of S shows two different behaviour zones at about 20 degrees C. In HDL, the plot of S values versus T is linear. DPH anisotropy and S increased in both LDL and HDL from treated chicks. This increase becomes more evident as temperature rises and also with dietary treatment.

  1. Achieving secondary prevention low-density lipoprotein particle concentration goals using lipoprotein cholesterol-based data.

    Directory of Open Access Journals (Sweden)

    Simon C Mathews

    Full Text Available BACKGROUND: Epidemiologic studies suggest that LDL particle concentration (LDL-P may remain elevated at guideline recommended LDL cholesterol goals, representing a source of residual risk. We examined the following seven separate lipid parameters in achieving the LDL-P goal of <1000 nmol/L goal for very high risk secondary prevention: total cholesterol to HDL cholesterol ratio, TC/HDL, <3; a composite of ATP-III very high risk targets, LDL-C<70 mg/dL, non-HDL-C<100 mg/dL and TG<150 mg/dL; a composite of standard secondary risk targets, LDL-C<100, non-HDL-C<130, TG<150; LDL phenotype; HDL-C ≥ 40; TG<150; and TG/HDL-C<3. METHODS: We measured ApoB, ApoAI, ultracentrifugation lipoprotein cholesterol and NMR lipoprotein particle concentration in 148 unselected primary and secondary prevention patients. RESULTS: TC/HDL-C<3 effectively discriminated subjects by LDL-P goal (F = 84.1, p<10(-6. The ATP-III very high risk composite target (LDL-C<70, nonHDL-C<100, TG<150 was also effective (F = 42.8, p<10(-5. However, the standard secondary prevention composite (LDL-C<100, non-HDL-C<130, TG<150 was also effective but yielded higher LDL-P than the very high risk composite (F = 42.0, p<10(-5 with upper 95% confidence interval of LDL-P less than 1000 nmol/L. TG<150 and TG/HDL-C<3 cutpoints both significantly discriminated subjects but the LDL-P upper 95% confidence intervals fell above goal of 1000 nmol/L (F = 15.8, p = 0.0001 and F = 9.7, p = 0.002 respectively. LDL density phenotype neared significance (F = 2.85, p = 0.094 and the HDL-C cutpoint of 40 mg/dL did not discriminate (F = 0.53, p = 0.47 alone or add discriminatory power to ATP-III targets. CONCLUSIONS: A simple composite of ATP-III very high risk lipoprotein cholesterol based treatment targets or TC/HDL-C ratio <3 most effectively identified subjects meeting the secondary prevention target level of LDL-P<1000 nmol/L, providing a potential alternative to advanced lipid testing in many clinical

  2. Effect of Curcumin on ABCA1, serum high density lipoprotein and total cholesterol in chronic cerebral hypoperfusion aging rats%姜黄素对慢性脑血流灌注不足老龄鼠三磷酸腺苷结合盒转运体A1、血清高密度脂蛋白和总胆固醇的影响

    Institute of Scientific and Technical Information of China (English)

    田茗源; 王林辉; 滕志朋; 王晨; 李昱

    2012-01-01

    目的:探讨姜黄素(Curcumin)对脑血流灌注不足老龄鼠海马组织CA1区三磷酸腺苷结合盒转运体A1(ATP binding cassette transporter A1,ABCA1)的表达及血清中总胆固醇(Total cholesterol,TC)、高密度脂蛋白(High density lipoprotein,HDL)的影响.方法:采用双侧颈总动脉永久性结扎模型制备慢性脑缺血模型,老龄鼠随机分为正常对照组、药物治疗组、单纯缺血组、假手术组,药物治疗组又分为高剂量组(姜黄素100mg/kg)和低剂量组(姜黄素50mg/kg),治疗组于术后24h开始用姜黄素每日腹腔注射,给药连续30d.采用苏木素-伊红染色观察大鼠海马CA1区锥体细胞形态学改变,采用生化方法检测血清HDL和TC水平,采用免疫组织化学染色方法分析大鼠海马组织ABCA1蛋白表达情况.结果:苏木素-伊红染色显示,与假手术组和正常对照组相比,单纯缺血组的海马CA1区的锥体细胞发生变性,部分神经元溶解消失.而药物治疗组CA1区未见明显缺血性改变,与正常对照组和假手术组相比,单纯缺血组的血清HDL和TC明显降低(P<0.05).与单纯缺血组相比,药物治疗组脑血流灌注不足老龄鼠血清HDL、TC水平明显升高(P<0.05).免疫组化结果表明:与单纯缺血组相比,药物治疗组海马CA1区锥体细胞ABCA1的表达水平明显升高(P<0.05).结论:姜黄素可以通过提高ABCA1的表达从而改善慢性脑血流灌注不足导致的海马CA1区损伤,并提高药物治疗组血清HDL和TC水平.这为血管性痴呆的治疗提供新的实验依据.%Objective: To investigate the effects of Curcumin on expressions of ATP binding cassette transporter A1 (ABCA1) in CA1 region of hippocampus and serum high density lipoprotein(HDL) and total cholesterol (TC) in rats induced by permanent bilateral common carotid artery ligation(2VO). Methods:The model of aging rats with cerebral hypoperfusion was successfully constructed by persistent bilateral common carotid

  3. Excess coronary artery disease risk in South Asian immigrants: Can dysfunctional high-density lipoprotein explain increased risk?

    Directory of Open Access Journals (Sweden)

    Sunita Dodani

    2008-08-01

    Full Text Available Sunita DodaniMedical College of Georgia, Augusta, GA, USABackground: Coronary artery disease (CAD is the leading cause of mortality and morbidity in the United States (US, and South Asian immigrants (SAIs have a higher risk of CAD compared to Caucasians. Traditional risk factors may not completely explain high risk, and some of the unknown risk factors need to be explored. This short review is mainly focused on the possible role of dysfunctional high-density lipoprotein (HDL in causing CAD and presents an overview of available literature on dysfunctional HDL.Discussion: The conventional risk factors, insulin resistance parameters, and metabolic syndrome, although important in predicting CAD risk, may not sufficiently predict risk in SAIs. HDL has antioxidant, antiinflammatory, and antithrombotic properties that contribute to its function as an antiatherogenic agent. Recent Caucasian studies have shown HDL is not only ineffective as an antioxidant but, paradoxically, appears to be prooxidant, and has been found to be associated with CAD. Several causes have been hypothesized for HDL to become dysfunctional, including Apo lipoprotein A-I (Apo A-I polymorphisms. New risk factors and markers like dysfunctional HDL and genetic polymorphisms may be associated with CAD.Conclusions: More research is required in SAIs to explore associations with CAD and to enhance early detection and prevention of CAD in this high risk group.Keywords: South Asian immigrants, coronary heart disease, cardiovascular risk, high-density lipoprotein

  4. COMPARISION OF BODY MASS INDEX (BMI WITH HIGH DENSITY LIPOPROTEIN (HDL LEVELS IN OBESE PEOPLE

    Directory of Open Access Journals (Sweden)

    Anitha

    2015-11-01

    Full Text Available NTRODUCTION: Cardiovascular disease is a major cause of morbidity and mortality in industrialized nations. Serum lipid concentrations are related to cardiovascular disease risk and one notable association is a statistically significant inverse correlation between HDL-cholesterol concentrations and the probability of developing coronary artery disease. A major related cardiovascular disease risk factor is obesity. Excess body weight is closely linked to low serum HDL-cholesterol concentrations. The general assumption now is that excessive body weight is associated with enlarged adipose tissue deposits, visceral adipose tissue in particular, which in turn are accompanied by elevated serum triacylglycerol concentrations. A well-studied inverse association exists between serum triacylglycerol and HDL-cholesterol concentrations and this may explain the observed low serum HDL-cholesterol concentrations in obesity. This study is done to confirm the above fact. MATERIALS AND METHODS: The subjects for the study were 100 males in the age group of 21 to 40 years. The subjects taken as obese were 50 and those taken as controls were 50. Obesity was taken into account according to the Body Mass Index. RESULTS: Paired T test is done. Results show that 34/50 subjects with BMI 40mg/dl. 40/50 obese patients with BMI >25kg/m2 show HDL levels of <40mg/dl. Significant P value is seen. The study shows that BMI is inversely related to HDL cholesterol levels. DISCUSSION: High HDL cholesterol, above 60 mg/dl is associated with low risk of coronary heart disease. HDL cholesterol below 40 mg/dL is considered too low and appears to be an independent risk factor for coronary artery disease. Low HDL cholesterol is one of the most common phenotypes seen in persons with premature heart disease. Obesity is associated with low HDL cholesterol levels and high triglyceride levels. A negative correlation exists between HDL cholesterol and body-mass index (BMI, meaning that HDL

  5. Lipoprotein Cholesterol and the Analysis of the Acute Cerebral Infarction%脂蛋白胆固醇与发生急性脑梗死的分析

    Institute of Scientific and Technical Information of China (English)

    赵彦坡

    2015-01-01

    Objective To observe the relationships between non-high-density lipoprotein cholesterol and acute cerebral infaction. Methods 88 patients were divided into 2 groups: cerebral infaction group, non-cerebral infaction group group. Al zhe patients were taken the blood with fasting after admission, the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c),triglyceride (TG) were measured and non-high-density lipoprotein cholesterol (non-HDL-c) calculated.The date were analysed with SPSS 3.0. Results There were no significant dif erences in the total cholesterol(TC), low density lipoprotein cholesterol(LDL-c), non-high-density lipoprotein cholesterol(non-HDL-c) between the two groups(>0.05).Conclusion The abnormal metabolism of lipoprotein cholesterol are important risk factors of cerebrovascular disease, acute cerebral infarction group and nonacute cerebral infarction groups have no significant dif erence, indicate that acute cerebral infarction occurs eventual y may have other more risk factors involved in.%目的探讨脂蛋白胆固醇与急性脑梗死的关系。方法88例患者分为急性脑梗死组和非急性脑梗死组,均在入院后采集空腹血清,检测总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-c),高密度脂蛋白胆固醇(HDL-c),计算非高密度脂蛋白胆固醇(non-HDL-c),对数据均采用SPSS13.0进行分析。结果两组的总胆固醇,甘油三酯及低密度脂蛋白胆固醇及非高密度脂蛋白胆固醇比较及统计学分析,差异无显著统计学意义(跃0.05)。结论脂蛋白胆固醇代谢异常是脑血管病的重要危险因素,急性脑梗死组与非急性脑梗死组差别不明显,表明急性脑梗死发生可能有其它更多危险因素参与有关。

  6. Osbpl8 Deficiency in Mouse Causes an Elevation of High-Density Lipoproteins and Gender-Specific Alterations of Lipid Metabolism

    Science.gov (United States)

    Béaslas, Olivier; Metso, Jari; Nissilä, Eija; Laurila, Pirkka-Pekka; Kaiharju, Essi; Batchu, Krishna Chaithanya; Kaipiainen, Leena; Mäyränpää, Mikko I.; Yan, Daoguang; Gylling, Helena; Jauhiainen, Matti; Olkkonen, Vesa M.

    2013-01-01

    OSBP-related protein 8 (ORP8) encoded by Osbpl8 is an endoplasmic reticulum sterol sensor implicated in cellular lipid metabolism. We generated an Osbpl8−/− (KO) C57Bl/6 mouse strain. Wild-type and Osbpl8KO animals at the age of 13-weeks were fed for 5 weeks either chow or high-fat diet, and their plasma lipids/lipoproteins and hepatic lipids were analyzed. The chow-fed Osbpl8KO male mice showed a marked elevation of high-density lipoprotein (HDL) cholesterol (+79%) and phospholipids (+35%), while only minor increase of apolipoprotein A-I (apoA-I) was detected. In chow-fed female KO mice a less prominent increase of HDL cholesterol (+27%) was observed, while on western diet the HDL increment was prominent in both genders. The HDL increase was accompanied by an elevated level of HDL-associated apolipoprotein E in male, but not female KO animals. No differences between genotypes were observed in lecithin:cholesterol acyltransferase (LCAT) or hepatic lipase (HL) activity, or in the fractional catabolic rate of fluorescently labeled mouse HDL injected in chow-diet fed animals. The Osbpl8KO mice of both genders displayed reduced phospholipid transfer protein (PLTP) activity, but only on chow diet. These findings are consistent with a model in which Osbpl8 deficiency results in altered biosynthesis of HDL. Consistent with this hypothesis, ORP8 depleted mouse hepatocytes secreted an increased amount of nascent HDL into the culture medium. In addition to the HDL phenotype, distinct gender-specific alterations in lipid metabolism were detected: Female KO animals on chow diet showed reduced lipoprotein lipase (LPL) activity and increased plasma triglycerides, while the male KO mice displayed elevated plasma cholesterol biosynthetic markers cholestenol, desmosterol, and lathosterol. Moreover, modest gender-specific alterations in the hepatic expression of lipid homeostatic genes were observed. In conclusion, we report the first viable OsbplKO mouse model, demonstrating a

  7. Uptake of [3H]vitamin D3 from low and high density lipoproteins by cultured human fibroblasts

    International Nuclear Information System (INIS)

    The plasma distribution and cellular uptake of [3H]vitamin D3 was studied in vitro using cultured human fibroblasts. Incubation of [3H]vitamin D3 (cholecalciferol) with plasma followed by sequential ultracentrifugal fractionation of the lipoproteins indicated that 2-4% of the radioactivity associated with the very low density lipoprotein (VLDL), 12% with low density lipoprotein (LDL), and approximately 60% with the high density lipoprotein (HDL). The remaining radioactivity, 25%, was associated with the sedimented plasma fractions. By comparison, an average of 86% of the radioactivity from [3H] 1,25-dihydroxycholecalciferol associated with the sedimented plasma fractions. The uptake of [3H]vitamin D3 from plasma, LDL, or HDL was studied in cultured human cells; uptake by normal fibroblasts was greatest from LDL and least from plasma. The cellular association of vitamin D3 was time, concentration, and temperature dependent. At a concentration of 50 μg LDL/ml of medium, the uptake of [3H]vitamin D3 from LDL at 370C was rapid and reached a maximum at approximately 4 hr; it was slower from HDL but continued to increase slowly up to 24 hr. The significance of these in vitro findings is uncertain since much of the vitamin D3 absorbed from the intestine reportedly associates with chylomicrons and is rapidly taken up by the liver

  8. Soy milk powder supplemented with phytosterol esters reduced serum cholesterol level in hypercholesterolemia independently of lipoprotein E genotype: a random clinical placebo-controlled trial.

    Science.gov (United States)

    Dong, Shan; Zhang, Ran; Ji, Ya-Cheng; Hao, Jia-Yin; Ma, Wei-Wei; Chen, Xu-Dong; Xiao, Rong; Yu, Huan-Ling

    2016-08-01

    Phytosterols (PSs) are reported to lower the serum total cholesterol and low-density lipoprotein cholesterol concentrations enriched in some fatty foods, such as margarine. However, these high-fat foods are not very suitable for older people. Soy milk is the favorite food for elderly people in China; therefore, we hypothesized that the consumption of soy milk powder supplemented with PSs would decrease the serum cholesterol levels in older Chinese people independent of the genotypes of apolipoprotein E (ApoE). Mild to moderate hyperlipidemic patients (n = 170) were recruited from different communities and treated with placebo soy milk powder or 3.4 g PS esters-enriched soy milk powder (2.0 g/d free PS in 30 g soy milk powder). The fasting serum lipid profiles at the baseline and after 3 and 6 months of intervention were measured. The ApoE genotype was also determined. After 3 months of PS intervention, the serum lipid profile was not changed significantly in either group. The serum total cholesterol, low-density lipoprotein cholesterol, and non- high-density lipoprotein cholesterol levels decreased by 9.3%, 11.4%, and 12.6%, respectively, in the PS group at the end of the intervention (6 months) compared with the control group, whereas the serum high-density lipoprotein cholesterol and triglyceride levels were not affected significantly. In the PS group, both the ApoE3 and ApoE4 carriers had a similar response to PS consumption. These findings suggested that PS-fortified soy milk powder was effective in lowering the serum cholesterol levels in older Chinese volunteers with mild to moderate hypercholesterolemia in both the ApoE3 and ApoE4 carriers. PMID:27440543

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

    Science.gov (United States)

    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

  10. Measurement of low-density lipoprotein cholesterol in assessment and management of cardiovascular disease risk.

    Science.gov (United States)

    Jialal, I; Remaley, A T

    2014-07-01

    The deposition of cholesterol in the arterial wall by the infiltration of low-density lipoproteins (LDLs) is a key step in the development of atherosclerosis. In this Commentary, we discuss recent recommendations for clinical laboratory measurement of low-density lipoprotein cholesterol (LDL-C) and its utility both for assessing cardiovascular disease risk and as a tool in the management of patients receiving lipid-lowering therapy.

  11. The secondary structure of apolipoprotein A-I on 9.6-nm reconstituted high-density lipoprotein determined by EPR spectroscopy

    Science.gov (United States)

    Oda, Michael N; Budamagunta, Madhu S; Borja, Mark S; Petrlova, Jitka; Voss, John C; Lagerstedt, Jens O

    2013-01-01

    Apolipoprotein A-I (ApoA-I) is the major protein component of high-density lipoprotein (HDL), and is critical for maintenance of cholesterol homeostasis. During reverse cholesterol transport, HDL transitions between an array of subclasses, differing in size and composition. This process requires ApoA-I to adapt to changes in the shape of the HDL particle, transiting from an apolipoprotein to a myriad of HDL subclass-specific conformations. Changes in ApoA-I structure cause alterations in HDL-specific enzyme and receptor-binding properties, and thereby direct the HDL particle through the reverse cholesterol transport pathway. In this study, we used site-directed spin label spectroscopy to examine the conformational details of the ApoA-I central domain on HDL. The motional dynamics and accessibility to hydrophobic/hydrophilic relaxation agents of ApoA-I residues 99–163 on 9.6-nm reconstituted HDL was analyzed by EPR. In previous analyses, we examined residues 6–98 and 164–238 (of ApoA-I's 243 residues), and combining these findings with the current results, we have generated a full-length map of the backbone structure of reconstituted HDL-associated ApoA-I. Remarkably, given that the majority of ApoA-I's length is composed of amphipathic helices, we have identified nonhelical residues, specifically the presence of a β-strand (residues 149–157). The significance of these nonhelical residues is discussed, along with the other features, in the context of ApoA-I function in contrast to recent models derived by other methods. PMID:23668303

  12. Effect of Probucol on Enzyme and Receptors of High Density Lipoprotein During Reverse Cholesterol Transportation in Experimental Rabbits With Atherosclerosis%普罗布考对动脉粥样硬化兔的高密度脂蛋白逆转运功能中酶蛋白和受体的影响

    Institute of Scientific and Technical Information of China (English)

    钟建开; 吴焱贤; 陈盈文; 李琛; 黎文生; 郭志刚

    2016-01-01

    目的:探讨普罗布考对动脉粥样硬化(AS)兔的高密度脂蛋白逆转运功能中酶蛋白和受体的影响。方法:新西兰大白兔(共24只)随机分为3组:对照组(n=8):用普通饲料饲养;高脂组(n=8):用高脂饲料喂养;普罗布考组(n=8):在高脂饲料的基础上给予普罗布考喂养。饲养12周通过比色法测定血脂,通过酶联免疫吸附法检测血清磷脂胆固醇酰基转移酶(LCAT)和胆固醇酯转移蛋白(CETP),并采用免疫组化方法检测主动脉壁斑块内三磷酸腺苷结合盒转运体A1(ABCA1)和清道夫受体-BI (SR-BI)表达水平。结果:实验后第12周(1)血脂指标:与高脂组比较,普罗布考组血清总胆固醇[TC,(15.95±1.51)mmol/L vs (21.95±3.71)mmol/L]、低密度脂蛋白胆固醇[LDL-C,(13.01±2.28) mmol/L vs (17.90±3.51)mmol/L]、高密度脂蛋白胆固醇[HDL-C,(0.56±0.10) mmol/L vs(1.13±0.12)mmol/L]水平明显下降,差异均有统计学意义(P Results: ① for blood lipids by mmol/L, the following indexes in Probucol group were lower than High cholesterol group: TC (15.95±1.51 vs 21.95±3.71), LDL-C (13.01±2.28 vs 17.90±3.51), HDL-C (0.56±0.10 vs 1.13±0.12), all P Conclusion: Probucol may increase blood levels of LCAT, CETP via up-regulating the expressions of ABCA1, SR-B1 and elevating the reverse cholesterol transportation of HDL, therefore improve HDL function in experimental rabbits with atherosclerosis.

  13. Anti-Brownian ELectrokinetic (ABEL) Trapping of Single High Density Lipoprotein (HDL) Particles

    Science.gov (United States)

    Bockenhauer, Samuel; Furstenberg, Alexandre; Wang, Quan; Devree, Brian; Jie Yao, Xiao; Bokoch, Michael; Kobilka, Brian; Sunahara, Roger; Moerner, W. E.

    2010-03-01

    The ABEL trap is a novel device for trapping single biomolecules in solution for extended observation. The trap estimates the position of a fluorescently-labeled object as small as ˜10 nm in solution and then applies a feedback electrokinetic drift every 20 us to trap the object by canceling its Brownian motion. We use the ABEL trap to study HDL particles at the single-copy level. HDL particles, essential in regulation of ``good'' cholesterol in humans, comprise a small (˜10 nm) lipid bilayer disc bounded by a belt of apolipoproteins. By engineering HDL particles with single fluorescent donor/acceptor probes and varying lipid compositions, we are working to study lipid diffusion on small length scales. We also use HDL particles as hosts for single transmembrane receptors, which should enable study of receptor conformational dynamics on long timescales.

  14. Beneficial effects of omega-3 fatty acids in the proteome of high-density lipoprotein proteome

    Directory of Open Access Journals (Sweden)

    Burillo Elena

    2012-09-01

    Full Text Available Abstract Background Omega-3 poly-unsaturated fatty acids (ω-3 PUFAs have demonstrated to be beneficial in the prevention of cardiovascular disease, however, the mechanisms by which they perform their cardiovascular protection have not been clarified. Intriguingly, some of these protective effects have also been linked to HDL. The hypothesis of this study was that ω-3 PUFAs could modify the protein cargo of HDL particle in a triglyceride non-dependent mode. The objective of the study was to compare the proteome of HDL before and after ω-3 PUFAs supplemented diet. Methods A comparative proteomic analysis in 6 smoker subjects HDL before and after a 5 weeks ω-3 PUFAs enriched diet has been performed. Results Among the altered proteins, clusterin, paraoxonase, and apoAI were found to increase, while fibronectin, α-1-antitrypsin, complement C1r subcomponent and complement factor H decreased after diet supplementation with ω-3 PUFAs. Immunodetection assays confirmed these results. The up-regulated proteins are related to anti-oxidant, anti-inflammatory and anti-atherosclerotic properties of HDL, while the down-regulated proteins are related to regulation of complement activation and acute phase response. Conclusions Despite the low number of subjects included in the study, our findings demonstrate that ω-3 PUFAs supplementation modifies lipoprotein containing apoAI (LpAI proteome and suggest that these protein changes improve the functionality of the particle.

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

    DEFF Research Database (Denmark)

    Whorton, Matthew R; Bokoch, Michael P; Rasmussen, Søren Gøgsig Faarup;

    2007-01-01

    G protein-coupled receptors (GPCRs) respond to a diverse array of ligands, mediating cellular responses to hormones and neurotransmitters, as well as the senses of smell and taste. The structures of the GPCR rhodopsin and several G proteins have been determined by x-ray crystallography, yet...... the organization of the signaling complex between GPCRs and G proteins is poorly understood. The observations that some GPCRs are obligate heterodimers, and that many GPCRs form both homo- and heterodimers, has led to speculation that GPCR dimers may be required for efficient activation of G proteins. However......, technical limitations have precluded a definitive analysis of G protein coupling to monomeric GPCRs in a biochemically defined and membrane-bound system. Here we demonstrate that a prototypical GPCR, the beta2-adrenergic receptor (beta2AR), can be incorporated into a reconstituted high-density lipoprotein...

  16. Remnant Cholesterol, Low-Density Lipoprotein Cholesterol, and Blood Pressure as Mediators From Obesity to Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Smith, George Davey;

    2015-01-01

    RATIONALE: Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. OBJECTIVE: To test the hypothesis that the increased IHD risk because of obesity is mediated through...... variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood...... obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. CONCLUSIONS: The increased IHD risk because...

  17. Changes in the triglyceride-rich lipoproteins and the response to dietary cholesterol in man.

    NARCIS (Netherlands)

    Demacker, P.N.M.; Glatz, J.F.C.; Katan, M.B.

    1988-01-01

    The effect of a cholesterol-enriched diet was studied in nine healthy volunteers with special emphasis to the changes which occurred in the triglyceride-rich lipoproteins (d<1.019 g/ml). Compared to the habitual diet, a moderately increased intake of cholesterol (from 300–900 mg/day) resulted in cha

  18. Development of a New High-throughput Screening Model for Human High Density Lipoprotein Receptor (CLA-1) Agonists

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To develop a new high-throughput screening model for human high-density lipoprotein (HDL) receptor (CD36 and LIMPII analogous-1, CLA-1) agonists using CLA-1-expressing insect cells. Methods With the total RNA of human hepatoma cells BEL-7402 as template, the complementary DNA (cDNA) of CLA-1 was amplified by reverse transcription-polymerase chain reaction (RT-PCR). Bac-to-Bac baculovirus expression system was used to express CLA-1 in insect cells. CLA-1 cDNA was cloned downstream of polyhedrin promoter of Autographa californica nuclear polyhedrosis virus (AcNPV) into donor vector pFastBac1 and recombinant pFastBac1-CLA-1 was transformed into E. coli DH10Bac to transpose CLA-1 cDNA to bacmid DNA. Recombinant bacmid-CLA-1 was transfected into Spodoptera frugiperda Sf9 insect cells to produce recombinant baculovirus particles. Recombinant CLA-1 was expressed on the membrane of Sf9 cells infected with the recombinant baculoviruses. A series of parameters of DiI-lipoprotein binding assays of CLA-1-expressing Sf9 cells in 96-well plates were optimized. Results Western blot analysis and DiI-lipoprotein binding assays confirmed that CLA-1 expressed in insect cells had similar immunoreactivity and ligand binding activity as its native counterpart. A reliable and sensitive in vitro cell-based assay was established to assess the activity of CLA-1 and used to screen agonists from different sample libraries. Conclusion Human HDL receptor CLA-1 was successfully expressed in Sf9 insect cells and a novel high-throughput screening model for CLA-1 agonists was developed. Utilization of this model allows us to identify potent and selective CLA-1 agonists which might possibly be used as therapeutics for atherosclerosis.

  19. Plasma levels of 27-hydroxycholesterol in humans and mice with monogenic disturbances of high density lipoprotein metabolism

    DEFF Research Database (Denmark)

    Karuna, Ratna; Holleboom, Adriaan G; Motazacker, Mohammad M;

    2011-01-01

    activities of LCAT and CETP, respectively, than the formation and transfer of cholesterylesters. 27OHC plasma levels were also decreased in apoA-I-, ABCA1- or LCAT-knockout mice but increased in SR-BI-knockout mice. Transplantation of ABCA1- and/or ABCG1-deficient bone marrow into LDL receptor deficient mice...... BI and hepatic lipase were associated with elevated HDL concentrations of either sterol. Compared to family controls and relative to the concentrations of total 27OHC and cholesterol, lower 27OHC-ester but normal cholesterylester levels were found in HDL of heterozygous LCAT mutation carriers and non...... decreased plasma levels of 27OHC. In conclusion, mutations or absence of HDL genes lead to distinct alterations in the quantity, esterification or lipoprotein distribution of 27OHC. These findings argue against the earlier suggestion that 27OHC-metabolism in plasma occurs independently of HDL....

  20. Prebeta-migrating high density lipoprotein: quantitation in normal and hyperlipidemic plasma by solid phase radioimmunoassay following electrophoretic transfer

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, B.Y.; Frolich, J.; Fielding, C.J.

    1987-07-01

    A quantitative solid phase immunoassay has been developed for the determination of the mass of electrophoretically separated prebeta apolipoprotein A-I (apoA-I) in human plasma. Conditions have been identified for the quantitative transfer and immunoblotting of the apolipoprotein in the absence of organic solvents or detergents. In normolipidemic plasma, the prebeta-migrating fraction of apoA-I represented 4.2 +/- 1.8% of total apoA-I (61 +/- 26 micrograms of apoA-I per ml of plasma). Significantly higher levels were found in hypercholesterolemia of genetic origin, in primary and secondary hypertriglyceridemia, and in congenital lecithin:cholesterol acyltransferase deficiency. In all cases prebeta-migrating apoA-I consisted in large part of low molecular weight lipoprotein species, compared to the size of the major, alpha-migrating apoA-I fraction.

  1. Prebeta-migrating high density lipoprotein: quantitation in normal and hyperlipidemic plasma by solid phase radioimmunoassay following electrophoretic transfer

    International Nuclear Information System (INIS)

    A quantitative solid phase immunoassay has been developed for the determination of the mass of electrophoretically separated prebeta apolipoprotein A-I (apoA-I) in human plasma. Conditions have been identified for the quantitative transfer and immunoblotting of the apolipoprotein in the absence of organic solvents or detergents. In normolipidemic plasma, the prebeta-migrating fraction of apoA-I represented 4.2 +/- 1.8% of total apoA-I (61 +/- 26 micrograms of apoA-I per ml of plasma). Significantly higher levels were found in hypercholesterolemia of genetic origin, in primary and secondary hypertriglyceridemia, and in congenital lecithin:cholesterol acyltransferase deficiency. In all cases prebeta-migrating apoA-I consisted in large part of low molecular weight lipoprotein species, compared to the size of the major, alpha-migrating apoA-I fraction

  2. Evidence of differential allelic effects between adolescents and adults for plasma high-density lipoprotein.

    Directory of Open Access Journals (Sweden)

    Rita P S Middelberg

    Full Text Available A recent meta-analysis of genome-wide association (GWA studies identified 95 loci that influence lipid traits in the adult population and found that collectively these explained about 25-30% of heritability for each trait. Little is known about how these loci affect lipid levels in early life, but there is evidence that genetic effects on HDL- and LDL-cholesterol (HDL-C, LDL-C and triglycerides vary with age. We studied Australian adults (N = 10,151 and adolescents (N = 2,363 who participated in twin and family studies and for whom we have lipid phenotypes and genotype information for 91 of the 95 genetic variants. Heterogeneity tests between effect sizes in adult and adolescent cohorts showed an excess of heterogeneity for HDL-C (p(Het<0.05 at 5 out of 37 loci, but no more than expected by chance for LDL-C (1 out of 14 loci, or trigycerides (0 out 24. There were 2 (out of 5 with opposite direction of effect in adolescents compared to adults for HDL-C, but none for LDL-C. The biggest difference in effect size was for LDL-C at rs6511720 near LDLR, adolescents (0.021 ± 0.033 mmol/L and adults (0.157 ± 0.023 mmol/L, p(Het = 0.013; followed by ZNF664 (p(Het = 0.018 and PABPC4 (p(Het = 0.034 for HDL-C. Our findings suggest that some of the previously identified variants associate differently with lipid traits in adolescents compared to adults, either because of developmental changes or because of greater interactions with environmental differences in adults.

  3. Distribution of electrophoretically separated serum high density lipoprotein subfraction levels among healthy students and its alteration in patients with liver diseases.

    Directory of Open Access Journals (Sweden)

    Ikeda,Satoru

    1986-06-01

    Full Text Available In an attempt to evaluate high density lipoprotein (HDL subfraction levels in liver diseases, HDL was separated by a precipitation method with dextran sulfate-Mg2+ from sera of 289 healthy adults and 50 patients with liver diseases. The HDL was subdivided into HDL2e and HDL3e by Utermann's polyacrylamide gel electrophoresis with lauric acid. Ultracentrifugally separated HDL2 and HDL3 roughly corresponded to HDL2e and HDL3e, respectively. Male and female groups had different distributions of HDL2e/HDL3e ratios. Among healthy males, 121 cases had ratios less than 1.0 (mean +/- SD = 0.72 +/- 0.39, n = 150, while among healthy females, the ratios were generally larger than those of males and varied widely from 0.2 to 6.6 (mean +/- SD = 1.77 +/- 1.05, n = 139. Low levels of HDL-cholesterol were found in patients with liver diseases, except those with mild alcoholic liver injury and intrahepatic cholestasis. Apparent decreases in HDL3e, but not in HDL2e, were found in all cases with liver diseases investigated, even in those who did not show decreases in the total HDL level, when male and female patients were analyzed separately. The analysis of HDL subfractions by the present method is simple and useful for the study on altered lipid metabolism in liver diseases.

  4. Reliability of Calculated Low-Density Lipoprotein Cholesterol.

    Science.gov (United States)

    Meeusen, Jeffrey W; Snozek, Christine L; Baumann, Nikola A; Jaffe, Allan S; Saenger, Amy K

    2015-08-15

    Aggressive low-density lipoprotein cholesterol (LDL-C)-lowering strategies are recommended for prevention of cardiovascular events in high-risk populations. Guidelines recommend a 30% to 50% reduction in at-risk patients even when LDL-C concentrations are between 70 and 130 mg/dl (1.8 to 3.4 mmol/L). However, calculation of LDL-C by the Friedewald equation is the primary laboratory method for routine LDL-C measurement. We compared the accuracy and reproducibility of calculated LDL-C <130 mg/dl (3.4 mmol/L) to LDL-C measured by β quantification (considered the gold standard method) in 15,917 patients with fasting triglyceride concentrations <400 mg/dl (4.5 mmol/L). Both variation and bias of calculated LDL-C increased at lower values of measured LDL-C. The 95% confidence intervals for a calculated LDL-C of 70 mg/dl (1.8 mmol/L) and 30 mg/dl (0.8 mmol/L) were 60 to 86 mg/dl (1.6 to 2.2 mmol/L) and 24 to 60 mg/dl (0.6 to 1.6 mmol/L), respectively. Previous recommendations have emphasized the requirement for a fasting sample with triglycerides <400 mg/dl (4.5 mmol/L) to calculate LDL-C by the Friedewald equation. However, no recommendations have addressed the appropriate lower reportable limit for calculated LDL-C. In conclusion, calculated LDL-C <30 mg/dl (0.8 mmol/L) should not be reported because of significant deviation from the gold standard measured LDL-C results, and caution is advised when using calculated LDL-CF values <70 mg/dl (1.8 mmol/L) to make treatment decisions.

  5. EFFECT OF DIETARY OLIVE OIL/CHOLESTEROL ON SERUM LIPOPROTEINS, LIPID PEROXIDATION, AND ATHEROSCLEROSIS IN RABBITS

    Directory of Open Access Journals (Sweden)

    R MAHDAVI

    2003-03-01

    Full Text Available Introduction: High plasma cholesterol levels, mainly LDL are a widely recognized major risk factor for Coronary Heart Disease (CHD. According to the epidemiologic studies findings, people from the Mediterranean countries, have lower CHD rats than other countries, in these countries usual diet is high in olive oil. The present study compares the effects of cholesterol enriched diet with or without adding olive oil on serum Lipoproteins, lipid per oxidation, and atherosclerosis development. Method: Twenty Dutch male rabbits were Categorized to four groups (one group as Control, and others as Experimental. They received one of standard, cholesterol - rich, olive oil rich and combined (cholesterol + olive oil diet for Twelve weeks. Fasting blood samples from heart were collected at the beginning, and the end of Experimental period. Means of total cholesterol, HDL-Ctriglycerides, MDA and antioxidant caperimental period, significant differences were showed in total cholesterol, HDL-C, triglyceride and MDA between groups. Results: The comparison of cholesterol rich diet with cholesterol + olive oil showed a higher mean of MDA in cholesterol rich group (P < 0.001. Biochemical factors and aortic lesion degree showed no significant difference between standard and olive oil group. Aortic lesions in cholesterol + olive oil showed nonsignificant lower degree than cholesterol group. Discussion: This findings showed preventive effect of olive oil against atherosclerosis which is independent of plasma lipoprotein effect, and suggested that probably olive oil acts on arteries directly.

  6. Znf202 Affects High Density Lipoprotein Cholesterol Levels and Promotes Hepatosteatosis in Hyperlipidemic Mice

    NARCIS (Netherlands)

    Vrins, C.L.J.; Out, R.; Santbrink, P. van; Zee, A. van der; Mahmoudi, T.; Groenendijk, M.; Havekes, L.M.; Berkel, T.J.C. van; Dijk, K.W. van; Biessen, E.A.L.

    2013-01-01

    Background: The zinc finger protein Znf202 is a transcriptional suppressor of lipid related genes and has been linked to hypoalphalipoproteinemia. A functional role of Znf202 in lipid metabolism in vivo still remains to be established. Methodology and Principal Findings: We generated mouse Znf202 ex

  7. Znf202 Affects High Density Lipoprotein Cholesterol Levels and Promotes Hepatosteatosis in Hyperlipidemic Mice

    NARCIS (Netherlands)

    C.L.J. Vrins (Carlos L.J.); R. Out (Ruud); P. van Santbrink (Peter); A. van der Zee (Anneke); T. Mahmoudi (Tokameh); M. Groenendijk (Martine); L.M. Havekes (Louis); Th.J.C. van Berkel (Theo); J.A.P. Willems van Dijk (Ko); E.A.L. Biessen (Erik)

    2013-01-01

    textabstractBackground: The zinc finger protein Znf202 is a transcriptional suppressor of lipid related genes and has been linked to hypoalphalipoproteinemia. A functional role of Znf202 in lipid metabolism in vivo still remains to be established. Methodology and Principal Findings: We generated mou

  8. CORRELATION OF BREAST CANCER AND SERUM HIGH DENSITY LIPOPROTEIN CHOLESTEROL LEVEL: A SINGLE CENTRE STUDY

    OpenAIRE

    Anjali; Deepak

    2015-01-01

    Breast cancer is the most common site specific cancer in women. Lots of etiological factors have been suggested regarding its causation. The risk is influenced by obesity, parity, exogenous and endogenous hormones, exposure to chemicals and radiation and many more. Various studies suggest that as HDL-C seems to be cardio protective, it is also protective for breast cancer. Serum HDL-C levels are found to be low in breast cancer patients. We studied this hypothesis in local population of South...

  9. CORRELATION OF BREAST CANCER AND SERUM HIGH DENSITY LIPOPROTEIN CHOLESTEROL LEVEL: A SINGLE CENTRE STUDY

    Directory of Open Access Journals (Sweden)

    Anjali

    2015-12-01

    Full Text Available Breast cancer is the most common site specific cancer in women. Lots of etiological factors have been suggested regarding its causation. The risk is influenced by obesity, parity, exogenous and endogenous hormones, exposure to chemicals and radiation and many more. Various studies suggest that as HDL-C seems to be cardio protective, it is also protective for breast cancer. Serum HDL-C levels are found to be low in breast cancer patients. We studied this hypothesis in local population of Southern Rajasthan and nearby region to see if low serum HDL-C is associated with increased risk of breast cancer. We studied serum HDL-C level in 50 female patients of breast cancer along with their menopausal status and compared it to their respective controls. We found that breast cancer patients had significantly low level of serum HDL-C and presented in advanced stage of cancer. It supports that low serum HDL-C level is associated with increased risk of breast cancer. So one should think about those dietary and lifestyle measures, which maintain high serum HDL-C level so that it might become preventive measure for breast cancer.

  10. THE RELATIONSHIPS BETWEEN PLASMA CHOLESTEROL、TRIGLYCERIDE、HIGH DENSITY LIPOPROTEIN AND ION TRANSPORT ENZYMES IN ERYTHROCYTE MEMBRANES

    Institute of Scientific and Technical Information of China (English)

    符云峰; 王素敏; 卢振敏; 李红

    2002-01-01

    Objective To investigate the relationships between levels of plasma cholesterol (Ch), triglyceride (TG)、high density lipoprotein(HDL) and ion transport enzyme activities in red cell membranes of essential hypertensive patients.Methods Plasma Ch, TG, HDL-c, activites of Na+ -K+ -ATPase and Ca2+-ATPase, Ca2+-binding capacity of interior membrane surface, and membrane Ch, phospholipid(PL) were measured in 32 normotensive (NT) subjects and 55 essential hypertensive patients(HT).Results ①Mean artery pressure(MAP), plasma Ch、TG and membrane Ch levels, and membrane cholesterol/phospholipid(C/P) molar ratio were significantly increased compared with those in NT group, respectively; ②The plasma HDL-c level, the activities of Na+-K+-ATPase and Ca2+-ATPase, and the Ca2+-binding capacity of the interior membrane surface in HT group were significantly lower than those in NT group, respectively.Conclusion The depressed activities of Na+-K+-ATPase and Ca2+-ATPase, and Ca2+-binding capacity of the interior surface in cell membranes are the major evidence of ion transport abnormalities in essential hypertension. The plasma TG and membrance C/P molar ratio-dependent changes in membrane microviscosity seem to be responsible for the modulation of particular ion transport pathways.

  11. 非高密度脂蛋白胆固醇与心脑血管疾病关系研究进展%Research Progress on Non-High-Density Lipoprotein Cholesteral and Cardiovascular and Cerebrovascular Diseases

    Institute of Scientific and Technical Information of China (English)

    刘洋; 郭阳

    2015-01-01

    非高密度脂蛋白胆固醇(non-high-density lipoprotein cholesterol,non-HDL-C)反映致动脉粥样硬化胆固醇的总量,美国国家胆固醇教育计划中的成人治疗专家方案第3号报告中首次提出这一概念,并且将其作为降脂治疗的第二目标。目前已广泛证实non-HDL-C在冠状动脉粥样硬化性心脏病发病率及死亡率方面的预测价值较高,甚至可能优于传统血脂指标。但non-HDL-C与脑血管病相关的研究有限且结果存在争议,本文就non-HDL-C与心脑血管病相关的研究现状做一综述。%Non-high-density lipoprotein cholesterol (non-HDL-C) relfects the total amount of atherogenic cholesterol. The concept of non-HDL-C was ifrst proposed on the National Cholesteral Education Program Adult Treatment Panel III and was assigned to be the second target for lipid-lowering therapy. More and more recent studies at home and abroad have shown that the non-HDL-C could be a more accurate predictor of morbidity and morality of coronary atherosclerotic heart disease than traditional markers such as low density lipoprotein cholesterol. Currently, there are less and scattered research on the association between non-HDL-C and cerebrovascular diseases. This review aims to summarize and analyze the research progress of non-HDL-C.

  12. Apolipoprotein E LDL receptor-binding domain-containing high-density lipoprotein: a nanovehicle to transport curcumin, an antioxidant and anti-amyloid bioflavonoid.

    Science.gov (United States)

    Khumsupan, Panupon; Ramirez, Ricardo; Khumsupan, Darin; Narayanaswami, Vasanthy

    2011-01-01

    Curcumin is an antioxidant and anti-inflammatory bioflavonoid that has been recently identified as an anti-amyloid agent as well. To make it more available in its potent form as a potential amyloid disaggregation agent, we employed high-density lipoproteins (HDL), which are lipid-protein complexes that transport plasma cholesterol, to transport curcumin. The objective of this study was to employ reconstituted HDL containing human apoE3 N-terminal (NT) domain, as a vehicle to transport curcumin. The NT domain serves as a ligand to mediate binding and uptake of lipoprotein complexes via the low-density lipoprotein receptor (LDLr) family of proteins located at the cell surface. Reconstituted HDL was prepared with phospholipids and recombinant apoE3-NT domain in the absence or presence of curcumin. Non-denaturing polyacrylamide gel electrophoresis indicated that the molecular mass and Stokes' diameter of HDL bearing curcumin were ~670kDa and ~17nm, respectively, while electron microscopy revealed the presence of discoidal particles. Fluorescence emission spectra of HDL bearing (the intrinsically fluorescent) curcumin indicated that the wavelength of maximal fluorescence emission (λ(max)) of curcumin was ~495nm, which is highly blue-shifted compared to λ(max) of curcumin in solvents of varying polarity (λ(max) ranging from 515-575nm) or in aqueous buffers. In addition, an enormous enhancement in fluorescence emission intensity was noted in curcumin-containing HDL compared to curcumin in aqueous buffers. Curcumin fluorescence emission was quenched to a significant extent by lipid-based quenchers but not by aqueous quenchers. These observations indicate that curcumin has partitioned efficiently into the hydrophobic milieu of the phospholipid bilayer of HDL. Functional assays indicated that the LDLr-binding ability of curcumin-containing HDL with apoE3-NT is similar to that of HDL without curcumin. Taken together, we report that apoE-containing HDL has a tremendous

  13. Anti-Aging and Tissue Regeneration Ability of Policosanol Along with Lipid-Lowering Effect in Hyperlipidemic Zebrafish via Enhancement of High-Density Lipoprotein Functionality.

    Science.gov (United States)

    Lee, Eun-Young; Yoo, Jeong-Ah; Lim, So-Mang; Cho, Kyung-Hyun

    2016-04-01

    We investigated the tissue regeneration and lipid-lowering effects of policosanol (PCO) by employing a hyperlipidemic zebrafish model. A reconstituted high-density lipoprotein containing policosanol (PCO-rHDL) facilitated greater cell growth and replication with less apoptosis and reactive oxygen species (ROS) production in BV-2 microglial cell lines. From in vivo study, injection of rHDL containing apolipoprotein A-I (ApoA-I) caused 76 ± 4% (p = 0.01) greater tissue regeneration activity than the phosphate-buffered saline (PBS) control, whereas PCO-rHDL caused 94 ± 7% (p = 0.002) increased regeneration. PCO in ethanol (EtOH) showed lower cholesteryl ester transfer protein (CETP) inhibitory ability than did anacetrapib, whereas PCO-rHDL showed higher inhibitory ability than anacetrapib, suggesting a synergistic effect between PCO and rHDL. Following 9 weeks of PCO consumption, the PCO group (0.003% PCO in Tetrabit) showed the highest survivability (80%), whereas normal diet (ND) and high-cholesterol diet (HCD) control groups showed 67% and 70% survival rates, respectively. Supplementation with a HCD resulted in two-fold elevation of CETP activity along with 3- and 2.5-fold increases in serum total cholesterol (TC) and triglycerides (TGs) levels, respectively. Consumption of PCO for 9 weeks resulted in 40 ± 5% (p = 0.01 vs. HCD) and 33 ± 4% (p = 0.02 vs. HCD) reduction of TC and TGs levels, respectively. Serum high-density lipoprotein cholesterol (HDL-C) level increased up to 37 ± 2 mg/dL (p = 0.004), whereas the percentage of HDL-C/TC increased up to 20 ± 2% from 5 ± 1% compared to the HCD control. The serum glucose level was reduced to 47 ± 2% (p = 0.002) compared to the HCD control. Fatty liver change and hepatic inflammation levels were remarkably increased upon HCD consumption and were two-fold higher than that under ND. However, the PCO group showed 58 ± 5% (p = 0.001) and 50 ± 3

  14. Characterization of human high-density lipoprotein subclasses LP A-I and LP A-I/A-II and binding to HepG2 cells

    OpenAIRE

    Kilsdonk, Liesbeth; van Gent, Teus; Tol, Arie

    1990-01-01

    markdownabstractAbstract Plasma HDL can be classified according to their apolipoprotein content into at least two types of lipoprotein particles: lipoproteins containing both apo A-I and apo A-II (LP A-I/A-II) and lipoproteins with apo A-I but without apo A-II (LP A-I). LP A-I and LP A-I/A-II were isolated by immuno-affinity chromatography. LP A-I has a higher cholesterol content and less protein compared to LP A-I/A-II. The average particle mass of LP A-I is higher (379 kDa) than the average...

  15. Effect of nutritional counseling on low-density lipoprotein cholesterol among Thai HIV-infected adults receiving antiretroviral therapy.

    Science.gov (United States)

    Chotivichien, Saipin; Arab, Lenore; Prasithsirikul, Wisit; Manosuthi, Weerawat; Sinawat, Sangsom; Detels, Roger

    2016-01-01

    HIV-infected patients receiving antiretroviral therapy have increased risk of metabolic syndrome, including dyslipidemia. In this study, we determined whether individual nutritional counseling reduced dyslipidemia, particularly low-density lipoprotein (LDL) cholesterol, among HIV-infected patients with dyslipidemia not currently taking lipid-lowering medication. We conducted a randomized 24-week trial among HIV-infected patients with dyslipidemia who were on antiretroviral therapy and were eligible to initiate therapeutic lifestyle changes according to the Thai National Cholesterol Education Program. Participants were randomly assigned to an intervention group that received individual counseling with a nutritionist for seven sessions (baseline, weeks 2, 4, 8, 12, 18, and 24) and a control group that received standard verbal diet information at baseline and nutritional counseling only at week 24. A 24-h recall technique was used to assess dietary intake for both groups at baseline and week 24. Lipid profile (total cholesterol, LDL, high-density lipoprotein (HDL), and triglyceride) was measured at baseline and after 12 and 24 weeks of therapy. An intention-to-treat and linear mixed model were used. Seventy-two patients were randomly assigned, and 62 (86%) participants completed their lipid profile test. After 12 weeks of follow-up, there were significant reductions in the intervention group for total cholesterol (-14.4 ± 4.6 mg/dL, P = .002), LDL cholesterol (-13.7 ± 4.1 mg/dL, P = .001), and triglyceride (-30.4 ± 13.8 mg/dL, P = .03). A significant reduction in LDL cholesterol was also observed in the control group (-7.7 ± 3.8 mg/dL, P = .04), but there were no significant differences in change of mean lipid levels between the groups at 12 weeks of follow-up. After 24 weeks, participants assigned to the intervention group demonstrated significantly greater decreases in serum total cholesterol (-19.0 ± 4.6 vs. 0.2

  16. High density lipoprotein suppresses lipoprotein associated phospholipase A2 in human monocytes-derived macrophages through peroxisome proliferator-activated receptor-γ pathway

    Institute of Scientific and Technical Information of China (English)

    HAN Guan-ping; REN Jing-yi; QIN Li; SONG Jun-xian; WANG Lan; CHEN Hong

    2012-01-01

    Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) is mainly secreted by macrophages,serving as a specific marker of atherosclerotic plaque and exerting pro-atherogenic effects.It is known that high-density lipoprotein (HDL) plays an important role against atherosclerosis by inhibiting pro-inflammatory factors,however,the relationship between HDL and Lp-PLA2 remains elusive.Methods In this study,reverse transcription-polymerase chain reaction (RT-PCR),Western blotting,and a platelet-activating factor (PAF) acetylhydrolase assay were performed to determine the Lp-PLA2 mRNA level,protein expression and activity in human monocyte-derived macrophages upon HDL treatment of different concentrations and durations.To investigate the underlying mechanism of HDL-induced Lp-PLA2 action,pioglitazone,a peroxisome proliferator-activated receptor-y (PPARy) ligand,was introduced to human monocyte-derived macrophages and mRNA and protein levels of Lp-PLA2,as well as its activity,were determined.Results Lp-PLA2 mRNA levels,protein expression and activity were significantly inhibited in response to HDL treatment in a dose and time dependent manner in human monocyte-derived macrophages.Pioglitazone treatment (1-10 ng/ml) upregulated the Lp-PLA2 mRNA level,protein expression and activity in human monocyte-derived macrophages,while the effects were markedly reversed by HDL.In addition,pioglitazone resulted in a significant increase in PPARY phosphorylation in human monocyte-derived macrophages,which could be inhibited by HDL.Conclusion These findings indicate that HDL suppresses the expression and activity of Lp-PLA2 in human monocyte-derived macrophages,and the underlying mechanisms may be mediated through the PPARY pathway.

  17. Reverse cholesterol transport revisited

    Institute of Scientific and Technical Information of China (English)

    Astrid; E; van; der; Velde

    2010-01-01

    Reverse cholesterol transport was originally described as the high-density lipoprotein-mediated cholesterol flux from the periphery via the hepatobiliary tract to the intestinal lumen, leading to fecal excretion. Since the introduction of reverse cholesterol transport in the 1970s, this pathway has been intensively investigated. In this topic highlight, the classical reverse cholesterol transport concepts are discussed and the subject reverse cholesterol transport is revisited.

  18. Regulation of reverse cholesterol transport - a comprehensive appraisal of available animal studies

    NARCIS (Netherlands)

    Annema, Wijtske; Tietge, Uwe J. F.

    2012-01-01

    Plasma levels of high density lipoprotein (HDL) cholesterol are strongly inversely correlated to the risk of atherosclerotic cardiovascular disease. A major recognized functional property of HDL particles is to elicit cholesterol efflux and consequently mediate reverse cholesterol transport (RCT). T

  19. Catalytic stimulation by restrained active-site floppiness--the case of high density lipoprotein-bound serum paraoxonase-1.

    Science.gov (United States)

    Ben-David, Moshe; Sussman, Joel L; Maxwell, Christopher I; Szeler, Klaudia; Kamerlin, Shina C L; Tawfik, Dan S

    2015-03-27

    Despite the abundance of membrane-associated enzymes, the mechanism by which membrane binding stabilizes these enzymes and stimulates their catalysis remains largely unknown. Serum paraoxonase-1 (PON1) is a lipophilic lactonase whose stability and enzymatic activity are dramatically stimulated when associated with high-density lipoprotein (HDL) particles. Our mutational and structural analyses, combined with empirical valence bond simulations, reveal a network of hydrogen bonds that connect HDL binding residues with Asn168--a key catalytic residue residing >15Å from the HDL contacting interface. This network ensures precise alignment of N168, which, in turn, ligates PON1's catalytic calcium and aligns the lactone substrate for catalysis. HDL binding restrains the overall motion of the active site and particularly of N168, thus reducing the catalytic activation energy barrier. We demonstrate herein that disturbance of this network, even at its most far-reaching periphery, undermines PON1's activity. Membrane binding thus immobilizes long-range interactions via second- and third-shell residues that reduce the active site's floppiness and pre-organize the catalytic residues. Although this network is critical for efficient catalysis, as demonstrated here, unraveling these long-rage interaction networks is challenging, let alone their implementation in artificial enzyme design.

  20. Blood-Borne Lipopolysaccharide Is Rapidly Eliminated by Liver Sinusoidal Endothelial Cells via High-Density Lipoprotein.

    Science.gov (United States)

    Yao, Zhili; Mates, Jessica M; Cheplowitz, Alana M; Hammer, Lindsay P; Maiseyeu, Andrei; Phillips, Gary S; Wewers, Mark D; Rajaram, Murugesan V S; Robinson, John M; Anderson, Clark L; Ganesan, Latha P

    2016-09-15

    During Gram-negative bacterial infections, excessive LPS induces inflammation and sepsis via action on immune cells. However, the bulk of LPS can be cleared from circulation by the liver. Liver clearance is thought to be a slow process mediated exclusively by phagocytic resident macrophages, Kupffer cells (KC). However, we discovered that LPS disappears rapidly from the circulation, with a half-life of 2-4 min in mice, and liver eliminates about three quarters of LPS from blood circulation. Using microscopic techniques, we found that ∼75% of fluor-tagged LPS in liver became associated with liver sinusoidal endothelial cells (LSEC) and only ∼25% with KC. Notably, the ratio of LSEC-KC-associated LPS remained unchanged 45 min after infusion, indicating that LSEC independently processes the LPS. Most interestingly, results of kinetic analysis of LPS bioactivity, using modified limulus amebocyte lysate assay, suggest that recombinant factor C, an LPS binding protein, competitively inhibits high-density lipoprotein (HDL)-mediated LPS association with LSEC early in the process. Supporting the previous notion, 3 min postinfusion, 75% of infused fluorescently tagged LPS-HDL complex associates with LSEC, suggesting that HDL facilitates LPS clearance. These results lead us to propose a new paradigm of LSEC and HDL in clearing LPS with a potential to avoid inflammation during sepsis. PMID:27534554

  1. Hubungan Kadar Low-Density Lipoprotein Cholesterol dengan Kejadian dan Keparahan Stroke Akut

    OpenAIRE

    Hasibuan, Azwita Effrina

    2016-01-01

    Introduction : The role of serum cholesterol as the stroke etiology is still uncertain. Studies that focused on the association between low-density lipoprotein cholesterol (LDLC) and acute stroke was still rare, with inconsistent results. The aim of this study is to evaluate the correlation between LDL-C level and the acute stroke occurance and severity. Methods : We conducted a cross-sectional study of 51-acute stroke patients in Adam Malik General Hospital, Medan. Subjects...

  2. Low-density lipoprotein analysis in microchip capillary electrophoresis systems

    NARCIS (Netherlands)

    Ceriotti, Laura; Shibata, Takayuki; Folmer, Britta; Weiller, Bruce H.; Roberts, Matthew A.; De Rooij, Nico F.; Verpoorte, Elisabeth

    2002-01-01

    Due to the mounting evidence for altered lipoprotein and cholesterol-lipoprotein content in several disease states, there has been an increasing interest in analytical methods for lipoprotein profiling for diagnosis. The separation of low- and high-density lipoproteins (LDL and HDL, respectively) ha

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

    Science.gov (United States)

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

  4. Glycated albumin and direct low density lipoprotein cholesterol levels in type 2 diabetes mellitus

    Science.gov (United States)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the ut...

  5. Effect of a high carbohydrate diet on the content of apolipoproteins C-II, C-III and E in human plasma high density lipoprotein subfractions.

    Science.gov (United States)

    Sasaki, N; Holdsworth, G; Barnhart, R L; Srivastava, L S; Glueck, C J; Kashyap, M L; Jackson, R L

    1983-03-01

    The effect of isocaloric high and low carbohydrate (Carb) diets on the structure and apoprotein composition of plasma high density lipoproteins (HDL) was assessed in four healthy men. The high Carb diet contained 65% calories as Carb and 15% as fat; the low Carb was 15% and 65%, respectively, with protein fixed at 20% of calories in each case. Cholesterol was 400 mg/day and the P/S ratio of the fat was 0.4. Each diet was sequentially consumed for periods of 3 weeks. At the end of each 3-week study period, plasma HDL2 and HDL3 were isolated by zonal ultracentrifugation and their apoprotein and lipid compositions were determined. Compared to the low Carb diet, the high Carb diet was associated with an increase in the size of HDL2 (116.0 +/- 1.8 vs. 109.1 +/- 1.8 A) and in the content (mean weight % +/- SEM) of apoE (2.81 +/- 0.71 vs. 1.79 +/- 0.49, P less than 0.01) and of apoC-II (1.73 +/- 0.09 vs. 1.11 +/- 0.12, P less than 0.01). HDL2 apoC-III content was not significantly different on the two diets (6.49 +/- 0.50 vs. 7.42 +/- 1.21). On the two diets, HDL3 size and HDL3 apoE content were not significantly changed. HDL3 apoC-II and apoC-III, however, were higher on the high Carb diet, P less than 0.05. The ratio (by weight) of HDL2 apoE/HDL2 apoC-II + C-III increased on the high Carb diet compared to the low Carb diet (0.344 +/- 0.058 vs. 0.228 +/- 0.053, P less than 0.01). We suggest that the increased amount of apolipoprotein E in HDL2 may influence its rate of catabolic clearance and may account for the well-known decrease in plasma HDL-cholesterol in subjects on high Carb diets. PMID:6847745

  6. Dietary Cholesterol Affects Plasma Lipid Levels, the Intravascular Processing of Lipoproteins and Reverse Cholesterol Transport without Increasing the Risk for Heart Disease

    OpenAIRE

    Jacqueline Barona; Maria Luz Fernandez

    2012-01-01

    The associations between dietary cholesterol and heart disease are highly controversial. While epidemiological studies and clinical interventions have shown the lack of correlation between cholesterol intake and cardiovascular disease (CVD) risk, there is still concern among health practitioners and the general population regarding dietary cholesterol. In this review, several clinical studies utilizing cholesterol challenges are analyzed in terms of changes that occur in lipoprotein metabolis...

  7. Facts about...Blood Cholesterol. Revised.

    Science.gov (United States)

    National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.

    This fact sheet on blood cholesterol examines the connection between cholesterol and heart disease, lists risk factors for heart disease that can and cannot be controlled, points out who can benefit from lowering blood cholesterol, distinguishes between blood and dietary cholesterol, describes low density lipoprotein and high density lipoprotein…

  8. Fractionation of human serum lipoproteins and simultaneous enzymatic determination of cholesterol and triglycerides

    Energy Technology Data Exchange (ETDEWEB)

    Qureshi, Rashid Nazir [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands); Kok, Wim Th., E-mail: W.Th.Kok@uva.nl [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands); Schoenmakers, Peter J. [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands)

    2009-11-03

    A method based on Asymmetric Flow Field-Flow Fractionation (AF4) was developed to separate different types of lipoproteins from human serum. The emphasis in the method optimization was on the possibilities to characterize the largest lipoprotein fractions (LDL and VLDL), which is usually not possible with the size-exclusion chromatography methods applied in routine analysis. Different channel geometries and flow programs were tested and compared. The use of a short fractionation channel was shown to give less sample dilution at the same fractionation power compared to a conventional, long channel. Different size selectivities were obtained with an exponential decay and a linear cross flow program. The ratio of the UV absorption signal to the light scattering signal was used to validate the relation between retention time and size of the fractionated particles. An experimental setup was developed for the simultaneous determination of the cholesterol and triglycerides distribution over the lipoprotein fractions, based on enzymatic reactions followed by UV detection at 500 nm. Coiled and knitted PTFE tubing reactors were compared. An improved peak sharpness and sensitivity were observed with the knitted tubing reactor. After optimization of the experimental conditions a satisfactory linearity and precision (2-3% rsd for cholesterol and 5-6% rsd for triglycerides) were obtained. Finally, serum samples, a pooled sample from healthy volunteers and samples of sepsis patients, were analyzed with the method developed. Lipoprotein fractionation and cholesterol and triglyceride distributions could be correlated with the clinical background of the samples.

  9. NMR and interval PLS as reliable methods for determination of cholesterol in rodent lipoprotein fractions

    DEFF Research Database (Denmark)

    Kristensen, Mette; Savorani, Francesco; Ravn-Haren, Gitte;

    2010-01-01

    data and the NMR spectra, an interval partial least-square (iPLS) regression model to predict the amount of cholesterol in the different lipoprotein fractions was developed. The relative errors of the prediction models were between 12 and 33% and had correlation coefficients (r) between 0.96 and 0...... fractions in rat plasma is presented in this paper. Plasma from two rat studies (n = 68) was used in determining the lipoprotein profile by an established ultracentrifugation method and proton nuclear magnetic resonance (NMR) spectra of replicate samples was obtained. From the ultracentrifugation reference...

  10. Rice bran oil and oryzanol reduce plasma lipid and lipoprotein cholesterol concentrations and aortic cholesterol ester accumulation to a greater extent than ferulic acid in hypercholesterolemic hamsters.

    Science.gov (United States)

    Wilson, Thomas A; Nicolosi, Robert J; Woolfrey, Benjamin; Kritchevsky, David

    2007-02-01

    Our laboratory has reported that the hypolipidemic effect of rice bran oil (RBO) is not entirely explained by its fatty acid composition. Because RBO has a greater content of the unsaponifiables, which also lower cholesterol compared to most vegetable oils, we wanted to know whether oryzanol or ferulic acid, two major unsaponifiables in RBO, has a greater cholesterol-lowering activity. Forty-eight F(1)B Golden Syrian hamsters (Mesocricetus auratus) (BioBreeders, Watertown, MA) were group housed (three per cage) in cages with bedding in an air-conditioned facility maintained on a 12-h light/dark cycle. The hamsters were fed a chow-based hypercholesterolemic diet (HCD) containing 10% coconut oil and 0.1% cholesterol for 2 weeks, at which time they were bled after an overnight fast (16 h) and segregated into 4 groups of 12 with similar plasma cholesterol concentrations. Group 1 (control) continued on the HCD, group 2 was fed the HCD containing 10% RBO in place of coconut oil, group 3 was fed the HCD plus 0.5% ferulic acid and group 4 was fed the HCD plus 0.5% oryzanol for an additional 10 weeks. After 10 weeks on the diets, plasma total cholesterol (TC) and non-high-density lipoprotein cholesterol (HDL-C) (very low- and low-density lipoprotein) concentrations were significantly lower in the RBO (-64% and -70%, respectively), the ferulic acid (-22% and -24%, respectively) and the oryzanol (-70% and -77%, respectively) diets compared to control. Plasma TC and non-HDL-C concentrations were also significantly lower in the RBO (-53% and -61%, respectively) and oryzanol (-61% and -70%, respectively) diets compared to the ferulic acid. Compared to control and ferulic acid, plasma HDL-C concentrations were significantly higher in the RBO (10% and 20%, respectively) and oryzanol (13% and 24%, respectively) diets. The ferulic acid diet had significantly lower plasma HDL-C concentrations compared to the control (-9%). The RBO and oryzanol diets were significantly lower for

  11. Rice bran oil and oryzanol reduce plasma lipid and lipoprotein cholesterol concentrations and aortic cholesterol ester accumulation to a greater extent than ferulic acid in hypercholesterolemic hamsters.

    Science.gov (United States)

    Wilson, Thomas A; Nicolosi, Robert J; Woolfrey, Benjamin; Kritchevsky, David

    2007-02-01

    Our laboratory has reported that the hypolipidemic effect of rice bran oil (RBO) is not entirely explained by its fatty acid composition. Because RBO has a greater content of the unsaponifiables, which also lower cholesterol compared to most vegetable oils, we wanted to know whether oryzanol or ferulic acid, two major unsaponifiables in RBO, has a greater cholesterol-lowering activity. Forty-eight F(1)B Golden Syrian hamsters (Mesocricetus auratus) (BioBreeders, Watertown, MA) were group housed (three per cage) in cages with bedding in an air-conditioned facility maintained on a 12-h light/dark cycle. The hamsters were fed a chow-based hypercholesterolemic diet (HCD) containing 10% coconut oil and 0.1% cholesterol for 2 weeks, at which time they were bled after an overnight fast (16 h) and segregated into 4 groups of 12 with similar plasma cholesterol concentrations. Group 1 (control) continued on the HCD, group 2 was fed the HCD containing 10% RBO in place of coconut oil, group 3 was fed the HCD plus 0.5% ferulic acid and group 4 was fed the HCD plus 0.5% oryzanol for an additional 10 weeks. After 10 weeks on the diets, plasma total cholesterol (TC) and non-high-density lipoprotein cholesterol (HDL-C) (very low- and low-density lipoprotein) concentrations were significantly lower in the RBO (-64% and -70%, respectively), the ferulic acid (-22% and -24%, respectively) and the oryzanol (-70% and -77%, respectively) diets compared to control. Plasma TC and non-HDL-C concentrations were also significantly lower in the RBO (-53% and -61%, respectively) and oryzanol (-61% and -70%, respectively) diets compared to the ferulic acid. Compared to control and ferulic acid, plasma HDL-C concentrations were significantly higher in the RBO (10% and 20%, respectively) and oryzanol (13% and 24%, respectively) diets. The ferulic acid diet had significantly lower plasma HDL-C concentrations compared to the control (-9%). The RBO and oryzanol diets were significantly lower for

  12. Genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the rat.

    Directory of Open Access Journals (Sweden)

    Miloslava Hodúlová

    Full Text Available The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n = 8-13/strain and two progenitor strains SHR-Lx (n = 13 and BXH2/Cub (n = 18 were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG and cholesterol (C concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl. We have identified 14 loci (encompassing 1 to 65 genes on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b. Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant

  13. High-density lipoprotein associated factors apoA-I and serum amyloid A in Chinese non-diabetic patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    CHEN Guo-liang; LIU Li-wei; XIE Shuang; LIU Hong; LIU Yu-qing; LI Yi-shi

    2010-01-01

    Background High-density lipoprotein cholesterol(HDL-C)levels are a strong,independent inverse predictor of coronary heart disease (CHD).In this cross-sectional study we investigated the interrelationships between HDL-C and HDL relaled factors apolipoprotein A-I(apoA-I)and serum amyloid A(SAA)and the presence and extent of CHD in a population of Chinese patients with CHD. Methods Two hundred and twenty-four consecutive patients took part in this study.Demographic data were obtained from hospital records.Serum chemical concentrations were measured by standard laboratory methods.Reaults The concentrations of high-sensitive C-reactive protein(hsCRP)(median:1.85 mg/L)and SAP,(median:9.40 mg/L)were significantly higher in the CHD group(P<0.05),while concentrations of HDL-C(0.03±0.25)mmol/L)and apoA-I((604.59±1 05.79)mmol/L)were significantly lower than those in the non-CHD group(P<0.05).The concentrations of apoA-l decreased with the increase in vascular damage.but the difference did not reach statistical significance.However, the concentrations of hsCRP and SAA increased with the increase in vascular damage.The unadjusted odd ratios(ORs)(CI) for apoA-I and SAA of the presence of CHD were 0.093(0.990-0.997)(P=0.00)and 2.571(1.029-6.424)(P<0.05),respectively.The association between elevated SAA and the presence of CHD was lost after adjusting for lipid status parameter concentrations.The associations between apoA-I.SAA and the extent of CHD remained strong,regardless of confounding variables.Conclusions Increased concentrations of SAA represent the inflammatory marker of the extent of coronary stenosis in patients with CHD.In contrast to SAA, the level of apoA-I was also associated with the presence of CHD, indicating that apoA-I was not only a marker of CHD presence but also a quantitative indicator of CHD extent.In short.determining the change apolipoprotein content within HDL particle is a more accurate and effective method to evaluate the impact of HDL on CHD.

  14. The relationship between serum amyloid A and apolipoprotein A-I in high-density lipoprotein isolated from patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    WANG Dong-xue; LIU Hong; YAN Li-rong; ZHANG Ye-ping; GUAN Xiao-yuan; XU Zhi-min; JIA You-hong

    2013-01-01

    Background Alteration in the protein composition of high-density lipoprotein (HDL) has been proposed as a mechanism for the development of coronary heart disease (CHD).In HDL,an increase in serum amyloid A protein (SAA) accompanying the decrease in apolipoprotein A-I (apoA-I) has been found during the acute inflammation period.However,whether this phenomenon persists in CHD patients,a disease related to inflammation,is unknown.The purpose of the present study was to explore the relationship between SAA and apoA-I in HDL isolated from CHD patients.Methods Overall,98 patients with confirmed stable CHD and 90 control subjects matched for age and gender were enrolled in this case-control study.Potassium bromide (KBr) density gradient ultracentrifugation was used to isolate HDL from plasma.The levels of SAA and apoA-I in the HDL samples were detected by enzyme-linked immunosorbent assay kits.Pearson's correlation and general linear models were used in the analysis.Results Compared with controls,patients with CHD had a significant decrease in the amount of apoA-I ((14.21±8.44) μg/ml vs.(10.95±5.95) μg/ml,P =0.003) in HDL and a significant increase in the amount of log SAA (1.21±0.46 vs.1.51±0.55,P <0.00001).Differences were independent of age,body mass index (BMI),HDL cholesterol (HDL-C),and other factors.An independently and statistically significant positive correlation between log SAA and apoA-I in HDL was observed only in the CHD group (β =2.0,P =0.026).In the general linear model,changes in Iog(SAA),age,age2,gender,BMI and HDL-C could explain a statistically significant 43% of the variance in apoA-I.Conclusions This study provides direct evidence for the first time that there was an independent positive correlation between log SAA and apoA-I in the HDL of CHD patients,indicating the alteration of protein composition in HDL.However,the question of whether this alteration in HDL is associated with impairment of HDL functions requires further research.

  15. Low-density lipoprotein cholesterol and the risk of cancer: a mendelian randomization study

    DEFF Research Database (Denmark)

    Benn, Marianne; Tybjærg-Hansen, Anne; Stender, Stefan;

    2011-01-01

    Background Low plasma levels of low-density lipoprotein (LDL) cholesterol are associated with an increased risk of cancer, but whether this association is causal is unclear. Methods We studied 10¿613 participants in the Copenhagen City Heart Study (CCHS) and 59¿566 participants in the Copenhagen...... General Population Study, 6816 of whom had developed cancer by May 2009. Individuals were genotyped for PCSK9 R46L (rs11591147), ABCG8 D19H (rs11887534), and APOE R112C (rs429358) and R158C (rs7412) polymorphisms, all of which are associated with lifelong reduced plasma LDL cholesterol levels. Plasma LDL......-sectionally by logistic regression analyses. Causality was studied using instrumental variable analysis. All statistical tests were two-sided. Results In the CCHS, compared with plasma LDL cholesterol levels greater than the 66th percentile (>158 mg/dL), those lower than the 10th percentile (

  16. Anti-Aging and Tissue Regeneration Ability of Policosanol Along with Lipid-Lowering Effect in Hyperlipidemic Zebrafish via Enhancement of High-Density Lipoprotein Functionality

    OpenAIRE

    Lee, Eun-Young; Yoo, Jeong-Ah; Lim, So-Mang; Cho, Kyung-Hyun

    2016-01-01

    Abstract We investigated the tissue regeneration and lipid-lowering effects of policosanol (PCO) by employing a hyperlipidemic zebrafish model. A reconstituted high-density lipoprotein containing policosanol (PCO-rHDL) facilitated greater cell growth and replication with less apoptosis and reactive oxygen species (ROS) production in BV-2 microglial cell lines. From in vivo study, injection of rHDL containing apolipoprotein A-I (ApoA-I) caused 76 ± 4% (p = 0.01) greater tissue regeneration act...

  17. Design, Synthesis and Biological Evaluation of Hydroxamic Acid Derivatives as Potential High Density Lipoprotein (HDL) Receptor CLA-1 Up-Regulating Agents

    OpenAIRE

    Yu Du; Yanbin Wu; Bin Hong; Yuan Yang; Xiaojian Jia; Li Wang; Xiaofang Chen

    2011-01-01

    Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) were reported in our recent publication as novel human high density lipoprotein (HDL) receptor CD36 and Lysosomal integral membrane protein-II Analogous-1 (CLA-1) up-regulators. As part of a broader effort to more fully explore the structure-activity relationships (SAR) of CLA-1 up-regulators, we synthesized a series of hydroxamic acid derivatives and evaluated their CLA-1 up-regulating activities in HepG2 cells. Some compounds e...

  18. The V227A polymorphism at the PPARA locus is associated with serum lipid concentrations and modulates the association between dietary polyunsaturated fatty acid intake and serum high density lipoprotein concentrations in Chinese women.

    Science.gov (United States)

    Chan, Edmund; Tan, Chuen Seng; Deurenberg-Yap, Mabel; Chia, Kee Seng; Chew, Suok Kai; Tai, E Shyong

    2006-08-01

    Peroxisome proliferators activated receptor alpha (PPARalpha) regulates the transcription of several proteins involved in human lipoprotein metabolism. We screened the PPARA locus for polymorphisms in 20 unrelated subjects from each of three ethnic groups (Chinese, Malays and Asian Indians). Only the V227A polymorphism was observed. We genotyped 4248 subjects (2899 Chinese, 761 Malay and 588 Asian Indians) and found allele frequencies for the A227 allele of 0.04 in Chinese, 0.006 in Malays and 0.003 in Asian Indians. We examined the associations between this polymorphism and serum lipid concentrations in Chinese. In women, but not in men, the presence of the A227 allele was associated with lower serum concentrations of total cholesterol [5.38mmol/l (95%CI: 5.22-5.54) versus 5.21mmol/l (95%CI: 4.99-5.43), p=0.047] and triglycerides [1.19mmol/l (95%CI: 1.10-1.28) versus 1.09mmol/l (95%CI: 0.98-1.21), p=0.048]. We also found that the V227A polymorphism modulates the association between dietary polyunsaturated fatty acid intake and serum high density lipoprotein concentration (p-value for interaction=0.049). Our findings implicate PPARalpha in the lipid lowering associated with diets high in PUFA and suggests that genetic variation at the PPARA locus may determine the lipid response to changes in PUFA intake. PMID:16288935

  19. Remnant cholesterol as a causal risk factor for ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Tybjærg-Hansen, Anne;

    2013-01-01

    The aim of this study was to test the hypothesis that elevated nonfasting remnant cholesterol is a causal risk factor for ischemic heart disease independent of reduced high-density lipoprotein (HDL) cholesterol.......The aim of this study was to test the hypothesis that elevated nonfasting remnant cholesterol is a causal risk factor for ischemic heart disease independent of reduced high-density lipoprotein (HDL) cholesterol....

  20. Effect of 6 dietary fatty acids on the postprandial lipid profile, plasma fatty acids, lipoprotein lipase, and cholesterol ester transfer activities in healthy young men

    DEFF Research Database (Denmark)

    Tholstrup, T.; Sandstrøm, B.; Bysted, Anette;

    2001-01-01

    Background: There is increasing evidence that postprandial triacylglycerol-rich lipoproteins may be related to atherogenic risk. Objective: The objective was to investigate the effect of individual fatty acid intakes on postprandial plasma lipoprotein triacylglycerol and cholesterol concentrations...

  1. Phenolic-extract from argan oil (Argania spinosa L.) inhibits human low-density lipoprotein (LDL) oxidation and enhances cholesterol efflux from human THP-1 macrophages.

    Science.gov (United States)

    Berrougui, Hicham; Cloutier, Martin; Isabelle, Maxim; Khalil, Abdelouahed

    2006-02-01

    Argan oil is rich in unsaturated fatty acids, tocopherol and phenolic compounds. These protective molecules make further study of its cardiovascular diseases (CVDs) action interesting. Furthermore, no previous study has explored the antioxidant activity of argan oil in comparison with olive oil. The present study was conducted to evaluate the beneficial properties of Virgin argan oil phenolic extracts (VAO-PE) towards CVD by: (A) protecting human (low-density lipoprotein, LDL) against lipid peroxidation and (B) promoting high-density lipoprotein (HDL)-mediated cholesterol efflux. Human LDLs were oxidized by incubation with CuSO(4) in the presence of different concentrations of VAO-PE (0-320mug/ml). LDL lipid peroxidation was evaluated by conjugated diene and MDA formation as well as Vitamin E disappearance. Incubation of LDL with VAO-PE significantly prolonged the lag-phase and lowered the progression rate of lipid peroxidation (P<0.01) and reduced the disappearance of Vitamin E in a concentration-dependent manner. Incubation of HDL with VAO-PE significantly increased the fluidity of the HDL phospholipidic bilayer (P=0.0004) and HDL-mediated cholesterol efflux from THP-1 macrophages. These results suggest that Virgin argan oil provides a source of dietary phenolic antioxidants, which prevent cardiovascular diseases by inhibiting LDL-oxidation and enhancing reverse cholesterol transport. These properties increase the anti-atherogenic potential of HDL. PMID:16019008

  2. A review on lecithin:cholesterol acyltransferase deficiency.

    Science.gov (United States)

    Saeedi, Ramesh; Li, Min; Frohlich, Jiri

    2015-05-01

    Lecithin cholesterol acyl transferase (LCAT) is a plasma enzyme which esterifies cholesterol, and plays a key role in the metabolism of high-density lipoprotein cholesterol (HDL-C). Genetic disorders of LCAT are associated with lipoprotein abnormalities including low levels of HDL-C and presence of lipoprotein X, and clinical features mainly corneal opacities, changes in erythrocyte morphology and renal failure. Recombinant LCAT is being developed for the treatment of patients with LCAT deficiency. PMID:25172171

  3. Phytosterols, Phytostanols, and Lipoprotein Metabolism

    Directory of Open Access Journals (Sweden)

    Helena Gylling

    2015-09-01

    Full Text Available 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

  4. Total Lipid Profile, Faecal Cholesterol, very Low Density Lipoprotein Cholesterol (VLDL-C, Atherogenic Index (A.I and Percent Atherosclerosis with Aqueous Fruit Extract of Solanum macrocarpum in Chronic Triton-Induced Hyperlipidemic Albino Rats

    Directory of Open Access Journals (Sweden)

    Sodipo O. Adebola

    2012-03-01

    Full Text Available Studies were undertaken to investigate the effect of the aqueous fruit extract of Solanum macrocarpum on the total lipid profile [total cholesterol, triglyceride, high density lipoprotein-cholesterol (LDL-C and low density liprotein cholesterol (LDL-C], faecal cholesterol, very low density lipoproteincholesterol (VLDL-C, atherogenic index (A.I and percent atherosclerosis on chronic titron-induced hyperlipidemic rats. The increase in HDL-C was dose-dependent and statistically significant (p0.05 with increase in extract dose for both total cholesterol and triglycerides throughout the period of study while the decrease in LDL-C was significant (p0.05. The results shows that the plant may be capable of reducing circulating lipids in chronic triton-induced hyperlipidemic rats probably by reducing absorption of lipids, thus, reducing hyperlipidemia. At the same time, the aqueous fruit extract probably has the potential to reduce the risk of development of heart diseases since VLDL-C has been shown to be beneficial and indicative of a lower risk of coronary heart diseases. Also, a reduction in percent atherosclerosis is desirable as this implies that atherosclerosis is reduced.

  5. Modified high-density lipoproteins by artificial sweetener, aspartame, and saccharin, showed loss of anti-atherosclerotic activity and toxicity in zebrafish.

    Science.gov (United States)

    Kim, Jae-Yong; Park, Ki-Hoon; Kim, Jihoe; Choi, Inho; Cho, Kyung-Hyun

    2015-01-01

    Safety concerns have been raised regarding the association of chronic consumption of artificial sweeteners (ASs) with metabolic disorders, especially in the heart and brain. There has been no information on the in vivo physiological effects of AS consumption in lipoprotein metabolism. High-dosage treatment (final 25, 50, and 100 mM) with AS (aspartame, acesulfame K, and saccharin) to human high-density lipoprotein (HDL) induced loss of antioxidant ability along with elevated atherogenic effects. Aspartame-treated HDL3 (final 100 mM) almost all disappeared due to putative proteolytic degradation. Aspartame- and saccharin-treated HDL3 showed more enhanced cholesteryl ester transfer activity, while their antioxidant ability was disappeared. Microinjection of the modified HDL3 exacerbated the inflammatory death in zebrafish embryos in the presence of oxLDL. These results show that AS treatment impaired the beneficial functions of HDL, resulting in loss of antioxidant and anti-atherogenic activities. These results suggest that aspartame and saccharin could be toxic to the human circulation system as well as embryonic development via impairment of lipoprotein function.

  6. Modified high-density lipoproteins by artificial sweetener, aspartame, and saccharin, showed loss of anti-atherosclerotic activity and toxicity in zebrafish.

    Science.gov (United States)

    Kim, Jae-Yong; Park, Ki-Hoon; Kim, Jihoe; Choi, Inho; Cho, Kyung-Hyun

    2015-01-01

    Safety concerns have been raised regarding the association of chronic consumption of artificial sweeteners (ASs) with metabolic disorders, especially in the heart and brain. There has been no information on the in vivo physiological effects of AS consumption in lipoprotein metabolism. High-dosage treatment (final 25, 50, and 100 mM) with AS (aspartame, acesulfame K, and saccharin) to human high-density lipoprotein (HDL) induced loss of antioxidant ability along with elevated atherogenic effects. Aspartame-treated HDL3 (final 100 mM) almost all disappeared due to putative proteolytic degradation. Aspartame- and saccharin-treated HDL3 showed more enhanced cholesteryl ester transfer activity, while their antioxidant ability was disappeared. Microinjection of the modified HDL3 exacerbated the inflammatory death in zebrafish embryos in the presence of oxLDL. These results show that AS treatment impaired the beneficial functions of HDL, resulting in loss of antioxidant and anti-atherogenic activities. These results suggest that aspartame and saccharin could be toxic to the human circulation system as well as embryonic development via impairment of lipoprotein function. PMID:25142179

  7. Inhibition of cholesterol ester transfer protein CGS 25159 and changes in lipoproteins in hamsters.

    Science.gov (United States)

    Kothari, H V; Poirier, K J; Lee, W H; Satoh, Y

    1997-01-01

    As a result of screening, several isoflavans were identified to be antagonists of cholesterol ester transfer protein (CETP) activity. The present study evaluates CGS 25159, a synthetic isoflavan, as a putative inhibitor of CETP activity of human and hamster plasma. Determined by [3]CE transfer from HDL to VLDL + LDL fraction or by fluorescent-CE transfer assay, CGS 25159 inhibited CETP in both human plasma bottom fraction (d = 1.21 g/ml) and in plasma from Golden Syrian Hamsters with an IC50 contention that pharmacological down regulation of CETP activity could result in favorable changes in lipoprotein profile. PMID:9051198

  8. Serum Cholesterol Levels in College Students: Opportunities for Education and Intervention.

    Science.gov (United States)

    Sparling, Phillip B.; Snow, Teresa K.; Beavers, Bill D.

    1999-01-01

    Analyzed lipid profiles in 1,088 college students at a university where lipid profiles were available to students in selected health/wellness courses. Mean total cholesterol levels were similar for men and women, but men had significantly lower high-density lipoprotein cholesterol and higher low-density lipoprotein cholesterol than women. About 11…

  9. 21-Methylpyrenyl-cholesterol stably and specifically associates with lipoprotein peripheral hemi-membrane: A new labelling tool

    Energy Technology Data Exchange (ETDEWEB)

    Gaibelet, Gérald [INSERM U563, CHU Purpan, Toulouse (France); CEA, SB2SM and UMR8221 CNRS, IBiTec-Saclay, Gif-sur-Yvette (France); Tercé, François [Université Toulouse III, UMR 1048, Toulouse (France); INSERM U1048, Toulouse (France); Bertrand-Michel, Justine [Université Toulouse III, UMR 1048, Toulouse (France); INSERM U1048, Lipidomic Platform Metatoul, Toulouse (France); Allart, Sophie [Plateau Technique d’Imagerie Cellulaire, INSERM U1043, Toulouse (France); Azalbert, Vincent [Université Toulouse III, UMR 1048, Toulouse (France); INSERM U1048, Toulouse (France); Lecompte, Marie-France [INSERM U563, Faculté de Médecine de Rangueil, Toulouse (France); Collet, Xavier [Université Toulouse III, UMR 1048, Toulouse (France); INSERM U1048, Toulouse (France); Orlowski, Stéphane, E-mail: stephane.orlowski@cea.fr [INSERM U563, CHU Purpan, Toulouse (France); CEA, SB2SM and UMR8221 CNRS, IBiTec-Saclay, Gif-sur-Yvette (France)

    2013-11-01

    Highlights: •21-Methylpyrenyl-cholesterol specifically and stably associates to lipoproteins. •It is not esterified by LCAT, and thus reliably labels their peripheral hemi-membrane. •HDL vs. LDL are well distinguishable by various fluorescent labelling characteristics. •LDL peripheral hemi-membrane harbors cholesterol-rich ordered lipid (micro)domains. •Cultured cells can be stained by such labelled lipoproteins-mediated delivery. -- Abstract: Lipoproteins are important biological components. However, they have few convenient fluorescent labelling probes currently reported, and their physiological reliability can be questioned. We compared the association of two fluorescent cholesterol derivatives, 22-nitrobenzoxadiazole-cholesterol (NBD-Chol) and 21-methylpyrenyl-cholesterol (Pyr-met-Chol), to serum lipoproteins and to purified HDL and LDL. Both lipoproteins could be stably labelled by Pyr-met-Chol, but virtually not by NBD-Chol. At variance with NBD-Chol, LCAT did not esterify Pyr-met-Chol. The labelling characteristics of lipoproteins by Pyr-met-Chol were well distinguishable between HDL and LDL, regarding dializability, associated probe amount and labelling kinetics. We took benefit of the pyrene labelling to approach the structural organization of LDL peripheral hemi-membrane, since Pyr-met-Chol-labelled LDL, but not HDL, presented a fluorescence emission of pyrene excimers, indicating that the probe was present in an ordered lipid micro-environment. Since the peripheral membrane of LDL contains more sphingomyelin (SM) than HDL, this excimer formation was consistent with the existence of cholesterol- and SM-enriched lipid microdomains in LDL, as already suggested in model membranes of similar composition and reminiscent to the well-described “lipid rafts” in bilayer membranes. Finally, we showed that Pyr-met-Chol could stain cultured PC-3 cells via lipoprotein-mediated delivery, with a staining pattern well different to that observed with NBD

  10. Anthocyanins increase low-density lipoprotein and plasma cholesterol and do not reduce atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Nielsen, I. L. F.; Rasmussen, S.E.; Mortensen, Alicja;

    2005-01-01

    a purified anthocyanin fraction front black currants, a black currant juice, probucol or control diet for 16 weeks. Purified anthocyanins significantly increased plasma cholesterol and low-density lipoprotein (LDL) cholesterol. Intake of black currant juice had no effect on total plasma cholesterol......, antioxidant enzymes, protein and lipid oxidation were not affected by any of the anthocyanin treatments. Adverse effects of purified anthocyanins were observed on plasma- and LDL-cholesterol. These effects were not observed with black currant juice, suggesting that black currants may contain components...

  11. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol.

    Science.gov (United States)

    Della Badia, Laura A; Elshourbagy, Nabil A; Mousa, Shaker A

    2016-08-01

    Statins and other lipid-lowering drugs have dominated the market for many years for achievement of recommended levels of low-density lipoprotein cholesterol (LDL-C). However, a substantial number of high-risk patients are unable to achieve the LDL-C goal. Proprotein convertase subtilisin/kexin 9 (PCSK9) has recently emerged as a new, promising key therapeutic target for hypercholesterolemia. PCSK9 is a protease involved in chaperoning the low-density lipoprotein receptor to the process of degradation. PCSK9 inhibitors and statins effectively lower LDL-C. The PCSK9 inhibitors decrease the degradation of the LDL receptors, whereas statins mainly interfere with the synthetic machinery of cholesterol by inhibiting the key rate limiting enzyme, the HMG CoA reductase. PCSK9 inhibitors are currently being developed as monoclonal antibodies for their primary use in lowering LDL-C. They may be especially useful for patients with homozygous familial hypercholesterolemia, who at present receive minimal benefit from traditional statin therapy. The monoclonal antibody PCSK9 inhibitors, recently granted FDA approval, show the most promising safety and efficacy profile compared to other, newer LDL-C lowering therapies. This review will primarily focus on the safety and efficacy of monoclonal antibody PCSK9 inhibitors in comparison to statins. The review will also address new, alternative PCSK9 targeting drug classes such as small molecules, gene silencing agents, apolipoprotein B antisense oligonucleotides, and microsomal triglyceride transfer protein inhibitors. PMID:27133571

  12. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol.

    Science.gov (United States)

    Della Badia, Laura A; Elshourbagy, Nabil A; Mousa, Shaker A

    2016-08-01

    Statins and other lipid-lowering drugs have dominated the market for many years for achievement of recommended levels of low-density lipoprotein cholesterol (LDL-C). However, a substantial number of high-risk patients are unable to achieve the LDL-C goal. Proprotein convertase subtilisin/kexin 9 (PCSK9) has recently emerged as a new, promising key therapeutic target for hypercholesterolemia. PCSK9 is a protease involved in chaperoning the low-density lipoprotein receptor to the process of degradation. PCSK9 inhibitors and statins effectively lower LDL-C. The PCSK9 inhibitors decrease the degradation of the LDL receptors, whereas statins mainly interfere with the synthetic machinery of cholesterol by inhibiting the key rate limiting enzyme, the HMG CoA reductase. PCSK9 inhibitors are currently being developed as monoclonal antibodies for their primary use in lowering LDL-C. They may be especially useful for patients with homozygous familial hypercholesterolemia, who at present receive minimal benefit from traditional statin therapy. The monoclonal antibody PCSK9 inhibitors, recently granted FDA approval, show the most promising safety and efficacy profile compared to other, newer LDL-C lowering therapies. This review will primarily focus on the safety and efficacy of monoclonal antibody PCSK9 inhibitors in comparison to statins. The review will also address new, alternative PCSK9 targeting drug classes such as small molecules, gene silencing agents, apolipoprotein B antisense oligonucleotides, and microsomal triglyceride transfer protein inhibitors.

  13. High-density lipoprotein as a potential carrier for delivery of a lipophilic antitumoral drug into hepatoma cells

    Institute of Scientific and Technical Information of China (English)

    Bin Lou; Xue-Ling Liao; Man-Ping Wu; Pei-Fang Cheng; Chun-Yan Yin; Zheng Fei

    2005-01-01

    AIM: To investigate the possibility of recombinant highdensity lipoprotein (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells.METHODS: Recombinant complex of HDL and aclacinomycin(rHDL-ACM) was prepared by cosonication of apoproteins from HDL (Apo HDL) and ACM as well as phosphatidylcholine.Characteristics of the rHDL-ACM were elucidated by electrophoretic mobility, including the size of particles,morphology and entrapment efficiency. Binding activity of rHDL-ACM to human hepatoma cells was determined by competition assay in the presence of excess native HDL. The cytotoxicity of rHDL-ACM was assessed by MTT method.RESULTS: The density range of rHDL-ACM was 1.063-1.210g/mL, and the same as that of native HDL. The purity of all rHDL-ACM preparations was more than 92%.Encapsulated efficiencies of rHDL-ACM were more than90%. rHDL-ACM particles were typical sphere model of lipoproteins and heterogeneous in particle size. The average diameter was 31.26±5.62 nm by measure of 110rHDL-ACM particles in the range of diameter of lipoproteins.rHDL-ACM could bind on SMMC-7721 cells, and such binding could be competed against in the presence of excess native HDL. rHDL-ACM had same binding capacity as native HDL. The cellular uptake of rHDL-ACM by SMMC-7721 hepatoma cells was significantly higher than that of free ACM at the concentration range of 0.5-10 μg/mL(P<0.01). Cytotoxicity of rHDL-ACM to SMMC-7721 cells was significantly higher than that of free ACM at concentration range of less than 5 μg/mL (P<0.01) and IC50 of rHDL-ACM was lower than IC50 of free ACM(1.68 nmol/L vs3 nmol/L). Compared to L02 hepatocytes,a normal liver cell line, the cellular uptake of rHDL-ACM by SMMC-7721 cells was significantly higher (P<0.01) and in a dose-dependent manner at the concentration range of 0.5-10 μg/mL. Cytotoxicity of the rHDL-ACM to SMMC-7721 cells was significantly higher than that to L02 cells at concentration range of 1-7.5 μg/mL (P<0.01). IC50 for

  14. Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol-fed APOE*3-Leiden.CETP mice

    NARCIS (Netherlands)

    Haan, W. de; Hoogt, C.C. van der; Westerterp, M.; Hoekstra, M.; Dallinga-Thie, G.M.; Princen, H.M.G.; Romijn, J.A.; Jukema, J.W.; Havekes, L.M.; Rensen, P.C.N.

    2008-01-01

    Objective: In addition to lowering low-density lipoprotein (LDL)-cholesterol, statins modestly increase high-density lipoprotein (HDL)-cholesterol in humans and decrease cholesteryl ester transfer protein (CETP) mass and activity. Our aim was to determine whether the increase in HDL depends on CETP

  15. Low density lipoprotein cholesterol level inversely correlated with coronary flow velocity reserve in patients with Type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Jie Yu; Jiang-Li Han; Li-Yun He; Xin-Heng Feng; Wei-Hong Li; Jie-Ming Mao; Wei Gao; Guang Wang

    2013-01-01

    Objectives To evaluate the association of coronary artery endothelial function and plasma levels of low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in patients with Type 2 Diabetes Mellitus (DM). Methods We investigated 90 participants from our institution between October 2007 to March 2010: non-DM (n = 60) and DM (n = 30). As an indicator of coronary endothelial dysfunction, we used non-invasive Doppler echocardiography to quantify coronary flow velocity reserve (CFVR) in the distal part of the left descending artery after rest and after intravenous adenosine administration. Results Plasma level of LDL-C was significantly higher in patients with DM than in non-DM (3.21 0.64 vs. 2.86 0.72 mmo/L, P < 0.05), but HDL-C level did not differ between the groups (1.01 0.17 vs. 1.05 0.19 mmo/L). Furthermore, the CFVR value was lower in DM patients than non-diabetics (2.45±0.62 vs. 2.98±0.68, P < 0.001). Plasma levels of LDL-C were negatively correlated with CFVR in all subjects (r = 0.35, P < 0.001; 95% confidence interval (CI): 0.52 -C0.15) and in the non-DM (r = 0.29, P < 0.05; 95% CI: 0.51–0.05), with an even stronger negative correlation in the DM group (r = 0.42, P < 0.05; 95% CI: 0.68 –0.06). Age (β = 0.019, s = 0.007, sβ = 0.435, 95% CI: 0.033 –0.005, P = 0.008), LDL-C (β = 0.217, s = 0.105, sβ = 0.282, 95% CI: 0.428 –0.005, P = 0.045) remained independently correlated with CFVR in the DM group. However, we found no correlation between HDL-C level and CFVR in any group. Conclusions Diabetes may contribute to coronary artery disease (CAD) by inducing dysfunction of the coronary artery endothelium. Increased LDL-C level may adversely impair coronary endothelial function in DM. HDL-C may lose its endothelial-protective effects, in part as a result of pathological conditions, especially under abnormal glucose metabolism.

  16. 21-Methylpyrenyl-cholesterol stably and specifically associates with lipoprotein peripheral hemi-membrane: a new labelling tool.

    Science.gov (United States)

    Gaibelet, Gérald; Tercé, François; Bertrand-Michel, Justine; Allart, Sophie; Azalbert, Vincent; Lecompte, Marie-France; Collet, Xavier; Orlowski, Stéphane

    2013-11-01

    Lipoproteins are important biological components. However, they have few convenient fluorescent labelling probes currently reported, and their physiological reliability can be questioned. We compared the association of two fluorescent cholesterol derivatives, 22-nitrobenzoxadiazole-cholesterol (NBD-Chol) and 21-methylpyrenyl-cholesterol (Pyr-met-Chol), to serum lipoproteins and to purified HDL and LDL. Both lipoproteins could be stably labelled by Pyr-met-Chol, but virtually not by NBD-Chol. At variance with NBD-Chol, LCAT did not esterify Pyr-met-Chol. The labelling characteristics of lipoproteins by Pyr-met-Chol were well distinguishable between HDL and LDL, regarding dializability, associated probe amount and labelling kinetics. We took benefit of the pyrene labelling to approach the structural organization of LDL peripheral hemi-membrane, since Pyr-met-Chol-labelled LDL, but not HDL, presented a fluorescence emission of pyrene excimers, indicating that the probe was present in an ordered lipid micro-environment. Since the peripheral membrane of LDL contains more sphingomyelin (SM) than HDL, this excimer formation was consistent with the existence of cholesterol- and SM-enriched lipid microdomains in LDL, as already suggested in model membranes of similar composition and reminiscent to the well-described "lipid rafts" in bilayer membranes. Finally, we showed that Pyr-met-Chol could stain cultured PC-3 cells via lipoprotein-mediated delivery, with a staining pattern well different to that observed with NBD-Chol non-specifically delivered to the cells. PMID:24103760

  17. OXIDIZED HIGH-DENSITY LIPOPROTEIN PROMOTES MATURATION AND MIGRATION OF BONE MARROW DERIVED DENDRITIC CELLS FROM C57BL/6J MICE

    Institute of Scientific and Technical Information of China (English)

    Zeng-xiang Xu; Yong-zong Yang; Da-ming Feng; Shuang Wang; Ya-ling Tang; Fan He; Yan Xia; Fang Li

    2008-01-01

    Objective To explore the influence of oxidized high-density lipoprotein (oxHDL) on the maturation and migration of bone marrow-derived dendritic cells (BMDCs) from C57BL/6J mice.Methods The C57BL/6J mice bone marrow cell suspension was prepared and purified.Recombinant granulocyte-maerophage colony-stimulating factor (rmGM-CSF) and recombinant interleukin-4 (rmIL-4) were used to promote monocytes to differentiate and suppress lymphoeytes.Then 50 μg/mL oxHDL was added to stimulate BMDCs,using 50 μg/mL high-density lipoprotein (HDL) as homologous protein control,PBS as negative control,and 1 μg/mL lipopolysaccharide (LPS) as positive control.The CD86 and MHCII expression rates were detected with fluorescence-activated cell sorting (FACS).Liquid seintillatiun counting (LSC) was used in mixed lymphocyte reactions (MLRs) to reflect the ability of BMDCs in stimulating the proliferation of homologous T cells.Levels of eytokines IL-12 and IL-10 were detected by ELISA.The cell migration was evaluated with the transwell system.Results Compared with PBS group,the expressions of CD86 and MHCII,counts per minute of MLRs,secretion of IL-12 and IL-10,and number of migrated cells in oxHDL group and LPS group significantly increased (all P<0.05),while the increment was less in oxHDL group than LPS group.The number of migrated cells in oxHDL group was about twice of that in HDL group.Conclusion OxHDL may promote the maturation and migration of BMDCs in vitro.

  18. [Comparative study of the consumption of virgin olive oil or seje on lipid profile and oxidation resistance of high density lipoprotein (HDL) of rat plasma].

    Science.gov (United States)

    Isabel Giacopini, María; Guerrero, Omaira; Moya, Manuel; Bosch, Virgilio

    2011-06-01

    We compared the effect of the consumption of seje oil (Oenocarpus bataua), with that of olive oil, on plasma lipids and susceptibility in vitro to oxidation of high density lipoprotein (HDL) in the rat. Two groups often male Sprague Dawley rats were fed ad libitum, for a lapse of eight week, with a purified diets with 10g de seje oil or olive oil/100 g of diet (GS y GO respectively). The animals were exsanguinated at the end of the experimental after a 14 hour fast. Plasma was isolated by centrifugation, and the fractions of lipoproteins were separated from the plasma by sequential ultracentrifugation. Rats of GO had a statistically significant lower in concentration of TG (p < 0.05) compared with GS group. HDL fractions in both groups were oxidatively modified by incubation with copper ions. Differences in the fractions susceptibilities to peroxidation were studied by measuring the formation of thiobarbituric acid reactive substance (TBARS) for 3 hours. HDL in GS had a statistically significant decrease in TBARS formation (p < 0.05) relative to HDL of GO. This may be explained by the lower concentration of polyunsaturated fatty acids of HDL in GS compared with HDL in GO.

  19. Isolation and characterization of senile amyloid--related antigenic substance (SASSAM) from mouse serum. Apo SASSAM is a low molecular weight apoprotein of high density lipoprotein.

    Science.gov (United States)

    Higuchi, K; Matsumura, A; Hashimoto, K; Honma, A; Takeshita, S; Hosokawa, M; Yasuhira, K; Takeda, T

    1983-11-01

    Sera obtained from senescence-accelerated mouse (SAM) and normal mice contained a substance that reacted with antiserum raised against ASSAM, a novel senile amyloid fibril protein isolated from the liver of SAM. This physiological substance, termed "SASSAM" (serum ASSAM-related antigenic substance), migrated to the albumin/prealbumin region in immunoelectrophoresis and the precipitation line formed with anti-ASSAM antiserum was stained positively with both Amide Black 10 B and Oil Red O/Fat Red 7B solutions, thereby suggesting that SASSAM is an alpha lipoprotein. Using Sephadex G-200 gel chromatography, SASSAM was eluted as a high mol wt form of approximately 200,000 daltons. Fractionation of lipoprotein from normal mouse serum by preparative ultra-centrifugation disclosed that SASSAM was found mainly in high density lipoprotein, HDL (the density is between 1.063 and 1.21 g/cm3). The largest amount of SASSAM was found in the HDL2 fraction (the density is between 1.063 and 1.125) and in this fraction SAA was not detected. Furthermore, ASSAM immunoreactivity appeared in the low mol wt proteins (below 10,000 daltons) of apo HDL separated in the buffer containing 8 M urea through Sephadex G-200. In 8 M urea sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE), the major components of apolipoproteins in this position, possibly corresponding to apo C proteins, have the same molecular weight, 5,200 daltons, as ASSAM and this component was labeled by anti-ASSAM antiserum after transfer to nitrocellulose paper.

  20. Associations between airway hyperresponsiveness, obesity, and lipoproteins in a longitudinal cohort

    DEFF Research Database (Denmark)

    Rasmussen, Finn; Hancox, Robert; Nair, Parameswaran;

    2013-01-01

    . The present study investigated the association between airway hyperresponsiveness (AHR) to methacholine and body mass index (BMI) and plasma lipoproteins [low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol]. Methods Associations between AHR, BMI and plasma lipoproteins were...... assessed in a population-based cohort at ages 14 and 20 years. Results In unadjusted analyses, higher LDL cholesterol levels at age 14 were associated with AHR at age 20 in both sexes (P...

  1. Phenolic-extract from argan oil (Argania spinosa L.) inhibits human low-density lipoprotein (LDL) oxidation and enhances cholesterol efflux from human THP-1 macrophages.

    Science.gov (United States)

    Berrougui, Hicham; Cloutier, Martin; Isabelle, Maxim; Khalil, Abdelouahed

    2006-02-01

    Argan oil is rich in unsaturated fatty acids, tocopherol and phenolic compounds. These protective molecules make further study of its cardiovascular diseases (CVDs) action interesting. Furthermore, no previous study has explored the antioxidant activity of argan oil in comparison with olive oil. The present study was conducted to evaluate the beneficial properties of Virgin argan oil phenolic extracts (VAO-PE) towards CVD by: (A) protecting human (low-density lipoprotein, LDL) against lipid peroxidation and (B) promoting high-density lipoprotein (HDL)-mediated cholesterol efflux. Human LDLs were oxidized by incubation with CuSO(4) in the presence of different concentrations of VAO-PE (0-320mug/ml). LDL lipid peroxidation was evaluated by conjugated diene and MDA formation as well as Vitamin E disappearance. Incubation of LDL with VAO-PE significantly prolonged the lag-phase and lowered the progression rate of lipid peroxidation (Pargan oil provides a source of dietary phenolic antioxidants, which prevent cardiovascular diseases by inhibiting LDL-oxidation and enhancing reverse cholesterol transport. These properties increase the anti-atherogenic potential of HDL.

  2. A new framework for reverse cholesterol transport: Non-biliary contributions to reverse cholesterol transport

    Institute of Scientific and Technical Information of China (English)

    Ryan; E; Temel; J; Mark; Brown

    2010-01-01

    Reduction of low-density lipoprotein-cholesterol through statin therapy has only modestly decreased coronary heart disease (CHD)-associated mortality in developed countries, which has prompted the search for alternative therapeutic strategies for CHD. Major efforts are now focused on therapies that augment high-density lipoprotein (HDL)-mediated reverse cholesterol transport (RCT), and ultimately increase the fecal disposal of cholesterol. The process of RCT has long been thought to simply involve HDL-media...

  3. Dietary Carbohydrate Modifies the Inverse Association Between Saturated Fat Intake and Cholesterol on Very Low-Density Lipoproteins

    OpenAIRE

    Wood, A C; Kabagambe, E. K.; Borecki, I. B.; Tiwari, H.K.; Ordovas, J M; Arnett, D. K.

    2011-01-01

    We aimed to investigate the relationship between dietary saturated fat on fasting triglyceride (TG) and cholesterol levels, and any mediation of this relationship by dietary carbohydrate intake. Men and women in the NHLBI Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) study (n = 1036, mean age ± SD = 49 ± 16 y) were included. Mixed linear models were run with saturated fat as a predictor variable and fasting TG, very low density lipoprotein cholesterol (VLDL-C), low density cholest...

  4. ApoL1 levels in high density lipoprotein and cardiovascular event presentation in patients with familial hypercholesterolemia.

    Science.gov (United States)

    Cubedo, Judit; Padró, Teresa; Alonso, Rodrigo; Mata, Pedro; Badimon, Lina

    2016-06-01

    HDL composition rather than HDL-cholesterol (HDL-C) levels seems to be a key determinant of HDL-induced atheroprotection. Heterozygous familial hypercholesterolemia (FH) patients, with lifelong exposure to high LDL levels, show a high prevalence of premature coronary artery disease. We hypothesized that HDL of FH patients might have a modified protein composition and investigated the proteomic signature of HDL obtained from FH patients and their unaffected relatives. HDLs were characterized by 2D electrophoresis/MS in 10 families from the SAFEHEART cohort (3 individuals/family: 2 with genetic FH diagnosis and 1 non-FH relative) clinically characterized and treated as per guidelines. FH patients had lower apoA-I levels and a differential HDL distribution profile of apoL1 and apoA-IV. ELISA validation revealed decreased apoL1 serum levels in FH patients. ApoL1 levels were able to predict presentation of an ischemic cardiac event, and apoL1/HDL-C ratio was associated with the survival rate after the event. FH patients who died because of a fatal cardiac event had lower apoL1 and LCAT content in HDL3 an average of 3.5 years before the event than those who survived. Changes in HDL protein composition could affect patients' prognosis. The proteomic profile of apoL1 is modified in HDLs of high cardiovascular risk patients, and apoL1 plasma levels are significantly lower in serum and in HDL3 of patients that will suffer an adverse cardiac event within 3 years. PMID:27112635

  5. The Associations of High-Density Lipoprotein Subclasses With Insulin and Glucose Levels, Physical Activity, Resting Heart Rate, and Regional Adiposity in Men With Coronary Artery Disease: The Stanford Coronary Risk Intervention Project Baseline Survey

    OpenAIRE

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

    1995-01-01

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

  6. Body Fatness and Risk for Elevated Blood Pressure, Total Cholesterol, and Serum Lipoprotein Ratios in Children and Adolescents.

    Science.gov (United States)

    Williams, Daniel P.; And Others

    1992-01-01

    Examines the relationship between body fat percent and risk for elevated blood pressure, serum total cholesterol, and serum lipoprotein ratios in 1,230 African-American and 2,090 white 5-18 year olds (1,667 males and 1,653 females). Results support body fatness standards in children and adolescents as cardiovascular risk factors. (SLD)

  7. Correlation Between Obesity and High Density Lipoprotein Cholesterol (HDL-C) in Breast Cancer Patients of Southern Rajasthan

    OpenAIRE

    Inamdar, Padmanabh; Mehta, Garima

    2011-01-01

    Despite advances in management of breast cancer, etiology is still elusive. Diet, obesity and other life style factors have been implicated in its etiology. We assessed the role of obesity and HDL-C levels in patients with rural background in etiology of breast cancer. To know the relation between obesity and incidence of breast cancer in local population. Also to know serum HDL-C level in breast cancer and its correlation with breast cancer. A nested pilot study of 50 breast cancer patients ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-10-01

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

  9. 重组肝靶向高密度脂蛋白-药物纳米粒的制备及处方优化%Preparation and Optimization of Reconstituted High Density Lipoprotein-drug Nanoparticles for Liver Targeting

    Institute of Scientific and Technical Information of China (English)

    袁媛; 王晓芸; 王维娜; 冯美卿

    2012-01-01

    High density lipoprotein (HDL) can reverse transport cholesterol from plasma to liver, which has the considerable potential for development and application as a liver targeting delivery system. Apolipoprotein A-I (apo A-1) is the major component of HDL. The reconstituted high density lipoprotein-drug nanoparticles were prepared by thin-film dispersion method or ammonium sulfate-gradient method with apo A- I as the carrier and water-soluble antineoplastic agent doxorubicin hydrochloride as the model drug. The two preparation methods were optimized with mean diameter or entrapment efficiency as the index. The mean diameter of optimal products prepared by thin-film dispersion method and ammonium sulfate-gradient method were (48.3±16.1)nm and (113.8±10.3)nm, with the entrapment efficiency of (20.2±4.2) % and (83.3±8.5) %, respectively. The product prepared by the latter method had no hemolysis in vitro and the lyophilized product with 5% sucrose as the lyoprotectant stored at -20 °C for 8 months was fairly stable.%高密度脂蛋白(HDL)可逆向转运血浆中胆固醇至肝脏代谢,在肝靶向传递系统方面具有较大的开发潜力和应用价值.载脂蛋白A-Ⅰ(apoA-Ⅰ)是HDL的主要组成部分.以apoA-Ⅰ为载体,水溶性抗肿瘤药盐酸多柔比星为模型药,采用薄膜分散法或硫酸铵梯度法制备重组高密度脂蛋白-盐酸多柔比星纳米粒,并以平均粒径或包封率为指标进行优化.结果表明,优化后的薄膜分散法所得制品平均粒径为(48.3±16.1)nm,包封率为(20.2±4.2)%.优化后的硫酸铵梯度法所得制品平均粒径为(113.8±10.3)nm,包封率为(83.3±8.5)%,且无溶血性.采用5%蔗糖为冻干保护剂制得的冻干品于-20℃放置8个月,稳定性较好.

  10. Intracellular transport of low density lipoprotein-derived cholesterol is defective in Niemann-Pick type C fibroblasts

    International Nuclear Information System (INIS)

    Niemann-Pick disease type C (NPC) is characterized by substantial intracellular accumulation of unesterified cholesterol. The accumulation of unesterified cholesterol in NPC fibroblasts cultured with low density lipoprotein (LDL) appears to result from the inability of LDL to stimulate cholesterol esterification in addition to impaired LDL-mediated downregulation of LDL receptor activity and cellular cholesterol synthesis. Although a defect in cholesterol transport in NPC cells has been inferred from previous studies, no experiments have been reported that measure the intracellular movement of LDL-cholesterol specifically. We have used four approaches to assess intracellular cholesterol transport in normal and NPC cells and have determined the following: (a) mevinolin-inhibited NPC cells are defective in using LDL-cholesterol for growth. However, exogenously added mevalonate restores cell growth equally in normal and NPC cells; (b) the transport of LDL-derived [3H]cholesterol to the plasma membrane is slower in NPC cells, while the rate of appearance of [3H]acetate-derived, endogenously synthesized [3H]cholesterol at the plasma membrane is the same for normal and NPC cells; (c) in NPC cells, LDL-derived [3H]cholesterol accumulates in lysosomes to higher levels than normal, resulting in defective movement to other cell membranes; and (d) incubation of cells with LDL causes an increase in cholesterol content of NPC lysosomes that is threefold greater than that observed in normal lysosomes. Our results indicate that a cholesterol transport defect exists in NPC that is specific for LDL-derived cholesterol

  11. Intracellular transport of low density lipoprotein-derived cholesterol is defective in Niemann-Pick type C fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Liscum, L.; Ruggiero, R.M.; Faust, J.R.

    1989-05-01

    Niemann-Pick disease type C (NPC) is characterized by substantial intracellular accumulation of unesterified cholesterol. The accumulation of unesterified cholesterol in NPC fibroblasts cultured with low density lipoprotein (LDL) appears to result from the inability of LDL to stimulate cholesterol esterification in addition to impaired LDL-mediated downregulation of LDL receptor activity and cellular cholesterol synthesis. Although a defect in cholesterol transport in NPC cells has been inferred from previous studies, no experiments have been reported that measure the intracellular movement of LDL-cholesterol specifically. We have used four approaches to assess intracellular cholesterol transport in normal and NPC cells and have determined the following: (a) mevinolin-inhibited NPC cells are defective in using LDL-cholesterol for growth. However, exogenously added mevalonate restores cell growth equally in normal and NPC cells; (b) the transport of LDL-derived (3H)cholesterol to the plasma membrane is slower in NPC cells, while the rate of appearance of (3H)acetate-derived, endogenously synthesized (3H)cholesterol at the plasma membrane is the same for normal and NPC cells; (c) in NPC cells, LDL-derived (3H)cholesterol accumulates in lysosomes to higher levels than normal, resulting in defective movement to other cell membranes; and (d) incubation of cells with LDL causes an increase in cholesterol content of NPC lysosomes that is threefold greater than that observed in normal lysosomes. Our results indicate that a cholesterol transport defect exists in NPC that is specific for LDL-derived cholesterol.

  12. Reconstituted high density lipoprotein mediated targeted co-delivery of HZ08 and paclitaxel enhances the efficacy of paclitaxel in multidrug-resistant MCF-7 breast cancer cells.

    Science.gov (United States)

    Zhang, Fangrong; Wang, Xiaoyi; Xu, Xiangting; Li, Min; Zhou, Jianping; Wang, Wei

    2016-09-20

    In the past decades, reconstituted high density lipoprotein (rHDL) has been successfully developed as a drug carrier since the enhanced HDL-lipids uptake is demonstrated in several human cancers. In this paper, rHDL, for the first time, was utilized to co-encapsulate two hydrophobic drugs: an anticancer drug, paclitaxel (PTX), and a new reversal agent for P-gp (P-glycoprotein)-mediated multidrug resistance (MDR) of cancer, N-cyano-1-[(3,4-dimethoxyphenyl)methyl]-3,4-dihydro-6,7-dimethoxy-N'-octyl-2(1H)-isoquinoline-carboximidamide (HZ08). We proposed this drug co-delivery strategy to reverse PTX resistance. The study aimed to develop a biomimetic nanovector, reconstituted high density lipoprotein (rHDL), mediating targeted PTX-HZ08 delivery for cancer therapy. Using sodium cholate dialysis method, we successfully formulated dual-agent co-delivering rHDL nanoparticles (PTX-HZ08-rHDL NPs) with a typical spherical morphology, well-distributed size (~100nm), high drug encapsulation efficiency (approximately 90%), sustained drug release properties and exceptional stability even after storage for 1month or incubation in 10% fetal bovine serum (FBS) DMEM for up to 2days. Results demonstrated that PTX-HZ08-rHDL NPs significantly enhanced anticancer efficacy in vitro, including higher cytotoxicity and better ability to induce cell apoptosis against both PTX-sensitive and -resistant MCF-7 human breast cancer cell lines (MCF-7 and MCF-7/PTX cells). Mechanism studies demonstrated that these improvements could be correlated with increased cellular uptake of PTX mediated by scavenger receptor class B type I (SR-BI) as well as prolonged intracellular retention of PTX due to the HZ08 mediated drug-efflux inhibition. In addition, in vivo investigation showed that the PTX-HZ08-rHDL NPs were substantially safer, have higher tumor-targeted capacity and have stronger antitumor activity than the corresponding dosage of paclitaxel injection. These findings suggested that rHDL NPs could

  13. EFEK PEMBERIAN SUSU SAPI BUBUK TERHADAP KADAR SERUM HDL (HIGH DENSITY LIPOPROTEIN PADA TIKUS PUTIH (Rattus norvegicus GALUR WISTAR MODEL DIABETES MELITUS TIPE 2

    Directory of Open Access Journals (Sweden)

    Zakia Umami

    2015-05-01

    Full Text Available ABSTRACTThe purpose of this study was to determine the cow’s milk powder to increased serum levels of High Density Lipoprotein (HDL of white male rat model with diabetes mellitus type 2. The design of this study was a post-test control group study conducted in 30 male rats which randomly divided into five groups. Negative control group was the group of rats which fed normally, the positive control group was induced by streptozotocin (STZ without given cow’s milk, group P1, P2, P3 were given a normal diet and cow’s milk 0.9; 1.8, and 2.7 g orally every day. The results of this study were the levels of HDL in K(-=44.22 mg/dl, K(+=47.45 mg/dl, P1=56.56 mg/dl, P2=51.82 mg/dl, and P3=59.45 mg/dl. The conclusion was the milk powder was not significantly increase levels of HDL (p>0.05. More longer intervention was suggested for further research to get more significant of HDL level on type 2 diabetes mellitus.Keywords: HDL serum level, high fat diet, milk powder, streptozotocinABSTRAKTujuan penelitian ini adalah menganalisis pengaruh pemberian susu sapi bubuk terhadap peningkatan kadar serum High Density Lipoprotein (HDL tikus putih (Rattus norvegicus berjenis kelamin jantan model diabetes melitus (DM tipe 2. Penelitian ini menggunakan desain penelitian post test control group dengan 30 ekor tikus dibagi secara acak menjadi lima kelompok. Kelompok K(- adalah tikus yang diberi pakan normal, kelompok K(+ diinduksi dengan streptozotocin (STZ tanpa diberi susu, kelompok P1 sampai P3 diberi diet normal dan susu 0,9; 1,8, dan 2,7 g secara oral setiap hari. Hasil penelitian menunjukkan kadar HDL pada K(-=44,22 mg/dl, K(+=47,45 mg/dl, P1=56,56 mg/dl, P2=51,82 mg/dl, dan P3=59,45 mg/dl. Susu sapi bubuk mampu meningkatkan kadar HDL tikus model DM tipe 2 akan tetapi tidak signifikan (p>0,05. Perlu dilakukan penelitian lebih lanjut dengan waktu lama penelitian yang berbeda sehingga bisa berdampak yang lebih signifikan untuk kadar HDL pada DM tipe 2.Kata kunci

  14. Effect of Moderate Alcohol Consumption on Parameters of Reverse Cholesterol Transport in Postmenopausal Women

    NARCIS (Netherlands)

    Sierksma, A.; Vermunt, S.H.F.; Lankhuizen, I.M.; Gaag, M.S. van der; Scheek, L.M.; Grobbee, D.E.; Tol, A. van; Hendriks, H.F.J.

    2004-01-01

    Background: Alcohol consumption is associated with increased high-density lipoprotein (HDL) cholesterol levels. One of the main antiatherogenic functions of HDL is reverse cholesterol transport. Three early steps of reverse cholesterol transport are (1) cellular cholesterol efflux, (2) plasma choles

  15. Antiproteinuric therapy decreases LDL-cholesterol as well as HDL-cholesterol in non-diabetic proteinuric patients: relationships with cholesteryl ester transfer protein mass and adiponectin

    NARCIS (Netherlands)

    J.A. Krikken; F. Waanders; G.M. Dallinga-Thie; L.D. Dikkeschei; L. Vogt; G.J. Navis; R.P.F. Dullaart

    2009-01-01

    Objective: Dyslipidemia contributes to increased cardiovascular risk in nephrotic syndrome. We questioned whether reduction in proteinuria not only lowers low-density lipoprotein cholesterol (LDL-C), but also high-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP)

  16. Antiproteinuric therapy decreases LDL-cholesterol as well as HDL-cholesterol in non-diabetic proteinuric patients : relationships with cholesteryl ester transfer protein mass and adiponectin

    NARCIS (Netherlands)

    Krikken, J. A.; Waanders, F.; Dallinga-Thie, G. M.; Dikkeschei, L. D.; Vogt, L.; Navis, G. J.; Dullaart, R. P. F.

    2009-01-01

    Objective: Dyslipidemia contributes to increased cardiovascular risk in nephrotic syndrome. We questioned whether reduction in proteinuria not only lowers low-density lipoprotein cholesterol (LDL-C), but also high-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP)

  17. Specific cellular incorporation of a pyrene-labelled cholesterol: lipoprotein-mediated delivery toward ordered intracellular membranes.

    Directory of Open Access Journals (Sweden)

    Gérald Gaibelet

    Full Text Available In the aim of testing tools for tracing cell trafficking of exogenous cholesterol, two fluorescent derivatives of cholesterol, 22-nitrobenzoxadiazole-cholesterol (NBD-Chol and 21-methylpyrenyl-cholesterol (Pyr-met-Chol, with distinctive chemico-physical characteristics, have been compared for their cell incorporation properties, using two cell models differently handling cholesterol, with two incorporation routes. In the Caco-2 cell model, the cholesterol probes were delivered in bile salt micelles, as a model of intestinal absorption. The two probes displayed contrasting behaviors for cell uptake characteristics, cell staining, and efflux kinetics. In particular, Pyr-met-Chol cell incorporation involved SR-BI, while that of NBD-Chol appeared purely passive. In the PC-3 cell model, which overexpresses lipoprotein receptors, the cholesterol probes were delivered via the serum components, as a model of systemic delivery. We showed that Pyr-met-Chol-labelled purified LDL or HDL were able to specifically deliver Pyr-met-Chol to the PC-3 cells, while NBD-Chol incorporation was independent of lipoproteins. Observations by fluorescence microscopy evidenced that, while NBD-Chol readily stained the cytosolic lipid droplets, Pyr-met-Chol labelling led to the intense staining of intracellular structures of membranous nature, in agreement with the absence of detectable esterification of Pyr-met-Chol. A 48 h incubation of PC-3 cells with either Pyr-met-Chol-labelled LDL or HDL gave same staining patterns, mainly colocalizing with Lamp1, caveolin-1 and CD63. These data indicated convergent trafficking downwards their respective receptors, LDL-R and SR-BI, toward the cholesterol-rich internal membrane compartments, late endosomes and multivesicular bodies. Interestingly, Pyr-met-Chol staining of these structures exhibited a high excimer fluorescence emission, revealing their ordered membrane environment, and indicating that Pyr-met-Chol behaves as a fair

  18. Specific cellular incorporation of a pyrene-labelled cholesterol: lipoprotein-mediated delivery toward ordered intracellular membranes.

    Science.gov (United States)

    Gaibelet, Gérald; Allart, Sophie; Tercé, François; Azalbert, Vincent; Bertrand-Michel, Justine; Hamdi, Safouane; Collet, Xavier; Orlowski, Stéphane

    2015-01-01

    In the aim of testing tools for tracing cell trafficking of exogenous cholesterol, two fluorescent derivatives of cholesterol, 22-nitrobenzoxadiazole-cholesterol (NBD-Chol) and 21-methylpyrenyl-cholesterol (Pyr-met-Chol), with distinctive chemico-physical characteristics, have been compared for their cell incorporation properties, using two cell models differently handling cholesterol, with two incorporation routes. In the Caco-2 cell model, the cholesterol probes were delivered in bile salt micelles, as a model of intestinal absorption. The two probes displayed contrasting behaviors for cell uptake characteristics, cell staining, and efflux kinetics. In particular, Pyr-met-Chol cell incorporation involved SR-BI, while that of NBD-Chol appeared purely passive. In the PC-3 cell model, which overexpresses lipoprotein receptors, the cholesterol probes were delivered via the serum components, as a model of systemic delivery. We showed that Pyr-met-Chol-labelled purified LDL or HDL were able to specifically deliver Pyr-met-Chol to the PC-3 cells, while NBD-Chol incorporation was independent of lipoproteins. Observations by fluorescence microscopy evidenced that, while NBD-Chol readily stained the cytosolic lipid droplets, Pyr-met-Chol labelling led to the intense staining of intracellular structures of membranous nature, in agreement with the absence of detectable esterification of Pyr-met-Chol. A 48 h incubation of PC-3 cells with either Pyr-met-Chol-labelled LDL or HDL gave same staining patterns, mainly colocalizing with Lamp1, caveolin-1 and CD63. These data indicated convergent trafficking downwards their respective receptors, LDL-R and SR-BI, toward the cholesterol-rich internal membrane compartments, late endosomes and multivesicular bodies. Interestingly, Pyr-met-Chol staining of these structures exhibited a high excimer fluorescence emission, revealing their ordered membrane environment, and indicating that Pyr-met-Chol behaves as a fair cholesterol tracer

  19. Effect of estrogen receptor-alpha (ESR1 gene polymorphism on high density lipoprotein levels in response to hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    N.C. Nogueira-de-Souza

    2009-12-01

    Full Text Available Studies have shown that estrogen replacement therapy and estrogen plus progestin replacement therapy alter serum levels of total, LDL and HDL cholesterol levels. However, HDL cholesterol levels in women vary considerably in response to hormone replacement therapy (HRT. A significant portion of the variability of these levels has been attributed to genetic factors. Therefore, we investigated the influence of estrogen receptor-alpha (ESR1 gene polymorphisms on HDL levels in response to postmenopausal HRT. We performed a prospective cohort study on 54 postmenopausal women who had not used HRT before the study and had no significant general medical illness. HRT consisted of conjugated equine estrogen and medroxyprogesterone acetate continuously for 1 year. The lipoprotein levels were measured from blood samples taken before the start of therapy and after 1 year of HRT. ESR1 polymorphism (MspI C>T, HaeIII C>T, PvuII C>T, and XbaI A>G frequencies were assayed by restriction fragment length polymorphism. A general linear model was used to describe the relationships between HDL levels and genotypes after adjusting for age. A significant increase in HDL levels was observed after HRT (P = 0.029. Women with the ESR1 PvuII TT genotype showed a statistically significant increase in HDL levels after HRT (P = 0.032. No association was found between other ESR1 polymorphisms and HDL levels. According to our results, the ESR1 PvuII TT genotype was associated with increased levels of HDL after 1 year of HRT.

  20. A Biomimic Reconstituted High-Density-Lipoprotein-Based Drug and p53 Gene Co-delivery System for Effective Antiangiogenesis Therapy of Bladder Cancer

    Science.gov (United States)

    Ouyang, Qiaohong; Duan, Zhongxiang; Jiao, Guangli; Lei, Jixiao

    2015-07-01

    A biomimic reconstituted high-density-lipoprotein-based drug and p53 gene co-delivery system (rHDL/CD-PEI/p53 complexes) was fabricated as a targeted co-delivery nanovector of drug and gene for potential bladder cancer therapy. Here, CD-PEI was utilized to effectively condense the p53 plasmid, to incorporate the plasmid into rHDL, and to act as an antitumor drug to suppress tumor angiogenesis. The rHDL/CD-PEI/p53 complexes exhibited desirable and homogenous particle size, neutral surface charge, and low cytotoxicity in vitro. The results of confocal laser scanning microscopy and flow cytometry confirmed that SR-BI-targeted function induced specific cytoplasmic delivery and high gene transfection efficiency in MBT-2 murine bladder cells. In addition, rHDL/CD-PEI/p53 complexes co-delivering CD and p53 gene achieved synergistic angiogenesis suppression by more effectively downregulating the expression of vascular endothelial growth factor (VEGF) messenger RNA (mRNA) and protein via different pathways in vitro. In vivo investigation on C3H/He mice bearing MBT-2 tumor xenografts revealed that rHDL/CD-PEI/p53 complexes possessed strong antitumor activity. These findings suggested that rHDL/CD-PEI/p53 complexes could be an ideal tumor-targeting system for simultaneous transfer of drug and gene, which might be a new promising strategy for effective bladder cancer therapy.

  1. Synthetic high-density lipoprotein-like nanoparticles potently inhibit cell signaling and production of inflammatory mediators induced by lipopolysaccharide binding Toll-like receptor 4.

    Science.gov (United States)

    Foit, Linda; Thaxton, C Shad

    2016-09-01

    Toll-like receptor 4 (TLR4) plays a critical role in the innate immune system. Stimulation of TLR4 occurs upon binding lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls. Due to the potency of the induced inflammatory response, there is a growing interest in agents that can most proximally modulate this LPS/TLR4 interaction to prevent downstream cell signaling events and the production of inflammatory mediators. Building on the natural ability of human high-density lipoprotein (HDL) to bind LPS, we synthesized a suite of HDL-like nanoparticles (HDL-like NP). We identified one HDL-like NP that was particularly effective at decreasing TLR4 signaling caused by addition of purified LPS or Gram-negative bacteria to model human cell lines or primary human peripheral blood cells. The HDL-like NP functioned to inhibit TLR4-dependent inflammatory response to LPS derived from multiple bacterial species. Mechanistically, data show that the NP mainly functions by scavenging and neutralizing the LPS toxin. Taken together, HDL-like NPs constitute a powerful endotoxin scavenger with the potential to significantly reduce LPS-mediated inflammation. PMID:27244690

  2. Prosopis farcta beans increase HDL cholesterol and decrease LDL cholesterol in ostriches (Struthio camelus).

    Science.gov (United States)

    Omidi, Arash; Ansari nik, Hossein; Ghazaghi, Mahmood

    2013-02-01

    Ten blue-neck male ostriches (Struthio camelus) were fed Prosopis farcta beans throughout a 30-day experiment. Blood samples were collected from ostriches on days 0 and 30 to measure levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, total serum protein, albumin, globulin, cholesterol, calcium, inorganic phosphorus, the activity of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase (γ-GT). From days 0 to 30, HDL cholesterol, total protein, and globulins levels increased significantly whereas LDL cholesterol, inorganic phosphorus, and γ-GT activity decreased significantly.

  3. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

    DEFF Research Database (Denmark)

    Postmus, Iris; Warren, Helen R; Trompet, Stella;

    2016-01-01

    BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. METHODS AND RESULTS: We perform...

  4. Influence of infant and juvenile diets on serum cholesterol, lipoprotein cholesterol, and apolipoprotein concentrations in juvenile baboons (Papio sp.).

    Science.gov (United States)

    Mott, G E; McMahan, C A; Kelley, J L; Farley, C M; McGill, H C

    1982-11-01

    The long-term effects of infant diet (breast milk or formula containing 2, 30, or 60 mg/dl cholesterol) and subsequent dietary cholesterol (1 mg/kcal) and fat (saturated or unsaturated) on serum lipid and apolipoprotein concentrations were estimated using 82 juvenile baboons 4-6 years of age. A significant interaction of infant diet (breast vs formula) with type of fat (saturated vs unsaturated) at 4-6 years of age was observed on HDL cholesterol and apolipoprotein A-I (apoA-I) concentrations. That is, animals breast-fed as infants had higher HDL cholesterol and apoA-I concentrations when fed unsaturated fat from weaning to 4-6 years of age than those fed saturated fat (77 vs 68 mg/dl). In contrast, animals fed formulas in infancy followed by a diet containing unsaturated fat had lower HDL cholesterol and apoA-I concentrations at 4-6 years of age than did those fed saturated fat (67 vs 78 mg/dl). However, breast feeding or feeding formulas containing various levels of cholesterol for 3 months during infancy did not result in statistically significant differences in total serum cholesterol, VLDL + LDL cholesterol and apolipoprotein B (apoB) concentrations. Dietary cholesterol after infancy significantly increased serum total cholesterol, VLDL + LDL and HDL cholesterol, apoA-I and apoB concentrations. All of these response variables also were higher in animals fed saturated fat compared to those fed unsaturated fat on the same level of cholesterol. At 4-6 years of age, regardless of diet, females had significantly higher serum VLDL + LDL cholesterol (57 vs 43 mg/dl) and apoB concentrations (39 vs 30 mg/dl) than did males.

  5. Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction.

    Science.gov (United States)

    Henry, Courtney A; Lyon, Ronald A; Ling, Hua

    2016-01-01

    Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2) directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost-benefit ratio.

  6. How Do PCSK9 Inhibitors Stack Up to Statins for Low-Density Lipoprotein Cholesterol Control?

    Science.gov (United States)

    Zimmerman, Marj P.

    2015-01-01

    Despite advances in the approach toward treating hypercholesterolemia and widespread access to statin medications, not all people are able to reach target low-density lipoprotein cholesterol (LDL-C) levels to reduce their cardiovascular risk. Some of the reasons include the inability to tolerate statin therapy, LDL-C levels that remain high even in the presence of statin therapy, and a familial disorder that is characterized by extremely high levels of LDL-C. A new therapeutic class, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, represents a novel and promising approach to reducing LDL-C levels using a mechanism at the LDL receptor level. The recent approval of the first 2 PCSK9 inhibitors and the anticipated approval of the third agent in this class within approximately 1 year may provide clinicians powerful new weapons to lower LDL-C levels in patients who are not satisfactorily managed with statins. However, the results of long-term studies of the ability of these new medications to influence cardiovascular outcomes will not be known for several years. PMID:26702335

  7. A predictor of atheroma progression in patients achieving very low levels of low-density lipoprotein cholesterol

    OpenAIRE

    Nozue, Tsuyoshi; Yamamoto, Shingo; Tohyama, Shinichi; Fukui, Kazuki; Umezawa, Shigeo; Onishi, Yuko; Kunishima, Tomoyuki; Hibi, Kiyoshi; Terashima, Mitsuyasu; Michishita, Ichiro

    2013-01-01

    An aggressive reduction in low-density lipoprotein cholesterol (LDL-C) with statins produces regression or stabilization of coronary artery plaques. However, after achieving very low levels of LDL-C, atheroma regression is not observed in all patients. The purpose of the present study was to evaluate the determinants of atheroma progression despite achieving very low levels of LDL-C. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated using virtual histology intra...

  8. A role for the high-density lipoprotein receptor SR-B1 in synovial inflammation via serum amyloid-A.

    LENUS (Irish Health Repository)

    Mullan, Ronan Hugh

    2012-02-01

    Acute phase apoprotein Serum Amyloid A (A-SAA), which is strongly expressed in rheumatoid arthritis synovial membrane (RA SM), induces angiogenesis, adhesion molecule expression, and matrix metalloproteinase production through the G-coupled receptor FPRL-1. Here we report alternative signaling through the high-density lipoprotein receptor scavenger receptor-class B type 1 (SR-B1). Quantitative expression\\/localization of SR-B1 in RA SM, RA fibroblast-like cells (FLCs), and microvascular endothelial cells (ECs) was assessed by Western blotting and immunohistology\\/fluorescence. A-SAA-mediated effects were examined using a specific antibody against SR-B1 or amphipathic alpha-Helical Peptides (the SR-B1 antagonists L-37pA and D-37pA), in RA FLCs and ECs. Adhesion molecule expression and cytokine production were quantified using flow cytometry and ELISA. SR-B1 was strongly expressed in the RA SM lining layer and endothelial\\/perivascular regions compared with osteoarthritis SM or normal control synovium. Differential SR-B1 expression in RA FLC lines (n = 5) and ECs correlated closely with A-SAA, but not tumor necrosis factor alpha-induced intercellular adhesion molecule-1 upregulation. A-SAA-induced interleukin-6 and -8 production was inhibited in the presence of anti-SR-B1 in human microvascular endothelial cells and RA FLCs. Moreover, D-37pA and L-37pA inhibited A-SAA-induced vascular cell adhesion molecule-1 and intercellular adhesion molecule expression from ECs in a dose-dependent manner. As SR-B1 is expressed in RA synovial tissue and mediates A-SAA-induced pro-inflammatory pathways, a better understanding of A-SAA-mediated inflammatory pathways may lead to novel treatment strategies for RA.

  9. Measurement of very low density and low density lipoprotein apolipoprotein (Apo) B-100 and high density lipoprotein Apo A-I production in human subjects using deuterated leucine. Effect of fasting and feeding

    International Nuclear Information System (INIS)

    Six normolipidemic male subjects, after an 8-h overnight fast, were given a bolus injection and then a 15-h constant intravenous infusion of [D3]L-leucine. Subjects were studied in the fasted state and on a second occasion in the fed state (small, physiological meals were given every hour for 15 h). Apolipoproteins were isolated by preparative gradient gel electrophoresis from plasma lipoproteins separated by sequential ultracentrifugation. Incorporation of [D3]L-leucine into apolipoproteins was monitored by negative ionization, gas chromatography-mass spectrometry. Production rates were determined by multiplying plasma apolipoprotein pool sizes by fractional production rates calculated as the rate of isotopic enrichment [IE] of each protein as a fraction of IE achieved by VLDL (d less than 1.006 g/ml) apo B-100 at plateau. VLDL apo B-100 production was greater, and LDL (1.019 less than d less than 1.063 g/ml) apo B-100 production was less in the fed compared with the fasted state (9.9 +/- 1.7 vs. 6.4 +/- 1.7 mg/kg per d, P less than 0.01, and 8.9 +/- 1.2 vs. 13.1 +/- 1.2 mg/kg per d, P less than 0.05, respectively). No mean change was observed in high density lipoprotein apo A-I production. We conclude that: (a) this stable isotope, endogenous-labeling technique, for the first time allows for the in vivo measurement of apolipoprotein production in the fasted and fed state; and (b) since LDL apo B-100 production was greater than VLDL apo B-100 production in the fasted state, this study provides in vivo evidence that LDL apo B-100 can be produced independently of VLDL apo B-100 in normolipidemic subjects

  10. PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta-analyses

    DEFF Research Database (Denmark)

    2010-01-01

    The aim of this study was to examine the effect of PCSK9 R46L on low-density lipoprotein cholesterol (LDL-C), risk of ischemic heart disease (IHD), and mortality.......The aim of this study was to examine the effect of PCSK9 R46L on low-density lipoprotein cholesterol (LDL-C), risk of ischemic heart disease (IHD), and mortality....

  11. Association of small dense lowdensity lipoprotein cholesterol in type 2 diabetics with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Ya-Ching Huang

    2014-12-01

    Full Text Available Background: The risk of coronary artery disease (CAD increases two- to fourfold in diabetes. Small dense low-density lipoprotein (sdLDL particles have been linked to an increased risk for CAD. In this study, we sought to compare the sdLDL cholesterol (sdLDL-C level between the healthy control group and diabetics with CAD in the Taiwanese population. Methods: Serum specimens were collected from healthy females and males of various age groups (n = 294, type 2 diabetics (DM without complications (n = 113, and patients having DM with CAD (DM-CAD (n = 46. The commercial kit was used for the measurement of sdLDL-C level, which employs a simpler method. After heparin-magnesium precipitation of lipoproteins with density <1.044 g/ml, sdLDL (density = 1.044-1.063 g/ml remained in the supernatant and this sdLDL-C was measured using an automated chemistry analyzer. Results: The sdLDL-C level was significantly higher in males than in females (p < 0.001 and there was an age effect on sdLDL-C (p < 0.001. The DM-CAD group had significantly higher sdLDL-C levels than the healthy control group (p < 0.001, but there was no statistical difference in the LDL-C level between DM-CAD group and the healthy control group. In addition, only individuals having both high LDL-C and sdLDL-C levels had a higher risk for DM-CAD, compared to those with low LDL-C levels and low sdLDL-C levels [Odds Ratio (OR 4.97; 95% Confidence Interval (CI 1.96-12.57; p = 0.001]. Conclusions: Our data suggest that the sdLDL-C level together with the LDL-C level are better risk assessment markers for type 2 diabetics with CAD than the LDL-C level alone.

  12. Probucol selectively increases oxidation of atherogenic lipoproteins in cholesterol-fed mice and in Watanabe heritable hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Lauridsen, S.T.; Mortensen, Alicja

    1999-01-01

    The anti-atherogenic and cholesterol-lowering drug probucol (0.5-1%) or quercetin (1%), a natural antioxidant, was given to cholesterol-fed (1.5%) mice for a period of 6 weeks and to Watanabe heritable hyperlipidemic (WHHL) rabbits for a period of 8 weeks to investigate the oxidative changes...... in plasma and lipoproteins. Oxidation was measured as the total amount of malondialdehyde (nmol MDA/g protein) by a very specific MDA-HPLC method. A large and significant increase in MDA was seen in LDL from probucol treated WHHL rabbits (1778.7 +/- 585.5 nmol/g vs. 394.4 +/- 144.5 nmol/g, P ....001) and cholesterol-fed mice (579.7 +/- 47.3 nmol/g vs. 408.1 +/- 85.8 nmol/g, P rabbits: P rabbits VLDL oxidation was determined additionally, and also revealed a large increase in the probucol group (2102...

  13. Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction

    Directory of Open Access Journals (Sweden)

    Henry CA

    2016-04-01

    Full Text Available Courtney A Henry, Ronald A Lyon, Hua Ling Department of Pharmacy Practice, School of Pharmacy, Hampton University, Hampton, VA, USA Abstract: Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9 was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2 directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost–benefit ratio. Keywords: PCSK9, hyperlipidemia, evolocumab, LDL-C, familial hypercholesterolemia

  14. Apolipoprotein E genotype is a determinant of low-density lipoprotein cholesterol and of its response to a low-cholesterol diet in type 1 diabetic patients with elevated urinary albumin excretion

    NARCIS (Netherlands)

    Blaauwwiekel, EE; Beusekamp, BJ; Sluiter, WJ; Hoogenberg, K; Dullaart, RPF

    1998-01-01

    The effect of the apolipoprotein (apo) E genotype on the lipoprotein response to a 1 year low cholesterol diet (200 mg cholesterol per day) was evaluated in 36 patients with Type 1 diabetes mellitus with albuminuria between 10 and 200 mu g min(-1). Apo E genotype was characterized by polymerase chai

  15. Elevated Remnant Cholesterol in 25-Hydroxyvitamin D Deficiency in the General Population

    DEFF Research Database (Denmark)

    Ooi, Esther M; Afzal, Shoaib; Nordestgaard, Børge G

    2014-01-01

    cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. Lipoprotein levels were measured in all and 25(OH)D levels in 31,435. A doubling in nonfasting remnant cholesterol levels was observationally and genetically associated with -6.0%(95% confidence interval [CI], -6.......5% to -5.5%) and -8.9% (95% CI, -15% to -2.3%) lower plasma 25(OH)D levels. For low-density lipoprotein-cholesterol levels, corresponding values were -4.6% (95% CI, -5.4% to -3.7%) observationally and -11% (95% CI, -29% to +6.9%) genetically. In contrast, a halving in high-density lipoprotein-cholesterol...... of remnant and low-density lipoprotein-cholesterol. CONCLUSIONS: Genetically elevated nonfasting remnant cholesterol is associated with low 25(OH)D levels, whereas genetically reduced high-density lipoprotein-cholesterol is not associated with low 25(OH)D levels. These findings suggest that low 25(OH...

  16. [Possibility of New Circulating Atherosclerosis-Related Lipid Markers Measurement in Medical and Complete Medical Checkups: Small Dense Low-Density Lipoprotein Cholesterol and Lipoprotein Lipase].

    Science.gov (United States)

    Sumino, Hiroyuki; Nakajima, Katsuyuki; Murakami, Masami

    2016-03-01

    Small dense low-density lipoprotein cholesterol (sdLDL-C) concentrations correlate more strongly with cardiovascular disease (CVD) than other LDL-C and large LDL particle concentrations. Lipoprotein lipase (LPL) plays a central role in triglyceride-rich lipoprotein metabolism by catalyzing the hydrolysis of triglycerides in chylomicrons and very low-density lipoprotein particles and is a useful biomarker in diagnosing Type I, Type IV, and Type V hyperlipidemia. Therefore, the measurement of circulating sdLDL-C and LPL concentrations contributes to the assessment of circulating atherosclerosis-related lipid markers. However, the measurement of these lipids has not been fully adopted in medical and complete medical checkups. Recently, novel automated homogenous assay for measuring sdLDL-C and latex particle-enhanced turbidimetric immunoassay (LTIA) for measuring LPL have been developed, respectively. Using these new assays, sdLDL-C values showed excellent agreement with those obtained by isolation of the d = 1.044 - 1.063 g/mL plasma fraction by sequential ultracentrifugation, and LPL values measured with and without heparin injection were highly correlated with the values measured by the LPL-enzyme-linked immunosorbent assay (ELISA). These assays may be superior to the previous assays for the measurement of sdLDL-C and LPL concentrations due their simplicity and reproducibility. The measurements of sdLDL-C and LPL concentrations may be useful as lipid markers in the assessment of the development and progression of atherosclerosis and the detection of pathological conditions and diseases if these markers are measured in medical and complete medical checkups. We have introduced the possibility of the novel measurement of circulating atherosclerosis-related lipid markers such as sdLDL-C and LPL in medical and complete medical checkups. Further studies are needed to clarify whether sdLDL-C and LPL concentrations are related to the development and progression of

  17. The effect of semipurified diets containing either casein or soybean protein on the concentration of serum cholesterol and the lipoprotein composition in rabbits

    OpenAIRE

    Terpstra, A.H.M.

    1981-01-01

    This thesis deals with the effect of dietary casein and soybean protein on the concentration of serum cholesterol and the lipoprotein composition in rabbits. Special attention has been paid to the time course of the changes produced by the protein in the diet.After a short introduction, a review of the studies on the effect of dietary protein on serum cholesterol is presented. From these studies, it was concluded that the effect of dietary protein on the concentration of serum cholesterol is ...

  18. Low density lipoprotein receptor-independent hepatic uptake of a synthetic, cholesterol-scavenging lipoprotein: implications for the treatment of receptor-deficient atherosclerosis

    International Nuclear Information System (INIS)

    The metabolism of infused 111In-labeled phospholipid liposomes was examined in Watanabe heritable hyperlipidemic (WHHL) rabbits, which lack low density lipoprotein (LDL) receptors, and in normal control rabbits. The half-times (t/sub 1/2/) for clearance of 111In and excess phospholipid from plasma were 20.8 +/- 0.9 hr and 20.3 +/- 4.6 hr in WHHL and 20.0 +/- 0.8 hr and 19.6 +/- 2.2 hr in the normal rabbits. By 6 hr postinfusion, the plasma concentration of unesterified cholesterol increased by 2.2 +/- 0.23 mmol/liter in WHHL and 2.1 +/- 0.04 mmol/liter in normal rabbits, presumably reflecting mobilization of tissue sores. Disappearance of excess plasma cholesterol was > 90% complete in both groups of rabbits by 70 hr postinfusion. By quantitative γ camera imaging, hepatic trapping of 111In-labeled liposomes over time was indistinguishable between the two groups. At autopsy, the liver was the major organ of clearance. Aortic uptake of 111In was < 0.02%. Thus, mobilization of cholesterol and hepatic uptake of phospholipid liposomes do not require LDL receptors. Because phospholipid infusions produce rapid substantial regression of atherosclerosis in genetically normal animals, the results suggest that phospholipid liposomes or triglyceride phospholipid emulsions (e.g., Intralipid) might reduce atherosclerosis in WHHL rabbits and in humans with familial hypercholesterolemia

  19. Biological function and exercise regulation of high-density lipoprotein%高密度脂蛋白生物学功能及运动调节的研究与进展

    Institute of Scientific and Technical Information of China (English)

    苏中军; 张肃; 姜军

    2015-01-01

    BACKGROUND:High-density lipoprotein is related to lipid metabolism, but its function cannot be restricted to the scope of lipid metabolism. Simultaneously, exercise regulation has effects on the activity and amount of high-density lipoprotein, but the optimal movement pattern needs to be studied. OBJECTIVE:To offer the theoretical support for formulating fitness training and prospect the possible direction and reference in fol ow-up studying the biological function and exercise regulation of high-density lipoprotein. METHODS:PubMed database was searched for relevant articles published from 1990 to 2015 using the keywords of“HDL and exercise, HDL and biological function”in English. Final y, 44 articles were included in result analysis. RESULTS AND CONCLUSION:The biological functions of high-density lipoprotein mainly include high-density lipoprotein-mediated metabolism of glucose, protein and fat, anti-inflammation, antioxidation and insulin secretion, and at the same time, we summarize the effects of exercise on the concentration, numbers of molecular and components of high-density lipoprotein. The results indicate that the combination of resistance and endurance training is the best way for raising the concentration and functional effects of high-density lipoprotein.%背景:高密度脂蛋白是指与脂代谢有关的高密度脂蛋白,但研究表明其功能不仅局限于脂代谢范畴;同时运动调节高密度脂蛋白的活性和数量,但最佳的运动方式有待于研究。  目的:总结高密度脂蛋白的生物学功能及运动调节高密度脂蛋白研究进展,展望了高密度脂蛋白研究的可能方向,旨在为健身训练方案的制定提供理论支持,为后续研究提供参考;  方法:以关键词“HDL and exercise,HDL and biological function”搜索PubMed数据库,筛选到1990至2015年间文章98篇;按纳入、排除标准最后纳入文献44篇。  结果与结论:高密度脂

  20. Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis.

    Directory of Open Access Journals (Sweden)

    Daniel I Chasman

    2009-11-01

    Full Text Available While conventional LDL-C, HDL-C, and triglyceride measurements reflect aggregate properties of plasma lipoprotein fractions, NMR-based measurements more accurately reflect lipoprotein particle concentrations according to class (LDL, HDL, and VLDL and particle size (small, medium, and large. The concentrations of these lipoprotein sub-fractions may be related to risk of cardiovascular disease and related metabolic disorders. We performed a genome-wide association study of 17 lipoprotein measures determined by NMR together with LDL-C, HDL-C, triglycerides, ApoA1, and ApoB in 17,296 women from the Women's Genome Health Study (WGHS. Among 36 loci with genome-wide significance (P<5x10(-8 in primary and secondary analysis, ten (PCCB/STAG1 (3q22.3, GMPR/MYLIP (6p22.3, BTNL2 (6p21.32, KLF14 (7q32.2, 8p23.1, JMJD1C (10q21.3, SBF2 (11p15.4, 12q23.2, CCDC92/DNAH10/ZNF664 (12q24.31.B, and WIPI1 (17q24.2 have not been reported in prior genome-wide association studies for plasma lipid concentration. Associations with mean lipoprotein particle size but not cholesterol content were found for LDL at four loci (7q11.23, LPL (8p21.3, 12q24.31.B, and LIPG (18q21.1 and for HDL at one locus (GCKR (2p23.3. In addition, genetic determinants of total IDL and total VLDL concentration were found at many loci, most strongly at LIPC (15q22.1 and APOC-APOE complex (19q13.32, respectively. Associations at seven more loci previously known for effects on conventional plasma lipid measures reveal additional genetic influences on lipoprotein profiles and bring the total number of loci to 43. Thus, genome-wide associations identified novel loci involved with lipoprotein metabolism-including loci that affect the NMR-based measures of concentration or size of LDL, HDL, and VLDL particles-all characteristics of lipoprotein profiles that may impact disease risk but are not available by conventional assay.

  1. Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis.

    Science.gov (United States)

    Chasman, Daniel I; Paré, Guillaume; Mora, Samia; Hopewell, Jemma C; Peloso, Gina; Clarke, Robert; Cupples, L Adrienne; Hamsten, Anders; Kathiresan, Sekar; Mälarstig, Anders; Ordovas, José M; Ripatti, Samuli; Parker, Alex N; Miletich, Joseph P; Ridker, Paul M

    2009-11-01

    While conventional LDL-C, HDL-C, and triglyceride measurements reflect aggregate properties of plasma lipoprotein fractions, NMR-based measurements more accurately reflect lipoprotein particle concentrations according to class (LDL, HDL, and VLDL) and particle size (small, medium, and large). The concentrations of these lipoprotein sub-fractions may be related to risk of cardiovascular disease and related metabolic disorders. We performed a genome-wide association study of 17 lipoprotein measures determined by NMR together with LDL-C, HDL-C, triglycerides, ApoA1, and ApoB in 17,296 women from the Women's Genome Health Study (WGHS). Among 36 loci with genome-wide significance (PKLF14 (7q32.2), 8p23.1, JMJD1C (10q21.3), SBF2 (11p15.4), 12q23.2, CCDC92/DNAH10/ZNF664 (12q24.31.B), and WIPI1 (17q24.2)) have not been reported in prior genome-wide association studies for plasma lipid concentration. Associations with mean lipoprotein particle size but not cholesterol content were found for LDL at four loci (7q11.23, LPL (8p21.3), 12q24.31.B, and LIPG (18q21.1)) and for HDL at one locus (GCKR (2p23.3)). In addition, genetic determinants of total IDL and total VLDL concentration were found at many loci, most strongly at LIPC (15q22.1) and APOC-APOE complex (19q13.32), respectively. Associations at seven more loci previously known for effects on conventional plasma lipid measures reveal additional genetic influences on lipoprotein profiles and bring the total number of loci to 43. Thus, genome-wide associations identified novel loci involved with lipoprotein metabolism-including loci that affect the NMR-based measures of concentration or size of LDL, HDL, and VLDL particles-all characteristics of lipoprotein profiles that may impact disease risk but are not available by conventional assay. PMID:19936222

  2. Associations between APOE and low-density lipoprotein cholesterol genotypes and cognitive and physical capability: the HALCyon programme

    OpenAIRE

    Alfred, T.; Ben-Shlomo, Y.; Cooper, R; Hardy, R.; Cooper, C.; Deary, I J; Elliott, J.; GUNNELL, D.; Harris, S.E.; Kivimaki, M.; M. Kumari; Martin, R.M.; Power, C; Sayer, A.A.; Starr, J. M.

    2014-01-01

    The APOE ε2/3/4 genotype has been associated with low-density lipoprotein cholesterol (LDL-C) and Alzheimer disease. However, evidence for associations with measures of cognitive performance in adults without dementia has been mixed, as it is for physical performance. Associations may also be evident in other genotypes implicated in LDL-C levels. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, genotypic information was obtained for APOE ε2/3/4,...

  3. Apolipoprotein B Is Related to Metabolic Syndrome Independently of Low Density Lipoprotein Cholesterol in Patients with Type 2 Diabetes

    OpenAIRE

    Lim, Younghyup; Yoo, Soyeon; Lee, Sang Ah; Chin, Sang Ouk; Heo, Dahee; Moon, Jae Cheol; Moon, Shinhang; Boo, Kiyoung; Kim, Seong Taeg; Seo, Hye Mi; Jwa, Hyeyoung; Koh, Gwanpyo

    2015-01-01

    Background Increased low density lipoprotein cholesterol (LDL-C) level and the presence of metabolic syndrome (MetS) are important risk factors for cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). Recent studies demonstrated apolipoprotein B (apoB), a protein mainly located in LDL-C, was an independent predictor of the development of CVD especially in patients with T2DM. The aim of this study was to investigate the relationship between apoB and MetS in T2DM patients. Methods W...

  4. [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].

    Science.gov (United States)

    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

  5. pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Shin JY

    2012-06-01

    Full Text Available Jae-Yoon Shin,1,* Yoosoo Yang,1,* Paul Heo,1 Ji-Chun Lee,1 ByoungJae Kong,1 Jae Youl Cho,1 Keejung Yoon,1 Cheol-Su Shin,2 Jin-Ho Seo,3 Sung-Gun Kim,4 Dae-Hyuk Kweon11Department of Genetic Engineering, College of Biotechnology and Bioengineering, and Center for Human Interface Nano Technology, Sungkyunkwan University, 2APTech Research Center, Suwon, 3Department of Agricultural Biotechnology, Seoul National University, Seoul, 4Department of Biomedical Science, Youngdong University, Chungbuk, South Korea*These authors contributed equally to this workBackground: Nanoparticles undergoing physicochemical changes to release enclosed drugs at acidic pH conditions are promising vehicles for antitumor drug delivery. Among the various drug carriers, high-density lipoprotein (HDL-like nanoparticles have been shown to be beneficial for cancer chemotherapy, but have not yet been designed to be pH-responsive.Methods and results: In this study, we developed a pH-responsive HDL-like nanoparticle that selectively releases paclitaxel, a model antitumor drug, at acidic pH. While the well known HDL-like nanoparticle containing phospholipids, phosphatidylcholine, and apolipoprotein A-I, as well as paclitaxel (PTX-PL-NP was structurally robust at a wide range of pH values (3.8–10.0, the paclitaxel nanoparticle that only contained paclitaxel and apoA-I selectively released paclitaxel into the medium at low pH. The paclitaxel nanoparticle was stable at physiological and basic pH values, and over a wide range of temperatures, which is a required feature for efficient cancer chemotherapy. The homogeneous assembly enabled high paclitaxel loading per nanoparticle, which was 62.2% (w/w. The molar ratio of apolipoprotein A-I and paclitaxel was 1:55, suggesting that a single nanoparticle contained approximately 110 paclitaxel particles in a spherical structure with a 9.2 nm diameter. Among the several reconstitution methods applied, simple dilution following sonication

  6. Importance of measuring Non-HDL cholesterol in type 2 diabetes patients

    International Nuclear Information System (INIS)

    Objective: To study the correlation between Non-high-density lipoprotein and low-density lipoprotein cholesterol in patients with Type 2 diabetes mellitus and the proportion of patients achieving Adult Treatment Panel III recommended goals. Methods: The cross sectional study was conducted at the Diabetic Clinic, Aga Khan University Hospital, Karachi. Data of Type 2 diabetes mellitus patients who attended the clinic between 2007 and 2011 was reviewed. All Type 2 diabetic patients of either gender with fasting lipid profile irrespective of taking lipid lowering therapy were included. Type-1 DM, gestational diabetes, type 2 diabetes patients with pregnancy and those with incomplete data were excluded. Correlation between the low-density lipoprotein and Non- high-density lipoprotein was assessed by applying Cramer V and phi. Proportion of patients achieving Adult Treatment Panel III recommended goals was checked. Multivariable regression was done to identify common factors associated with elevated Non- high-density lipoprotein cholesterol. Results: A total of 1352 patients fulfilling the eligibility criteria were included in the study. Mean age of the patients was 54.5+-11.3 years; 797 (59%) were males; 1122 (83%) had Body Mass Index above 25; and 1016 (75%) had HbA1c >7%. Mean Non-high-density lipoprotein cholesterol was 129+-42mg/dl. Mean low-density lipoprotein cholesterol was 100+-37mg/dl. Both low-density lipoprotein 130mg/dl (p100mg/dl was independently associated with having Non-high-density lipoprotein cholesterol >130mg/dl (Adjusted Odds Ratio 38.6; 95% Confidance Interval 28.1-53.1). Similarly, age 130 mg/dl (Adjusted Odds Ratio 1.6; 95% Confidance Interval = 1.01 - 2.3). Whereas having obesity Body Mass Index >25 was 3.6 times more associated to have Non-high-density lipoprotein >130mg/dl (Adjusted Odds Ratio 3.6; 95% Confidance Interval = 1.6-7.7). In patients with coronary artery disease, combined goal achievement of low-density lipoprotein 100mg/dl (p <0

  7. Chlordecone, a mixed pregnane X receptor (PXR) and estrogen receptor alpha (ERα) agonist, alters cholesterol homeostasis and lipoprotein metabolism in C57BL/6 mice

    International Nuclear Information System (INIS)

    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 [14C]CD or [14C]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 α (ERα) in a concentration-dependent manner (0-50 μM). 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. Effect of serum, cholesterol and low density lipoprotein on the functionality and structure of lung surfactant films.

    Science.gov (United States)

    Nahak, Prasant; Nag, Kaushik; Hillier, Ashley; Devraj, Ravi; Thompson, David W; Manna, Kausik; Makino, Kimiko; Ohshima, Hiroyuki; Nakahara, Hiromichi; Shibata, Osamu; Panda, Amiya Kumar

    2014-01-01

    Lung surfactant is a complex mixture of lipid and protein, responsible for alveolar stability, becomes dysfunctional due to alteration of its structure and function by leaked serum materials in disease. Serum proteins, cholesterol and low density lipoprotein (LDL) were studied with bovine lipid extract surfactant (BLES) using Langmuir films, and bilayer dispersions using Raman spectroscopy. While small amount of cholesterol (10 wt%) and LDL did not significantly affect the adsorption and surface tension lowering properties of BLES. However serum lipids, whole serum as well as higher amounts of cholesterol, and LDL dramatically altered the surface properties of BLES films, as well as gel-fluid structures formed in such films observed using atomic force microscopy (AFM). Raman-spectroscopic studies revealed that serum proteins, LDL and excess cholesterol had fluidizing effects on BLES bilayers dispersion, monitored from the changes in hydrocarbon vibrational modes during gel-fluid thermal phase transitions. This study clearly suggests that patho-physiological amounts of serum lipids (and not proteins) significantly alter the molecular arrangement of surfactant in films and bilayers, and can be used to model lung disease. PMID:25409691

  9. [THE SPIRIT CHOLESTEROL, BIOLOGICA L ROLE AT STAGES OF PHYLOGENESIS, MECHANISMS OF INHIBITION OF SYNTHESIS OF STEROL BY STATINS, FACTORS OF PHARMACOGENOMICS AND DIAGNOSTIC SIGNIFICANCE OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY].

    Science.gov (United States)

    Titov, V N; Kotlovskii, M Yu; Pokrovskii, A A; Kotlovskaia, O S; Osedko, A V; Titova, N M; Kotlovskii, Yu V; Digaii, A M

    2015-04-01

    The hypolipidemic effect of statins is realized by inhibition of synthesis of local pool of cholesterol spirit in endoplasmic net of hepatocytes. The cholesterol spirit covers all hydrophobic medium of triglycerides with polar mono layer of phosphatidylcholines and cholesterol spirit prior to secretion of lipoproteins of very low density into hydrophilic medium. The lesser mono layer between lipase enzyme and triglycerides substrate contains of cholesterol spirit the higher are the parameters of hydrolysis of palmitic and oleic lipoproteins of very low density. The sequence of effect of statins is as follows: blocking of synthesis in hepatocytes and decreasing of content of unesterified cholesterol spirit in blood plasma; activation of hydrolysis of triglycerides in palmitic and oleic lipoproteins of very low density; formation of ligand lipoproteins of very low density and their absorption by cells by force of apoB-100 endocytosis; decreasing in blood of content of polyenoic fatty acids, equimolar esterified by cholesterol spirit, polyethers of cholesterol spirit and decreasing of level of cholesterol spirit-lipoproteins of very low density. There is no way to eliminate aphysiological effect of disordered biological function of trophology (nutrition) on metabolism of fatty acids in population by means of pharmaceuticals intake. It is necessary to eliminate aphysiological effect of environment. To decrease rate of diseases of cardiovascular system one has to decrease in food content of saturated fatty acids and in the first instance palmitic saturated fatty acid, trans-form fatty acid, palmitoleic fatty acids up to physiological values and increase to the same degree the content of polyenoic fatty acids. The saturated fatty acids block absorption of polyenoic fatty acids by cells. The atherosclerosis is a deficiency of polyenoic fatty acids under surplus of palmitic saturated fatty acid. PMID:26189285

  10. Effect of Synthetic Truncated Apolipoprotein C-I Peptide on Plasma Lipoprotein Cholesterol in Nonhuman Primates

    Directory of Open Access Journals (Sweden)

    Rampratap S. Kushwaha

    2004-01-01

    Full Text Available The present studies were conducted to determine whether a synthetic truncated apoC-I peptide that inhibits CETP activity in baboons would raise plasma HDL cholesterol levels in nonhuman primates with low HDL levels. We used 2 cynomolgus monkeys and 3 baboons fed a cholesterol- and fat-enriched diet. In cynomolgus monkeys, we injected synthetic truncated apoC-I inhibitor peptide at a dose of 20 mg/kg and, in baboons, at doses of 10, 15, and 20 mg/kg at weekly intervals. Blood samples were collected 3 times a week and VLDL + LDL and HDL cholesterol concentrations were measured. In cynomolgus monkeys, administration of the inhibitor peptide caused a rapid decrease in VLDL + LDL cholesterol concentrations (30%–60% and an increase in HDL cholesterol concentrations (10%–20%. VLDL + LDL cholesterol concentrations returned to baseline levels in approximately 15 days. In baboons, administration of the synthetic inhibitor peptide caused a decrease in VLDL + LDL cholesterol (20%–60% and an increase in HDL cholesterol (10%–20%. VLDL + LDL cholesterol returned to baseline levels by day 21, whereas HDL cholesterol concentrations remained elevated for up to 26 days. ApoA-I concentrations increased, whereas apoE and triglyceride concentrations decreased. Subcutaneous and intravenous administrations of the inhibitor peptide had similar effects on LDL and HDL cholesterol concentrations. There was no change in body weight, food consumption, or plasma IgG levels of any baboon during the study. These studies suggest that the truncated apoC-I peptide can be used to raise HDL in humans.

  11. ABCC6 : a new player in cellular cholesterol and lipoprotein metabolism?

    OpenAIRE

    Kuzaj, Patricia; Kuhn, Joachim; Dabisch-Ruthe, Mareike; Faust, Isabel; Götting, Christian; Knabbe, Cornelius; Hendig, Doris

    2014-01-01

    Background Dysregulations in cholesterol and lipid metabolism have been linked to human diseases like hypercholesterolemia, atherosclerosis or the metabolic syndrome. Many ABC transporters are involved in trafficking of metabolites derived from these pathways. Pseudoxanthoma elasticum (PXE), an autosomal-recessive disease caused by ABCC6 mutations, is characterized by atherogenesis and soft tissue calcification. Methods In this study we investigated the regulation of cholesterol biosynthesis ...

  12. Influence of human diets containing casein, soy protein isolate, and soy protein concentrate on serum cholesterol and lipoproteins in humans, rabbits and rats

    OpenAIRE

    Raaij, van, J.M.A.

    1982-01-01

    It is well known that feeding animals such as rabbits with semipurified diets containing animal proteins, as for example casein, results in hypercholesterolemia and atherosclerosis. On the other hand, diets containing vegetable proteins such as soybean protein maintain low levels of serum cholesterol. Little is known about the effects of the type of protein in the diet in humans.This thesis deals with the effects of casein and soy protein on serum cholesterol and lipoproteins, as observed in ...

  13. Emerging roles of the intestine in control of cholesterol metabolism

    Institute of Scientific and Technical Information of China (English)

    Janine K Kruit; Albert K Groen; Theo J van Berkel; Folkert Kuipers

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis,clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor to high density lipoprotein (HDL; good cholesterol) formation. The liver has a central position in the classical definition of the reverse cholesterol transport pathway by taking up peripheryderived cholesterol from lipoprotein particles followed by conversion into bile acids or its direct secretion into bile for eventual removal via the feces. During the past couple of years, however, an additional important role of the intestine in maintenance of cholesterol homeostasis and regulation of plasma cholesterol levels has become apparent. Firstly, molecular mechanisms of cholesterol absorption have been elucidated and novel pharmacological compounds have been identified that interfere with the process and positively impact plasma cholesterol levels. Secondly, it is now evident that the intestine itself contributes to fecal neutral sterol loss as a cholesterol-secreting organ. Finally, very recent work has unequivocally demonstrated that the intestine contributes significantly to plasma HDL cholesterol levels.Thus, the intestine is a potential target for novel antiatherosclerotic treatment strategies that, in addition to interference with cholesterol absorption, modulate direct cholesterol excretion and plasma HDL cholesterol levels.

  14. 他汀、高密度脂蛋白胆固醇与冠状动脉粥样硬化消退%Statins, High-Density Lipoprotein Cholesteol, and Regression of Coronary Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Stephen J. Nicholls; Stanley L. Hazen; Samir R. Kapadia; Steven E. Nissen; 李呈亿; E. Murat Tuzcu; IIke Sipahi; Adam W. Grasso; Paul Schoenhagen; Tingfei Hu; Kathy Wolski; Tim Crowe; Milind Y. Desai

    2007-01-01

    背景:他汀类药物可以降低低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)水平并减缓冠状动脉粥样硬化的进展.然而,对于他汀类药物所致高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)变化与疾病进展的关系,目前仍无相关数据描述.目的:了解LDL-C和HDL-C水平变化与动脉粥样硬化的相互关系.设计、地点及患者:对4项前瞻性随机试验(1999~2005年在美国、北美、欧洲和澳大利亚进行)的原始数据进行事后分析.其中1455例经血管造影证实的冠心病患者在接受他汀治疗(18个月或24个月)时进行了系列血管内超声扫描.所有超声分析均在相同的核心实验室中进行.主要观测指标:脂蛋白水平变化与冠状动脉粥样斑块体积的相互关系.结果:他汀治疗期间,LDL-C平均(SD)水平从124.0(38.3)mg/dL(3.2[0.99]mmol/L)降至87.5(28.8)mg/dL(2.3[0.75]mmoL/L)(下降23.5%;P<0.001),HDL-C水平从42.5(11.0)mg/dL(1.1[0.28]mmol/L)升至45.1(11.4)mg/dL(1.2[0.29]mmol/L)(上升7.5%;P<0.001).LDL-C与HDL-C比值从平均(SD)3.0(1.1)降至2.1(0.9)(下降26.7%;P<0.001).这些变化同时伴随平均(SD)百分粥样斑块体积的增加(从39.7%[9.8%]增至40.1%[9.7%])(增加0.5%[3.9%];P=0.001)以及平均(SD)总粥样斑块体积的减小(2.4[23.6]mm3;P<0.001).在单变量分析中,LDL-C、总胆固醇、非HDL胆固醇、载脂蛋白B以及载脂蛋白B与载脂蛋白A-1比值平均水平和治疗引起的变化与动脉粥样硬化进展速率显著相关,而治疗所致HDL-C变化则与动脉粥样斑块体积负相关.在多变量分析中,平均LDL-C水平(β系数,0.11[95%可信区间,0.07~0.15])以及HDL-C升高(β系数,-0.26[95%可信区间,-0.41~-0.10])依然为动脉粥样硬化消退的独立预测因子.动脉硬化显著消退(动脉粥样斑块体积减少≥5%)见于治疗期间LDL-C水平低于均值(87.5 mg/dL)和HDL-C升高百分比大于均值(7.5%;P<0.001)的患者.

  15. Hyaluronan Accumulation Is Elevated in Cultures of Low Density Lipoprotein Receptor-deficient Cells and Is Altered by Manipulation of Cell Cholesterol Content*

    OpenAIRE

    Sakr, Sana W.; Potter-Perigo, Susan; Kinsella, Michael G.; Johnson, Pamela Y.; Braun, Kathleen R.; Goueffic, Yann; Rosenfeld, Michael E.; Wight, Thomas N.

    2008-01-01

    The extracellular matrix molecule hyaluronan (HA) accumulates in human atherosclerotic lesions. Yet the reasons for this accumulation have not been adequately addressed. Because abnormalities in lipid metabolism promote atherosclerosis, we have asked whether disrupted cholesterol homeostasis alters HA accumulation in low density lipoprotein receptor-deficient cell cultures. Cultured aortic smooth muscle cells (ASMC) from Watanabe heritable hyperlipidemic (WHHL) rabbits...

  16. The effect of semipurified diets containing either casein or soybean protein on the concentration of serum cholesterol and the lipoprotein composition in rabbits

    NARCIS (Netherlands)

    Terpstra, A.H.M.

    1981-01-01

    This thesis deals with the effect of dietary casein and soybean protein on the concentration of serum cholesterol and the lipoprotein composition in rabbits. Special attention has been paid to the time course of the changes produced by the protein in the diet.After a short introduction, a review of

  17. Low-density lipoprotein cholesterol and radiotherapy-induced carotid atherosclerosis in subjects with head and neck cancer

    International Nuclear Information System (INIS)

    Radiotherapy (RT) is a risk factor for accelerated carotid artery atherosclerotic disease in subjects with head and neck cancer. However, the risk factors of RT-induced carotid artery remodeling are not established. This study aimed to investigate the effects of RT on carotid and popliteal arteries in subjects with head and neck cancer and to evaluate the relationship between baseline clinical and laboratory features and the progression of RT-induced atherosclerosis. Eleven men (age = 57.9 ± 6.2years) with head and neck cancer who underwent cervical bilateral irradiation were prospectively examined by clinical and laboratory analysis and by carotid and popliteal ultrasound before and after treatment (mean interval between the end of RT and the post-RT assessment = 181 ± 47 days). No studied subject used hypocholesterolemic medications. Significant increases in carotid intima-media thickness (IMT) (0.95 ± 0.08 vs. 0.87 ± 0.05 mm; p < 0.0001) and carotid IMT/diameter ratio (0.138 ± 0.013 vs. 0.129 ± 0.014; p = 0.001) were observed after RT, while no changes in popliteal structural features were detected. In addition, baseline low-density lipoprotein cholesterol levels showed a direct correlation with RT-induced carotid IMT change (r = 0.66; p = 0.027), while no other studied variable exhibited a significant relationship with carotid IMT change. These results indicate that RT-induced atherosclerosis is limited to the irradiated area and also suggest that it may be predicted by low-density lipoprotein cholesterol levels in subjects with head and neck cancer

  18. Effect of repeated apoA-IMilano/POPC infusion on lipids, (apo)lipoproteins, and serum cholesterol efflux capacity in cynomolgus monkeys[S

    OpenAIRE

    Herman J. Kempen; Gomaraschi, Monica; Bellibas, S. Eralp; Plassmann, Stephanie; Zerler, Brad; Collins, Heidi L.; Adelman, Steven J.; Calabresi, Laura; Wijngaard, Peter L. J.

    2013-01-01

    MDCO-216, a complex of dimeric recombinant apoA-IMilano (apoA-IM) and palmitoyl-oleoyl-phosphatidylcholine (POPC), was administered to cynomolgus monkeys at 30, 100, and 300 mg/kg every other day for a total of 21 infusions, and effects on lipids, (apo)lipoproteins, and ex-vivo cholesterol efflux capacity were monitored. After 7 or 20 infusions, free cholesterol (FC) and phospholipids (PL) were strongly increased, and HDL-cholesterol (HDL-C), apoA-I, and apoA-II were strongly decreased. We th...

  19. Small dense low density lipoprotein cholesterol and coronary heart disease: results from the Framingham Offspring Study

    Science.gov (United States)

    We sought to establish reference values for a new direct assay for small dense LDL cholesterol (sdLDL-C) and to measure sdLDL-C concentrations in patients with established coronary heart disease (CHD) vs controls. Direct LDL-C and sdLDL-C were measured in samples from 3188 male and female participan...

  20. Elevated plasma cholesteryl ester transfer in NIDDM : relationships with apolipoprotein B-containing lipoproteins and phospholipid transfer protein

    NARCIS (Netherlands)

    Riemens, S; van Tol, A; Sluiter, W; Dullaart, R

    1998-01-01

    Lecithin:cholesteryl acyl transferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of cholesterol and the subsequent transfer of cholesteryl ester from high density lipoproteins (HDL) towards very low and low density lipoproteins (VLDL + LDL). Phospholip

  1. LDL Cholesterol Test

    Science.gov (United States)

    ... limited. Home Visit Global Sites Search Help? LDL Cholesterol Share this page: Was this page helpful? Also ... LDL; LDL-C Formal name: Low-Density Lipoprotein Cholesterol Related tests: Cholesterol ; HDL Cholesterol ; Triglycerides ; Lipid Profile ; ...

  2. Effects of hormones on lipids and lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. A predictor of atheroma progression in patients achieving very low levels of low-density lipoprotein cholesterol.

    Science.gov (United States)

    Nozue, Tsuyoshi; Yamamoto, Shingo; Tohyama, Shinichi; Fukui, Kazuki; Umezawa, Shigeo; Onishi, Yuko; Kunishima, Tomoyuki; Hibi, Kiyoshi; Terashima, Mitsuyasu; Michishita, Ichiro

    2013-01-01

    An aggressive reduction in low-density lipoprotein cholesterol (LDL-C) with statins produces regression or stabilization of coronary artery plaques. However, after achieving very low levels of LDL-C, atheroma regression is not observed in all patients. The purpose of the present study was to evaluate the determinants of atheroma progression despite achieving very low levels of LDL-C. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated using virtual histology intravascular ultrasound in the TRUTH study. Of these, 33 patients who achieved an on-treatment LDL-C level of cholesterol and apolipoprotein AI and decreases in high-sensitivity C-reactive protein and oxidized LDL were observed only in regressors. The changes in the n-3 to n-6 polyunsaturated fatty acid ratios significantly differed between the 2 groups. Multivariate regression analysis showed that a decrease in the eicosapentaenoic acid + docosahexaenoic acid/arachidonic acid ratio was a significant predictor associated with atheroma progression (β= -0.512, p= 0.004). In conclusions, n-3 to n-6 polyunsaturated fatty acid ratios affected coronary artery plaque progression and regression in patients who achieved very low levels of LDL-C during statin therapy. PMID:24224137

  4. [Effect of raw and cooked nopal (Opuntia ficus indica) ingestion on growth and profile of total cholesterol, lipoproteins, and blood glucose in rats].

    Science.gov (United States)

    Cárdenas Medellín, M L; Serna Saldívar, S O; Velazco de la Garza, J

    1998-12-01

    Two different concentrations (approx. 6 and 12%) and two presentations (raw and cooked) of dehydrated nopal were fed to laboratory rats and growth and serum total cholesterol, lipoprotein profile and glucose determined. Samples of raw and cooked nopal were chemically characterized for moisture, protein, ash, crude fiber, ether extract, total dietary fiber, reducing sugars, amino acids, minerals and gross energy. Cooking slightly affected some of the nutrients analyzed. After one month feeding, blood was withdrawn via intracardiac puncture and serum glucose, total cholesterol, HDL, LDL, and VLDL were determined. Rats fed 12% nopal had lower weight gains (P nopal or the control diet. Consumption of nopal did not affect (P > 0.05) glucose, total cholesterol and HDL cholesterol levels. However, rats fed raw nopal at the 12% concentration level had a 34% reduction in LDL cholesterol levels; thus, it was concluded that raw nopal had a potentially beneficial effect for hypercholesterolemic individuals. PMID:10347696

  5. Evaluation of the Novel Method and the Regression Equation for Calculation of Low-Density Lipoprotein Cholesterol

    Directory of Open Access Journals (Sweden)

    Muhammad Saiedullah

    2015-01-01

    Full Text Available Background: Friedewald’s formula (FF is used worldwide to calculate low-density lipoprotein cholesterol (LDL-chol. But it has several shortcomings: overestimation at lower triglyceride (TG concentrations and underestimation at higher concentrations. In FF, TG to very low-density lipoprotein cholesterol (VLDL-chol ratio (TG/VLDL-chol is considered as constant, but practically it is not a fixed value. Recently, by analyzing lipid profiles in a large population, continuously adjustable values of TG/VLDL-chol were used to derive a novel method (NM for the calculation of LDL-chol. Objective: The aim of this study was to evaluate the performance of the novel method compared with direct measurement and regression equation (RE developed for Bangladeshi population. Materials and Methods: In this cross-sectional comparative study we used lipid profiles of 955 adult Bangladeshi subjects. Total cholesterol (TC, TG, HDL-chol and LDL-chol were measured by direct methods using automation. LDL-chol was also calculated by NM and RE. LDL-chol calculated by NM and RE were compared with measured LDL-chol by twotailed paired t test, Pearson’s correlation test, bias against measured LDL-chol by Bland-Altman test, accuracy within ±5% and ±12% of measured LDL-chol and by inter-rater agreements with measured LDL-chol at different cut-off values. Results: The mean values of LDL-chol were 110.7 ± 32.0 mg/dL for direct measurement, 111.9 ± 34.8 mg/dL for NM and 113.2 ± 31.7 mg/dL for RE. Mean values of calculated LDL-chol by both NM and RE differed from that of measured LDL-chol (p130 mg/dL were 0.816 vs 0.815, 0.637 vs 0.649 and 0.791 vs 0.791 for NM and RE respectively. Conclusion: This study reveals that NM and RE developed for Bangladeshi population have similar performance and can be used for the calculation of LDL-chol.

  6. Atherosclerosis in low density lipoprotein receptor knockout mice fed cholesterol and soybean oil

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Olsen, P.; Frandsen, H.

    1999-01-01

    In order to study aortic atherosclerosis and atherosclerotic response to dietary cholesterol and soybean oil in homozygous LDLR-/- mice, the 16 weeks old animals were randomized in 4 groups either fed standard diet (no cholesterol added, group I, 12 male and 12 female), standard diet added 0.......9 +/- 0.07 (group III), 32.6 +/-0.1 (group IV), and of females 6.9 +/- 2.7 (group I) and 31.7 +/- 4.4 (group II). No apparent difference in plasma triglyceride levels was observed between the groups of either sexes. Aortic atherosclerosis (ratio intima/media) in males was 0.17 +/- 0.09 (SD) (group I), 0...

  7. Mechanism of action of gemfibrozil on lipoprotein metabolism.

    OpenAIRE

    Saku, K; Gartside, P S; Hynd, B A; Kashyap, M L

    1985-01-01

    Gemfibrozil is a potent lipid regulating drug whose major effects are to increase plasma high density lipoproteins (HDL) and to decrease plasma triglycerides (TG) in a wide variety of primary and secondary dyslipoproteinemias. Its mechanism of action is not clear. Six patients with primary familial endogenous hypertriglyceridemia with fasting chylomicronemia (type V lipoprotein phenotype) with concurrent subnormal HDL cholesterol levels (HDL deficiency) were treated initially by diet and once...

  8. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Langsted, A.; Freiberg, J.J.; Nordestgaard, Børge

    2008-01-01

    cholesterol, high-density lipoprotein (HDL) cholesterol, and albumin levels were reduced up to 3 to 5 hours after the last meal; triglycerides levels were increased up to 6 hours after the last meal; and non-HDL cholesterol level, apolipoprotein A1 level, apolipoprotein B level, ratio of total cholesterol...... years of age from the Copenhagen General Population Study. We also studied 9319 individuals 20 to 93 years of age from the Copenhagen City Heart Study, 1166 of whom developed cardiovascular events during 14 years of follow-up. Compared with fasting levels, total cholesterol, low-density lipoprotein...... to HDL cholesterol, and ratio of apolipoprotein B to apolipoprotein A1 did not change in response to normal food intake. The maximum changes after normal food and fluid intake from fasting levels were -0.2 mmol/L for total cholesterol, -0.2 mmol/L for low-density lipoprotein cholesterol, -0.1 mmol...

  9. Plasma-Serum Cholesterol Differences in Children and Use of Measurements from Different Specimens

    NARCIS (Netherlands)

    Berentzen, N.E.; Wijga, A.H.; Rossem, van L.; Jongste, de J.C.; Boshuizen, H.C.; Smit, H.A.

    2013-01-01

    Background: We aimed to assess absolute plasma-serum differences and differences in ranking of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and TC/HDLC ratio in children. Methods: We analysed data of 412 children participating in a Dutch birth cohort. TC, HDLC, and TC/HDLC ra

  10. Pharmacogenetic interaction between dexamethasone and Cd36-deficient segment of spontaneously hypertensive rat chromosome 4 affects triacylglycerol and cholesterol distribution into lipoprotein fractions.

    Science.gov (United States)

    Krupková, Michaela; Sedová, Lucie; Liska, Frantisek; Krenová, Drahomíra; Kren, Vladimír; Seda, Ondrej

    2010-04-16

    Dexamethasone (DEX) is known to induce diabetes and dyslipidemia. We have compared fasting triacylglycerol and cholesterol concentrations across 20 lipoprotein fractions and glucose tolerance in control (standard diet) and DEX-treated 7-month-old males of two rat strains, Brown Norway (BN) and congenic BN.SHR-(Il6-Cd36)/Cub (BN.SHR4). These two inbred strains differ in a defined segment of chromosome 4, originally transferred from the spontaneously hypertensive rat (SHR) including the mutant Cd36 gene, a known target of DEX. Compared to BN, the standard-diet-fed BN.SHR4 showed higher cholesterol and triacylglycerol concentrations across many lipoprotein fractions, particularly in small VLDL and LDL particles. Total cholesterol was decreased by DEX by more than 21% in BN.SHR4 contrasting with the tendency to increase in BN (strain*DEX interaction p = 0.0017). Similar pattern was observed for triacylglycerol concentrations in LDL. The LDL particle size was significantly reduced by DEX in both strains. Also, while control BN and BN.SHR4 displayed comparable glycaemic profiles during oral glucose tolerance test, we observed a markedly blunted DEX induction of glucose intolerance in BN.SHR4 compared to BN. In summary, we report a pharmacogenetic interaction between limited genomic segment with mutated Cd36 gene and dexamethasone-induced glucose intolerance and triacylglycerol and cholesterol redistribution into lipoprotein fractions.

  11. Low-density-lipoprotein cholesterol concentrations and risk of incident diabetes

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Lyass, Asya; Larson, Martin G;

    2015-01-01

    AIMS/HYPOTHESIS: Statins and niacin (nicotinic acid) reduce circulating LDL-cholesterol (LDL-C) levels by different mechanisms. Yet, both increase the risk of diabetes mellitus. Our objective was to relate blood LDL-C concentrations and a genetic risk score (GRS) for LDL-C to the risk of incident...... contribute to our understanding of why lipid-lowering treatment may cause diabetes in some individuals. Additional studies are warranted to elucidate the molecular mechanisms underlying our observations.......AIMS/HYPOTHESIS: Statins and niacin (nicotinic acid) reduce circulating LDL-cholesterol (LDL-C) levels by different mechanisms. Yet, both increase the risk of diabetes mellitus. Our objective was to relate blood LDL-C concentrations and a genetic risk score (GRS) for LDL-C to the risk of incident...... diabetes in individuals not treated with lipid-modifying therapy. METHODS: We evaluated participants of the Framingham Heart Study who attended any of Offspring cohort examination cycles 3-8 and Third Generation cohort examination cycle 1 (N =14,120 person-observations, 6,011 unique individuals; mean age...

  12. The improvement of large High-Density Lipoprotein (HDL) particle levels, and presumably HDL metabolism, depend on effects of low-carbohydrate diet and weight loss

    Science.gov (United States)

    Finelli, C.; Crispino, P.; Gioia, S.; La Sala, N.; D'amico, L.; La Grotta, M.; Miro, O.; Colarusso, D.

    2016-01-01

    Depressed levels of atheroprotective large HDL particles are common in obesity and cardiovascular disease (CVD). Increases in large HDL particles are favourably associated with reduced CVD event risk and coronary plaque burden. The objective of the study is to compare the effectiveness of low-carbohydrate diets and weight loss for increasing blood levels of large HDL particles at 1 year. This study was performed by screening for body mass index (BMI) and metabolic syndrome in 160 consecutive subjects referred to our out-patient Metabolic Unit in South Italy. We administered dietary advice to four small groups rather than individually. A single team comprised of a dietitian and physician administered diet-specific advice to each group. Large HDL particles at baseline and 1 year were measured using two-dimensional gel electrophoresis. Dietary intake was assessed via 3-day diet records. Although 1-year weight loss did not differ between diet groups (mean 4.4 %), increases in large HDL particles paralleled the degree of carbohydrate restriction across the four diets (p<0.001 for trend). Regression analysis indicated that magnitude of carbohydrate restriction (percentage of calories as carbohydrate at 1 year) and weight loss were each independent predictors of 1-year increases in large HDL concentration. Changes in HDL cholesterol concentration were modestly correlated with changes in large HDL particle concentration (r=0.47, p=.001). In conclusion, reduction of excess dietary carbohydrate and body weight improved large HDL levels. Comparison trials with cardiovascular outcomes are needed to more fully evaluate these findings. PMID:27103896

  13. Trends in the Levels of Serum Lipids and Lipoproteins and the Prevalence of Dyslipidemia in Adults with Newly Diagnosed Type 2 Diabetes in the Southwest Chinese Han Population during 2003–2012

    OpenAIRE

    Jing Tian; Hewen Chen; Fang Jia; Gangyi Yang; Shengbing Li; Ke Li; Lili Zhang; Jinlin Wu; Dongfang Liu

    2015-01-01

    Objective. To determine the trends of serum lipid levels and dyslipidemia in adults newly diagnosed with type 2 diabetes mellitus during 2003–2012 in Southwest China. Methods. Serum lipid measurements of 994 adults were obtained from 5 independent, cross-sectional studies (2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012). The main outcome measures were mean serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels; bo...

  14. HDL2-C和HDL3-C与老年男性冠心病发病相关性分析%Correlation analysis of high-density lipoprotein subfractions(HDL2,HDL3)and coronary heart disease in the male elderly

    Institute of Scientific and Technical Information of China (English)

    赵勇; 任红旗; 史跃; 项军

    2012-01-01

    目的 探讨高密度脂蛋白胆固醇亚组分(HDL2-C和HDL3-C)与老年男性冠心病发病相关性.方法 随机选择老年男性冠心病60例,无冠心病老年男性60例为对照组.应用硫酸葡聚糖-镁法测定HDL-C亚组分HDL2-C和HDL3-C,并分析其与冠心病发生的相关性.结果 与对照组相比,老年男性冠心病组HDL-C和HDL3-C均显著下降(P均0.05).Logistic回归分析显示HDL3-C、低密度脂蛋白胆固醇(LDL-C)、糖化血红蛋白(HbA1c)及高血压病作为老年男性冠心病发病的独立危险因子进入回归方程,HDL-C和HDL2-C未进入方程.Spearman秩相关分析显示HDL3-C与冠心病发病的负相关性(r=-0.310,P=0.030)优于HDL-C(r=-0.154,P=0.274)和HDL2-C(r=-0.014,P=0.924).结论 HDL3-C与老年男性冠心病发病的负相关性优于HDL-C和HDL2-C,HDL3-C是老年男性冠心病发生的独立危险因子,HDL-C抗冠状动脉粥样硬化作用可能主要是通过HDL3-C实现的.%Objective To evaluate whether one or both of the major high-density lipoprotein ( HDL) subfractions ( HDL2, HDL3 ) is associated with the risk of coronary heart disease ( CHD ) in the male elderly. Methods Sixty people with CHD were randomly selected as group A and 60 people without CHD as the control , all the examinations were the male elderly. The separation of HDL subfractions was carried out by dextran sulfate -magnesium chloride technique , and the correlation between HDL subfractions ( HDL2, HDL3 ) and coronary heart disease were analyzed. Results The group A had significantly lower HDL and HDL 3 cholesterol levels compared to the control ( both P < 0. 01 ) , while HDL2 cholesterol levels was not significantly reduced . The Spearman rank correlation analysis indicated that CHD significantly correlated with HDL 3 cholesterol (r = - 0. 310 , P = 0. 030 ) , but not with HDL cholesterol ( r = - 0. 154, P = 0. 274 ) and HDL2 cholesterol ( r = - 0. 014 , P = 0. 924 ). Logistic regression analysis revealed that HDL3

  15. S447X variant of the lipoprotein lipase gene, lipids, and risk of coronary heart disease in 3 prospective cohort studies

    DEFF Research Database (Denmark)

    Jensen, M.K.; Rimm, E.B.; Rader, D.;

    2009-01-01

    Background Lipoprotein lipase (LPL) has a prominent role in the metabolism of triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C) and is a potential interesting target for the development of antiatherogenic treatment. To provide deeper insight into the role of natural variation i...

  16. Systematic review of green tea epigallocatechin gallate in reducing low-density lipoprotein cholesterol levels of humans.

    Science.gov (United States)

    Momose, Yuko; Maeda-Yamamoto, Mari; Nabetani, Hiroshi

    2016-09-01

    We conducted a systematic review of the literature for the ability of green tea epigallocatechin gallate (EGCG) to lower low-density lipoprotein cholesterol (LDL-C). Study subjects were limited to healthy individuals and randomized, controlled trials on human serum lipid levels, especially LDL-C, conducted. A total of 17 trials (n = 1356) met all of the inclusion criteria. According to weighted mean differences for changes from baseline with 95% confidence intervals (CI), 107-856 mg/d of EGCG for 4 to 14 weeks reduced LDL-C by -9.29 mg/dl (95% CI, -12.27 to -6.31). Sub-analysis was performed to compare the EGCG lowering effect on LDL-C between non-obese and obese subjects, EGCG dose, baseline of LDL-C levels, or BMI. We concluded that consumption of green tea EGCG resulted in a significant reduction of LDL-C at any baseline level and any dose between 107 and 856 mg/d, and the effect size was slightly dependent on the baseline lipid level of the subjects. PMID:27324590

  17. Low-density lipoprotein cholesterol target goal attainment rate and related factors in patients with acute coronary syndrome after percutaneous coronary intervention

    Institute of Scientific and Technical Information of China (English)

    张波

    2014-01-01

    Objective To observe the low-density lipoprotein cholesterol(LDL-C)target goal attainment rate and related factors in patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods From March 2011 to March 2012,a total of832 ACS patients were retrospectively evaluated in the Cardiology Department of the First Affiliated Hospital of Dalian Medical University.The target goal attainment

  18. Specific Cellular Incorporation of a Pyrene-Labelled Cholesterol: Lipoprotein-Mediated Delivery toward Ordered Intracellular Membranes

    OpenAIRE

    Gérald Gaibelet; Sophie Allart; François Tercé; Vincent Azalbert; Justine Bertrand-Michel; Safouane Hamdi; Xavier Collet; Stéphane Orlowski

    2015-01-01

    In the aim of testing tools for tracing cell trafficking of exogenous cholesterol, two fluorescent derivatives of cholesterol, 22-nitrobenzoxadiazole-cholesterol (NBD-Chol) and 21-methylpyrenyl-cholesterol (Pyr-met-Chol), with distinctive chemico-physical characteristics, have been compared for their cell incorporation properties, using two cell models differently handling cholesterol, with two incorporation routes. In the Caco-2 cell model, the cholesterol probes were delivered in bile salt ...

  19. A low-saturated-fat, low-cholesterol diet decreases plasma CETP activity and pre beta-HDL formation but does not affect cellular cholesterol efflux to plasma from type 1 diabetic patients

    NARCIS (Netherlands)

    De Vries, R; Beusekamp, BJ; Kerstens, MN; Groen, AK; Van Tol, A; Dullaart, RPF

    2005-01-01

    The aim of this study was to evaluate the effect of a low-saturated-fat, low-cholesterol diet on plasma lipopoproteins, pre beta-high density lipoprotein (HDL) formation, lecithin: cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP)

  20. Characterization of hepatic low density lipoprotein binding and cholesterol metabolism in normal and homozygous familial hypercholesterolemic subjects.

    OpenAIRE

    Hoeg, J M; Demosky, S J; Schaefer, E.J.; Starzl, T.E.; Brewer, H B

    1984-01-01

    Patients with familial hypercholesterolemia have elevated levels of plasma low density lipoproteins (LDL), increased hepatic synthesis of apolipoprotein B-containing lipoproteins, defective binding of low density lipoproteins to fibroblasts, and premature atherosclerosis. The role of a hepatic low density lipoprotein receptor in normal man and its importance in the pathogenesis of familial hypercholesterolemia have not been previously determined. In the present study, direct comparison was ma...

  1. Ethnic differences in total and HDL cholesterol among Turkish, Moroccan and Dutch ethnic groups living in Amsterdam, the Netherlands

    NARCIS (Netherlands)

    J.K. Ujcic-Voortman; G. Bos; C.A. Baan; D.G. Uitenbroek; A.P. Verhoeff; J.C. Seidell

    2011-01-01

    Background High total cholesterol and low HDL (high-density lipoprotein) cholesterol are important determinants of cardiovascular disease. Little is known about dyslipidemia among Turkish and Moroccan migrants, two of the largest ethnic minority groups in several European countries. This study exami

  2. The mechanism of dietary cholesterol effects on lipids metabolism in rats

    Directory of Open Access Journals (Sweden)

    Wang Jing-Feng

    2010-01-01

    Full Text Available Abstract Background Cholesterol administration has been reported to influence hepatic lipid metabolism in rats. In the present study, the effect of dietary cholesterol on hepatic activity and mRNA expression of the enzymes involved in lipid metabolism were investigated. Fourteen male Wistar rats were randomly divided into 2 groups and fed 1% cholesterol or cholesterol free AIN76 diets for 4 weeks. Results The serum triglyceride and high density lipoprotein cholesterol levels were significantly decreased but the total cholesterol and non high density lipoprotein cholesterol levels were significantly increased in the cholesterol-fed rats compared with the control rats. And the concentrations of the hepatic total cholesterol and triglyceride increased about 4-fold and 20-fold separately by dietary cholesterol. The activities of hepatic malic enzyme, glucose-6-phosphate dehydrogenase, fatty acid synthase, phosphatidate phophatase and carnitine palmitoyl transferase were depressed by the cholesterol feeding (40%, 70%, 50%, 15% and 25% respectively. The results of mRNA expression showed that fatty acid synthase, carnitine palmitoyl transferase 1, carnitine palmitoyl transferase 2, and HMG-CoA reductase were down-regulated (35%, 30%, 50% and 25% respectively and acyl-CoA: cholesterol acyltransferase and cholesterol 7α-hydroxylase were up regulated (1.6 and 6.5 folds in liver by the cholesterol administration. Conclusions The dietary cholesterol increased the triglyceride accumulation in liver, but did not stimulate the activity and the gene expression of hepatic enzymes related to triglyceride and fatty acid biosynthesis.

  3. Effects of short-term niacin treatment on plasma lipoprotein concentrations in African green monkeys (Chlorocebus aethiops)

    KAUST Repository

    Chauke, Chesa G.

    2014-01-22

    Niacin is the most effective drug available for raising levels of high-density lipoprotein (HDL) cholesterol. To evaluate its effects on plasma lipid concentrations, the authors administered a low dose of niacin to healthy, adult, female African green monkeys for 3 months. In the treated monkeys, low-density lipoprotein cholesterol concentrations decreased by 43% from baseline, whereas concentrations of HDL cholesterol and apolipoprotein A-I increased by 49% and 34%, respectively. The results suggest that in this primate model, a low dose of niacin can effectively increase concentrations of HDL cholesterol.©2014 Nature America, Inc. All rights reserved.

  4. Effects of short-term niacin treatment on plasma lipoprotein concentrations in African green monkeys (Chlorocebus aethiops).

    Science.gov (United States)

    Chauke, Chesa G; Arieff, Zainunisha; Kaur, Mandeep; Seier, Jurgen V

    2014-02-01

    Niacin is the most effective drug available for raising levels of high-density lipoprotein (HDL) cholesterol. To evaluate its effects on plasma lipid concentrations, the authors administered a low dose of niacin to healthy, adult, female African green monkeys for 3 months. In the treated monkeys, low-density lipoprotein cholesterol concentrations decreased by 43% from baseline, whereas concentrations of HDL cholesterol and apolipoprotein A-I increased by 49% and 34%, respectively. The results suggest that in this primate model, a low dose of niacin can effectively increase concentrations of HDL cholesterol.

  5. Apolipoprotein ε4 polymorphism does not modify the association between body mass index and high-density lipoprotein cholesterol: a cross-sectional cohort study

    Directory of Open Access Journals (Sweden)

    Ellison R Curtis

    2011-09-01

    Full Text Available Abstract Background We sought to examine whether ε4 carrier status modifies the relation between body mass index (BMI and HDL. The National Heart, Lung, and Blood Institute Family Heart Study included 657 families with high family risk scores for coronary heart disease and 588 randomly selected families of probands in the Framingham, Atherosclerosis Risk in Communities, and Utah Family Health Tree studies. We selected 1402 subjects who had ε4 carrier status available. We used generalized estimating equations to examine the interaction between BMI and ε4 allele carrier status on HDL after adjusting for age, gender, smoking, alcohol intake, mono- and poly-unsaturated fat intake, exercise, comorbidities, LDL, and family cluster. Results The mean (standard deviation age of included subjects was 56.4(11.0 years and 47% were male. Adjusted means of HDL for normal, overweight, and obese BMI categories were 51.2(± 0.97, 45.0(± 0.75, and 41.6(± 0.93, respectively, among 397 ε4 carriers (p for trend Conclusion Our findings do not support an interaction between ε4 allele status and BMI on HDL.

  6. High-density lipoprotein cholesterol is a favorable prognostic factor and negatively correlated with C-reactive protein level in non-small cell lung carcinoma.

    Directory of Open Access Journals (Sweden)

    Pei-Dong Chi

    Full Text Available Although the alterations of lipid profile in lung cancer have been documented, the prognostic value of serum HDL-C level and its correlation with inflammation in NSCLC remain unknown.Levels of preoperative serum lipid concentrations (including HDL-C, LDL-C, TC, and TG and the inflammatory biomarker C-reactive protein level (CRP were retrospectively analyzed in 228 patients with NSCLC and in 300 healthy controls. The serum lipid levels in these two populations were compared. Univariate and multivariate cox hazards analyses were performed to investigate the prognostic value of serum lipid levels in NSCLC. The correlation between CRP and lipid profile were also analyzed.Compared with those in normal controls, the serum HDL-C, LDL-C, and TC levels were statistically decreased and the TG levels were significantly increased in 228 NSCLC patients. The patients with decreased levels of HDL-C had significantly lower 5-year survival rates than those with normal HDL-C, not only in the whole NSCLC cohort but also in the subgroups stratified according to the disease T, N classifications, and metastasis, whereas the other lipid components were not independent prognostic factors for NSCLC. Of the lipid components, a lower HDL-C level was observed more often in patients with a high CRP level than in those with a normal CRP level. Spearman's rank correlation analysis revealed that the HDL-C level presented a negative correlation with the CRP level (r = -0.360, p<0.001.A decreased level of preoperative HDL-C was found to be associated with poor survival in patients with NSCLC. Serum HDL-C level may be a clinical prognosis factor for NSCLC patients. In addition, a negative correlation was present between the levels of HDL-C and CRP, the well-known inflammation biomarker.

  7. Atherogenic index and high-density lipoprotein cholesterol as cardiovascular risk determinants in rheumatoid arthritis: the impact of therapy with biologicals

    NARCIS (Netherlands)

    Popa, C.D.; Arts, E.; Fransen, J.; Riel, P.L. van

    2012-01-01

    Cardiovascular (CV) diseases are a serious concern in rheumatoid arthritis (RA), accounting for approximately one-third to one-half of all RA-related deaths. Besides the attempts to identify new risk factors, the proper management of traditional CV risk factors such as dyslipidemia should become a p

  8. Plasma lipoprotein profiles and arylesterase activities in two inbred strains of rabbits with high or low response of plasma cholesterol to dietary cholesterol

    NARCIS (Netherlands)

    Beynen, A.C.; Katan, M.B.; Zutphen, van L.F.M.

    1984-01-01

    1. 1. Cholesterol feeding for 4 weeks of female and male rabbits of two inbred strains increased plasma cholesterol concentrations by about 11 and 48 mmole/I in the hypo- and hyperresponsive strain, respectively. 2. 2. On the low-cholesterol pre-experimental diet, the hyporesponsive animals had sign

  9. Acute and chronic effects of a 24-hour intravenous triglyceride emulsion challenge on plasma lecithin : cholesterol acyltransferase, phospholipid transfer protein, and cholesteryl ester transfer protein activities

    NARCIS (Netherlands)

    Riemens, SC; Van Tol, A; Sluiter, WJ; Dullaart, RPF

    1999-01-01

    Lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), and cholesteryl ester transfer protein (CETP) are key factors in remodeling of high density lipoproteins (HDL) and triglyceride-rich lipoproteins. We examined the effect of a large, 24 h intravenous fat load on plasma

  10. A paradoxical severe decrease in serum HDL-cholesterol after treatment with a fibrate

    OpenAIRE

    Crook, M; Lynas, J; Wray, R

    2000-01-01

    There have been a handful of reports in the literature of a paradoxical decrease in serum high density lipoprotein (HDL)-cholesterol in patients on fibrate drugs. The reason for this decline in cardioprotective HDL-cholesterol is not known and may have potential deleterious effects on the patient. This report describes a decrease in serum HDL-cholesterol in a patient on both simvastatin and bezafibrate. This patient also developed abnormal renal function, probably interstitial nephritis. In a...

  11. A lipoprotein lipase gene polymorphism interacts with consumption of alcohol and unsaturated fat to modulate serum HDL-cholesterol concentrations.

    Science.gov (United States)

    Baik, Inkyung; Lee, Seungku; Kim, Seong Hwan; Shin, Chol

    2013-10-01

    There are limited data from prospective studies regarding interactions between lipoprotein lipase gene (LPL) and lifestyle factors in association with HDL-cholesterol (HDL-C) concentrations, a biomarker of coronary heart disease risk. Our prospective cohort study investigated the interactive effects of a common LPL polymorphism and lifestyle factors, including obesity, smoking, alcohol consumption, physical activity, and dietary intake, on follow-up measurements of HDL-C and triglyceride (TG) concentrations. A total of 5314 Korean men and women aged 40-69 y participated in the study. Serum HDL-C and TG concentrations were measured in all participants at baseline and 6-y follow-up examinations. On the basis of genome-wide association data for HDL-C and TG concentrations, we selected the most significant polymorphism (rs10503669), which was in high linkage disequilibrium with the serine 447 stop (S447×) mutation (D' = 0.99) of LPL. We found that carrying the T allele reflecting the LPL ×447 allele was positively associated with follow-up measurement of HDL-C concentrations (P HDL-C concentration and potential risk factors, we observed interactive effects of the polymorphism and consumption of alcohol (P-interaction unsaturated fat (P-interaction HDL-C concentrations. We also observed interactive effects of the polymorphism and body mass index (P-interaction unsaturated fat to minimize reduction of blood HDL-C concentrations and that obese persons who do not carry the LPL ×447 allele need to control body weight to prevent hypertriglyceridemia.

  12. Fine mapping of five loci associated with low-density lipoprotein cholesterol detects variants that double the explained heritability.

    Directory of Open Access Journals (Sweden)

    Serena Sanna

    2011-07-01

    Full Text Available 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.

  13. Development of alimentary cholesterol in the plasma and the plasmatic lipoproteins in man, after ingestion of a meal containing octa-deuterated cholesterol; Devenir du cholesterol alimentaire dans le plasma et les lipoproteines plasmatiques chez l`homme, apres ingestion d`un repas contenant du cholesterol octa-deutere

    Energy Technology Data Exchange (ETDEWEB)

    Becue, T.; Ferezou, J.; Simon, G. [Paris-11 Univ., 91 - Orsay (France); Bernard, P.M.; Portugal, H. [Hopital Sainte-Marguerite, 13 - Marseille (France); Dubois, C.; Lairon, D.

    1994-12-31

    Cholesterol absorbed after a test-meal has two origins with man: the biliary cholesterol and the alimentary cholesterol. In order to understand the mechanism of the modification of cholesterol intestinal absorption by oat bran, the alimentary cholesterol has been labelled with octa-deuterated cholesterol, in test-diets. The kinetics of D-cholesterol in plasma and chylomicrons is described. 1 fig., 6 refs.

  14. 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

    Directory of Open Access Journals (Sweden)

    Jane McEneny

    2015-01-01

    Full Text Available 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 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.

  15. Effects of niacin combination therapy with statin or bile acid resin on lipoproteins and cardiovascular disease.

    Science.gov (United States)

    Zambon, Alberto; Zhao, Xue-Qiao; Brown, B Greg; Brunzell, John D

    2014-05-01

    Two large studies in populations selected for cardiovascular disease (CVD) demonstrated that raising high-density lipoprotein (HDL) cholesterol with niacin added to statin therapy did not decrease CVD. We examine the association of lipoprotein subfractions with niacin and changes in coronary stenosis and CVD event risk. One hundred and seven patients from 2 previous studies using niacin in combination with either statin or bile acid-binding resin were selected to evaluate changes in lipoproteins separated by density-gradient ultracentrifugation to progression of coronary artery disease as assessed by quantitative coronary angiography. Improvement in coronary stenosis was significantly associated with the decrease of cholesterol in the dense low-density lipoprotein (LDL) particles and across most of the intermediate density lipoprotein (IDL) and very low density lipoprotein particle density range, but, not with any of the HDL fraction or of the more buoyant LDL fractions. Event-free survival was significantly associated with the decrease of cholesterol in the dense LDL and IDL; there was no association with changes in cholesterol in the HDL and buoyant LDL fractions. Niacin combination therapy raises HDL cholesterol and decreases dense LDL and IDL cholesterol levels. Changes in LDL and IDL are related to improvement in CVD. Lipoprotein subfraction analysis should be performed in larger studies utilizing niacin in combination with statins.

  16. Effect of repeated apoA-IMilano/POPC infusion on lipids, (apo)lipoproteins, and serum cholesterol efflux capacity in cynomolgus monkeys[S

    Science.gov (United States)

    Kempen, Herman J.; Gomaraschi, Monica; Bellibas, S. Eralp; Plassmann, Stephanie; Zerler, Brad; Collins, Heidi L.; Adelman, Steven J.; Calabresi, Laura; Wijngaard, Peter L. J.

    2013-01-01

    MDCO-216, a complex of dimeric recombinant apoA-IMilano (apoA-IM) and palmitoyl-oleoyl-phosphatidylcholine (POPC), was administered to cynomolgus monkeys at 30, 100, and 300 mg/kg every other day for a total of 21 infusions, and effects on lipids, (apo)lipoproteins, and ex-vivo cholesterol efflux capacity were monitored. After 7 or 20 infusions, free cholesterol (FC) and phospholipids (PL) were strongly increased, and HDL-cholesterol (HDL-C), apoA-I, and apoA-II were strongly decreased. We then measured short-term effects on apoA-IM, lipids, and (apo)lipoproteins after the first or the last infusion. After the first infusion, PL and FC went up in the HDL region and also in the LDL and VLDL regions. ApoE shifted from HDL to LDL and VLDL regions, while ApoA-IM remained located in the HDL region. On day 41, ApoE levels were 8-fold higher than on day 1, and FC, PL, and apoE resided mostly in LDL and VLDL regions. Drug infusion quickly decreased the endogenous cholesterol esterification rate. ABCA1-mediated cholesterol efflux on day 41 was markedly increased, whereas scavenger receptor type B1 (SRB1) and ABCG1-mediated effluxes were only weakly increased. Strong increase of FC is due to sustained stimulation of ABCA1-mediated efflux, and drop in HDL and formation of large apoE-rich particles are due to lack of LCAT activation. PMID:23828780

  17. Effect of repeated apoA-IMilano/POPC infusion on lipids, (apo)lipoproteins, and serum cholesterol efflux capacity in cynomolgus monkeys.

    Science.gov (United States)

    Kempen, Herman J; Gomaraschi, Monica; Bellibas, S Eralp; Plassmann, Stephanie; Zerler, Brad; Collins, Heidi L; Adelman, Steven J; Calabresi, Laura; Wijngaard, Peter L J

    2013-09-01

    MDCO-216, a complex of dimeric recombinant apoA-IMilano (apoA-IM) and palmitoyl-oleoyl-phosphatidylcholine (POPC), was administered to cynomolgus monkeys at 30, 100, and 300 mg/kg every other day for a total of 21 infusions, and effects on lipids, (apo)lipoproteins, and ex-vivo cholesterol efflux capacity were monitored. After 7 or 20 infusions, free cholesterol (FC) and phospholipids (PL) were strongly increased, and HDL-cholesterol (HDL-C), apoA-I, and apoA-II were strongly decreased. We then measured short-term effects on apoA-IM, lipids, and (apo)lipoproteins after the first or the last infusion. After the first infusion, PL and FC went up in the HDL region and also in the LDL and VLDL regions. ApoE shifted from HDL to LDL and VLDL regions, while ApoA-IM remained located in the HDL region. On day 41, ApoE levels were 8-fold higher than on day 1, and FC, PL, and apoE resided mostly in LDL and VLDL regions. Drug infusion quickly decreased the endogenous cholesterol esterification rate. ABCA1-mediated cholesterol efflux on day 41 was markedly increased, whereas scavenger receptor type B1 (SRB1) and ABCG1-mediated effluxes were only weakly increased. Strong increase of FC is due to sustained stimulation of ABCA1-mediated efflux, and drop in HDL and formation of large apoE-rich particles are due to lack of LCAT activation. PMID:23828780

  18. Computational studies of plasma lipoprotein lipids.

    Science.gov (United States)

    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

  19. Lp(a-cholesterol is associated with HDL-cholesterol in overweight and obese African American children and is not an independent risk factor for CVD

    Directory of Open Access Journals (Sweden)

    Sharma Sushma

    2012-01-01

    Full Text Available Abstract Background The role of Lipoprotein (a cholesterol {Lp(a-C}as an additional and/or independent risk factor for cardiovascular disease (CVD is not clear. We evaluated the associations between Lp(a-C and other CVD risk factors including plasma lipoprotein concentrations and body fatness in overweight and obese African American children. Methods A cross-sectional analysis was carried out using data from a sample of 121 African American children aged 9-11 years with Body Mass Index (BMI's greater than the 85th percentile. Body height, weight and waist circumference (WC were measured. Fasting plasma concentrations of Lp(a-C, Total cholesterol (TC, High density lipoprotein cholesterol (HDL-C, Very low density lipoprotein cholesterol (VLDL-C, Intermediate density lipoprotein cholesterol (IDL-C, Low density lipoprotein cholesterol (LDL-C, and Triacylglycerides (TAG were analyzed using the vertical auto profile (VAP cholesterol method. Results After adjusting for child age, gender, and pubertal status, Lp(a-C was positively associated with both HDL-C and TC, and negatively associated with VLDL-C and TAG. Including BMIz and WC as additional covariates did not alter the direction of the relationships between Lp(a-C and the other lipoproteins. Finally, after adjusting for the other plasma lipoproteins, Lp(a-C remained strongly associated with HDL-C, whereas the associations of Lp(a-C with the other lipoproteins were not significant when HDL-C was simultaneously included in the regression models. Conclusions Lp(a-C was positively associated with HDL-C and this association is not influenced by other lipoprotein subclasses or by the degree of obesity. We conclude that Lp(a cholesterol is not an independent risk factor for CVD in African American children.

  20. Serum apolipoprotein(a) levels and its effect on the measured values of low density lipoprotein cholesterol.

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    Serum low density lipoprotein cholesterl (LDL-C) and lipoprotein(a)[Lp(a)]levels were analyzed in 1032 sequential cases on routine physical check up, with special attention to the effect of Lp(a) on the LDL-C values. Since the determination of LDL-C by various

  1. The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol

    Directory of Open Access Journals (Sweden)

    Poirier S

    2013-10-01

    Full Text Available Steve Poirier,1,2 Gaétan Mayer1–31Laboratory of Molecular Cell Biology, Montreal Heart Institute, Montréal, QC, Canada; 2Départements de Pharmacologie, 3Médecine, Faculté de Médecine, Université de Montréal, Montréal, QC, CanadaAbstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9 directly binds to the epidermal growth factor-like repeat A domain of low-density lipoprotein receptor and induces its degradation, thereby controlling circulating low-density lipoprotein cholesterol (LDL-C concentration. Heterozygous loss-of-function mutations in PCSK9 can decrease the incidence of coronary heart disease by up to 88%, owing to lifelong reduction of LDL-C. Moreover, two subjects with PCSK9 loss-of-function mutations on both alleles, resulting in a total absence of functional PCSK9, were found to have extremely low circulating LDL-C levels without other apparent abnormalities. Accordingly, PCSK9 could represent a safe and effective pharmacological target to increase clearance of LDL-C and to reduce the risk of coronary heart disease. Recent clinical trials using anti-PCSK9 monoclonal antibodies that block the PCSK9:low-density lipoprotein receptor interaction were shown to considerably reduce LDL-C levels by up to 65% when given alone and by up to 72% in patients already receiving statin therapy. In this review, we will discuss how major scientific breakthroughs in PCSK9 cell biology have led to the development of new and forthcoming LDL-C-lowering pharmacological agents.Keywords: PCSK9, LDLR, LDL-cholesterol, lipoproteins, coronary heart disease, inhibitors, monoclonal antibody therapy

  2. Prevalence and characteristics of patients with low levels of low-density lipoprotein cholesterol in northern Denmark: a descriptive study

    Directory of Open Access Journals (Sweden)

    Schmidt SA

    2015-02-01

    Full Text Available Sigrun Alba Johannesdottir Schmidt,1 Uffe Heide-Jørgensen,1 Angelika D Manthripragada,2 Vera Ehrenstein1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA Background: With the emergence of new lipid-lowering therapies, more patients are expected to achieve substantial lowering of low-density lipoprotein cholesterol (LDL-C. However, there are limited data examining the clinical experience of patients with low (<1.3 mmol/L or very low (<0.65 mmol/L levels of LDL-C. To provide information on patients with low LDL-C, we identified and characterized persons with low LDL-C using data from Danish medical databases. Methods: Using a population-based clinical laboratory database, we identified adults with at least one LDL-C measurement in northern Denmark between 1998 and 2011 (population approximately 1.5 million persons. Based on the lowest measurement during the study period, we divided patients into groups with low (<1.3 mmol/L, moderate (1.3–3.3 mmol/L, or high (>3.3 mmol/L LDL-C. We described their demographic characteristics, entire comorbidity history, and 90-day prescription history prior to the lowest LDL-C value measured. Finally, we further restricted the analysis to individuals with very low LDL-C (<0.65 mmol/L. Results: Among 765,503 persons with an LDL-C measurement, 23% had high LDL-C, 73% had moderate LDL-C, and 4.8% had low LDL-C. In the latter group, 9.6% (0.46% of total had very low LDL-C. Compared with the moderate and high LDL-C categories, the low LDL-C group included more males and older persons with a higher prevalence of cardiovascular disease, diabetes, chronic pulmonary disease, ulcer disease, and obesity, as measured by hospital diagnoses or relevant prescription drugs for these diseases. Cancer and use of psychotropic drugs were also more prevalent. These patterns of distribution became even more pronounced when

  3. Common Low-Density Lipoprotein Receptor p.G116S Variant Has a Large Effect on Plasma Low-Density Lipoprotein Cholesterol in Circumpolar Inuit Populations

    DEFF Research Database (Denmark)

    Dube, J. B.; Wang, J.; Cao, H.;

    2015-01-01

    .G116S and p.R730W. METHODS AND RESULTS: Genotyping these variants in 3324 Inuit from Alaska, Canada, and Greenland showed they were common, with allele frequencies 10% to 15%. Only p.G116S was associated with dyslipidemia: the increase in LDL cholesterol was 0.54 mmol/L (20.9 mg/dL) per allele (P=5.6x....... In vitro, p.G116S showed 60% reduced ligand-binding activity compared with wild-type receptor. In contrast, p.R730W was associated with neither LDL cholesterol level nor altered in vitro activity. CONCLUSIONS: LDLR p.G116S is thus unique: a common dysfunctional variant in Inuit whose large effect on LDL...... cholesterol may have public health implications....

  4. Development and partial metabolic characterization of a dietary cholesterol-resistant colony of rabbits

    International Nuclear Information System (INIS)

    A colony of New Zealand white rabbits has been developed which, when fed a cholesterol-supplemented diet, exhibit unusual resistance to hypercholesterolemia and atherosclerosis, disorders usually observed in normal cholesterol-fed rabbits. When resistant rabbits (RT) were fed a normal low cholesterol diet (ND), their plasma lipoprotein patterns were significantly different from those of normal rabbits (NR) fed the same diet. The low density lipoprotein cholesterol (LDL-c)/high density lipoprotein cholesterol (HDL-c) ratio and LDL-c/very low density lipoprotein cholesterol (VLDL-c) ratio were lower in the resistant rabbits. The hydrated density of HDL of the normal-responsive rabbits was greater than that of the resistant rabbits. LDL from resistant rabbits contained a lower proportion of esterified cholesterol and protein than LDL from normal rabbits. Peripheral mononuclear cells from resistant rabbits bound about 30% more 125I-labeled rabbit LDL than mononuclear cells from normal rabbits. These results demonstrate that the plasma cholesterol levels of these animals is at least partly under genetic control and that compositional differences exist between the major plasma lipoprotein classes of normal and resistant rabbits even during the ingestion of low-cholesterol diet. The results indicate that at least a part of the difference in the cholesterolemic responses between the two rabbit groups is due to an enhanced LDL uptake by the mononuclear cells, and presumably by other somatic cells of the resistant group

  5. Common and rare alleles in apolipoprotein B contribute to plasma levels of low-density lipoprotein cholesterol in the general population

    DEFF Research Database (Denmark)

    Benn, M.; Stene, Maria Charlotte Aslaug; Nordestgaard, Børge;

    2008-01-01

    demonstrated to affect low-density lipoprotein (LDL) cholesterol levels. Objective: We tested the hypothesis that nonsynonymous SNPs in three important functional domains of APOB and APOB tag SNPs predict levels of LDL cholesterol and apolipoprotein B and risk of ischemic heart disease. Design......: This was a prospective study with 25 yr 100% follow up, The Copenhagen City Heart Study. Setting: The study was conducted in the Danish general population. Participants: Participants included 9185 women and men aged 20-80+ yr. Main Outcome Measures: Levels of LDL cholesterol and apolipoprotein B and risk of ischemic...... (0.21), R3611Q (0.09), E4154K (0.17), and N4311S (0.21). SNPs were associated with increases (T71I, Ivs181708g > t, T2488Tc > t, R3611) or decreases (Ivs4 + 171c > a, A591V, Ivs18 + 379a > c, P2712L, E4154, N4311S) in LDL cholesterol from -4.7 to +8.2% (-0.28 to 0.30 mmol/liter; P

  6. Z-Scan Analysis: a New Method to Determine the Oxidative State of Low-Density Lipoprotein and Its Association with Multiple Cardiometabolic Biomarkers

    Science.gov (United States)

    de Freitas, Maria Camila Pruper; Figueiredo Neto, Antonio Martins; Giampaoli, Viviane; da Conceição Quintaneiro Aubin, Elisete; de Araújo Lima Barbosa, Milena Maria; Damasceno, Nágila Raquel Teixeira

    2016-04-01

    The great atherogenic potential of oxidized low-density lipoprotein has been widely described in the literature. The objective of this study was to investigate whether the state of oxidized low-density lipoprotein in human plasma measured by the Z-scan technique has an association with different cardiometabolic biomarkers. Total cholesterol, high-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A-I and apolipoprotein B, paraoxonase-1, and glucose were analyzed using standard commercial kits, and low-density lipoprotein cholesterol was estimated using the Friedewald equation. A sandwich enzyme-linked immunosorbent assay was used to detect electronegative low-density lipoprotein. Low-density lipoprotein and high-density lipoprotein sizes were determined by Lipoprint® system. The Z-scan technique was used to measure the non-linear optical response of low-density lipoprotein solution. Principal component analysis and correlations were used respectively to resize the data from the sample and test association between the θ parameter, measured with the Z-scan technique, and the principal component. A total of 63 individuals, from both sexes, with mean age 52 years (±11), being overweight and having high levels of total cholesterol and low levels of high-density lipoprotein cholesterol, were enrolled in this study. A positive correlation between the θ parameter and more anti-atherogenic pattern for cardiometabolic biomarkers together with a negative correlation for an atherogenic pattern was found. Regarding the parameters related with an atherogenic low-density lipoprotein profile, the θ parameter was negatively correlated with a more atherogenic pattern. By using Z-scan measurements, we were able to find an association between oxidized low-density lipoprotein state and multiple cardiometabolic biomarkers in samples from individuals with different cardiovascular risk factors.

  7. Effect of a new herbo-mineral hypolipidemic agent on plasma lipoprotein pattern in rat atherosclerosis.

    Science.gov (United States)

    Tarvady, S; Dhar, S C

    1990-07-01

    Hyperlipidemia was induced in rats by feeding an atherogenic diet for 5 months. The effect of administration of an indigenous hypolipidemic agent, Anna Kaara Raaja Sindhooram (AKRS) on the plasma lipoprotein profile was studied in the presence and absence of dietary lipid stimuli. Hyperlipidemia produced an enormous increase in the cholesterol and triglyceride contents of the low density (LDL) and very low density (VLDL) lipoprotein fractions and reduced the level of the putative non-atherogenic high density cholesterol (HDL-C). The agarose gel electrophoretic pattern showed a decrease in alpha-lipoproteins and an increase in beta-lipoproteins in the hyperlipidemic rats. AKRS treatment for 5 months altered the lipoprotein pattern favourably by raising HDL-C and lowering LDL-C in the treated rats. PMID:2272653

  8. Linkage of the cholesterol 7α-hydroxylase gene and low-density lipoprotein cholesterol conditional on apolipoprotein E association: the National Heart, Lung, and Blood Institute Family Heart Study

    Institute of Scientific and Technical Information of China (English)

    Jing-Ping Lin; Richard H. Myers; Laura Almasy; Hilary H. Coon; Donna K. Arnett; Yuling Hong; Steven C. Hunt

    2005-01-01

    Background Genetic factors account for approximately 50% of the individual variation in plasma low-density lipoprotein cholesterol (LDL-C) concentrations in the general population. Several candidate genes have been proposed but their relative contributions to the variance in LDL-C are not known, except for apolipoprotein E (apoE). We report here an investigation of the relationship between LDL-C and cholesterol 7α-hydroxylase (CYP7), as well as apoE and low-density lipoprotein receptor (LDLR), three pivotal genes in LDL metabolism. Methods Our study population included more than 200 nuclear families with increased coronary heart disease (CHD) risk from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Variance-component linkage methods, a measured genotype approach, and a variance-component linkage analysis conditional on a measured genotype association were used. Results The results showed significant linkage between a genetic determinant of plasma LDL-C concentrations and a polymorphism near CYP7 with its allelic variation accounting for 27% of the total LDL-C variation. There is significant association between plasma LDL-C concentrations and apoE genotypes. Conditional on the apoE association, the total LDL-C variation accounted by allelic variation of a polymorphism near CYP7 was increased significantly.Conclusion Our results suggest the apoE and CYP7 may be two important genes accounting for the genetic variation of plasma LDL-C concentrations in a population with cardiovascular diseases.

  9. Diagnostic markers based on a computational model of lipoprotein metabolism

    NARCIS (Netherlands)

    Schalkwijk, D.B. van; Ommen, B. van; Freidig, A.P.; Greef, J. van der; Graaf, A.A. de

    2011-01-01

    Abstract Background: Dyslipidemia is an important risk factor for cardiovascular disease and type II diabetes. Lipoprotein diagnostics, such as LDL cholesterol and HDL cholesterol, help to diagnose these diseases. Lipoprotein profile measurements could improve lipoprotein diagnostics, but interpreta

  10. [Comparison of remnant lipoprotein-cholesterol measurements: the immune adsorption method (RLP-C) and the direct assay with detergent (RemL-C)].

    Science.gov (United States)

    Hihara, Mari; Sato, Itsuko; Hayashi, Fujio; Sugiyama, Daisuke; Kawano, Seiji; Fujioka, Yoshio; Ishikawa, Yuichi; Kumagai, Shunichi

    2009-01-01

    Elevation of serum remnant lipoprotein concentration is an emerging risk factor for coronary artery disease. An immunoseparation procedure for remnant-like particle cholesterol(RLP-C) has been evaluated extensively in recent years. In addition, a new detergent-based method has been developed and applied to automated analyzer as "MetaboLead RemL-C" (RemL-C, KYOWA MEDEX CO., LTD.). Then, we compared the concentrations of remnant lipoproteins as RemL-C with those as RLP-C in various conditions. RemL-C assay was intra-assay-reproducible (n=20, CVs: 0.6-2.2%), and reproducible for 2 days in the refrigeration and for 8 hours in room temperature. This assay was also inter-assay-reproducible (during 5 days in the deep freezing, CVs: 1.6-3.0%). The available range for RemL-C assay was between 0.09 and 121.1 mg/dl. There were no detectable interferences from hemoglobin, free/conjugated bilirubin, chyle, and Intrafat. However, heparin influenced the titer of RemL-C concentrations. Correlation of values between RLP-C and RemL-C in 123 samples was excellent (r=0.924, p<0.001). However, different responses to intermediate lipoprotein fraction derived from a patients with type III hyperlipidemia were observed. In conclusion, RemL-C and RLP-C measurements may have a similar clinical significance. Differences in sensitivity for intermediate lipoprotein fraction between both methods may exist.

  11. 重组高密度脂蛋白载基因纳米粒的制备及性质评价%Preparation of gene-loaded reconstituted high density lipoprotein nanoparticles and properties evaluation

    Institute of Scientific and Technical Information of China (English)

    张洁蕾; 李敏; 周建平; 陈键; 王伟

    2014-01-01

    目的:建立一种重组高密度脂蛋白(reconstituted high density lipoprotein,rHDL)载p53基因纳米粒的制备方法.方法:采用阳离子脂质材料包裹、压缩p53基因,形成复合物,考察其粒径、电位、体外稳定性;薄膜分散法制备rHDL载基因纳米粒,并研究rHDL载基因纳米粒的粒径、电位、形态、包封率和血清稳定性.结果:选用双十八烷基二甲基溴化铵(dimethyldioctadecylammonium bromide,DODAB)压缩p53基因形成DODAB/p53复合物;在最优N/P比时,该复合物粒径为(102.0±0.7) nm,电位为(10.50±0.75) mV,复合物仅在高浓度肝素条件下出现解聚,且其血清稳定性良好.rHDL能有效包载上述复合物形成rHDL载基因纳米粒,该纳米粒粒径为(104.3±5.8) nm,电位为(-10.70 ±3.24)mV,外观呈球形结构,p53基因包封率为78.09%,且血清稳定性良好.结论:成功制备了rHDL载p53基因纳米粒,且该纳米粒具有良好的理化性质及体外稳定性,为其后期体内外抗肿瘤作用的研究打下了实验基础.

  12. High-density lipoprotein of patients with breast cancer complicated with type 2 diabetes mellitus promotes cancer cells adhesion to vascular endothelium via ICAM-1 and VCAM-1 upregulation.

    Science.gov (United States)

    Huang, Xiaoqin; He, Dan; Ming, Jia; He, Yubin; Zhou, Champion; Ren, Hui; He, Xin; Wang, Chenguang; Jin, Jingru; Ji, Liang; Willard, Belinda; Pan, Bing; Zheng, Lemin

    2016-02-01

    Adhesion of disseminating tumor cells to vascular endothelium is a pivotal starting point in the metastasis cascade. We have shown previously that diabetic high-density lipoprotein (HDL) has the capability of promoting breast cancer metastasis, and this report summarizes our more recent work studying the role of abnormal HDL in facilitating the adhesion of the circulating tumor cells to the endothelium. This is an initiating step in breast cancer metastasis, and this work assesses the role of ICAM-1 and VCAM-1 in this process. MDA-MB-231, MCF 7, and human umbilical vein endothelial cells (HUVECs) were treated with normal HDL from healthy controls (N-HDL), HDL from breast cancer patients (B-HDL), or HDL from breast cancer patients complicated with type 2 diabetes mellitus (BD-HDL), and the cell adhesion abilities were determined. ICAM-1 and VCAM-1 expression as well as the protein kinase C (PKC) activity were evaluated. The effect of PKC inhibitor and PKC siRNA on adhesion was also studied. The immunohistochemical staining of ICAM-1, VCAM-1, and E-selectin from breast cancer patients and breast cancer patients complicated with type 2 diabetes mellitus (T2DM) were examined. Our results indicate that BD-HDL promoted an increase in breast cancer cell adhesion to HUVECs and stimulated higher ICAM-1 and VCAM-1 expression on the cells surface of both breast cancer and HUVEC cells, along with the activation of PKC. Increased tumor cell (TC)-HUVEC adhesion, as well as ICAM-1 and VCAM-1 expression induced by BD-HDL, could be inhibited by staurosporine and PKC siRNA. In addition, a Db/db type 2 diabetes mouse model has more TC-Vascular Endothelium adhesion compared to a normal model. However, BD patients have a lower expression of ICAM-1, VCAM-1, and E-selectin in their tumor tissues. BD-HDL facilitates the adhesion of tumor cells to vascular endothelium by upregulating the expression of ICAM-1 and VCAM-1, thereby promoting the initial progression of breast cancer metastasis

  13. Hepatic SR-BI, not endothelial lipase, expression determines biliary cholesterol secretion in mice

    NARCIS (Netherlands)

    Wiersma, Harmen; Gatti, Alberto; Nijstad, Niels; Kuipers, Folkert; Tietge, Uwe J. F.

    2009-01-01

    High density lipoprotein cholesterol is thought to represent a preferred source of sterols secreted into bile following hepatic uptake by scavenger receptor class B type I (SR-BI). The present study aimed to determine the metabolic effects of an endothelial lipase (EL)-mediated stimulation of HDL ch

  14. HDL cholesterol levels are an important factor for determining the lifespan of erythrocytes

    NARCIS (Netherlands)

    Meurs, I.; Hoekstra, M; van Wanrooij, EJA; Hildebrand, RB; Kuiper, J; Kuipers, F; Hardeman, MR; Van Berkel, TJC; Van Eck, M

    2005-01-01

    Objective. Scavenger receptor class B, type I (SR-BI) is a multifunctional receptor that promotes the selective uptake of cholesteryl esters from high-density lipoprotein (HDL). Disruption of SR-BI in mice results in a dramatic increase in HDL cholesterol. Interestingly, mice lacking SR-BI also deve

  15. Clinical relevance of non-fasting and postprandial hypertriglyceridemia and remnant cholesterol

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Freiberg, Jacob J

    2011-01-01

    -fasting/postprandial total cholesterol minus low-density lipoprotein (LDL) cholesterol minus high-density lipoprotein (HDL) cholesterol. Elevated levels of non-fasting/postprandial triglycerides directly correlate with elevated remnant cholesterol. In the general population, 38% of men have non......-fasting/postprandial triglycerides > 2mmol/L (>176 mg/dL) while 45% of men have non-fasting/postprandial triglyceride levels of 1-2 mmol/L (89-176 mg/dL); corresponding fractions in women are 20% and 47%. Also, 31% of men have remnant cholesterol levels > 1mmol/L (>39 mg/dL) while 46% of men have remnant cholesterol levels of 0...

  16. Laboratory approaches for predicting and managing the risk of cardiovascular disease: postanalytical opportunities of lipid and lipoprotein testing.

    Science.gov (United States)

    Langlois, Michel R

    2012-07-01

    Abstract Lipoprotein-related risk of cardiovascular disease (CVD) can be adequately predicted in subjects with elevated total cholesterol and low-density lipoprotein (LDL-)cholesterol using the available guidelines. However, individuals with dyslipidemia can have normal total- and LDL-cholesterol concentrations. Many statin-treated patients remain at high residual risk of CVD despite achieving LDL goals. The small dense LDL phenotype, frequently presenting with hypertriglyceridemia and low high-density lipoprotein (HDL-)cholesterol (lipid triad), may contribute to failure to identify and treat high-risk individuals. Therefore, calculated non-HDL-cholesterol is recommended as secondary therapeutic target to LDL-cholesterol in patients with hypertriglyceridemia and mixed dyslipidemia. On-treatment apolipoprotein B adds prognostic information to LDL- and non-HDL-cholesterol by indicating the total number of atherogenic lipoproteins, regardless of their cholesterol content. Risk may be higher than indicated in the risk estimation systems in additional subjects with elevated lipoprotein(a) and homocysteine concentrations. To improve the (post-)post-analytical phase of lipid tests, aiming for maximal health outcome effectiveness of test interpretation and utilization, laboratory professionals should deliver clinical added value services by providing readily interpreted and guideline-adjusted test reports, interpretative commenting, proactive reflex testing or recommending additional tests, and joining multidisciplinary cooperations in guideline development and cost/benefit studies. PMID:22850050

  17. Improving lipoprotein profiles by liver-directed gene transfer of low density lipoprotein receptor gene in hypercholesterolaemia mice

    Indian Academy of Sciences (India)

    HAILONG OU; QINGHAI ZHANG; JIA ZENG

    2016-06-01

    The defect of low density lipoprotein receptor disturbs cholesterol metabolism and causes familial hypercholesterolaemia(FH). In this study, we directly delivered exogenousLdlrgene into the liver of FH model mice (Ldlr − / −) by lentiviral genetransfer system. The results showed that theLdlrgene 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 lipopro-tein in serum was not significantly affected by theLdlrgene expression, the serum low density lipoprotein level was reducedby 46%, associated with a 30% and 28% decrease in triglyceride and total cholesterol, respectively, compared to uninjectedLdlr − / −mice. Moreover, the TBG directed expression ofLdlrsignificantly decreased the lipid accumulation in liver andreduced plaque burden in aorta (32%). Our results indicated that the hepatocyte-specific expression ofLdlrgene strikinglylowered serum lipid levels and resulted in amelioration of hypercholesterolaemia.

  18. How much does HDL cholesterol add to risk estimation? A report from the SCORE Investigators.

    LENUS (Irish Health Repository)

    Cooney, Marie Therese

    2009-06-01

    Systematic COronary Risk Evaluation (SCORE), the risk estimation system recommended by the European guidelines on cardiovascular disease prevention, estimates 10-year risk of cardiovascular disease mortality based on age, sex, country of origin, systolic blood pressure, smoking status and either total cholesterol (TC) or TC\\/high-density lipoprotein cholesterol (HDL-C) ratio. As, counterintuitively, these two systems perform very similarly, we have investigated whether incorporating HDL-C and TC as separate variables improves risk estimation.

  19. Cost Effectiveness of Treating Low HDL-Cholesterol in the Primary Prevention of Coronary Heart Disease

    OpenAIRE

    Joel W. Hay; Kimberly L. Sterling

    2005-01-01

    Background: A low serum level of high-density lipoprotein (HDL)-cholesterol is an independent risk factor for coronary heart disease (CHD). Fibrates, particularly gemfibrozil, have been shown to raise HDL-cholesterol levels and reduce the incidence of CHD. The literature on fibrate cost effectiveness is quite limited. Objective: The objective of this analysis is to determine the cost effectiveness of the fibrates gemfibrozil and fenofibrate in the primary prevention of CHD. The target populat...

  20. Antihyperlipidemic Effect of Syrian Mesquite (Prosopis farcta) Root in High Cholesterol Diet-Fed Rabbits.

    Science.gov (United States)

    Saidi, Mohammad Reza; Farzaei, Mohammad Hosein; Miraghaee, Shahram; Babaei, Atefeh; Mohammadi, Bahareh; Bahrami, Mohammad Taher; Bahrami, Gholamreza

    2016-10-01

    Prosopis farcta root has been proposed as an efficacious natural drug for cardiovascular disorders in traditional medicine. The present study evaluates the efficacy of aqueous extract of Prosopis farcta root on experimental atherosclerosis development in rabbits with high cholesterol diet-induced hypercholesterolemia. Serum lipid parameters were significantly increased in the high cholesterol diet groups in comparison with the normal control group (P Prosopis farcta root significantly reduced total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, and very low density lipoprotein levels compared to high cholesterol diet rabbits (P < .050). This finding may reflect a reduction of chest pain or the beneficial effects of this plant root extract on cardiovascular health. The present study can serve as a basis for future investigations on the other effects of this plant on cardiovascular health.

  1. Effects of extended-release niacin/laropiprant, simvastatin, and the combination on correlations between apolipoprotein B, LDL cholesterol, and non-HDL cholesterol in patients with dyslipidemia

    OpenAIRE

    Farnier M; Chen E; Johnson-Levonas AO; McCrary Sisk C; Mitchel YB

    2014-01-01

    Michel Farnier,1 Erluo Chen,2 Amy O Johnson-Levonas,2 Christine McCrary Sisk,2 Yale B Mitchel21Point Médical, Dijon, France; 2Merck and Co, Inc., Whitehouse Station, NJ, USABackground: Statins modify correlations between apolipoprotein B (apoB) and low-density lipoprotein cholesterol (LDL-C) and apoB and non-high-density lipoprotein cholesterol (non-HDL-C); however, it is not known whether niacin-based therapies have similar effects.Objective: To evaluate the effects of extended-re...

  2. [Serum phospholipids and processes of cholesterol esterification in the European North].

    Science.gov (United States)

    Boĭko, E R; Bichkaeva, F A; Tkachev, A V

    2002-01-01

    Lipid profile was studied in blood serum of 146 European northerns (trans-polar Nenets Autonomous district and Archangelsk). Monolayer chromatography was used to determine sphingomyelin (SP), phosphatidyl ethanolamine, phosphatidylcholine (PC), lisophosphatidylcholine, glycerophosphatides and phosphatide acides. The northerns were found to have very low concentrations of blood PC. At the same time, the NAD population have a little higher SP which may play an adaptive role in terms of the cell membrane function. The transpolar natives appear to possess an adaptive mechanism of increasing total cholesterol and reducing cholesterol of high-density lipoproteins, and activation of cholesterol esterification resulting in decrease in the free cholesterol fraction in serum.

  3. Cholesterol efflux monitoring in macrophage form cells by using fluorescence lifetime imaging

    Science.gov (United States)

    Song, Young Sik; Lee, Sang Hak; Park, Byoung Hee; Kim, Soo Hyeok; Hwang, Won Sang; Kim, Dug Young

    2015-03-01

    Macrophages play a key role in atherosclerotic plaque destabilization and rupture, since they accumulate large amounts of lipid through the uptake of modified lipoproteins which results in foam cell formation. Cholesterol efflux is the process of removing cholesterol from macrophages in the subintima of the vessel wall, and efflux mechanism in a cell is one of the critical issues for the prevention of cardiovascular diseases. High density lipoproteins (HDL) stimulate cholesterol efflux from macrophage foam cells in the arterial wall. Radioisotope-labeled cholesterol analysis method is well known conventional method for observing cholesterol efflux. The major drawback of this method is its long and complicated process. Fluorescence intensity imaging schemes are replacing the radioisotope-labeled method in recent years for cholesterol efflux monitoring. Various spectroscopic methods are also adapted for cholesterol efflux imaging. Here we present a fluorescence lifetime imaging method for more quantitative observation of cholesterol efflux process in macrophages, which enables us to observe cholesterol level changes with various conditions. We used J774 macrophage cell and 25-NBD-cholesterol which is a famous cholesterol specific dye. Our lifetime imaging results clearly show cholesterol efflux rate very effectively. We believe that fluorescence lifetime analysis is new and very powerful for cholesterol imaging or monitoring.

  4. REDUCTION DEGREE OF LOW-DENSITY LIPOPROTEINS CHOLESTEROL LEVELS ACCORDING TO DIFFERENT DOSES OF STATINS; ITS EFFECT ON THE RISK OF ISCHEMIC HEART DISEASE ACUTE EPISODES DEPENDING ON TREATMENT DURATION; AND RISK OF ISCHEMIC AND THROMBOEMBOLIC STROKE. COMMENT ON THE PAPER OF LAW M.R., WALD N.J., RUDNICKA A.R. QUANTIFYING EFFECT OF STATINS ON LOW DENSITY LIPOPROTEIN CHOLESTEROL, ISCHAEMIC HEART DISEASE, AND STROKE: SYSTEMATIC REVIEW AND META-ANALYSIS. BMJ 2003; 326:1423-1427

    Directory of Open Access Journals (Sweden)

    N. V. Perova

    2016-01-01

    Full Text Available Comparative dose-dependent ability of different statins to lower serum low-density lipoproteins (LDL cholesterol was determined in three large meta-analysis. Besides, it was found that standardized decrease in LDL cholesterol levels on 1.0 or 1.8 mmol/l leads to rate reduction in ischemic heart disease acute episodes as well as stroke depending on treatment duration. Effect of LDL cholesterol reduction on stroke occurrence was more significant in studies, which included a major share of patients with vascular disease, because these patients have a higher risk of thromboembolic stroke (rather than haemorrhagic stroke in comparison with the general population.

  5. Diet and the role of lipoproteins, lipases, and thyroid hormones in coronary lesion growth

    Science.gov (United States)

    Barth, Jacques D.; Jansen, Hans; Reiber, Johan H. C.; Birkenhager, Jan C.; Kromhout, Daan

    1987-01-01

    The relationships between the coronary lesion growth and the blood contents of lipoprotein fractions, thyroic hormones, and the lipoprotein lipase activity were investigated in male patients with severe coronary atherosclerosis, who participated in a lipid-lowering dietary intervention program. A quantitative computer-assisted image-processing technique was used to assess the severity of coronary obstructions at the beginning of the program and at its termination two years later. Based on absolute coronary scores, patients were divided into a no-lesion growth group (14 patients) and a progression group (21 paients). At the end of the trial, the very-low-density lipoprotein cholesterol and triglycerides were found to be significantly higher, while the high-density lipoprotein cholesterol and hepatic lipase (HL) were lower in the progression group. Multivariate regression analysis showed HL to be the most important determinant of changes in coronary atherosclerotic lesions.

  6. Polymorphisms at cholesterol 7α-hydroxylase, apolipoproteins B and E and low density lipoprotein receptor genes in patients with gallbladder stone disease

    Institute of Scientific and Technical Information of China (English)

    Zhao-Yan Jiang; Yu Jiang; Sheng-Dao Zhang; Tian-Quan Han; Guang-Jun Suo; Dian-Xu Feng; Sheng Chen; Xing-Xing Cai; Zhi-Hong Jiang; Jun Shang; Yi Zhang

    2004-01-01

    AIM: To investigate the relationship between gallbladder stone disease (GSD) and single nucleotide polymorphisms of cholesterol 7α-hydroxylase (CYP7A) gene promoter,apolipoprotein (4PO) B gene exon 26, 4POEgene exon 4 or microsatellite polymorphism of low density lipoprotein receptor (LDLR) gene exon 18.METHODS: Genotypes of CYP7A, APOB, APOE and LDLR genes were determined in 105 patients with GSD diagnosed by B-mode ultrasonography and 274 control subjects.Serum lipids were analyzed with HITACHI 7060 automaiC biochemical analyzer.RESULTS: Body mass index (BMI) was significantly higher in patients with GSD (24.47±3.09) than in controls (23.50±2.16).Plasma total cholesterol was lower in patients with GSD (4.66±0.92 mmol/L) than in controls (4.91±0.96 mmol/L),P<0.01 after adjusted for age, sex and BMI. The significantly higher frequency of A allele of CYP7,4 gene polymorphism and X+ allele of APOBgene polymorphism was seen in GSD patients. Percentages of A allele in patients and controls were 62.86% and 54.38% (P <0.05) and those of X+ allele 8.57% and 4.01% (P<0.01). Subjects with A allele had significantly lower plasma total cholesterol and LDL cholesterol than subjects with CC homozygote. In a multiple variable logistic regression model, the BMI (OR=1.13, 95% CI: 1.05-1.22), A allele (OR=1.48, 95% CI: 1.05-2.09) and X+ allele (OR=2.28, 95% CI: 1.14-4.59) were positively associated with GSD (P <0.05). Plasma total cholesterol (OR=0.69, 95% CI: 0.64-0.74) was negatively related to SSD (P<0.05).CONCLUSION: With an association analysis, it was determined that A allele of CYP74 gene and X+ allele of 4POBgene might be considered as risk genes for GSD. These alleles are related with differences of serum lipids among subjects.Multiple-variable logistic regression model analysis showed that besides BMI, GSD was affected by polygenetic factors.But the mechanism for these two alleles responsible for GSD requires further investigations.

  7. New horizons for cholesterol ester transfer protein inhibitors.

    Science.gov (United States)

    Schwartz, Gregory G

    2012-02-01

    High-density lipoprotein (HDL) cholesterol levels bear an inverse relationship to cardiovascular risk. To date, however, no intervention specifically targeting HDL has been demonstrated to reduce cardiovascular risk. Cholesterol ester transfer protein (CETP) mediates transfer of cholesterol ester from HDL to apolipoprotein B-containing particles. Most, but not all observational cohort studies indicate that genetic polymorphisms of CETP associated with reduced activity and higher HDL cholesterol levels are also associated with reduced cardiovascular risk. Some, but not all studies indicate that CETP inhibition in rabbits retards atherosclerosis, whereas transgenic CETP expression in mice promotes atherosclerosis. Torcetrapib, the first CETP inhibitor to reach phase III clinical development, was abandoned due to excess mortality associated with increases in aldosterone and blood pressure. Two other CETP inhibitors have entered phase III clinical development. Anacetrapib is a potent inhibitor of CETP that produces very large increases in HDL cholesterol and large reductions in low-density lipoprotein (LDL) cholesterol, beyond those achieved with statins. Dalcetrapib is a less potent CETP inhibitor that produces smaller increases in HDL cholesterol with minimal effect on LDL cholesterol. Both agents appear to allow efflux of cholesterol from macrophages to HDL in vitro, and neither agent affects blood pressure or aldosterone in vivo. Two large cardiovascular outcomes trials, one with anacetrapib and one with dalcetrapib, should provide a conclusive test of the hypothesis that inhibition of CETP decreases cardiovascular risk. PMID:22083134

  8. Survey on the levels of high density lipoprotein and low density lipoprotein among the staff in a college%某高校教职工血高密度脂蛋白和低密度脂蛋白检查结果分析

    Institute of Scientific and Technical Information of China (English)

    夏明惠; 唐海沁; 童程程

    2014-01-01

    Objective To analyze the levels of high density lipoprotein ( HDL) and low density lipoprotein ( LDL) among the staff in a college .Methods Fasting serum samples were collected from 2 234 paticipants .The lev-els of HDL and LDL in different sex and ages were estimated .Results The average value and abnormal rate of LDL in males were 3.20mmol/L and 49.1%,respectively.The average value of LDL in males was higher than normal val-ue.The average value and abnormal rate of LDL in females were 3.03mmol/L and 42.3%,respectively.The value of LDL in females who less than 54 years old was lower than that in males of the same age ( t=5.33,10.56,all P<0.01).Conclusion The abnormal rate of LDL had significant increase and the level in males was higher than that in females.The health education is necessary to prevent and control the abnormal level of LDL .%目的:分析高校教职工血HDL、LDL数值及其异常情况,为有效地进行预防和治疗提供科学依据,提高教职工的健康水平。方法对2234名教职工进行空腹血清检验,对各个年龄段的男性、女性血HDL、LDL检查结果进行综合分析。结果男性血LDL平均值3.20 mmol/L,高于正常,异常比率49.1%,女性血LDL平均值3.03 mmol/L,异常比率为42.3%,<34岁及≥34~54岁年龄段女性的LDL值均低于同年龄段男性(t=5.33、10.56,均P<0.01)。结论高校教职工血LDL值异常比率升高明显,男性较女性的异常比率亦有一定程度的升高。对血脂异常必须引起重视,应加大宣传和防治工作。

  9. Hypolipidemic effects of aqueous extract of Acalypha capitata leaves in rats fed on high cholesterol diet

    Institute of Scientific and Technical Information of China (English)

    Nnodim Johnkennedy; Emejulu Adamma; Nwadike Constance Nnedimma

    2011-01-01

    Objective:To evaluate the hypolipidemic effects of aqueous extract of Acalypha capitata (A. capitata) leaves in rats fed on high cholesterol diet. Methods:Cholesterol diet was administered to Wistar rats at a dose of 40 mg per 0.2 mL 3 times daily for 14 days while the control received distilled water. These animals were treated with extract of A. capitata at doses of 100 and 200 mg/kg. Lipid profiles were observed and compared. Results:Administration of A. capitata caused significant decrease in cholesterol, triglyceride and low density lipoprotein-cholesterol when compared with the control (P<0.05) which was dose dependent. Also, it was observed that high density lipoprotein-cholesterol was significantly increased when compared with the control. Conclusions:This observation suggests that the leaf extract of A. capitata could probably serve as a potential natural product for treatment of hyperlipidaemia.

  10. Dissecting the proteome of lipoproteins: New biomarkers for cardiovascular diseases?

    Directory of Open Access Journals (Sweden)

    Anne von Zychlinski

    2015-06-01

    Full Text Available Proteomics has proven to be a powerful tool for the characterization of lipoproteins and has provided important insights into the biochemistry and pathophysiology of various lipoprotein classes. It has significantly contributed to the way we now see lipoproteins as complex particles not only involved in lipid transport and exchange, but also in processes such as immune response, inflammation and wound healing. Ongoing proteomics research is focussing on the identification of new candidate markers for cardiovascular disease, the leading cause of death worldwide. The ratio between good cholesterol (high density lipoprotein and bad cholesterol (low density lipoprotein is routinely used to estimate an individual’s risk for developing premature coronary heart disease. While statin therapy has proven effects in reducing cardiovascular events, other therapies such as resins, fibrates and niacin have failed to substantially reduce cardiovascular risk. Thus new targets and candidate biomarkers for risk assessment and for the development of alternative drugs and treatments of disease are needed. Here we review the recent findings in lipoprotein proteomics with the main emphasis on studies that differentially displayed various states of diseases and on new targeted, high throughput strategies with the capability to translate discovery findings into the clinical context of large cohort analyzes.

  11. Lycopene stabilizes lipoprotein levels during D-galactosamine/lipopolysaccharide induced hepatitis in experimental rats

    Institute of Scientific and Technical Information of China (English)

    Sheik Abdulazeez Sheriff; Thiruvengadam Devaki

    2012-01-01

    Objective: To investigate the effect of lycopene on lipoprotein metabolism during D-galactosamine/lipopolysaccharide (D-Gal/LPS) induced hepatitis in experimental rats. Methods: The efficacy of lycopene was validated during D-Gal/LPS induced hepatitis by analyzing the activity of lipid metabolizing enzymes such as lipoprotein lipase (LPL), lecithin-cholesterol acyl transferase (LCAT) and hepatic triglyceride lipase (HTGL). Lipo protein analyses were done by the estimation of very low density lipoprotein cholesterol (VLDL), low density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL). Results: The toxic insult of D-galactosamine/lipopolysaccharide (D-Gal/LPS) in experimental group of animals reduces the normal values of lipid metabolizing enzymes due to liver injury. The significant drop in the levels of HDL and concomitant increase in the values of VLDL and LDL were observed. The pretreatment of lycopene restore these altered values to near normal level in experimental group of animals. Conclusions: In the light of results, it can be concluded that administration lycopene stabilizes the lipoprotein levels by regulating the lipid metabolizing enzymes through its antioxidant defense and helps to maintain the normal lipid metabolism during toxic injury in liver.

  12. Raising HDL cholesterol in women

    Directory of Open Access Journals (Sweden)

    Danny J Eapen

    2009-11-01

    Full Text Available Danny J Eapen1, Girish L Kalra1, Luay Rifai1, Christina A Eapen2, Nadya Merchant1, Bobby V Khan11Emory University School of Medicine, Atlanta, GA, USA; 2University of South Florida School of Medicine, Tampa, FL, USAAbstract: High-density lipoprotein cholesterol (HDL-C concentration is essential in the determination of coronary heart disease (CHD risk in women. This is especially true in the postmenopausal state, where lipid profiles and CHD risk mimic that of age-matched men. Thus, interventions designed to reduce CHD risk by raising HDL-C levels may have particular significance during the transition to menopause. This review discusses HDL-C-raising therapies and the role of HDL in the primary prevention of CHD in women. Lifestyle-based interventions such as dietary change, aerobic exercise regimens, and smoking cessation are initial steps that are effective in raising HDL-C, and available data suggest women respond similarly to men with these interventions. When combined with pharmacotherapy, the effects of these lifestyle alterations are further amplified. Though studies demonstrating gender-specific differences in therapy are limited, niacin continues to be the most effective agent in raising HDL-C levels, especially when used in combination with fibrate or statin therapy. Emerging treatments such as HDL mimetic therapy show much promise in further raising HDL-C levels and improving cardiovascular outcomes.Keywords: high-density lipoprotein, HDL, women, cholesterol, heart disease

  13. Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810

    Directory of Open Access Journals (Sweden)

    Mafu Akier

    2002-01-01

    Full Text Available Abstract Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent.

  14. Ability of Lactobacillus plantarum JR64 isolated from noni juice in lowering Cholesterol in vivo

    Directory of Open Access Journals (Sweden)

    Lanjar Sumarno

    2011-07-01

    Full Text Available Recently public’s attention to the importance of healthy food increases rapidly. Probiotic based food exploiting lactic acid bacteria is among the healthy food. Lactobacillus plantarum JR64 isolate from Morinda citrifolia fruit was assessed for its probiotic in-vivo by using Wistar  Rat. The purpose of this research was to study the ability of probiotic Lactobacillus plantarum JR64 in lowering serum LDL (Low Density Lipoprotein of Wistar Rat. Twenty Rats were grouped into 4, each group consisted of 5 Rats. First Group was a negative control  given standard normal diet of 20 gr/day plus aquadest. Second Grup was a positive control given cholesterol normal diet 20 gr /day plus Propil Tio Urasil (PTU 60 mg/kg body weight/day. Third Group was supplemented with normal diet 20 gr /day plus Propil Tio Urasil (PTU 60 mg  kg body weight /day and  1012 CFU Lactobacillus plantarum JR64. Fourth Group was the same as third Group unless the probiotic using commercial probiotic Lactobacillus bulgariccus at 1012 CFU. Blood samples were withdrawn for measurement of total cholesterol, triglyceride, High Density Lipoprotein (HDL, and Low Density Lipoprotein (LDL cholesterol every week and measured by using spectrophotometer with 546 nanometers wavelength. The results show that probiotic Lactobacillus plantarum JR64 isolated from noni juice significantly (p < 0,01 reduce Low Density Lipoprotein (LDL and Triglyceride in vivo  and tend to reduce High Density Lipoprotein (HDL and total cholesterol.

  15. Relations Between Atherogenic Index of Plasma, Ratio of Small Dense Low Density Lipoprotein/Lecithin Cholesterol Acyl Transferase and Ratio of Small Dense Low Density Lipoprotein/Cholesteryl Ester Transfer Protein of Controlled and Uncontrolled Type 2 DM

    Directory of Open Access Journals (Sweden)

    Ellis Susanti

    2009-08-01

    Full Text Available BACKGROUND: Patients with Diabetes Melitus are proven to be prone to atherosclerosis and coronary heart disease, especially type 2 Diabetes Melitus (T2DM patient who have higher risk and mortality for cardiovascular risk factor. The Dyslipidemia condition is very common in T2DM as one of the risk factors. Diabetic dyslipidemia is marked by the increased triglyceride (TG, low HDL cholesterol (HDL-C, and increased small dense LDL and apolipoprotein B. Therefore the aim of this study is to assess the differential and correlation between Atherogenic Index of Plasma (AIP, ratio of small dense low density lipoprotein (sdLDL/lecithin cholesterol acyl transferase (LCAT and ratio of sdLDL/cholesteryl ester transfer protein (CETP of controlled and uncontrolled T2DM. METHODS: This study was observational with cross sectional design. In total of 72 patients with T2DM consist of 36 controlled and 36 uncontrolled, participated in this study. The serum TG, HDL-C, sdLDL, LCAT and CETP were examined in their relationship with to T2DM risk. RESULTS: The results of the study indicate that the AIP (p<0.001 increase controlled and uncontrolled T2DM and the ratio of sdLDL/CETP (p=0.004, odds ratio of AIP was 4 (95% CI: 1.501-10.658 and odds ratio of sdLDL/CETP ratio was 4 (95% CI: 1.501-10.658 in uncontrolled T2DM. CONCLUSIONS: This study showed that the AIP and ratio of small dense LDL/CETP had a significant correlation with the uncontrolled T2DM. The AIP and ratio of small dense LDL/CETP increase was found at the uncontrolled T2DM to be 4 times greater than the controlled T2DM. KEYWORDS: T2DM, atherosclerosis, atherogenic index of plasma, small dense LDL, LCAT, CETP, ratio of sdLDL/LCAT, ratio of sdLDL/CETP.

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

    Science.gov (United States)

    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

  17. Ursodeoxycholic Acid for the Treatment of Cholesterol Gallstones

    International Nuclear Information System (INIS)

    Cholesterol is the principal constituent of more than three quarters of gallstones. Pure cholesterol crystals are quite soft, and protein contributes importantly to the strength of cholesterol stones. The risk of gallstones does not correlate with total serum cholesterol levels, but it does correlate with decreased high-density lipoprotein cholesterol and increased triglyceride levels. At least 10 percent of adults have gallstones where female: male ratio of about 2:1 in the younger age groups with increasing prevalence with age. Nine patients with gallstones (6 females and 3 males) were included in the study. Patients were treated with ursodeoxycholic acids tablets in two oral doses, one after breakfast, and the other after dinner for 9 months. Ultrasound examination was repeated every 3 months. Re-examination by abdominal ultrasonography revealed that gallstone 1 cm or less in diameter disappeared within 6 months, and the largest stone 3.06 cm in diameter disappeared within 9 months.

  18. LCAT, HDL Cholesterol and Ischemic Cardiovascular Disease: A Mendelian Randomization Study of HDL Cholesterol in 54,500 Individuals

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Ali Qayyum, Abbas;

    2012-01-01

    Background:Epidemiologically, high-density lipoprotein (HDL) cholesterol levels associate inversely with risk of ischemic cardiovascular disease. Whether this is a causal relation is unclear.Methods:We studied 10,281 participants in the Copenhagen City Heart Study (CCHS) and 50,523 participants...... in the Copenhagen General Population Study (CGPS), of which 991 and 1,693 participants, respectively, had developed myocardial infarction (MI) by August 2010. Participants in the CCHS were genotyped for all six variants identified by resequencing lecithin-cholesterol acyltransferase in 380 individuals. One variant......, S208T (rs4986970, allele frequency 4%), associated with HDL cholesterol levels in both the CCHS and the CGPS was used to study causality of HDL cholesterol using instrumental variable analysis.Results:Epidemiologically, in the CCHS, a 13% (0.21 mmol/liter) decrease in plasma HDL cholesterol levels...

  19. Androgen and FSH synergistically stimulate lipoprotein degradation and utilization by ovary granulosa cells

    International Nuclear Information System (INIS)

    Androgen can directly modulate the induction of steroidogenic enzymes by FSH (follicle stimulating hormone) in ovary granulosa cells. In studies of its mechanism of action, the authors examined the androgen effect on granulosa cell interaction with lipoproteins, the physiologic source of cholesterol. After granulosa cells were cultured for 48 hours with and without androgen and/or FSH, the cells were incubated for 24 hours with 125I-lipoproteins [human high density lipoprotein (HDL), rat HDL, or human low density lipoprotein (LDL)]. The media were then analyzed for lipoprotein protein coat degradation products (mainly 125I-monoiodotyrosine) and progestin [mainly 20 alpha-dihydroprogesterone (20 alpha-DHP)]. In the absence of FSH and androgen, 2 X 10(5) granulosa cells degraded basal levels of all three lipoproteins, but produced no measurable 20 alpha-DHP. The addition of 10(-7) M androstenedione (A), testosterone (T), or 5 alpha-dihydrotestosterone (DHT) had no effect on lipoprotein protein degradation or 20 alpha-DHP production. FSH alone stimulated lipoprotein protein degradation by 50 to 300% while the addition of androgen synergistically augmented the FSH-stimulated 20 alpha-DHP production as well as protein coat degradation of all three lipoproteins. DHT and T were both effective, indicating that androgens themselves, and not estrogen products, were responsible for the effect on lipoprotein protein degradation and 20 alpha-DHP production

  20. Regulatory Effects of Fenofibrate and Atorvastatin on Lipoprotein A-I and Lipoprotein A-I:A-II Kinetics in the Metabolic Syndrome

    OpenAIRE

    Chan, Dick C.; Watts, Gerald F.; Ooi, Esther M.M.; Rye, Kerry-Anne; Ji, Juying; Johnson, Anthony G.; Barrett, P Hugh R

    2009-01-01

    OBJECTIVE Subjects with the metabolic syndrome have reduced HDL cholesterol concentration and altered metabolism of high-density lipoprotein (Lp)A-I and LpA-I:A-II particles. In the metabolic syndrome, fenofibrate and atorvastatin may have differential effects on HDL particle kinetics. RESEARCH DESIGN AND METHODS Eleven men with metabolic syndrome were studied in a randomized, double-blind, crossover trial of 5-week intervention periods with placebo, fenofibrate (200 mg/day), and atorvastatin...

  1. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation

    Science.gov (United States)

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-08-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.

  2. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation.

    Science.gov (United States)

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-01-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease. PMID:27488468

  3. Dairy products and plasma cholesterol levels

    Directory of Open Access Journals (Sweden)

    Lena Ohlsson

    2010-08-01

    Full Text Available Cholesterol synthesized in the body or ingested is an essential lipid component for human survival from our earliest life. Newborns ingest about 3–4 times the amount per body weight through mother's milk compared to the dietary intake of adults. A birth level of 1.7 mmol/L plasma total cholesterol will increase to 4–4.5 mmol/L during the nursing period and continue to increase from adulthood around 40% throughout life. Coronary artery disease and other metabolic disorders are strongly associated with low-density lipoprotein (LDL and high-density lipoprotein (HDL cholesterol as well as triacylglycerol concentration. Milk fat contains a broad range of fatty acids and some have a negative impact on the cholesterol rich lipoproteins. The saturated fatty acids (SFAs, such as palmitic acid (C16:0, myristic acid (C14:0, and lauric acid (C12:0, increase total plasma cholesterol, especially LDL, and constitute 11.3 g/L of bovine milk, which is 44.8% of total fatty acid in milk fat. Replacement of dairy SFA and trans-fatty acids with polyunsaturated fatty acids decreases plasma cholesterol, especially LDL cholesterol, and is associated with a reduced risk of cardiovascular disease. Available data shows different effects on lipoproteins for different dairy products and there is uncertainty as to the impact a reasonable intake amount of dairy items has on cardiovascular risk. The aim of this review is to elucidate the effect of milk components and dairy products on total cholesterol, LDL, HDL, and the LDL/HDL quotients. Based on eight recent randomized controlled trials of parallel or cross-over design and recent reviews it can be concluded that replacement of saturated fat mainly (but not exclusively derived from high-fat dairy products with low-fat dairy products lowers LDL/HDL cholesterol and total/HDL cholesterol ratios. Whey, dairy fractions enriched in polar lipids, and techniques such as fermentation, or fortification of cows feeding can be used

  4. The effects of ABCG5/G8 polymorphisms on plasma HDL cholesterol concentrations depend on smoking habit in the Boston Puerto Rican Health Study

    Science.gov (United States)

    Background-Low high-density lipoprotein cholesterol (HDL-C) is associated with an increased risk for atherosclerosis and concentrations are modulated by genetic and environmental factors such as smoking. Objective- To assess whether the association of common single nucleotide polymorphisms (SNPs...

  5. Effect of growth hormone replacement therapy on plasma lecithin : cholesterol acyltransferase and lipid transfer protein activities in growth hormone-deficient adults

    NARCIS (Netherlands)

    Beentjes, JAM; van Tol, A; Sluiter, WJ; Dullaart, RPF

    2000-01-01

    The effects of growth hormone (GH) replacement on plasma lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP), factors involved in high density lipoprotein (HDL) metabolism, We unknown. We carried out a 6 mouths study in 24

  6. Serum lipid & lipoprotein profiles of obese Chinese children.

    Science.gov (United States)

    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 obese children should be carefully screened and managed to prevent long term morbidity and mortality of coronary artery disease. PMID:10967982

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

    Science.gov (United States)

    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 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 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.

  8. Effect of angiotensin Ⅰ-Ⅶ and angiotensin Ⅱ on expression of high density lipoprotein receptor in THP-1 macrophages%血管紧张素(1-7)与血管紧张素Ⅱ对THP-1巨噬细胞高密度脂蛋白受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    柴婵娟; 杨志明; 李芳; 梁斌; 边云飞; 康玉明

    2012-01-01

    Objective To observe the effect of angiotensin I -Ⅶ and angiotensinll on expression of high density lipoprotein receptor l(SR-BI) in THP-1 macrophages. Methods THP-1 macropha-ges were divided into blank control group, angiotensin TJ group, angiotensin TJ + angiotensinI -\\H group, angiotensin TJ +angiotensin I -VI+A-779 group according to their effect on expression of SR-BI in THP-1 macrophages. Expression of SR-BI Mrna and protein in THP-1 macrophages was detected by RT-PCR and Western blot,respectively. Results The expression level of SR-BI Mrna and protein in THP-1 macrophages was significantly lower in 10 nmol/L-10' nmol/L angiotensin TJ group and 102 nmol angiotensin TJ + A-779 group than in blank control group and significantly higher in 10 nmol/L-104 nmol/L angiotensin I -Ⅶ group and angiotensinTJ +102 nmol/L-104 nmol/L angiotensin I -Ⅶ group than in angiotensin TJ group and blank control group(P<0. 05). Conclusion Angiotensin TJ down-regulates the expression of SR-BI in a dose-dependent manner and promotes the outflow of cholesterol, thus improving its inverted tranport.%目的 观察血管紧张素(1-7)[Ang(1-7)]及AngⅡ对THP-1巨噬细胞高密度脂蛋白受体I(SR-BI)表达的影响.方法 将THP-1巨噬细胞根据AngⅡ和Ang(1-7)对SR BI表达的影响分别分为:空白对照组及不同浓度AngⅡ组(10~104 nmol/L组);空白对照组及不同浓度Ang(1-7)组(10~104 nmol/L组);空白对照组、AngⅡ102nmol/L组、AngⅡ102 nmol/L+ Ang(1-7)组(102~104 nmol/L组)、AngⅡ+Ang(1-7)+A-779组.运用RT-PCR和Western blot法检测各组SR-BI mRNA及SR-BI蛋白表达的变化.结果 与空白对照组比较,AngⅡ10~104nmol/L组SR-BI mRNA及蛋白表达明显下调,呈浓度依赖性(P<0.05);而Ang(1-7)10~104 nmol/L组SR-BImRNA及蛋白表达明显上调,呈浓度依赖性(P<0.05);与空白对照组和AngⅡ组比较,AngⅡ102 nmol/L+Ang(1-7)组(102~104 nmol/L组)SR-BI表达明显上调,呈浓度依赖性(P<0.05).

  9. Genetic determinants of LDL, lipoprotein(a), triglyceride-rich lipoproteins and HDL: concordance and discordance with cardiovascular disease risk

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2011-01-01

    To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance of such gene...... genetic determinants with cardiovascular disease risk will either favor or disfavor that these lipoproteins are causally related to cardiovascular disease.......To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance of such...

  10. Effect of improving glycemic control in patients with type 2 diabetes mellitus on low-density lipoprotein size, electronegative low-density lipoprotein and lipoprotein-associated phospholipase A2 distribution.

    Science.gov (United States)

    Sánchez-Quesada, José L; Vinagre, Irene; de Juan-Franco, Elena; Sánchez-Hernández, Juan; Blanco-Vaca, Francisco; Ordóñez-Llanos, Jordi; Pérez, Antonio

    2012-07-01

    The aim of this study was to determine the effect of intensified hypoglycemic therapy in patients with type 2 diabetes mellitus on the distribution of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity between high-density lipoprotein and low-density lipoprotein (LDL) and its relation with the lipid profile and other qualitative properties of LDL. Forty-two patients with type 2 diabetes on the basis of poor glycemic control and normal or near normal LDL cholesterol were recruited. Lifestyle counseling and pharmacologic hypoglycemic therapy were intensified to improve glycemic control, but lipid-lowering therapy was unchanged. At 4 ± 2 months, glycosylated hemoglobin had decreased by a mean of 2.1%, but the only effect on the lipid profile were statistically significant decreases in nonesterified fatty acids and apolipoprotein B concentration. LDL size increased and the proportion of electronegative LDL decreased significantly. In parallel, total Lp-PLA2 activity decreased significantly, promoting a redistribution of Lp-PLA2 activity toward a higher proportion in high-density lipoprotein. Improvements in glycemic control led to more marked changes in Lp-PLA2 activity and distribution in patients with diabetes who had not received previous lipid-lowering therapy. In conclusion, optimizing glycemic control in patients with type 2 diabetes promotes atheroprotective changes, including larger LDL size, decreased electronegative LDL, and a higher proportion of Lp-PLA2 activity in high-density lipoprotein. PMID:22481012

  11. Control of Angiogenesis by AIBP-mediated Cholesterol Efflux

    Science.gov (United States)

    Fang, Longhou; Choi, Soo-Ho; Baek, Ji Sun; Liu, Chao; Almazan, Felicidad; Ulrich, Florian; Wiesner, Philipp; Taleb, Adam; Deer, Elena; Pattison, Jennifer; Torres-Vázquez, Jesús; Li, Andrew C.; Miller, Yury I.

    2013-01-01

    Cholesterol is a structural component of the cell, indispensable for normal cellular function, but its excess often leads to abnormal proliferation, migration, inflammatory responses and/or cell death. To prevent cholesterol overload, ATP-binding cassette (ABC) transporters mediate cholesterol efflux from the cells to apolipoprotein A-I (ApoA-I) and to the ApoA-I-containing high-density lipoprotein (HDL)1-3. Maintaining efficient cholesterol efflux is essential for normal cellular function4-6. However, the role of cholesterol efflux in angiogenesis and the identity of its local regulators are poorly understood. Here we show that ApoA-I binding protein (AIBP) accelerates cholesterol efflux from endothelial cells (EC) to HDL and thereby regulates angiogenesis. AIBP/HDL-mediated cholesterol depletion reduces lipid rafts, interferes with VEGFR2 dimerization and signaling, and inhibits VEGF-induced angiogenesis in vitro and mouse aortic neovascularization ex vivo. Remarkably, Aibp regulates the membrane lipid order in embryonic zebrafish vasculature and functions as a non-cell autonomous regulator of zebrafish angiogenesis. Aibp knockdown results in dysregulated sprouting/branching angiogenesis, while forced Aibp expression inhibits angiogenesis. Dysregulated angiogenesis is phenocopied in Abca1/Abcg1-deficient embryos, and cholesterol levels are increased in Aibp-deficient and Abca1/Abcg1-deficient embryos. Our findings demonstrate that secreted AIBP positively regulates cholesterol efflux from EC and that effective cholesterol efflux is critical for proper angiogenesis. PMID:23719382

  12. Lipoprotein predictors of cardiovascular events in statin-treated patients with coronary heart disease

    DEFF Research Database (Denmark)

    Holme, Ingar; Cater, Nilo B; Faergeman, Ole;

    2008-01-01

    the relationships between on-treatment levels of lipoprotein components to subsequent major coronary events (MCE). FINDINGS: Variables related to low-density lipoprotein cholesterol (LDL-C) carried more predictive information than those related to high-density lipoprotein cholesterol (HDL-C), but LDL-C was less...... predictive than both non-HDL-C and apoB. The ratio of apoB to apoA-1 was most strongly related to MCE. However, for estimating differences in relative risk reduction between the treatment groups, apoB and non-HDL-C were the strongest predictors. INTERPRETATION: The on-treatment level of apoB/apoA-1...

  13. Improvement of HDL- and LDL-cholesterol levels in diabetic subjects by feeding bread containing chitosan.

    Science.gov (United States)

    Ausar, S F; Morcillo, M; León, A E; Ribotta, P D; Masih, R; Vilaro Mainero, M; Amigone, J L; Rubin, G; Lescano, C; Castagna, L F; Beltramo, D M; Diaz, G; Bianco, I D

    2003-01-01

    In this work we evaluated the efficacy and safety of a bread formulation containing chitosan in dyslipidemic type 2 diabetic subjects. For this purpose a total of 18 patients were allowed to incorporate to their habitual diets 120 g/day of bread containing 2% (wt/wt) chitosan (chitosan group, n= 9) or standard bread (control group, n= 9). Before the study and after 12 weeks on the modified diet, the following parameters were evaluated: body weight, plasma cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, and hemoglobin A(1c) (HbA(1c)). Compared with the control group, the patients receiving chitosan-containing bread decreased their mean levels of LDL-cholesterol and significantly increased their mean levels of HDL-cholesterol at the end of the study. There were no significant differences in the body weight, serum triglyceride, and HbA(1c). These results suggest that chitosan incorporated into bread formulations could improve the lipoprotein balance similar to typical biliary salts trappers, increasing the HDL- and lowering the LDL-cholesterol, without changing the triglyceride levels. These results warrant further studies over a longer period of time to evaluate if a persistent improvement in levels of lipoproteins can be attained with this strategy.

  14. High density matter

    CERN Document Server

    Stone, J R

    2013-01-01

    The microscopic composition and properties of matter at super-saturation densities have been the subject of intense investigation for decades. The scarcity of experimental and observational data has lead to the necessary reliance on theoretical models. However, there remains great uncertainty in these models, which, of necessity, have to go beyond the over-simple assumption that high density matter consists only of nucleons and leptons. Heavy strange baryons, mesons and quark matter in different forms and phases have to be included to fulfil basic requirements of fundamental laws of physics. In this review the latest developments in construction of the Equation of State (EoS) of high-density matter at zero and finite temperature assuming different composition of the matter are surveyed. Critical comparison of model EoS with available observational data on neutron stars, including gravitational masses, radii and cooling patterns is presented. The effect of changing rotational frequency on the composition of ne...

  15. Metabolism of a Lipid Nanoemulsion Resembling Low-Density Lipoprotein in Patients with Grade III Obesity

    Science.gov (United States)

    Dantas, Simone Alves; Ficker, Elisabeth Salvatori; Vinagre, Carmen G. C.; Ianni, Barbara Maria; Maranhão, Raul Cavalcante; Mady, Charles

    2010-01-01

    INTRODUCTION: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood. OBJECTIVE: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate. METHODS: A low-density emulsion was labeled with [14C]-cholesterol ester and [3H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m2] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate. RESULTS: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 ± 0.044 in the obese group and 0.122 ± 0.026 in the controls (p = 0.040), and the fractional clearance rate of cholesterol ester (h−1) was 0.052 ± 0.021 in the obese subjects and 0.058 ± 0.015 (p = 0.971) in the controls. CONCLUSION: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower. PMID:20126342

  16. Metabolism of a lipid nanoemulsion resembling low-density lipoprotein in patients with grade III obesity

    Directory of Open Access Journals (Sweden)

    Simone Alves Dantas

    2010-01-01

    Full Text Available INTRODUCTION: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood. OBJECTIVE: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate. METHODS: A low-density emulsion was labeled with [14C]-cholesterol ester and [³H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m²] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate. RESULTS: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 ± 0.044 in the obese group and 0.122 ± 0.026 in the controls (p = 0.040, and the fractional clearance rate of cholesterol ester (h-1 was 0.052 ± 0.021 in the obese subjects and 0.058 ± 0.015 (p = 0.971 in the controls. CONCLUSION: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower.

  17. High Density Matter

    Directory of Open Access Journals (Sweden)

    Stone J.R.

    2013-12-01

    Full Text Available The microscopic composition and properties of matter at super-saturation densities have been the subject of intense investigation for decades. The scarcity of experimental and observational data has led to the necessary reliance on theoretical models. There remains great uncertainty in these models which, of necessity, have to go beyond the over-simple assumption that high density matter consists only of nucleons and leptons. Heavy strange baryons, mesons and quark matter in different forms and phases have to be included to fulfil basic requirements of fundamental laws of physics. In this contribution latest developments in construction of the Equation of State (EoS of high-density matter at zero and finite temperature assuming different composition of matter will be discussed. Critical comparison of model EoS with available experimental data from heavy ion collisions and observations on neutron stars, including gravitational mass, radii and cooling patterns and data on X-ray burst sources and low mass X-ray binaries are made. Fundamental differences between the EoS of low-density, high temperature matter, such as is created in heavy ion collisions and of high-density, low temperature compact objects is discussed.

  18. Relationship between two common lipoprotein lipase variants and the metabolic syndrome and its individual components

    DEFF Research Database (Denmark)

    Vishram, Julie K K; Hansen, Tine W; Torp-Pedersen, Christian;

    2016-01-01

    BACKGROUND: Common lipoprotein lipase (LPL) variants are important determinants of triglycerides (TG) and high-density lipoprotein (HDL) cholesterol (C) concentrations. High TG/low HDL-C tend to cluster with hypertension, glucose intolerance, and abdominal obesity and comprise the metabolic...... syndrome (MetS). The role of LPL variants as a cause of MetS is unclear. This study investigated the relationship between two common LPL variants and the presence of MetS and its individual components. METHODS: Cross-sectional study, including 2348 Danish women (50.7%) and men, age 41-72 years, without...

  19. Use of health information technology (HIT) to improve statin adherence and low-density lipoprotein cholesterol goal attainment in high-risk patients: proceedings from a workshop.

    Science.gov (United States)

    Cohen, Jerome D; Aspry, Karen E; Brown, Alan S; Foody, Joanne M; Furman, Roy; Jacobson, Terry A; Karalis, Dean G; Kris-Etherton, Penny M; Laforge, Ralph; O'Toole, Michael F; Scott, Ronald D; Underberg, James A; Valuck, Thomas B; Willard, Kaye-Eileen; Ziajka, Paul E; Ito, Matthew K

    2013-01-01

    The workshop discussions focused on how low-density lipoprotein cholesterol (LDL-C) goal attainment can be enhanced with the use of health information technology (HIT) in different clinical settings. A gap is acknowledged in LDL-C goal attainment, but because of the passage of the American Recovery & Reinvestment Act and the Health Information Technology for Economic and Clinical Health Acts there is now reason for optimism that this gap can be narrowed. For HIT to be effectively used to achieve treatment goals, it must be implemented in a setting in which the health care team is fully committed to achieving these goals. Implementation of HIT alone has not resulted in reducing the gap. It is critical to build an effective management strategy into the HIT platform without increasing the overall work/time burden on staff. By enhancing communication between the health care team and the patient, more timely adjustments to treatment plans can be made with greater opportunity for LDL-C goal attainment and improved efficiency in the long run. Patients would be encouraged to take a more active role. Support tools are available. The National Lipid Association has developed a toolkit designed to improve patient compliance and could be modified for use in an HIT system. The importance of a collaborative approach between nongovernmental organizations such as the National Lipid Association, National Quality Forum, HIT partners, and other members of the health care industry offers the best opportunity for long-term success and the real possibility that such efforts could be applied to other chronic conditions, for example, diabetes and hypertension. PMID:24314357

  20. Effect of black tea intake on blood cholesterol concentrations in individuals with mild hypercholesterolemia: a diet-controlled randomized trial.

    Science.gov (United States)

    Troup, Rasa; Hayes, Jennifer H; Raatz, Susan K; Thyagarajan, Bharat; Khaliq, Waseem; Jacobs, David R; Key, Nigel S; Morawski, Bozena M; Kaiser, Daniel; Bank, Alan J; Gross, Myron

    2015-02-01

    Habitual intake of black tea has been associated with relatively lower serum cholesterol concentrations in observational studies. However, clinical trial results evaluating the effects of black tea on serum cholesterol have been inconsistent. Several factors could explain these mixed results, in particular, uncontrolled confounding caused by lifestyle factors (eg, diet). This diet-controlled clinical trial estimates the effect of black tea flavonoid consumption on cholesterol concentrations in 57 borderline hypercholesterolemic individuals (total cholesterol concentrations between 190 and 260 mg/dL [4.9 and 6.7 mmol/L]). A double-blind, randomized crossover trial was conducted in Minneapolis, MN, from April 2002 through April 2004 in which key conditions were tightly controlled to minimize possible confounding. Participants consumed a controlled low-flavonoid diet plus 5 cups per day of black tea or tea-like placebo during two 4-week treatment periods. The flavonoid-free caffeinated placebo matched the tea in color and taste. Differences in cholesterol concentrations at the end of each treatment period were evaluated via linear mixed models. Differences among those treated with tea vs placebo were 3.43 mg/dL (0.09 mmol/L) (95% CI -7.08 to 13.94) for total cholesterol, -1.02 mg/dL (-0.03 mmol/L) (95% CI -11.34 to 9.30) for low-density lipoprotein cholesterol, 0.58 mg/dL (0.02 mmol/L) (95% CI -2.98 to 4.14) for high-density lipoprotein cholesterol, 15.22 mg/dL (0.17 mmol/L) (95% CI -40.91 to 71.35) for triglycerides, and -0.39 mg/dL (-0.01 mmol/L) (95% CI -11.16 to 10.38) for low-density lipoprotein plus high-density lipoprotein cholesterol fraction. The low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio decreased by -0.1 units (95% CI -0.41 to 0.21). No results were statistically or clinically significant. The intake of 5 cups of black tea per day did not alter the lipid profile of borderline hypercholesterolemic subjects

  1. Evaluation of serum lipoprotein (a in young patients with myocardial infarction

    Directory of Open Access Journals (Sweden)

    Chandrakant Pragjibhai Kamariya

    2014-01-01

    Full Text Available Context: Indians are prone as a community to coronary artery disease (CAD at a much younger age. CAD is affecting Indians 5-10 years earlier than other communities. Lipoprotein (a (Lp (a is now recognized as an independent risk factor for CAD. It is a genetic risk factor. Aim: We evaluate the Lp (a in young patients with myocardial infarction (MI. Settings and design: Study population consisted of 50 patients having MI and 50 control groups. Subjects and Methods: Fasting samples were collected from patients and were analyzed for Lp (a, lipid profile, and blood sugar on fully automated analyzer. Statistical analysis used: Statistical analysis is carried out by using Student's t-test. Results: The difference in total cholesterol (P = 0.8192, high density lipoprotein-cholesterol (HDL-C (P = 0.11, low density lipoprotein-cholesterol (LDL-C (P = 0.8143, triglyceride (P = 0.1177 levels, and total cholesterol/HDL-cholesterol ratio (P = 0.2129 were observed between the case and control groups in this study was not statistically significant. The difference in the Lp (a levels between the case and control groups was highly significant (P-value = 0.0001. Conclusions: This study demonstrated that in young patients with MI there was a male predominance. Lp (a level is an important and independent risk factor for CAD. Serum Lp (a level is not dependent on serum total cholesterol level.

  2. The usefulness of information on HDL-cholesterol: potential pitfalls of conventional assumptions

    OpenAIRE

    Furberg Curt D

    2001-01-01

    Abstract Treatment decisions related to disease prevention are often based on two conventional and related assumptions. First, an intervention-induced change in a surrogate marker (such as high-density lipoprotein [HDL]-cholesterol) in the desired direction translates into health benefits (such as reduction in coronary events). Second, it is unimportant which interventions are used to alter surrogate markers, since an intervention benefit is independent of the means by which it is achieved. T...

  3. Vitamin D Supplementation Causes a Decrease in Blood Cholesterol in Professional Rowers.

    Science.gov (United States)

    Jastrzebski, Zbigniew; Kortas, Jakub; Kaczor, Katarzyna; Antosiewicz, Jedrzej

    2016-01-01

    In the skin vitamin D3 is synthesized from cholesterol, which leaves the question whether a feedback mechanism controlling the level of blood cholesterol exists. Here we investigate the effects of vitamin D3 supplementation on serum lipids in professional rowers. The rowers were divided into two groups following the same training schedule for 4 wk: one received placebo (TP) while the second received 5,000 IU of vitamin D3 every day (TD3). Plasma total antioxidant status, total triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL)-cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol (LDL-C) and 25-hydroxyvitamin D (25-OH-D3) were determined in pre- and post-intervention. The ratios of TC/HDL-C and LDL-C/HDL-C were also calculated. Furthermore, maximal oxygen uptake was also measured at baseline. There were significant decreases over time in the TD3 group in TC 186±18 vs 163±21 (pcaused a significant rise in blood 25-OH-D3 (+98%). Neither training nor vitamin D3 supplementation had an effect on total antioxidant status. In conclusion, the alterations in the lipoprotein profile seen in this study would suggest that effects of regular exercise on lipoprotein profile may linked to vitamin D3 status. PMID:27264092

  4. Effect of Dietary Fatty Acids on Human Lipoprotein Metabolism: A Comprehensive Update

    Directory of Open Access Journals (Sweden)

    Esther M.M. Ooi

    2015-06-01

    Full Text Available 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.

  5. Trends in low-density lipoprotein cholesterol goal achievement in high risk United States adults: longitudinal findings from the 1999-2008 National Health and Nutrition Examination Surveys.

    Directory of Open Access Journals (Sweden)

    Matthew C Tattersall

    Full Text Available BACKGROUND: Previous studies have demonstrated gaps in achievement of low-density lipoprotein-cholesterol (LDL-C goals among U.S. individuals at high cardiovascular disease risk; however, recent studies in selected populations indicate improvements. OBJECTIVE: We sought to define the longitudinal trends in achieving LDL-C goals among high-risk United States adults from 1999-2008. METHODS: We analyzed five sequential population-based cross-sectional National Health and Nutrition Examination Surveys 1999-2008, which included 18,656 participants aged 20-79 years. We calculated rates of LDL-C goal achievement and treatment in the high-risk population. RESULTS: The prevalence of high-risk individuals increased from 13% to 15.5% (p = 0.046. Achievement of LDL-C <100 mg/dL increased from 24% to 50.4% (p<0.0001 in the high-risk population with similar findings in subgroups with (27% to 64.8% p<0.0001 and without (21.8% to 43.7%, p<0.0001 coronary heart disease (CHD. Achievement of LDL-C <70 mg/dL improved from 2.4% to 17% (p<0.0001 in high-risk individuals and subgroups with (3.4% to 21.4%, p<0.0001 and without (1.7% to 14.9%, p<0.0001 CHD. The proportion with LDL-C ≥130 mg/dL and not on lipid medications decreased from 29.4% to 18% (p = 0.0002, with similar findings among CHD (25% to 11.9% p = 0.0013 and non-CHD (35.8% to 20.8% p<0.0001 subgroups. CONCLUSION: The proportions of the U.S. high-risk population achieving LDL-C <100 mg/dL and <70 mg/dL increased over the last decade. With 65% of the CHD subpopulation achieving an LDL-C <100 mg/dL in the most recent survey, U.S. LDL-C goal achievement exceeds previous reports and approximates rates achieved in highly selected patient cohorts.

  6. Cholesterol efflux capacity: An introduction for clinicians.

    Science.gov (United States)

    Anastasius, Malcolm; Kockx, Maaike; Jessup, Wendy; Sullivan, David; Rye, Kerry-Anne; Kritharides, Leonard

    2016-10-01

    Epidemiologic studies have shown an inverse correlation between high-density lipoprotein (HDL) cholesterol (HDL-C) levels and cardiovascular disease outcomes. However, the hypothesis of a causal relationship between HDL-C and cardiovascular disease has been challenged by genetic and clinical studies. Serum cholesterol efflux capacity (CEC) is an important measure of HDL function in humans. Recent large clinical studies have shown a correlation between in vitro CEC and cardiovascular disease prevalence and incidence, which appears to be independent of HDL-C concentration. The present review summarizes recent large clinical studies and introduces important methodological considerations. Further studies are required to standardize and establish the reproducibility of this measure of HDL function and clarify whether modulating CEC will emerge as a useful therapeutic target. PMID:27659883

  7. New targets and developments in lipoproteins control

    Directory of Open Access Journals (Sweden)

    Norata GD

    2013-05-01

    Full Text Available Giuseppe Danilo Norata1–31Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy; 2Center for the Study of Atherosclerosis, Società Italiana Studio Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy; 3The Blizard Institute, Centre for Diabetes, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, UKAbstract: Statins provide a very effective approach in reducing plasma cholesterol levels and cardiovascular risk. However, the proportion of patients who fail to achieve desirable plasma lipid levels ranges from 16%–53%, worldwide. This percentage reaches up to 80% in patients with familial hypercholesterolemia. Additionally, many patients are unable to tolerate statins, particularly at the highest approved dose level. New treatments that aggressively reduce lipid levels in patients with severe hypercholesterolemia, or those unable to reach their lipid targets, are therefore required. The most promising approaches in this context, such as inhibitors of the synthesis of apolipoprotein B (apoB containing lipoproteins (apoB silencing or microsomal triglyceride transfer protein [MTP] inhibition or proprotein convertase subtilisin/kexin type 9 (PCSK9 blockers, all decrease low-density lipoprotein (LDL extensively. Increasing low levels of high-density lipoprotein (HDL cholesterol via cholesteryl ester transfer protein inhibitors or apolipoprotein A-1 (ApoA-1 inducers and improving their quality with HDL or ApoA-1 mimetics represent also important options. Drugs affecting HDL, however, may not be all alike and require adequate scrutiny of the mechanisms involved. Until we have a better understanding of these issues, further LDL lowering in high-risk patients represents the soundest approach.Keywords: apolipoproteins, lipids, lipoprotein classes, hypercholesterolemia, synthesis, LDL lowering

  8. Scavenger receptor BI: A multi-purpose player in cholesterol and steroid metabolism

    Institute of Scientific and Technical Information of China (English)

    Menno; Hoekstra; Theo; JC; Van; Berkel; Miranda; Van; Eck

    2010-01-01

    Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepato...

  9. Cytomegalovirus Restructures Lipid Rafts via a US28/CDC42-Mediated Pathway, Enhancing Cholesterol Efflux from Host Cells.

    Science.gov (United States)

    Low, Hann; Mukhamedova, Nigora; Cui, Huanhuan L; McSharry, Brian P; Avdic, Selmir; Hoang, Anh; Ditiatkovski, Michael; Liu, Yingying; Fu, Ying; Meikle, Peter J; Blomberg, Martin; Polyzos, Konstantinos A; Miller, William E; Religa, Piotr; Bukrinsky, Michael; Soderberg-Naucler, Cecilia; Slobedman, Barry; Sviridov, Dmitri

    2016-06-28

    Cytomegalovirus (HCMV) contains cholesterol, but how HCMV interacts with host cholesterol metabolism is unknown. We found that, in human fibroblasts, HCMV infection increased the efflux of cellular cholesterol, despite reducing the abundance of ABCA1. Mechanistically, viral protein US28 was acting through CDC42, rearranging actin microfilaments, causing association of actin with lipid rafts, and leading to a dramatic change in the abundance and/or structure of lipid rafts. These changes displaced ABCA1 from the cell surface but created new binding sites for apolipoprotein A-I, resulting in enhanced cholesterol efflux. The changes also reduced the inflammatory response in macrophages. HCMV infection modified the host lipidome profile and expression of several genes and microRNAs involved in cholesterol metabolism. In mice, murine CMV infection elevated plasma triglycerides but did not affect the level and functionality of high-density lipoprotein. Thus, HCMV, through its protein US28, reorganizes lipid rafts and disturbs cell cholesterol metabolism.

  10. Turkish Heart Study: lipids, lipoproteins, and apolipoproteins.

    Science.gov (United States)

    Mahley, R W; Palaoğlu, K E; Atak, Z; Dawson-Pepin, J; Langlois, A M; Cheung, V; Onat, H; Fulks, P; Mahley, L L; Vakar, F

    1995-04-01

    We examined the plasma lipids, lipoproteins, and selected apolipoproteins in approximately 9,000 men and women from six different regions of Turkey with markedly different diets, ranging from an Aegean coast diet high in olive oil (plasma cholesteryl ester fatty acids enriched in monounsaturated fatty acids) to an inland Anatolian diet high in meat and dairy products (plasma cholesteryl esters enriched in saturated fatty acids). The rural population consuming an olive oil-rich diet had the lowest plasma cholesterol levels (men, 149 mg/dl; women, 150 mg/dl). The urban populations of Istanbul and Adana had higher plasma cholesterol levels (men, 202 and 184 mg/dl, respectively; women, 181 and 190 mg/dl, respectively). Affluent men had the highest cholesterol levels (207 mg/dl). The low density lipoprotein (LDL) cholesterol levels tended to parallel the total cholesterol levels (highest for Istanbul men at 136 mg/dl and lowest for Aegean coast men and women at approximately 100 mg/dl). Strikingly, the Turkish people were found to have very low levels of high density lipoprotein (HDL) cholesterol (HDL-C) (mean values for all six regions: men, 34-38 mg/dl; women, 37-45 mg/dl) and total cholesterol/HDL-C ratios that were high (mean values for all six regions: men, 4.5-5.5; women, 3.9-5.0). The low HDL-C levels appear to be caused, at least in part, by a genetic factor. Triglyceride levels also tended to be high in Turkish men (approximately 120-150 mg/dl) and women (approximately 90-110 mg/dl). Thus, even though the total plasma cholesterol levels are not excessively elevated in comparison to those in other populations, the presence of low HDL-C or low HDL-C coupled with mildly elevated triglyceride levels may represent a significant risk factor for heart disease in the Turkish population. Affluence and higher education were associated with higher cholesterol levels. Lack of physical activity, smoking, and alcohol consumption also tended to be associated with a

  11. Heart Disease Risk Factors | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... major kinds of lipoproteins are low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol. LDL cholesterol is sometimes called "bad" cholesterol. This is because ...

  12. Influence of liver cancer on lipid and lipoprotein metabolism

    Directory of Open Access Journals (Sweden)

    Nilsson-Ehle Peter

    2006-03-01

    Full Text Available Abstract Liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma (HCC is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. This has been attributed to the high incidence of hepatitis B infection. Hepatitis B proteins, such as the hepatitis B X protein (HBx that is large hepatitis B surface protein could regulate transcription of many candidate genes for liver carcinogenesis. It has known that patients who suffered from acute hepatitis B could have lipid disorders such as decreased plasma level of high-density lipoproteins (HDL. Furthermore, aberrations of lipid metabolism are often seen in the chronic hepatitis B infection. Plasma lipid profiles could be changed under HCC. In majority of the reports in HCC, plasma levels of triglycerides (TG, cholesterol, free fatty acids (FFA, HDL, low-density lipoproteins (LDL, lipoprotein (a (Lp(a, apolipoprotein AI (apoAI and apoB were slight to significantly decreased, however, in some cases plasma levels of TG and Lp(a might be increased. It has been suggested that analysis of plasma levels of lipids, lipoproteins and apolipoproteins in the patients suffered from HCC reflects on the hepatic cellular impairment status. Studies revealed that alterations seen in the plasma levels of lipids, lipoproteins and apolipoproteins reflecting patients' pathologic conditions. Decreased serum levels of cholesterol and apoAI may indicate a poor prognosis. Human leukaemic cells and certain tumor tissues have a higher receptor-mediated uptake of HDL and LDL than the corresponding normal cells or tissues. LDL and HDL have therefore been proposed as a carrier for the water-insoluble anti-cancer agents.

  13. Antihypertensive treatment, high triglycerides, and low high-density lipoprotein cholesterol and risk of ischemic heart disease mortality: a 16-year follow-up in the Copenhagen male study

    DEFF Research Database (Denmark)

    Suadicani, Poul; Hein, Hans Ole; Gyntelberg, Finn

    2010-01-01

    The aim of this study was to test the hypothesis that metabolic syndrome dyslipidemia is a major risk factor for ischemic heart disease (IHD) mortality among men taking antihypertensive medication....

  14. The -250G>A promoter variant in hepatic lipase associates with elevated fasting serum high-density lipoprotein cholesterol modulated by interaction with physical activity in a study of 16,156 Danish subjects

    DEFF Research Database (Denmark)

    Grarup, Niels; Andreasen, Camilla H; Andersen, Mette K;

    2008-01-01

    of variants in LIPC on metabolic traits and type 2 diabetes in a large sample of Danes. Because behavioral factors influence hepatic lipase activity, we furthermore examined possible gene-environment interactions in the population-based Inter99 study. DESIGN: The LIPC -250G>A (rs2070895) variant was genotyped...... Treatment in People with Screen Detected Diabetes in Primary Care study [0.038 mmol/liter per allele (95% CI 0.024-0.053); P = 2 x 10(-7)). The allelic effect on HDL-c was modulated by interaction with self-reported physical activity (P(interaction) = 0.002) because vigorous physically active homozygous A......-allele carriers had a 0.30 mmol/liter (95% CI 0.22-0.37) increase in HDL-c compared with homozygous G-allele carriers. CONCLUSIONS: We validate the association of LIPC promoter variation with fasting serum HDL-c and present data supporting an interaction with physical activity implying an increased effect on HDL...

  15. Antihypertensive treatment, high triglycerides, and low high-density lipoprotein cholesterol and risk of ischemic heart disease mortality: a 16-year follow-up in the Copenhagen male study

    DEFF Research Database (Denmark)

    Suadicani, Poul; Hein, Hans Ole; Gyntelberg, Finn

    2010-01-01

    The aim of this study was to test the hypothesis that metabolic syndrome dyslipidemia is a major risk factor for ischemic heart disease (IHD) mortality among men taking antihypertensive medication.......The aim of this study was to test the hypothesis that metabolic syndrome dyslipidemia is a major risk factor for ischemic heart disease (IHD) mortality among men taking antihypertensive medication....

  16. Effects of physical examination and diet consultation on serum cholesterol and health-behavior in the Korean pilots employed in commercial airline.

    Science.gov (United States)

    Choi, Yun Young; Kim, Ki Youn

    2013-01-01

    An objective of this study is to search how physical examination and diet consultation can influence those risk factors of cardiovascular disease. The subjects were 326 pilots of the "B" airline company in Korea whose total cholesterol values were over 220 mg/dl on their regular physical examinations from April 2006 to December 2008. They were divided into two groups, one who had diet consultation (an intervention group) and a control group. The physical examination components used to each group were body mass index (BMI), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride (TG). The behavioral, anthropometric and biomedical measurements were collected at each visit. This study compares and investigates the changes of serum cholesterol and also the health-behavior at each physical examination. Within the intervention group significant improvements were observed for total cholesterol, BMI (body mass index) and HDL (high density lipoprotein). The normalizing rates for cholesterol level to decrease down to lower than 200 mg/dl were 17.7% in intervention group and 8.7% in control group, which is statistically significantly higher among the intervention group. The odds ratio of diet consultation was 2.80 (95% CI=1.35-5.79), which indicates that it is a significantly contributing factor to normalize the serum cholesterol value down to lower than 200 mg/dl. Based on result, it is recommended to have regular physical examination and intensive management with diet and exercise consultation.

  17. Long-term safety and efficacy of a cholesterol-lowering diet in children with elevated low-density lipoprotein cholesterol : Seven-year results of the Dietary Intervention Study in Children (DISC)

    NARCIS (Netherlands)

    Obarzanek, E; Kimm, SYS; Barton, BA; Van Horn, L; Kwiterovich, PO; Simons-Morton, DG; Hunsberger, SA; Lasser, NL; Robson, AM; Franklin, FA; Lauer, RM; Stevens, VJ; Friedman, LA; Dorgan, JF; Greenlick, MR

    2001-01-01

    Objective. Diets reduced in fat and cholesterol are recommended for children over 2 years of age, yet long-term safety and efficacy are unknown. This study tests the long-term efficacy and safety of a cholesterol-lowering dietary intervention in children. Methods. Six hundred sixty-three children 8

  18. To investigate the impact of triglyceride freed glycerol for low density lipoprotein cholesterol concentration calculated by Friedewald formula%去游离甘油三酰甘油对Friedewald公式计算低密度脂蛋白胆固醇的影响

    Institute of Scientific and Technical Information of China (English)

    刘运双; 曾平; 陈曦

    2012-01-01

    目的 评估去游离甘油三酰甘油对Friedewald公式计算低密度脂蛋白胆固醇的影响.方法 样本来源于本院就诊患者,共5302例.测定其血清总胆固醇、高密度脂蛋白胆固醇及低密度脂蛋白胆固醇浓度(LDL-C),用去除游离甘油的方法测定血清三酰甘油浓度(TG),纳入TG≤4.51 mmol/L的样本5016例,用Friedewald公式(F公式)计算其低密度脂蛋白胆固醇浓度[(LDL-C(F)],与直接法测定的LDL-C浓度[(LDL-C(M)]进行比较.依据美国国家胆固醇教育计划(NCEP)对TG和LDLC分组.结果 LDL-C(F)与LDL-C(M)在TG正常组(γ=0.880)、TG边缘升高组(γ=0.943)和TG升高组(γ=0.897)都显示了良好的相关性(P<0.01).TG正常组、TG边缘升高组和TG升高组的LDL-C(F)都明显高于LDL-C(M) (P <0.001).在NCEP危险度分类中LDL-C(F)与LDL-C(M)的一致性平均为77.4%.结论 用F公式计算LDL-C浓度时,去游离甘油TG会高估LDL-C浓度.%Objective To evaluate the impact of triglyceride freed glycerol for low density lipoprotein cholesterol concentration calculated by Friedewald formula. Methods Serum total cholesterol (TC) , triglyceride (TG) , high density lipoprolen cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) concentrations were measured in 5302 patients, TG were measured by glycerol-blanked assay. A total 5016 patients with TG concentrations ≤4. 51mmol/l were enrolled, the LDL-C concentrations were also calculated by Friedewald formula. Comparison of LDL-C concentrations calculated by the Friedewald formula (LDL-C(F)) and measured by direct homogeneous (LDL-C(M)) assay were performed. The concordances of the National Cholesterol Education Program (NCEP) risk category were estimated. Results Both in normal and moderate high and high TG group, LDL-C ( F) correlated with LDL-C (M): γ = 0. 880, 0. 943,and 0. 897 respectively. The mean concentrations of LDL-C (F) were significantly higher than those of LDL-C (M) in normal and moderate high and

  19. Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells.

    Science.gov (United States)

    Hao, Shuangying; Ji, Jiajie; Zhao, Hongting; Shang, Longcheng; Wu, Jing; Li, Huihui; Qiao, Tong; Li, Kuanyu

    2015-12-01

    Foam cell formation as a result of imbalance of modified cholesterol influx and efflux by macrophages is a key to the occurrence and development of atherosclerosis. Oxidative stress is thought to be involved in the pathogenesis of atherosclerosis. SS-31 is a member of the Szeto-Schiller (SS) peptides shown to specifically target the inner mitochondrial membrane to scavenge reactive oxygen species. In this study, we investigated whether SS-31 may provide protective effect on macrophage from foam cell formation in RAW264.7 cells. The results showed that SS-31 inhibited oxidized low-density lipoproteins (ox-LDL)-induced foam cell formation and cholesterol accumulation, demonstrated by intracellular oil red O staining and measurement of cholesterol content. The mechanism was revealed that SS-31 did not only significantly attenuated ox-LDL-induced generation of reactive oxygen species (ROS) and increased the activities of superoxide dismutases, but also dose-dependently inhibited the expression of CD36 and LOX-1, two scavenger receptors of ox-LDL, while the expression of ATP-binding cassette A1 and G1, playing a pivotal role in cholesterol efflux, was not affected. As a result, SS-31 decreased pro-inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, suggesting the prevention of inflammatory responses. In conclusion, our results demonstrate that SS-31 provides a beneficial effect on macrophages from foam cell formation, likely, through both ROS scavenging and inhibition of cholesterol influx. Therefore, SS-31 may potentially be of therapeutic relevance in prevention of human atherogenesis.

  20. Stimulation of cholesteryl ester synthesis in mouse peritoneal macrophages by cholesterol-rich very low density lipoproteins from the Watanabe heritable hyperlipidemic rabbit, an animal model of familial hypercholesterolemia

    International Nuclear Information System (INIS)

    Cholesterol-rich very low density lipoproteins (VLDL) from the homozygous Watanabe heritable hyperlipidemic (WHHL) rabbit induced marked cholesteryl ester accumulation in mouse peritoneal macrophages. This WHHL rabbit, an animal model of human familial hypercholesterolemia, has severe hypercholesterolemia, cutaneous xanthomas, and fulminant atherosclerosis due to the deficiency of the low density lipoprotein (LDL) receptor. When incubated with mouse peritoneal macrophages, the VLDL from WHHL rabbit (WHHL-VLDL) stimulated cholesteryl [14C]oleate synthesis 124-fold more than did VLDL from the normal Japanese White rabbit (control-VLDL). The enhancement in cholesteryl ester synthesis and accumulation of WHHL-VLDL was due to the presence of a high affinity binding receptor site on the macrophage cell surface that mediated the uptake and lysosomal degradation of WHHL-VLDL. Competition studies showed that the uptake and degradation of 125I-WHHL-VLDL was inhibited by unlabeled excess WHHL-VLDL and beta-migrating VLDL (beta-VLDL), but not LDL. Furthermore, the degradation of WHHL-VLDL was not blocked by either fucoidin, polyinosinic acid, or polyguanylic acid, potent inhibitors of the acetylated (acetyl)-LDL binding site, or by acetyl-LDL. These results suggest that macrophages possess a high affinity receptor that recognizes the cholesterol-rich VLDL present in the plasma of the WHHL rabbit and that the receptor which mediates ingestion of WHHL-VLDL seems to be the same as that for beta-VLDL and leads to cholesteryl ester deposition within macrophages. Thus, the uptake of the cholesterol-rich VLDL from the WHHL rabbit by macrophages in vivo may play a significant role in the pathogenesis of atherosclerosis in the WHHL rabbit

  1. Chronic Moderate Alcohol Intakes Accelerate SR-B1 Mediated Reverse Cholesterol Transport.

    Science.gov (United States)

    Li, Menghua; Diao, Yan; Liu, Ying; Huang, Hui; Li, Yanze; Tan, Peizhu; Liang, Huan; He, Qi; Nie, Junhui; Dong, Xingli; Wang, Yang; Zhou, Lingyun; Gao, Xu

    2016-01-01

    Cholesterol is essential for all animal life. However, a high level of cholesterol in the body is strongly associated with the progression of various severe diseases. In our study, the potential involvement of alcohol in the regulation of high density lipoprotein (HDL) receptor scavenger receptor class B and type I (SR-B1)-mediated reverse cholesterol transport was investigated. We separated male C57BL/6 mice into four diets: control, alcohol, Control + HC and alcohol + HC. The SR-B1 level and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate- high- density lipoprotein (DiI-HDL) uptake were also measured in AML12 cells and HL7702 cells treated with alcohol. The control + HC diet led to increased hepatic triglyceride and cholesterol levels while alcohol + HC led no significant change. Compared with that of the control group, the SR-B1 mRNA level was elevated by 27.1% (P alcohol, control + HC and alcohol + HC groups, respectively. In AML12 and HL7702 cells, SR-B1 level and DiI-HDL uptake were repressed by SR-B1 siRNA or GW9662. However, these effects were reversed through alcohol treatment. These data suggest that a moderate amount of alcohol plays a novel role in reverse cholesterol transport, mainly mediated by PPARγ and SR-B1. PMID:27618957

  2. Resveratrol Protects Rabbits Against Cholesterol Diet-Induced Hyperlipidaemia.

    Science.gov (United States)

    Tanko, Y; Jimoh, A; Ahmed, A; Mohammed, A; Ayo, J O

    2016-01-01

    The excessive consumption of high cholesterol diet has been associated with an increased incidence oflipidaemia. Lipidaemia is enhanced by formation of oxidative stress, lipid peroxidation and hyperglycaemia. The aim ofthese experiments was to investigate the protective effect of resveratrol co-administered with cholesterol diet inducedhyperlipidaemia in rabbits. Thirty rabbits divided into six groups of five animal (group= 5) each: group 1 = normal control,group 2 = cholesterol diet/high fat diet group only (HFD), group 3 = resveratrol 200 mg/kg (R200), group 4 = resveratrol400 mg/kg (R400), group 5 = HFD + R200 and group 6 = HFD + R400. The normal group was fed with standard animalfeeds only; while the HFD groups were fed with standard animal feeds + cholesterol diet (10% Groundnut oil, 20%Groundnut mill and 2% cholesterol). Resveratrol-treated rabbits received resveratrol suspended in 10 g/Lcarboxymethylcellulose (CMC) and the control group received the vehicle only, CMC. The preparations were administeredfor 8 weeks of experimental protocol. At the end of the study period, the animals were sacrificed. Blood and plasma sampleswere collected. Serum evaluation of lipid profile such as total cholesterol (TC), triacylglycerol (Tg), low density lipoproteincholesterol (LDP-c) and high density lipoprotein cholesterol (HDL-c) were also assessed. The results obtained showsignificant (P resveratrol treated groups compared to HFD group only.In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrationsand might be beneficial in treatment of hyperlipidemia and atherosclerosis. PMID:27574767

  3. Genetic determinants of LDL, lipoprotein(a), triglyceride-rich lipoproteins and HDL: concordance and discordance with cardiovascular disease risk

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2011-01-01

    To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance...

  4. Low High-Density Lipoprotein and Risk of Myocardial Infarction

    Science.gov (United States)

    Ramirez, A.; Hu, P. P.

    2015-01-01

    Low HDL is an independent risk factor for myocardial infarction. This paper reviews our current understanding of HDL, HDL structure and function, HDL subclasses, the relationship of low HDL with myocardial infarction, HDL targeted therapy, and clinical trials and studies. Furthermore potential new agents, such as alirocumab (praluent) and evolocumab (repatha) are discussed. PMID:26692765

  5. High-density lipoprotein particles, coronary heart disease, and niacin

    Science.gov (United States)

    In clinical trials, the use of statins in patients with high risk for cardiovascular disease (CVD) has resulted in a 25% to 40% decrease in major clinical events. However, despite a marked reduction (up to 60%) in LDL-C, approximately 50% (or more) of patients continue to have CVD events. This high ...

  6. Acute effects of moderate exercise on serum lipids, lipoproteins and apolipoproteins in sedentary young women.

    Science.gov (United States)

    Imamura, H; Katagiri, S; Uchid, K; Miyamoto, N; Nakano, H; Shirota, T

    2000-12-01

    1. The aim of the present study was to examine the effects of moderate exercise on serum lipids, lipoproteins and apolipoproteins in seven sedentary young women under controlled conditions. 2. The subjects exercised on separate days for 30 or 60 min at an intensity of 60% of maximal oxygen uptake on a cycle ergometer. Total cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL-C), HDL2-C, HDL3-C, low-density lipoprotein-cholesterol, apolipoproteins A-I, A-II and B were measured in the serum at the end of the 60 min rest period before each exercise, immediately after the performance of each exercise and at 30 min and 1, 2 and 24 h after each exercise. 3. The results showed that there were no significant differences between the pre- and postexercise samples for any of the parameters tested. 4. The results of the present study suggest that a single bout of exercise designed to simulate a typical training workout has no noticeable effect on serum lipids, lipoproteins and apolipoproteins in normal sedentary young women who have normal lipid profiles, are in the follicular phase of their menstrual cycle and who consume a relatively low-fat diet. PMID:11117233

  7. An enzyme thermistor-based assay for total and free cholesterol.

    Science.gov (United States)

    Raghavan, V; Ramanathan, K; Sundaram, P V; Danielsson, B

    1999-11-01

    A method to evaluate the free (FC) and total cholesterol (TC) in human serum, bile and gallstone extract using an enzyme thermistor (ET)-based flow injection analysis (FIA) is presented. The cholesterol in high-density (HDL-C) and low density lipoprotein (LDL-C) have also been evaluated. A heparin functionalized Sepharose column was employed for the isolation of HDL and LDL fractions from serum. The estimation of cholesterol and its esters was based on their reaction with cholesterol oxidase (CO), cholesterol esterase (CE) and catalase (CAT). Three different enzyme columns, i.e. co-immobilized CO/CAT (column A), only CE (column B) and co-immobilized CO/CE/CAT (column C) were prepared by cross-linking the enzymes on glass beads using glutaraldehyde. Column A was used for estimating FC and column C was used for estimating total cholesterol (cholesterol plus esterified cholesterol). Column B was used as a pre-column which could be switched 'in' or 'out' in conjunction with column A for the estimation of TC or FC, respectively. A calibration between 1.0 and 8.0 mmol/l for FC and 0. 25 and 4.0 mmol/l for TC was obtained. For more than 2000 assays with the ET device a C.V. of less than 4% was obtained. The assay time was approximately 4 min per assay. The cholesterol estimations on the ET correlated well with similar estimations using a commercially available cholesterol diagnostic kit.

  8. Clinical relevance of non-fasting and postprandial hypertriglyceridemia and remnant cholesterol

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Freiberg, Jacob J

    2011-01-01

    -fasting/postprandial total cholesterol minus low-density lipoprotein (LDL) cholesterol minus high-density lipoprotein (HDL) cholesterol. Elevated levels of non-fasting/postprandial triglycerides directly correlate with elevated remnant cholesterol. In the general population, 38% of men have non......Non-fasting triglycerides are measured at any time within up to 8 h (14 h) after any normal meal, while postprandial triglycerides are measured at a fixed time point within up to 8 h (14 h) of a standardised fat tolerance test. The simplest possible way of evaluating remnant cholesterol is non......-fasting/postprandial triglycerides > 2mmol/L (>176 mg/dL) while 45% of men have non-fasting/postprandial triglyceride levels of 1-2 mmol/L (89-176 mg/dL); corresponding fractions in women are 20% and 47%. Also, 31% of men have remnant cholesterol levels > 1mmol/L (>39 mg/dL) while 46% of men have remnant cholesterol levels of 0...

  9. Comparative Study of Tomato and Tomato Paste Supplementation on the Level of Serum Lipids and Lipoproteins Levels in Rats Fed With High Cholesterol

    OpenAIRE

    Khayat Nouri, Mir Hadi; Namvaran Abbas Abad, Ali

    2013-01-01

    Background Hypercholesterolemia is one of the risk factors of cardiovascular diseases. Increased blood cholesterol affects general health and increases mortality due to cardiovascular disease. Poor nutrition increases LDL cholesterol and decreases LDL receptor activities in the liver. Scientists have shown that consumption of antioxidants can reduce hypercholesterolemia and proved benefits of fruit and vegetables. Tomato reduces oxidative stress by increasing serum total antioxidant level. Ob...

  10. Are post-treatment low-density lipoprotein subclass pattern analyses potentially misleading?

    Directory of Open Access Journals (Sweden)

    Hanson Mary E

    2010-11-01

    Full Text Available Abstract Background Some patients administered cholesterol-lowering therapies may experience an increase in the proportion of small LDL particles, which may be misinterpreted as a worsening of atherosclerotic coronary heart disease risk. This study assessed the lipid effects of adding ezetimibe to atorvastatin or doubling the atorvastatin dose on low-density lipoprotein cholesterol (LDL-C levels (and the cholesterol content of LDL subclasses, LDL particle number (approximated by apolipoprotein B, and LDL particle size. This was a multicenter, double-blind, randomized, parallel-group study of hypercholesterolemic, high atherosclerotic coronary heart disease risk patients. After stabilization of atorvastatin 40 mg, 579 patients with LDL-C >70 mg/dL were randomized to 6 weeks of ezetimibe + atorvastatin 40 mg or atorvastatin 80 mg. Efficacy parameters included changes from baseline in LDL-C, apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C, and lipoprotein subclasses (Vertical Auto Profile II and pattern for the overall population, as well as patient subgroups with baseline triglyceride levels Results Both treatments significantly reduced LDL-C (and the cholesterol content of most LDL subfractions [LDL1-4] apolipoprotein B, non-HDL-C levels, but did not reduce the proportion of smaller, more dense LDL particles; in fact, the proportion of Pattern B was numerically increased. Results were generally similar in patients with triglyceride levels Conclusions When assessing the effects of escalating cholesterol-lowering therapy, effects upon Pattern B alone to assess coronary heart disease risk may be misleading when interpreted without considerations of other lipid effects, such as reductions in LDL-C, atherogenic lipoprotein particle concentration, and non-HDL-C levels. Trial Registration (Registered at clinicaltrials.gov: Clinical trial # NCT00276484

  11. A comparison of various cholesterol lowering diets in young healthy volunteers; effects on serum lipoproteins and on other risk indicators for card. diseases

    NARCIS (Netherlands)

    Brussaard, J.H.

    1981-01-01

    This thesis deals with the effect of type and amount of dietary fat on the concentration and composition of serum lipoproteins, colonic function, plasma glucose and serum insulin levels and blood pressure in healthy human volunteers.Two experiments were carried out. In the first experiment with 60 v

  12. KIF6, LPA, TAS2R50, and VAMP8 genetic variation, low density lipoprotein cholesterol lowering response to pravastatin, and heart disease risk reduction in the elderly

    Science.gov (United States)

    Single nucleotide polymorphisms (SNPs) at the KIF6 (kinesin like protein 6, rs20455 or 719Arg), LPA (lipoprotein(a), rs3798220), TAS2R50 (taste receptor type 2, member 50, rs1376251) and VAMP8 (vesicle-associated membrane protein 8, rs1010) have previously been associated with low density lipoprotei...

  13. 桔梗皂苷对高胆固醇血大鼠低密度脂蛋白受体的调节%Regulation of PlatycodonGrandiflorumSaponin on Low Density Lipoprotein Receptor in High Blood Cholesterol Rats

    Institute of Scientific and Technical Information of China (English)

    杨桂英; 吴敬涛

    2015-01-01

    以高脂乳剂诱导高胆固醇血大鼠模型,研究肝脏胆固醇代谢相关的低密度脂蛋白受体( LDL-r)的活性.灌喂SD大鼠高脂乳剂饮食42d,建立高胆固醇血模型;随机将高胆固醇血大鼠分成4组:空白组、高脂组、低皂苷剂量组、高皂苷剂量组,分别按每千克体质量30、100 mg给以桔梗皂苷降胆固醇,连续21d;分别利用免疫组织化学方法和免疫印迹方法检测LDL-r的蛋白变化,利用PCR方法检测LDL-r基因表达水平.结果表明,低、高剂量桔梗皂苷均能显著降低( P<0.01)高脂乳剂诱导的高胆固醇血大鼠的LDL-r,提示桔梗皂苷降低血胆固醇的作用是通过LDL-r转运胆固醇的作用实现的.%The high cholesterol blood model of the rats induced by high fat emulsion was established to study the activity of platycodongrandiflorumsaponin on cholesterol metabolism -related low density lipoprotein receptor ( LDL-r) in liver.After SD rats were fed foods with high fat emulsion 42 d, high cholesterol blood model was set up .Random , high cholesterol blood rats were divided into 4 groups:Blank group , High fat and Low saponin dose group .Respectively , according to 30 or 100 mg of saponin per kilogram of body to drop cho-lesterol , continuous 21 d.Immunohistochemical method and Western blot method to detect changes of LDL -rprotein expression levels in liver , Polymerase chain reaction ( PCR) to detect of LDL-r gene expression lev-els were used.The results show that the low and high dose of saponin can significantly (P<0.01) reduce the LDL-r of high cholesterol blood rats induced by high fat emulsion , which prompt that the action of platyc-odongrandiflorumsaponin on highcholesterol b