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Sample records for lowering plasma cholesterol

  1. Wheat germ policosanol failed to lower plasma cholesterol in subjects with normal to mildly elevated cholesterol concentrations.

    PubMed

    Lin, Yuguang; Rudrum, Mike; van der Wielen, Reggy P J; Trautwein, Elke A; McNeill, Gerald; Sierksma, Aafje; Meijer, Gert W

    2004-10-01

    Sugar cane policosanol, a mixture of long-chain primary alcohols (approximately 67% as octacosanol), has been reported to lower plasma low-density lipoprotein (LDL)-cholesterol. We investigated the effect of wheat germ policosanol (WGP) on plasma lipid profiles in 58 adults (30 men and 28 women, aged 49 +/- 11 years) with normal to mildly elevated plasma cholesterol concentrations in a double-blind, randomized, parallel placebo-controlled study. Subjects consumed chocolate pellets with or without 20 mg/d WGP for 4 weeks. Plasma lipid concentrations, routine blood chemistry and hematology were determined at the start and the end of the study. The initial plasma total, LDL-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triacylglycerol concentrations in the WGP and the control groups were identical. Over the 4 weeks, neither the WGP nor the control treatment significantly changed plasma total cholesterol, LDL- and HDL-cholesterol, or triacylglycerol concentrations when compared to baseline values. In addition, there was no significant difference in plasma lipid profiles between the WGP and the control groups at the end of the study. WGP did not result in any adverse effects as indicated by plasma activities of L-gamma-glutamyltransferase (gamma-GT), ALT, AST, bilirubin concentrations, and blood cell profiles. Chemical analysis showed that WGP consists of 8% hexacosanol, 67% octacosanol, 12% triacosanol, and 13% other long-chain alcohols, which is similar to the composition of sugar cane policosanol. In conclusion, WGP at 20 mg/d had no beneficial effects on blood lipid profiles. It therefore seems unlikely that the long chain (C24-34) alcohols have any cholesterol-lowering activity.

  2. Lowering of plasma cholesterol in herbivores and omnivores by low molecular weight dextran.

    PubMed

    Adam, O; Krejci, K

    1989-01-01

    Two rabbits and two home pigs were infused in a cross-over design with equal volumes, adapted to the plasma volumes of the animals, of dextran-40 and saline. The infusions resulted in a reduction of plasma cholesterol and control parameters, such as plasma protein, hemoglobin, and hematocrit. The reduction of hemoglobin and hematocrit was related to plasma expansion with both infusion regimens. With dextran-40 infusions the reduction of plasma protein was greater than hemodilution in both species (-18% in rabbits and -20% in home pigs), because of steric exclusion of the protein. Lowering of plasma cholesterol in rabbits was comparable to the reduction in plasma protein, whereas in home pigs the reduction of plasma cholesterol (-25%) surpassed that of plasma protein. Reports in the literature have shown that dextran infusions increase cholesterol concentration in liver cells, leading to a reduction of intestinal cholesterol resorption in omnivores. This dextran effect is supposed to be responsible for the observed additional reduction of plasma cholesterol levels in omnivores.

  3. Macadamia nut consumption lowers plasma total and LDL cholesterol levels in hypercholesterolemic men.

    PubMed

    Garg, Manohar L; Blake, Robert J; Wills, Ron B H

    2003-04-01

    This study was conducted to assess the cholesterol-lowering potential of macadamia nuts. Seventeen hypercholesterolemic men (mean age 54 y) were given macadamia nuts (40-90 g/d), equivalent to 15% energy intake, for 4 wk. Plasma total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and homocysteine concentrations and the fatty acid composition of plasma lipids were determined before and after treatment. Plasma MUFA 16:1(n-7), 18:1(n-7) and 20:1(n-9) were elevated after intervention with macadamia nuts. Plasma (n-6) and (n-3) PUFA concentrations were unaffected by macadamia nut consumption. Plasma total cholesterol and LDL cholesterol concentrations decreased by 3.0 and 5.3%, respectively, and HDL cholesterol levels increased by 7.9% in hypercholesterolemic men after macadamia nut consumption. Plasma triglyceride and homocysteine concentrations were not affected by treatment. Macadamia nut consumption was associated with a significant increase in the relative intake of MUFA and a reduced relative intake of saturated fatty acids and PUFA. This study demonstrates that macadamia nut consumption as part of a healthy diet favorably modifies the plasma lipid profile in hypercholesterolemic men despite their diet being high in fat.

  4. Macadamia nut consumption lowers plasma total and LDL cholesterol levels in hypercholesterolemic men.

    PubMed

    Garg, Manohar L; Blake, Robert J; Wills, Ron B H

    2003-04-01

    This study was conducted to assess the cholesterol-lowering potential of macadamia nuts. Seventeen hypercholesterolemic men (mean age 54 y) were given macadamia nuts (40-90 g/d), equivalent to 15% energy intake, for 4 wk. Plasma total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and homocysteine concentrations and the fatty acid composition of plasma lipids were determined before and after treatment. Plasma MUFA 16:1(n-7), 18:1(n-7) and 20:1(n-9) were elevated after intervention with macadamia nuts. Plasma (n-6) and (n-3) PUFA concentrations were unaffected by macadamia nut consumption. Plasma total cholesterol and LDL cholesterol concentrations decreased by 3.0 and 5.3%, respectively, and HDL cholesterol levels increased by 7.9% in hypercholesterolemic men after macadamia nut consumption. Plasma triglyceride and homocysteine concentrations were not affected by treatment. Macadamia nut consumption was associated with a significant increase in the relative intake of MUFA and a reduced relative intake of saturated fatty acids and PUFA. This study demonstrates that macadamia nut consumption as part of a healthy diet favorably modifies the plasma lipid profile in hypercholesterolemic men despite their diet being high in fat. PMID:12672919

  5. Plasma cholesterol-lowering effect on rats of dietary fiber extracted from immature plants.

    PubMed

    Nishimura, N; Taniguchi, Y; Kiriyama, S

    2000-12-01

    Crude dietary fiber samples were prepared from beet, cabbage, Japanese radish, onion and mung bean sprouts (BF, CF, RF, OF and MF, respectively). These samples contained total dietary fiber at the levels of 814, 699, 760, 693 and 666 g/kg, respectively. To examine the effect of these dietary fiber sources on the plasma cholesterol concentration, male Sprague-Dawley rats were fed on a fiber-free (FF) diet or on an FF diet supplemented with 5% or 10% dietary fiber. Dietary fiber extracted from vegetables, wood cellulose (CL), pectin (PE) and guar gum (GG) were used as the fiber sources. Compared with the rats fed on the FF diet, a significant reduction in the plasma cholesterol concentration was observed in the rats fed on BF, CF, RF, MF, PE or GG after a 21-d feeding period. Cecal acetate, n-butyrate and total short-chain fatty acids were significantly higher in the rats fed on these dietary fibers, except for CF, than in those fed on the FF diet. A negative correlation was apparent between the total dietary fiber content, hemicellulose content and pectin content of each dietary fiber source and the plasma cholesterol concentration. These results suggest that some vegetable fibers exert a plasma cholesterol-lowering effect through cecal fermentation of these fibers.

  6. Effect of cholesterol lowering treatment on plasma markers of endothelial dysfunction in chronic kidney disease.

    PubMed

    Zinellu, Angelo; Sotgia, Salvatore; Mangoni, Arduino A; Sotgiu, Elisabetta; Ena, Sara; Satta, Andrea E; Carru, Ciriaco

    2016-09-10

    The elevated cardiovascular morbidity and mortality in chronic kidney disease (CKD) is linked with endothelial dysfunction secondary to the pro-inflammatory and pro-oxidative state typical of this pathology. In consideration of the well-known pleiotropic effect of statins, we investigated the effect of cholesterol lowering treatment on endothelial dysfunction markers (MED), asymmetric dimethylarginine (ADMA), vascular cell (VCAM) and intercellular (ICAM) adhesion molecule. Plasma MED concentrations, inflammation and oxidative stress indices [Kynurenine/Tryptophan (Kyn/Trp) ratio, malondialdehyde (MDA) and allantoin/uric acid (All/UA) ratio] were measured in 30 CKD patients randomized to three cholesterol lowering regimens for 12 months (simvastatin 40mg/day, ezetimibe/simvastatin 10/20mg/day, or ezetimibe/simvastatin 10/40mg/day). Treatment significantly reduced ADMA concentrations in all patients [0.694μmol/L (0.606-0.761) at baseline vs. 0.622μmol/L (0.563-0.681) after treatment, p<0.001]. ADMA reduction was paralleled by a significant decrease of MDA, All/AU ratio and Kyn/Trp ratio, but not VCAM and ICAM plasma concentrations. Cholesterol lowering treatment was associated with a significant reduction in plasma ADMA concentrations in CKD patients. This might be mediated by reduced oxidative stress and inflammation.

  7. Ileorectostomy or cecectomy but not colectomy abolishes the plasma cholesterol-lowering effect of dietary beet fiber in rats.

    PubMed

    Nishimura, N; Nishikawa, H; Kiriyama, S

    1993-07-01

    Adult male rats were fed a cholesterol-free diet with no added fiber (fiber-free) or with 10% cellulose or beet fiber. After 7 d of feeding, plasma total cholesterol concentrations were significantly lower in rats fed beet fiber than in those fed fiber-free or cellulose diets. This difference was due mainly to lower HDL cholesterol concentrations and remained significant for 28 d. The hypocholesterolemic effect of beet fiber relative to fiber-free disappeared when the cecum and colon were concurrently resected (ileorectostomy). Plasma cholesterol concentrations were the same in colectomized rats as in sham-operated rats fed the same diet and significantly lower in animals fed the beet fiber diet than in those fed the fiber-free diet. In cecectomized rats fed beet fiber, plasma cholesterol concentrations were intermediate between sham-operated rats fed the beet fiber diet and cecectomized or sham-operated rats fed the fiber-free diet. Fecal bile acid excretion was higher in rats fed the beet fiber diet than in those fed the fiber-free diet but did not correlate with plasma total cholesterol concentration. In rats with intact ceca, cecal total and individual short-chain fatty acids correlated negatively with plasma total cholesterol concentration. Dietary beet fiber lowers plasma cholesterol concentrations in rats, and the lower digestive tract, especially the cecum, seems to be necessary for this effect.

  8. Corn fiber oil lowers plasma cholesterol levels and increases cholesterol excretion greater than corn oil and similar to diets containing soy sterols and soy stanols in hamsters.

    PubMed

    Wilson, T A; DeSimone, A P; Romano, C A; Nicolosi, R J

    2000-09-01

    The aims of this study were to compare the cholesterol-lowering properties of corn fiber oil (CFO) to corn oil (CO), whether the addition of soy stanols or soy sterols to CO at similar levels in CFO would increase CO's cholesterol-lowering properties, and the mechanism(s) of action of these dietary ingredients. Fifty male Golden Syrian hamsters were divided into 5 groups of 10 hamsters each, based on similar plasma total cholesterol (TC) levels. The first group of hamsters was fed a chow-based hypercholesterolemic diet containing either 5% coconut oil + 0.24% cholesterol (coconut oil), 5% CO, 5% CFO, 5% CO + 0.6% soy sterols (sterol), or 5% CO + 0.6% soy stanols (stanol) in place of the coconut oil for 4 weeks. The stanol diet significantly inhibited the elevation of plasma TC compared to all other dietary treatments. Also, the CFO and sterol diets significantly inhibited the elevation of plasma TC compared to the CO and coconut oil diets. The CFO, sterol, and stanol diets significantly inhibited the elevation of plasma non-high density lipoprotein cholesterol compared to the CO and coconut oil diets. The stanol diet significantly inhibited the elevation of plasma high density lipoprotein cholesterol (HDL-C) compared to all other dietary treatments. The sterol diet significantly inhibited the elevation of plasma HDL-C compared to the CO and coconut oil diets, whereas the CFO diet significantly inhibited the elevation of plasma HDL-C compared to the coconut oil diet only. No differences were observed between the CFO and CO for plasma HDL-C. There were no differences observed between groups for plasma triglycerides. The CO and CFO diets had significantly less hepatic TC compared to the coconut oil, sterol, and stanol diets. The CO and CFO diets had significantly less hepatic free cholesterol compared to the sterol and stanol diets but not compared to the coconut oil diet; whereas the coconut oil and sterol diets had significantly less hepatic free cholesterol

  9. Rationale and design of a secondary prevention trial of lowering normal plasma cholesterol levels after acute myocardial infarction: the Cholesterol and Recurrent Events trial (CARE)

    PubMed

    Sacks, F M; Pfeffer, M A; Moye', L; Brown, L E; Hamm, P; Cole, T G; Hawkins, C M; Braunwald, E

    1991-12-01

    Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol decreases the incidence of coronary heart disease in patients with elevated plasma cholesterol. However, it is not known whether patients with established coronary artery disease and normal plasma cholesterol can be benefited. Several previous prevention trials reviewed in this report found that patients who had plasma cholesterol levels at baseline in the upper portion of the eligibility range (e.g., greater than 240 mg/dl) received greater benefit from hypolipidemic diet or drug therapy than patients who had lower plasma cholesterol levels at baseline. The recent availability of drugs that are more potent and less prone to cause adverse reactions than previous regimens permits this important question to be addressed. The Cholesterol and Recurrent Events trial is testing whether pravastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, will decrease the sum of fatal coronary heart disease and nonfatal myocardial infarction (MI) in patients who have recovered from a MI and who have normal total cholesterol levels. Fatal cardiovascular disease and total mortality are important secondary end points. The trial is enrolling 4,000 men and women from 80 centers throughout North America, age 21 to 75 years, who have survived MI for 3 to 20 months, who have plasma total cholesterol less than 240 mg/dl (6.2 mmol/liter) and low-density cholesterol of 115 to 174 mg/dl (3.0 to 4.5 mmol/liter), and who are representative of the general population of patients with MI. Patients are randomized to either active or inactive drug therapy. Active therapy consists of pravastatin, 40 mg/day, designed to achieve an average decrease in low-density lipoprotein cholesterol of approximately 30%, and an increase in high-density lipoprotein of 5%. The average duration of follow-up will be greater than or equal to 5 years. To protect against a lower

  10. Does cholesterol lowering prevent stroke?

    PubMed

    Henry, R Y; Kendall, M J

    1998-10-01

    The importance of lowering plasma cholesterol to reduce the incidence of coronary events is well established. However, in the prevention of stroke disease, control of hypertension has been the main aim of treatment and lipid lowering therapy has not hitherto been considered to be desirable or necessary. In this review, the evidence from large multicentre trials, imaging studies and meta-analyses is presented. It shows convincingly that HMG-CoA reductase inhibitors (Statins) reduce stroke risk. PMID:9875681

  11. Gel coating of edible Brasenia schreberi leaves lowers plasma cholesterol in hamsters (abstract)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The young leaves of B. schreberi are coated with gelatinous water-insoluble mucilage. This mucilage is a polysaccharide composed of galactose, mannose, fucose and other monosaccharides. Since some carbohydrate gels are hypocholesterolemic, we evaluated the cholesterol lowering properties in male h...

  12. Capsaicinoids but not their analogue capsinoids lower plasma cholesterol and possess beneficial vascular activity.

    PubMed

    Huang, Weihuan; Cheang, Wai San; Wang, Xiaobo; Lei, Lin; Liu, Yuwei; Ma, Ka Ying; Zheng, Fangrui; Huang, Yu; Chen, Zhen-Yu

    2014-08-20

    Capsaicinoids exist in chili peppers, whereas capsinoids are present in some sweet peppers. The present study investigated the effects of capsaicinoids and capsinoids on plasma lipids, relaxation of the aorta, atherosclerotic plaque development, and fecal sterol excretion in hamsters fed a high-cholesterol diet. Five groups of male hamsters were given the control diet or one of the four experimental diets containing 1.3 mmol of capsaicinoids (NL), 2.6 mmol of capsaicinoids (NH), 1.3 mmol of capsinoids (OL), or 2.6 mmol of capsinoids (OH), respectively. Results showed capsaicinoids but not capsinoids could decrease plasma total cholesterol (TC), reduce the formation of atherosclerotic plaque, and relax the aortic artery. This was accompanied by a 28-175% increase in fecal excretion of acidic sterols in hamsters fed the diets containing capsaicinoids. Similarly, capsaicinoids but not capsinoids could decrease the pad weights of epididymal and prerenal adipose tissues. It was concluded that capsaicinoids but not capsinoids could favorably modulate plasma lipids and possess beneficial vascular activity. PMID:25078570

  13. Capsaicinoids but not their analogue capsinoids lower plasma cholesterol and possess beneficial vascular activity.

    PubMed

    Huang, Weihuan; Cheang, Wai San; Wang, Xiaobo; Lei, Lin; Liu, Yuwei; Ma, Ka Ying; Zheng, Fangrui; Huang, Yu; Chen, Zhen-Yu

    2014-08-20

    Capsaicinoids exist in chili peppers, whereas capsinoids are present in some sweet peppers. The present study investigated the effects of capsaicinoids and capsinoids on plasma lipids, relaxation of the aorta, atherosclerotic plaque development, and fecal sterol excretion in hamsters fed a high-cholesterol diet. Five groups of male hamsters were given the control diet or one of the four experimental diets containing 1.3 mmol of capsaicinoids (NL), 2.6 mmol of capsaicinoids (NH), 1.3 mmol of capsinoids (OL), or 2.6 mmol of capsinoids (OH), respectively. Results showed capsaicinoids but not capsinoids could decrease plasma total cholesterol (TC), reduce the formation of atherosclerotic plaque, and relax the aortic artery. This was accompanied by a 28-175% increase in fecal excretion of acidic sterols in hamsters fed the diets containing capsaicinoids. Similarly, capsaicinoids but not capsinoids could decrease the pad weights of epididymal and prerenal adipose tissues. It was concluded that capsaicinoids but not capsinoids could favorably modulate plasma lipids and possess beneficial vascular activity.

  14. The Food Matrix and Sterol Characteristics Affect the Plasma Cholesterol Lowering of Phytosterol/Phytostanol1

    PubMed Central

    Cusack, Laura Kells; Fernandez, Maria Luz; Volek, Jeff S.

    2013-01-01

    Foods with added phytosterols/phytostanols (PS) are recommended to lower LDL cholesterol (LDL-c) concentrations. Manufacturers have incorporated PS into a variety of common foods. Understanding the cholesterol-lowering impact of the food matrix and the PS characteristics would maximize their success and increase the benefit to consumers. This review systematically examines whether the PS characteristics and the fatty acid composition of foods with added PS affects serum LDL-c. A total of 33 studies published between the years 1998 and 2011 inclusive of 66 individual primary variables (strata) were evaluated. The functional food matrices included margarine, mayonnaise, yogurt, milk, cheese, meat, grain, juice, and chocolate. Consistently, ≥10% reductions in LDL-c were reported when the characteristics of the food matrix included poly- and monounsaturated fatty acids known to lower LDL-c. Also, >10% mean reductions in LDL-c were reported when β-sitostanol and campestanol as well as stanol esters were used. These characteristics allow both low-fat and high-fat foods to successfully incorporate PS and significantly lower LDL-c. PMID:24228192

  15. The food matrix and sterol characteristics affect the plasma cholesterol lowering of phytosterol/phytostanol.

    PubMed

    Cusack, Laura Kells; Fernandez, Maria Luz; Volek, Jeff S

    2013-11-01

    Foods with added phytosterols/phytostanols (PS) are recommended to lower LDL cholesterol (LDL-c) concentrations. Manufacturers have incorporated PS into a variety of common foods. Understanding the cholesterol-lowering impact of the food matrix and the PS characteristics would maximize their success and increase the benefit to consumers. This review systematically examines whether the PS characteristics and the fatty acid composition of foods with added PS affects serum LDL-c. A total of 33 studies published between the years 1998 and 2011 inclusive of 66 individual primary variables (strata) were evaluated. The functional food matrices included margarine, mayonnaise, yogurt, milk, cheese, meat, grain, juice, and chocolate. Consistently, ≥10% reductions in LDL-c were reported when the characteristics of the food matrix included poly- and monounsaturated fatty acids known to lower LDL-c. Also, >10% mean reductions in LDL-c were reported when β-sitostanol and campestanol as well as stanol esters were used. These characteristics allow both low-fat and high-fat foods to successfully incorporate PS and significantly lower LDL-c.

  16. Lowering plasma cholesterol levels halts progression of aortic valve disease in mice

    PubMed Central

    Miller, Jordan D.; Weiss, Robert M.; Serrano, Kristine M.; Brooks, Robert M.; Berry, Christopher J.; Zimmerman, Kathy; Young, Stephen G.; Heistad, Donald D.

    2009-01-01

    Background Treatment of hyperlipidemia produces functional and structural improvements in atherosclerotic vessels. However, the effects of treating hyperlipidemia on the structure and function of the aortic valve has been controversial, and any effects could be confounded by pleiotropic effects of hypolipidemic treatment. The goal of this study was to determine whether reducing elevated plasma lipid levels with a “genetic switch” in Reversa mice (Ldlr−/−/Apob100/100/Mttpfl/fl/Mx1Cre+/+) reduces oxidative stress, reduces proosteogenic signaling, and retards the progression of aortic valve disease. Methods and Results After 6 months of hypercholesterolemia, Reversa mice exhibited increases in superoxide, lipid deposition, myofibroblast activation, calcium deposition, and pro-osteogenic protein expression in the aortic valve. Maximum aortic valve cusp separation, as judged by echocardiography, was not altered. During an additional 6 months of hypercholesterolemia, superoxide levels, valvular lipid deposition, and myofibroblast activation remained elevated. Furthermore, calcium deposition and pro-osteogenic gene expression became more pronounced and the aortic cusp separation decreased from 0.85 ± 0.04 to 0.70 ± 0.04 mm (mean ± SE; p < 0.05). Rapid normalization of cholesterol levels at 6 months of age (by inducing expression of Cre recombinase) normalized aortic valve superoxide levels, decreased myofibroblast activation, reduced valvular calcium burden, suppressed pro-osteogenic signaling cascades, and prevented the reductions in aortic valve cusp separation. Conclusions Collectively, these data indicate that reducing plasma lipid levels by genetic inactivation of the mttp gene in hypercholesterolemic mice with early aortic valve disease normalizes oxidative stress, reduces pro-osteogenic signaling, and halts the progression of aortic valve stenosis. PMID:19433756

  17. SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion

    PubMed Central

    Chen, Xiao-Wei; Wang, He; Bajaj, Kanika; Zhang, Pengcheng; Meng, Zhuo-Xian; Ma, Danjun; Bai, Yongsheng; Liu, Hui-Hui; Adams, Elizabeth; Baines, Andrea; Yu, Genggeng; Sartor, Maureen A; Zhang, Bin; Yi, Zhengping; Lin, Jiandie; Young, Stephen G; Schekman, Randy; Ginsburg, David

    2013-01-01

    The secretory pathway of eukaryotic cells packages cargo proteins into COPII-coated vesicles for transport from the endoplasmic reticulum (ER) to the Golgi. We now report that complete genetic deficiency for the COPII component SEC24A is compatible with normal survival and development in the mouse, despite the fundamental role of SEC24 in COPII vesicle formation and cargo recruitment. However, these animals exhibit markedly reduced plasma cholesterol, with mutations in Apoe and Ldlr epistatic to Sec24a, suggesting a receptor-mediated lipoprotein clearance mechanism. Consistent with these data, hepatic LDLR levels are up-regulated in SEC24A-deficient cells as a consequence of specific dependence of PCSK9, a negative regulator of LDLR, on SEC24A for efficient exit from the ER. Our findings also identify partial overlap in cargo selectivity between SEC24A and SEC24B, suggesting a previously unappreciated heterogeneity in the recruitment of secretory proteins to the COPII vesicles that extends to soluble as well as trans-membrane cargoes. DOI: http://dx.doi.org/10.7554/eLife.00444.001 PMID:23580231

  18. Hepatic Gene Expression Related to Lower Plasma Cholesterol in Hamsters Fed High Fat Diets Supplemented with Blueberry Pomace and Extract

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We analyzed plasma lipid profiles, and genes related to cholesterol and bile acid metabolism, and inflammation in livers as well as adipose tissue from Syrian Golden hamsters fed high-fat diets supplemented with blueberry (BB) pomace byproducts including 8% dried whole blueberry peels (BBPWHL), 2% d...

  19. Does Glycine max leaves or Garcinia Cambogia promote weight-loss or lower plasma cholesterol in overweight individuals: a randomized control trial

    PubMed Central

    2011-01-01

    Background Natural food supplements with high flavonoid content are often claimed to promote weight-loss and lower plasma cholesterol in animal studies, but human studies have been more equivocal. The aim of this study was firstly to determine the effectiveness of natural food supplements containing Glycine max leaves extract (EGML) or Garcinia cambogia extract (GCE) to promote weight-loss and lower plasma cholesterol. Secondly to examine whether these supplements have any beneficial effect on lipid, adipocytokine or antioxidant profiles. Methods Eighty-six overweight subjects (Male:Female = 46:40, age: 20~50 yr, BMI > 23 < 29) were randomly assigned to three groups and administered tablets containing EGML (2 g/day), GCE (2 g/day) or placebo (starch, 2 g/day) for 10 weeks. At baseline and after 10 weeks, body composition, plasma cholesterol and diet were assessed. Blood analysis was also conducted to examine plasma lipoproteins, triglycerides, adipocytokines and antioxidants. Results EGML and GCE supplementation failed to promote weight-loss or any clinically significant change in %body fat. The EGML group had lower total cholesterol after 10 weeks compared to the placebo group (p < 0.05). EGML and GCE had no effect on triglycerides, non-HDL-C, adipocytokines or antioxidants when compared to placebo supplementation. However, HDL-C was higher in the EGML group (p < 0.001) after 10 weeks compared to the placebo group. Conclusions Ten weeks of EGML or GCE supplementation did not promote weight-loss or lower total cholesterol in overweight individuals consuming their habitual diet. Although, EGML did increase plasma HDL-C levels which is associated with a lower risk of atherosclerosis. PMID:21936892

  20. Gel coating of leaves of the water plant, Brasenia schreberi, lowers plasma cholesterol in hamsters on high fat diets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An edible, gelatinous water-insoluble coating surrounds the young leaves of the water plant, Brasenia schreberi. This mucilage is a polysaccharide of galactose, mannose, fucose and other monosaccharides. In order to determine if this edible gel has cholesterol lowering properties, we fed male hams...

  1. Immunization against proprotein convertase subtilisin-like/kexin type 9 lowers plasma LDL-cholesterol levels in mice.

    PubMed

    Fattori, Elena; Cappelletti, Manuela; Lo Surdo, Paola; Calzetta, Alessandra; Bendtsen, Claus; Ni, Yan G; Pandit, Shilpa; Sitlani, Ayesha; Mesiti, Giuseppe; Carfí, Andrea; Monaci, Paolo

    2012-08-01

    Successful development of drugs against novel targets crucially depends on reliable identification of the activity of the target gene product in vivo and a clear demonstration of its specific functional role for disease development. Here, we describe an immunological knockdown (IKD) method, a novel approach for the in vivo validation and functional study of endogenous gene products. This method relies on the ability to elicit a transient humoral response against the selected endogenous target protein. Anti-target antibodies specifically bind to the target protein and a fraction of them effectively neutralize its activity. We applied the IKD method to the in vivo validation of plasma PCSK9 as a potential target for the treatment of elevated levels of plasma LDL-cholesterol. We show that immunization with human-PCSK9 in mice is able to raise antibodies that cross-react and neutralize circulating mouse-PCSK9 protein thus resulting in increased liver LDL receptor levels and plasma cholesterol uptake. These findings closely resemble those described in PCSK9 knockout mice or in mice treated with antibodies that inhibit PCSK9 by preventing the PCSK9/LDLR interaction. Our data support the IKD approach as an effective method to the rapid validation of new target proteins.

  2. Omega-3 Fatty Acid Enriched Chevon (Goat Meat) Lowers Plasma Cholesterol Levels and Alters Gene Expressions in Rats

    PubMed Central

    Rajion, Mohamed Ali; Meng, Goh Yong; Soleimani Farjam, Abdoreza

    2014-01-01

    In this study, control chevon (goat meat) and omega-3 fatty acid enriched chevon were obtained from goats fed a 50% oil palm frond diet and commercial goat concentrate for 100 days, respectively. Goats fed the 50% oil palm frond diet contained high amounts of α-linolenic acid (ALA) in their meat compared to goats fed the control diet. The chevon was then used to prepare two types of pellets (control or enriched chevon) that were then fed to twenty-male-four-month-old Sprague-Dawley rats (n = 10 in each group) for 12 weeks to evaluate their effects on plasma cholesterol levels, tissue fatty acids, and gene expression. There was a significant increase in ALA and docosahexaenoic acid (DHA) in the muscle tissues and liver of the rats fed the enriched chevon compared with the control group. Plasma cholesterol also decreased (P < 0.05) in rats fed the enriched chevon compared to the control group. The rat pellets containing enriched chevon significantly upregulated the key transcription factor PPAR-γ and downregulated SREBP-1c expression relative to the control group. The results showed that the omega-3 fatty acid enriched chevon increased the omega-3 fatty acids in the rat tissues and altered PPAR-γ and SREBP-1c genes expression. PMID:24719886

  3. Omega-3 fatty acid enriched chevon (goat meat) lowers plasma cholesterol levels and alters gene expressions in rats.

    PubMed

    Ebrahimi, Mahdi; Rajion, Mohamed Ali; Meng, Goh Yong; Soleimani Farjam, Abdoreza

    2014-01-01

    In this study, control chevon (goat meat) and omega-3 fatty acid enriched chevon were obtained from goats fed a 50% oil palm frond diet and commercial goat concentrate for 100 days, respectively. Goats fed the 50% oil palm frond diet contained high amounts of α-linolenic acid (ALA) in their meat compared to goats fed the control diet. The chevon was then used to prepare two types of pellets (control or enriched chevon) that were then fed to twenty-male-four-month-old Sprague-Dawley rats (n = 10 in each group) for 12 weeks to evaluate their effects on plasma cholesterol levels, tissue fatty acids, and gene expression. There was a significant increase in ALA and docosahexaenoic acid (DHA) in the muscle tissues and liver of the rats fed the enriched chevon compared with the control group. Plasma cholesterol also decreased (P < 0.05) in rats fed the enriched chevon compared to the control group. The rat pellets containing enriched chevon significantly upregulated the key transcription factor PPAR-γ and downregulated SREBP-1c expression relative to the control group. The results showed that the omega-3 fatty acid enriched chevon increased the omega-3 fatty acids in the rat tissues and altered PPAR-γ and SREBP-1c genes expression.

  4. Plasma cholesterol transport in anhepatic rats.

    PubMed Central

    Quarfordt, S H; Landis, B; Cucchiaro, G; Yamaguchi, Y; Oswald, B

    1992-01-01

    The plasma appearance of newly synthesized cholesterol in anhepatic laboratory diet-fed rats was 10% of the intact rat. In intact rats this cholesterol was mainly ester in lower density lipoproteins, but for anhepatic rats it was virtually only free in high density lipoprotein. Chylomicron cholesterol ester was removed much more slowly from anhepatic than control plasma and returned primarily as free in high density lipoproteins, with the control return 10 times the anhepatic return. Lower density lipoprotein cholesterol ester transfer to an extravascular pool in anhepatic rats was less than 10% of controls. The liver was responsible for 95% of the extravascular lower density lipoprotein ester pool and only 50% of the for high density lipoprotein ester. Despite decreased anhepatic lipoprotein catabolism, the mass of both plasma low and high density lipoproteins progressively decreased indicating an even greater decrease in influx. The anhepatic fractional catabolic rate of apo A1 was similar to controls, but that of apo E was considerably less. Despite the unchanged catabolism of apo A1 and the reduced catabolism of apo E, plasma apo A1 decreased less than apo E after hepatectomy. The anhepatic data confirm the pivotal role of the liver in maintaining plasma low and high density lipoprotein cholesterol concentrations. They suggest that, in addition to its anabolic and catabolic functions, the liver also acts as a reservoir buffering changes in plasma concentration. Images PMID:1569195

  5. Food combinations for cholesterol lowering.

    PubMed

    Harland, Janice I

    2012-12-01

    Reducing elevated LDL-cholesterol is a key public health challenge. There is substantial evidence from randomised controlled trials (RCT) that a number of foods and food components can significantly reduce LDL-cholesterol. Data from RCT have been reviewed to determine whether effects are additive when two or more of these components are consumed together. Typically components, such as plant stanols and sterols, soya protein, β-glucans and tree nuts, when consumed individually at their target rate, reduce LDL-cholesterol by 3-9 %. Improved dietary fat quality, achieved by replacing SFA with unsaturated fat, reduces LDL-cholesterol and can increase HDL-cholesterol, further improving blood lipid profile. It appears that the effect of combining these interventions is largely additive; however, compliance with multiple changes may reduce over time. Food combinations used in ten 'portfolio diet' studies have been reviewed. In clinical efficacy studies of about 1 month where all foods were provided, LDL-cholesterol is reduced by 22-30 %, whereas in community-based studies of >6 months' duration, where dietary advice is the basis of the intervention, reduction in LDL-cholesterol is about 15 %. Inclusion of MUFA into 'portfolio diets' increases HDL-cholesterol, in addition to LDL-cholesterol effects. Compliance with some of these dietary changes can be achieved more easily compared with others. By careful food component selection, appropriate to the individual, the effect of including only two components in the diet with good compliance could be a sustainable 10 % reduction in LDL-cholesterol; this is sufficient to make a substantial impact on cholesterol management and reduce the need for pharmaceutical intervention.

  6. Cholesterol-Lowering Effect of Calcium Alginate in Rats.

    PubMed

    Idota, Yoko; Kogure, Yumi; Kato, Takako; Ogawa, Mana; Kobayashi, Shoko; Kakinuma, Chihaya; Yano, Kentaro; Arakawa, Hiroshi; Miyajima, Chihiro; Kasahara, Fumiyoshi; Ogihara, Takuo

    2016-01-01

    We examined whether calcium alginate (Ca-Alg) reduces blood cholesterol levels in rats fed a high-cholesterol diet. First, we examined taurocholate adsorption in vitro by various types of sodium alginate (Na-Alg). High molecular-weight, guluronic acid-rich Na-Alg showed the greatest adsorption of taurocholate, and therefore the corresponding Ca-Alg was chosen for the in vivo study. Rats were fed a high-cholesterol diet or a Ca-Alg-containing diet for 2 weeks. Body weight and diet intake were measured, and the general condition of the animals was monitored during this period. After 14 d, the plasma concentration of cholesterol, portal plasma concentration of bile acid, and bile acid in feces were measured. The plasma concentration of cholesterol was significantly reduced in rats fed a 2% Ca-Alg-containing diet. Furthermore, the portal concentration of bile acid was significantly lowered in the 2% Ca-Alg group. A tendency for a Ca-Alg concentration-dependent increase in fecal excretion of bile acid was also seen, although it was not statistically significant. While several changes in biochemical parameters and histopathological findings were observed, all the values remained within the physiological range. These results indicate that Ca-Alg is effective in reducing plasma cholesterol. A possible mechanism would be enhanced fecal excretion of bile acid due to reduced intestinal reabsorption, which in turn might stimulate bile acid synthesis from cholesterol in the liver, leading to a decrease in plasma cholesterol.

  7. Anthocyanin-Rich Juice Lowers Serum Cholesterol, Leptin, and Resistin and Improves Plasma Fatty Acid Composition in Fischer Rats

    PubMed Central

    Graf, Daniela; Seifert, Stephanie; Jaudszus, Anke; Bub, Achim; Watzl, Bernhard

    2013-01-01

    Obesity and obesity-associated diseases e.g. cardiovascular diseases and type 2 diabetes are spread worldwide. Anthocyanins are supposed to have health-promoting properties, although convincing evidence is lacking. The aim of the present study was to investigate the effect of anthocyanins on several risk factors for obesity-associated diseases. Therefore, Fischer rats were fed anthocyanin-rich grape-bilberry juice or an anthocyanin-depleted control juice for 10 weeks. Intervention with anthocyanin-rich grape-bilberry juice reduced serum cholesterol and tended to decrease serum triglycerides. No effects were seen for serum non-esterified fatty acids, glucose, and insulin. Anthocyanin-rich grape-bilberry juice intervention reduced serum leptin and resistin, but showed no influence on serum adiponectin and secretion of adipokines from mesenteric adipose tissue. Furthermore, anthocyanin-rich grape-bilberry juice increased the proportion of polyunsaturated fatty acids and decreased the amount of saturated fatty acids in plasma. These results indicate that anthocyanins possess a preventive potential for obesity-associated diseases. PMID:23825152

  8. Nutraceutical pill containing berberine versus ezetimibe on plasma lipid pattern in hypercholesterolemic subjects and its additive effect in patients with familial hypercholesterolemia on stable cholesterol-lowering treatment

    PubMed Central

    2012-01-01

    Background Although statins (STs) are drugs of first choice in hypercholesterolemic patients, especially in those at high cardiovascular risk, some of them are intolerant to STs or refuse treatment with these drugs. In view of this, we have evaluated the lipid-lowering effect of a nutraceutical pill containing berberine (BBR) and of ezetimibe, as alternative treatments, in monotherapy or in combination, in 228 subjects with primary hypercholesterolemia (HCH), with history of STs intolerance or refusing STs treatment. In addition, since PCSK9 was found up-regulated by STs dampening their effect through an LDL receptors (LDLRs) degradation, and BBR suppressed PCSK9 expression in cellular studies, we supplemented the stable lipid-lowering therapy of 30 genotype-confirmed Familial Hypercholesterolemia heterozygotes (HeFH) with BBR, searching for a further plasma cholesterol reduction. Plasma lipid pattern was evaluated at baseline and during treatments. Results In HCH subjects the nutraceutical pill resulted more effective than EZE in lowering LDL cholesterol (−31.7% vs −25.4%, P < 0.001) and better tolerated. On treatment, LDL-C level below 3.36 mmol/L (≤130 mg/dl) was observed in 28.9% of subjects treated with the nutraceutical pill and 11.8% of those treated with EZE (P <0.007). In the group treated with EZE the subjects carrying the G allele of the g.1679 C > G silent polymorphism of NPC1L1 gene showed a higher response to EZE than homozygous for the common allele (GG + CG: LDL-C −29.4±5.0%, CC −23.6±6.5%, P <0.001). Combined treatment with these drugs was as effective as STs in moderate doses (LDL cholesterol −37%, triglycerides −23%). In HeFH patients the addition of BBR resulted in LDL cholesterol reductions inversely related to those induced by the stable therapy (r = −0.617, P <0.0001), with mean 10.5% further decrease. Conclusions The alternative treatments tested in our HCH subjects were rather effective and safe. The findings in

  9. Genetic therapies to lower cholesterol.

    PubMed

    Khoo, Bernard

    2015-01-01

    This review surveys the state-of-the-art in genetic therapies for familial hypercholesterolaemia (FH), caused most commonly by mutations in the LDL receptor (LDLR) gene. FH manifests as highly elevated low density lipoprotein (LDL) cholesterol levels and consequently accelerated atherosclerosis. Modern pharmacological therapies for FH are insufficiently efficacious to prevent premature cardiovascular disease, can cause significant adverse effects and can be expensive. Genetic therapies for FH have been mooted since the mid 1990s but gene replacement strategies using viral vectors have so far been unsuccessful. Other strategies involve knocking down the expression of Apolipoprotein B100 (APOB100) and the protease PCSK9 which designates LDLR for degradation. The antisense oligonucleotide mipomersen, which knocks down APOB100, is currently marketed (with restrictions) in the USA, but is not approved in Europe due to its adverse effects. To address this problem, we have devised a novel therapeutic concept, APO-skip, which is based on modulation of APOB splicing, and which has the potential to deliver a cost-effective, efficacious and safe therapy for FH.

  10. Effect of ezetimibe on plasma cholesterol levels, cholesterol absorption, and secretion of biliary cholesterol in laboratory opossums with high and low responses to dietary cholesterol.

    PubMed

    Chan, Jeannie; Kushwaha, Rampratap S; Vandeberg, Jane F; Vandeberg, John L

    2008-12-01

    Partially inbred lines of laboratory opossums differ in plasma low-density lipoprotein cholesterol concentration and cholesterol absorption on a high-cholesterol diet. The aim of the present studies was to determine whether ezetimibe inhibits cholesterol absorption and eliminates the differences in plasma cholesterol and hepatic cholesterol metabolism between high and low responders on a high-cholesterol diet. Initially, we determined that the optimum dose of ezetimibe was 5 mg/(kg d) and treated 6 high- and 6 low-responding opossums with this dose (with equal numbers of controls) for 3 weeks while the opossums consumed a high-cholesterol and low-fat diet. Plasma and low-density lipoprotein cholesterol concentrations decreased significantly (P < .05) in treated but not in untreated high-responding opossums. Plasma cholesterol concentrations increased slightly (P < .05) in untreated low responders but not in treated low responders. The percentage of cholesterol absorption was significantly higher in untreated high responders than in other groups. Livers from high responders with or without treatment were significantly (P < .01) heavier than livers from low responders with or without treatment. Hepatic cholesterol concentrations in untreated high responders were significantly (P < .05) higher than those in low responders with or without treatment (P < .001). The gall bladder bile cholesterol concentrations in untreated high responders were significantly (P < .05) lower than those in other groups. A decrease in biliary cholesterol in low responders treated with ezetimibe was associated with a decrease in hepatic expression of ABCG5 and ABCG8. These studies suggest that ezetimibe decreases plasma cholesterol levels in high responders mainly by decreasing cholesterol absorption and increasing biliary cholesterol concentrations. Because ezetimibe's target is NPC1L1 and NPC1L1 is expressed in the intestine of opossums, its effect on cholesterol absorption may be mediated

  11. Cholesterol-lowering effect of plant sterols.

    PubMed

    AbuMweis, Suhad S; Jones, Peter J H

    2008-12-01

    Plant sterols are plant components that have a chemical structure similar to cholesterol except for the addition of an extra methyl or ethyl group; however, plant sterol absorption in humans is considerably less than that of cholesterol. In fact, plant sterols reduce cholesterol absorption and thus reduce circulating levels of cholesterol. Earlier studies that have tested the efficacy of plant sterols as cholesterol-lowering agents incorporated plant sterols into fat spreads. Later on, plant sterols were added to other food matrices, including juices, nonfat beverages, milk and yogurt, cheese, meat, croissants and muffins, and cereal and chocolate bars. The beneficial physiologic effects of plant sterols could be further enhanced by combining them with other beneficial substances, such as olive and fish oils, fibers, and soy proteins, or with exercise. The addition of plant sterols to the diet is suggested by health experts as a safe and effective way to reduce the risk of coronary heart disease. PMID:18937893

  12. Plasma and hepatic cholesterol-lowering in hamsters by tomato pomace, tomato seed oil and defatted tomato seed supplemented in high fat diets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We determined the cholesterol-lowering effects of tomato pomace (TP), a byproduct of tomato processing, and its components such as tomato seed oil (TSO) and defatted tomato seed (DTS) in hamsters, a widely used animal model for cholesterol metabolism. Male Syrian Golden hamsters were fed high-fat di...

  13. Rapid labeling of lipoproteins in plasma with radioactive cholesterol. Application for measurement of plasma cholesterol esterification

    SciTech Connect

    Yen, F.T.; Nishida, T. )

    1990-02-01

    In order to efficiently and rapidly label lipoproteins in plasma with ({sup 3}H)cholesterol, micelles consisting of lysophosphatidylcholine (lysoPC) and ({sup 3}H)cholesterol (molar ratio, 50:1) were prepared. When trace amounts of these micelles were injected into plasma, ({sup 3}H)cholesterol rapidly equilibrated among the plasma lipoproteins, as compared to ({sup 3}H)cholesterol from an albumin-stabilized emulsion. The distributions of both ({sup 3}H)cholesterol and unlabeled free cholesterol in plasma lipoproteins were similar in labeled plasma samples. This method of labeling can be used for the measurement of cholesterol esterification, or lecithin:cholesterol acyltransferase activity, in small amounts (20-40 microliters) of plasma samples.

  14. Plasma Cholesterol-Lowering Activity of Lard Functionalized with Mushroom Extracts Is Independent of Niemann-Pick C1-like 1 Protein and ABC Sterol Transporter Gene Expression in Hypercholesterolemic Mice.

    PubMed

    Caz, Víctor; Gil-Ramírez, Alicia; Santamaría, Mónica; Tabernero, María; Soler-Rivas, Cristina; Martín-Hernández, Roberto; Marín, Francisco R; Reglero, Guillermo; Largo, Carlota

    2016-03-01

    Interest in food matrices supplemented with mushrooms as hypocholesterolemic functional foods is increasing. This study was to (i) investigate the hypocholesterolemic activity of lard functionalized with mushroom extracts (LF) including fungal β-glucans, water-soluble polysaccharides, or ergosterol and (ii) examine the LF influence on transcriptional mechanisms involved in cholesterol metabolism. mRNA levels of 17 cholesterol-related genes were evaluated in jejunum, cecum, and liver of high cholesterol-fed mice. The four tested LFs decreased plasma cholesterol by 22-42%, HDLc by 18-40%, and LDLc by 27-51%, and two of them increased mRNA levels of jejunal Npc1l1 and Abcg5 and hepatic Npc1l1. mRNA levels of other cholesterol-related genes were unchanged. These findings suggest that LF may have potential as a dietary supplement for counteracting diet-induced hypercholesterolemia and could be a source for the development of novel cholesterol-lowering functional foods. However, the cholesterol-lowering effect was unrelated to transcriptional changes, suggesting that post-transcriptional mechanisms could be involved.

  15. The Success Story of LDL Cholesterol Lowering.

    PubMed

    Pedersen, Terje R

    2016-02-19

    We can look back at >100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein-cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence. PMID:26892969

  16. An immunomodulating fatty acid analogue targeting mitochondria exerts anti-atherosclerotic effect beyond plasma cholesterol-lowering activity in apoe(-/-) mice.

    PubMed

    Vik, Rita; Busnelli, Marco; Parolini, Cinzia; Bjørndal, Bodil; Holm, Sverre; Bohov, Pavol; Halvorsen, Bente; Brattelid, Trond; Manzini, Stefano; Ganzetti, Giulia S; Dellera, Federica; Nygård, Ottar K; Aukrust, Pål; Sirtori, Cesare R; Chiesa, Giulia; Berge, Rolf K

    2013-01-01

    Tetradecylthioacetic acid (TTA) is a hypolipidemic antioxidant with immunomodulating properties involving activation of peroxisome proliferator-activated receptors (PPARs) and proliferation of mitochondria. This study aimed to penetrate the effect of TTA on the development of atherosclerotic lesions in apolipoprotein (apo)-E(-/-) mice fed a high-fat diet containing 0.3% TTA for 12 weeks. These mice displayed a significantly less atherosclerotic development vs control. Plasma cholesterol was increased by TTA administration and triacylglycerol (TAG) levels in plasma and liver were decreased by TTA supplementation, the latter, probably due to increased mitochondrial fatty acid oxidation and reduced lipogenesis. TTA administration also changed the fatty acid composition in the heart, and the amount of arachidonic acid (ARA) and eicosapentaenoic acid (EPA) was reduced and increased, respectively. The heart mRNA expression of inducible nitric oxidase (NOS)-2 was decreased in TTA-treated mice, whereas the mRNA level of catalase was increased. Finally, reduced plasma levels of inflammatory mediators as IL-1α, IL-6, IL-17, TNF-α and IFN-γ were detected in TTA-treated mice. These data show that TTA reduces atherosclerosis in apoE(-/-) mice and modulates risk factors related to atherosclerotic disorders. TTA probably acts at both systemic and vascular levels in a manner independent of changes in plasma cholesterol, and triggers TAG catabolism through improved mitochondrial function. PMID:24324736

  17. Cholesterol Asymmetry in Synaptic Plasma Membranes

    PubMed Central

    Wood, W. Gibson; Igbavboa, Urule; Müller, Walter E.; Eckert, Gunter P.

    2010-01-01

    Lipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. A common characteristic of these membrane domains is their association with cholesterol. Lipid rafts and caveolae are examples of cholesterol enriched domains, which have attracted keen interest. However, two other important cholesterol domains are the exofacial and cytofacial leaflets of the plasma membrane. The two leaflets that make up the bilayer differ in their fluidity, electrical charge, lipid distribution, and active sites of certain proteins. The synaptic plasma membrane (SPM) cytofacial leaflet contains over 85% of the total SPM cholesterol as compared with the exofacial leaflet. This asymmetric distribution of cholesterol is not fixed or immobile but can be modified by different conditions in vivo: 1) chronic ethanol consumption; 2) statins; 3) aging; and 4) apoE isoform. Several potential candidates have been proposed as mechanisms involved in regulation of SPM cholesterol asymmetry: apoE, low-density-lipoprotein receptor, sterol carrier protein-2, fatty acid binding proteins, polyunsaturated fatty acids, p-glycoprotein and caveolin-1. This review examines cholesterol asymmetry in SPM, potential mechanisms of regulation and impact on membrane structure and function. PMID:21214553

  18. Effect of plant sterol-enriched diets on plasma and egg yolk cholesterol concentrations and cholesterol metabolism in laying hens.

    PubMed

    Liu, X; Zhao, H L; Thiessen, S; House, J D; Jones, P J H

    2010-02-01

    Egg exists as a major dietary source of cholesterol in Western diets. In North America, laying hen diets are usually devoid of cholesterol when diets are formulated to exclude animal-based products. Hence, laying hens meet their physiological cholesterol requirement through de novo synthesis. Plant sterols exert a cholesterol-lowering effect in humans by interfering with intestinal sterol absorption. However, it is unknown whether plant sterol supplementation could be effective in reducing intestinal reabsorption of biliary cholesterol in laying hens, thus modulating whole body cholesterol in favor of lower plasma and yolk cholesterol content. The current study was designed to investigate the effect of diets enriched with 0, 0.5, 1, and 2% plant sterols on cholesterol absorption, synthesis, as well as plasma, liver, and egg yolk cholesterol concentrations in laying hens. After 8 wk of plant sterol intervention (first 2 wk were acclimatization), feed intake, BW, egg weight, egg yolk weight, egg production, Haugh units, liver mass, plasma, and hepatic cholesterol concentrations did not differ as a function of plant sterol supplementation. Egg cholesterol concentrations (mg/g) fluctuated during the 6-wk experimental period. At wk 6, a minor reduction in egg yolk cholesterol concentration (mg per g of yolk, P<0.05, vs. control) was observed in hens fed 1 and 2% cholesterol-enriched diets, respectively. However, such result failed to affect total egg cholesterol content. No statistical difference was observed across treatments over 6 wk. Neither cholesterol absorption rates nor synthesis differed as a function of treatment. Results suggested that overall cholesterol content in egg yolk was not affected by feeding hens plant sterol-enriched diets over 6 wk. PMID:20075279

  19. Relationship between plasma cholesterol levels and cholesterol esterification in isolated human mononuclear cells

    SciTech Connect

    Dallongeville, J.; Davignon, J.; Lussier-Cacan, S. )

    1990-01-01

    The authors studied the relationship between plasma lipoprotein concentrations and cholesterol esterification in freshly isolated human mononuclear cells from 27 normolipidemic and 32 hyperlipidemic individuals. Cells were either incubated for 5 hours with radiolabeled oleate immediately after isolation or were preincubated for 18 hours in the presence of exogenous cholesterol, and then incubated with ({sup 14}C)sodium-oleate-albumin complex. In the absence of exogenous cholesterol, control and hypercholesterolemic subjects had similarly low values of intracellular cholesterol esterification. In the presence of exogenous cholesterol, both hypertriglyceridemic and hypercholesterolemic subjects had higher cholesterol esterification than controls. There was a significant correlation between the rate of cholesterol esterification and plasma total cholesterol. These results suggest that plasma cholesterol levels may regulate mononuclear cell intra-cellular cholesterol esterification in humans.

  20. Human plasma lecithin-cholesterol acyltransferase

    SciTech Connect

    Jauhiainen, M.; Stevenson, K.J.; Dolphin, P.J.

    1988-05-15

    Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme which catalyzes the transacylation of the fatty acid at the sn-2 position of lecithin to cholesterol forming lysolecithin and cholesteryl ester. The substrates for and products of this reaction are present within the plasma lipoproteins upon which the enzyme acts to form the majority of cholesteryl ester in human plasma. The authors proposed a covalent catalytic mechanism of action for LCAT in which serine and histidine residues mediate lecithin cleavage and two cysteine residues cholesterol esterification. With the aid of sulfhydryl reactive trivalent organoarsenical compounds which are specific for vicinal thiols they have probed the geometry of the catalytic site. They conclude that the two catalytic cysteine residues of LCAT (Cys/sup 31/ and Cys /sup 184/) are vicinal with a calculated distance between their sulfur atoms of 3.50-3.62 A. The additional residue alkylated by teh bifunctional reagent is within the catalytic site and may represent a previously identified catalytic serine or histidine residue.

  1. Differences in synthesis and absorption of cholesterol of two effective lipid-lowering therapies

    PubMed Central

    Kasmas, S.H.; Izar, M.C.; França, C.N.; Ramos, S.C.; Moreira, F.T.; Helfenstein, T.; Moreno, R.A.; Borges, N.C.; Figueiredo-Neto, A.M.; Fonseca, F.A.

    2012-01-01

    Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and β-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and β-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and β-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and β-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies. PMID:22801416

  2. Step by Step: Eating To Lower Your High Blood Cholesterol. Revised.

    ERIC Educational Resources Information Center

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

    This booklet offers advice for adults who want to lower their blood cholesterol level. The first section, "What You Need To Know about High Blood Cholesterol," discusses blood cholesterol and why it matters, what cholesterol numbers mean, and what affects blood cholesterol levels. Section 2, "What You Need To Do To Lower Blood Cholesterol,"…

  3. Unrefined and refined black raspberry seed oils significantly lower triglycerides and moderately affect cholesterol metabolism in male Syrian hamsters.

    PubMed

    Ash, Mark M; Wolford, Kate A; Carden, Trevor J; Hwang, Keum Taek; Carr, Timothy P

    2011-09-01

    Unrefined and refined black raspberry seed oils (RSOs) were examined for their lipid-modulating effects in male Syrian hamsters fed high-cholesterol (0.12% g/g), high-fat (9% g/g) diets. Hamsters fed the refined and the unrefined RSO diets had equivalently lower plasma total cholesterol and high-density lipoprotein (HDL) cholesterol in comparison with the atherogenic coconut oil diet. The unrefined RSO treatment group did not differ in liver total and esterified cholesterol from the coconut oil-fed control animals, but the refined RSO resulted in significantly elevated liver total and esterified cholesterol concentrations. The unrefined RSO diets significantly lowered plasma triglycerides (46%; P=.0126) in comparison with the coconut oil diet, whereas the refined RSO only tended to lower plasma triglyceride (29%; P=.1630). Liver triglyceride concentrations were lower in the unrefined (46%; P=.0002) and refined (36%; P=.0005) RSO-fed animals than the coconut oil group, with the unrefined RSO diet eliciting a lower concentration than the soybean oil diet. Both RSOs demonstrated a null or moderate effect on cholesterol metabolism despite enrichment in linoleic acid, significantly lowering HDL cholesterol but not non-HDL cholesterol. Dramatically, both RSOs significantly reduced hypertriglyceridemia, most likely due to enrichment in α-linolenic acid. As a terrestrial source of α-linolenic acid, black RSOs, both refined and unrefined, provide a promising alternative to fish oil supplementation in management of hypertriglyceridemia, as demonstrated in hamsters fed high levels of dietary triglyceride and cholesterol.

  4. A fluorescent cholesterol analogue for observation of free cholesterol in the plasma membrane of live cells.

    PubMed

    Ogawa, Yoshikatsu; Tanaka, Mutsuo

    2016-01-01

    Free cholesterol in mammalian cells resides mostly in the plasma membrane, where it plays an important role in cellular homeostasis. We synthesized a new fluorescent cholesterol analogue that retained an intact alkyl chain and the sterane backbone of cholesterol. The hydroxyl group of cholesterol was converted into an amino group that was covalently linked to the fluorophore tetramethylrhodamine to retain the ability to form hydrogen bonds with adjacent molecules. Incubating live MDCK (Madin-Darby canine kidney) cells with our fluorescent cholesterol analogue resulted in the generation of intense signals that were detected by microscopy at the plasma membrane. Incubation with the analogue exerted minimal, if any, influence on cell growth, indicating that it could serve as a useful tool for analyzing free cholesterol at the plasma membrane.

  5. Adeno-associated virus serotype 8 gene therapy leads to significant lowering of plasma cholesterol levels in humanized mouse models of homozygous and heterozygous familial hypercholesterolemia.

    PubMed

    Kassim, Sadik H; Li, Hui; Bell, Peter; Somanathan, Suryanarayan; Lagor, William; Jacobs, Frank; Billheimer, Jeffrey; Wilson, James M; Rader, Daniel J

    2013-01-01

    Familial hypercholesterolemia (FH) is a life-threatening genetic disease caused by mutations in the gene encoding low-density lipoprotein receptor (LDLR). As a bridge to clinical trials, we generated a "humanized" mouse model lacking LDLR and apolipoprotein B (ApoB) mRNA editing catalytic polypeptide-1 (APOBEC-1) expression and expressing a human ApoB100 transgene in order to permit more authentic simulation of in vivo interactions between the clinical transgene product, human LDLR (hLDLR), and its endogenous ligand, human ApoB100. On a chow diet, the humanized LDLR-deficient mice have substantial hypercholesterolemia and a lipoprotein phenotype more closely resembling human homozygous FH (hoFH) than in previous mouse models of FH. On injection of an adeno-associated virus serotype 8 (AAV8) vector encoding the human LDLR cDNA, significant correction of hypercholesterolemia was realized at doses as low as 1.5 × 10(11) genome copies (GC)/kg. Given that some patients with heterozygous FH (heFH) cannot be adequately treated with current therapy, we then extended our studies to similarly "humanized" mice that were heterozygous for LDLR deficiency, and that have a lipoprotein phenotype resembling heterozygous FH. Injection of AAV8-hLDLR brought about significant reduction in total and LDL cholesterol at doses as low as 5 × 10(11) GC/kg. Collectively, these data demonstrate the safety and efficacy of the liver-specific AAV8-hLDLR vector in the treatment of humanized mice modeling both hoFH and heFH. PMID:22985273

  6. Adeno-Associated Virus Serotype 8 Gene Therapy Leads to Significant Lowering of Plasma Cholesterol Levels in Humanized Mouse Models of Homozygous and Heterozygous Familial Hypercholesterolemia

    PubMed Central

    Kassim, Sadik H.; Li, Hui; Bell, Peter; Somanathan, Suryanarayan; Lagor, William; Jacobs, Frank; Billheimer, Jeffrey; Rader, Daniel J.

    2013-01-01

    Abstract Familial hypercholesterolemia (FH) is a life-threatening genetic disease caused by mutations in the gene encoding low-density lipoprotein receptor (LDLR). As a bridge to clinical trials, we generated a “humanized” mouse model lacking LDLR and apolipoprotein B (ApoB) mRNA editing catalytic polypeptide-1 (APOBEC-1) expression and expressing a human ApoB100 transgene in order to permit more authentic simulation of in vivo interactions between the clinical transgene product, human LDLR (hLDLR), and its endogenous ligand, human ApoB100. On a chow diet, the humanized LDLR-deficient mice have substantial hypercholesterolemia and a lipoprotein phenotype more closely resembling human homozygous FH (hoFH) than in previous mouse models of FH. On injection of an adeno-associated virus serotype 8 (AAV8) vector encoding the human LDLR cDNA, significant correction of hypercholesterolemia was realized at doses as low as 1.5×1011 genome copies (GC)/kg. Given that some patients with heterozygous FH (heFH) cannot be adequately treated with current therapy, we then extended our studies to similarly “humanized” mice that were heterozygous for LDLR deficiency, and that have a lipoprotein phenotype resembling heterozygous FH. Injection of AAV8-hLDLR brought about significant reduction in total and LDL cholesterol at doses as low as 5×1011 GC/kg. Collectively, these data demonstrate the safety and efficacy of the liver-specific AAV8-hLDLR vector in the treatment of humanized mice modeling both hoFH and heFH. PMID:22985273

  7. Plasma cholesterol-suppressing effect of papain-hydrolyzed pork meat in rats fed hypercholesterolemic diet.

    PubMed

    Morimatsu, F; Ito, M; Budijanto, S; Watanabe, I; Furukawa, Y; Kimura, S

    1996-04-01

    The effects of papain-hydrolyzed pork meat on plasma and liver cholesterol levels were studied in rats fed a cholesterol-enriched diet. In rats fed the low-molecular-weight fraction of papain-hydrolyzed pork meat, the plasma cholesterol concentration, more particularly the VLDL and LDL cholesterol concentrations, were significantly lower (p < 0.01) than in the rats fed untreated pork meat or soybean protein. Feeding with this fraction rather than with untreated pork meat also led to a significantly lower liver cholesterol concentration (p < 0.01) and increased fecal excretion of neutral and acidic steroids. The low-molecular-weight fraction contained peptides with molecular weights of 3,000 or less and had an amino acid composition similar to that of pork meat itself. This study suggests that peptides produced by papain-hydrolysis of pork meat have a hypocholesterolemic activity through their interference with the steroid absorption process. PMID:8780972

  8. Cholesterol-lowering benefits of oat-containing cereal in Hispanic americans.

    PubMed

    Karmally, Wahida; Montez, Maria G; Palmas, Walter; Martinez, Wendy; Branstetter, Anita; Ramakrishnan, Rajasekhar; Holleran, Steve F; Haffner, Steven M; Ginsberg, Henry N

    2005-06-01

    This randomized, controlled trial of cholesterol lowering by an oat bran cereal containing beta glucan vs a corn cereal without soluble fiber in Hispanic Americans was conducted for 11 weeks. One-hundred fifty-two men and women, ages 30 to 70 years, with baseline low-density lipoprotein cholesterol (LDL-C) levels between 120 and 190 mg/dL and triglycerides <400 mg/dL were included. After eating a National Cholesterol Education Program Step 1 diet for 5 weeks, subjects were randomly assigned to the corn or the oat cereal for the next 6 weeks. The daily dose of beta glucan was 3 g. Consumption of oat cereal was associated with a reduction in plasma levels of both total cholesterol (-10.9+/-21.6 mg/dL; -4.5%) and LDL-C (-9.4+/-20.3 mg/dL; -5.3%). Consumption of corn cereal did not affect either total cholesterol (+1.2+/-18.3 mg/dL; 1.1%) or LDL-C (+1.2+/-17.5 mg/dL; 2.2%). Differences between the effects of the two cereals on total cholesterol and LDL-C were significant, P =.0003 and P =.0007, respectively. PMID:15942550

  9. Cholesterol-Lowering Effect of Beta Glucan Extracted from Saccharomyces cerevisiae in Rats

    PubMed Central

    Kusmiati; Dhewantara, F. X. Rizky

    2016-01-01

    Glucans are present in fungi, plants, algae, and bacteria. β-Glucan, one of the major cell wall components of Saccharomyces cerevisiae, has been found to enhance immune functions. Glucans are glucose polymers with an α- or β-type glycosidic chain. The role of (1→3)-β-D-glucan is in the maintenance of yeast cell wall shape and rigidity. Studies reveal that soluble glucans can lower total cholesterol and LDL levels in patients with hypercholesterolemia. The important benefit of β-glucan is to improve the immune system and to decrease cholesterol levels in the blood. Several studies have reported the benefits of β-glucan as: antiseptic, antioxidant, anti-aging, immune system activators, protection against radiation, anti-inflammatory, anti-diabetic, anti-cholesterol etc. In this research S. cerevisiae was cultured in yeast extract–peptone–glucose (YPG) broth medium to produce beta-glucan. Cells were harvested at the stationary phase, washed, and disrupted by means of sonication method. The obtained cell walls were used to prepare alkali-soluble β-glucan (glucan-S1). In this regard, 2% sodium hydroxide (NaOH) and 3% acetic acid were used in alkaline–acid extraction, respectively. Potential use of beta-glucan extract as an anticholesterol agent was tested using Sprague dawley strain rats. The experiments were divided into eight groups with four replicates: Group I (normal control), group II (fed with cholesterol without beta-glucan), group III (fed with cholesterol + atorvastatin), group IV (fed with cholesterol + β-glucan standard), group V–VIII (fed of cholesterol + β-glucan of S. cerevisiae with each dose of 10, 20, 30, and 40 mg / BW. Rats were fed with cholesterol for 14 days, except for group I. Analysis of blood was carried out to determine total cholesterol, triglycerides, and malondialdehyde. The results showed that beta-glucan crude obtained from S. cerevisiae cultures was 6.890g.L−1. Βeta-glucan extract of S. cerevisiae can reduce total

  10. Cholesterol-Lowering Effect of Beta Glucan Extracted from Saccharomyces cerevisiae in Rats.

    PubMed

    Kusmiati; Dhewantara, F X Rizky

    2016-01-01

    Glucans are present in fungi, plants, algae, and bacteria. β-Glucan, one of the major cell wall components of Saccharomyces cerevisiae, has been found to enhance immune functions. Glucans are glucose polymers with an α- or β-type glycosidic chain. The role of (1→3)-β-D-glucan is in the maintenance of yeast cell wall shape and rigidity. Studies reveal that soluble glucans can lower total cholesterol and LDL levels in patients with hypercholesterolemia. The important benefit of β-glucan is to improve the immune system and to decrease cholesterol levels in the blood. Several studies have reported the benefits of β-glucan as: antiseptic, antioxidant, anti-aging, immune system activators, protection against radiation, anti-inflammatory, anti-diabetic, anti-cholesterol etc. In this research S. cerevisiae was cultured in yeast extract-peptone-glucose (YPG) broth medium to produce beta-glucan. Cells were harvested at the stationary phase, washed, and disrupted by means of sonication method. The obtained cell walls were used to prepare alkali-soluble β-glucan (glucan-S1). In this regard, 2% sodium hydroxide (NaOH) and 3% acetic acid were used in alkaline-acid extraction, respectively. Potential use of beta-glucan extract as an anticholesterol agent was tested using Sprague dawley strain rats. The experiments were divided into eight groups with four replicates: Group I (normal control), group II (fed with cholesterol without beta-glucan), group III (fed with cholesterol + atorvastatin), group IV (fed with cholesterol + β-glucan standard), group V-VIII (fed of cholesterol + β-glucan of S. cerevisiae with each dose of 10, 20, 30, and 40 mg / BW. Rats were fed with cholesterol for 14 days, except for group I. Analysis of blood was carried out to determine total cholesterol, triglycerides, and malondialdehyde. The results showed that beta-glucan crude obtained from S. cerevisiae cultures was 6.890g.L(-1). Βeta-glucan extract of S. cerevisiae can reduce total

  11. Cholesterol-Lowering Effect of Beta Glucan Extracted from Saccharomyces cerevisiae in Rats.

    PubMed

    Kusmiati; Dhewantara, F X Rizky

    2016-01-01

    Glucans are present in fungi, plants, algae, and bacteria. β-Glucan, one of the major cell wall components of Saccharomyces cerevisiae, has been found to enhance immune functions. Glucans are glucose polymers with an α- or β-type glycosidic chain. The role of (1→3)-β-D-glucan is in the maintenance of yeast cell wall shape and rigidity. Studies reveal that soluble glucans can lower total cholesterol and LDL levels in patients with hypercholesterolemia. The important benefit of β-glucan is to improve the immune system and to decrease cholesterol levels in the blood. Several studies have reported the benefits of β-glucan as: antiseptic, antioxidant, anti-aging, immune system activators, protection against radiation, anti-inflammatory, anti-diabetic, anti-cholesterol etc. In this research S. cerevisiae was cultured in yeast extract-peptone-glucose (YPG) broth medium to produce beta-glucan. Cells were harvested at the stationary phase, washed, and disrupted by means of sonication method. The obtained cell walls were used to prepare alkali-soluble β-glucan (glucan-S1). In this regard, 2% sodium hydroxide (NaOH) and 3% acetic acid were used in alkaline-acid extraction, respectively. Potential use of beta-glucan extract as an anticholesterol agent was tested using Sprague dawley strain rats. The experiments were divided into eight groups with four replicates: Group I (normal control), group II (fed with cholesterol without beta-glucan), group III (fed with cholesterol + atorvastatin), group IV (fed with cholesterol + β-glucan standard), group V-VIII (fed of cholesterol + β-glucan of S. cerevisiae with each dose of 10, 20, 30, and 40 mg / BW. Rats were fed with cholesterol for 14 days, except for group I. Analysis of blood was carried out to determine total cholesterol, triglycerides, and malondialdehyde. The results showed that beta-glucan crude obtained from S. cerevisiae cultures was 6.890g.L(-1). Βeta-glucan extract of S. cerevisiae can reduce total

  12. Different palm oil preparations reduce plasma cholesterol concentrations and aortic cholesterol accumulation compared to coconut oil in hypercholesterolemic hamsters.

    PubMed

    Wilson, Thomas A; Nicolosi, Robert J; Kotyla, Timothy; Sundram, Kalyana; Kritchevsky, David

    2005-10-01

    Several studies have reported on the effect of refined, bleached and deodorized palm oil (RBD-PO) incorporation into the diet on blood cholesterol concentrations and on the development of atherosclerosis. However, very little work has been reported on the influence of red palm oil (RPO), which is higher in carotenoid and tocopherol content than RBD-PO. Thus, we studied the influence of RPO, RBD-PO and a RBD-PO plus red palm oil extract (reconstituted RBD-PO) on plasma cholesterol concentrations and aortic accumulation vs. hamsters fed coconut oil. Forty-eight F1B Golden Syrian hamsters (Mesocricetus auratus) (BioBreeders, Watertown, MA) were group housed (three/cage) in hanging polystyrene 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 and segregated into four groups of 12 with similar plasma cholesterol concentrations. Group 1 continued on the HCD, Group 2 was fed the HCD containing 10% RPO in place of coconut oil, Group 3 was fed the HCD containing 10% RBD-PO in place of coconut oil and Group 4 was fed the HCD with 10% reconstituted RBD-PO for an additional 10 weeks. Plasma total cholesterol (TC) and non-high-density lipoprotein-cholesterol (HDL-C) (very low- and low-density lipoprotein) concentrations were significantly lower in the hamsters fed the RPO (-42% and -48%), RBD-PO (-32% and -36%) and the reconstituted RBD-PO (-37% and -41%) compared to the coconut oil-fed hamsters. Plasma HDL-C concentrations were significantly higher by 14% and 31% in hamsters fed the RBD-PO and RPO compared to the coconut oil-fed hamsters. Plasma triglyceride (TG) concentrations were significantly lower in hamsters fed RBD-PO (-32%) and the reconstituted RBD-PO (-31%) compared to the coconut oil-fed hamsters. The plasma gamma-tocopherol concentrations were higher

  13. Different palm oil preparations reduce plasma cholesterol concentrations and aortic cholesterol accumulation compared to coconut oil in hypercholesterolemic hamsters.

    PubMed

    Wilson, Thomas A; Nicolosi, Robert J; Kotyla, Timothy; Sundram, Kalyana; Kritchevsky, David

    2005-10-01

    Several studies have reported on the effect of refined, bleached and deodorized palm oil (RBD-PO) incorporation into the diet on blood cholesterol concentrations and on the development of atherosclerosis. However, very little work has been reported on the influence of red palm oil (RPO), which is higher in carotenoid and tocopherol content than RBD-PO. Thus, we studied the influence of RPO, RBD-PO and a RBD-PO plus red palm oil extract (reconstituted RBD-PO) on plasma cholesterol concentrations and aortic accumulation vs. hamsters fed coconut oil. Forty-eight F1B Golden Syrian hamsters (Mesocricetus auratus) (BioBreeders, Watertown, MA) were group housed (three/cage) in hanging polystyrene 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 and segregated into four groups of 12 with similar plasma cholesterol concentrations. Group 1 continued on the HCD, Group 2 was fed the HCD containing 10% RPO in place of coconut oil, Group 3 was fed the HCD containing 10% RBD-PO in place of coconut oil and Group 4 was fed the HCD with 10% reconstituted RBD-PO for an additional 10 weeks. Plasma total cholesterol (TC) and non-high-density lipoprotein-cholesterol (HDL-C) (very low- and low-density lipoprotein) concentrations were significantly lower in the hamsters fed the RPO (-42% and -48%), RBD-PO (-32% and -36%) and the reconstituted RBD-PO (-37% and -41%) compared to the coconut oil-fed hamsters. Plasma HDL-C concentrations were significantly higher by 14% and 31% in hamsters fed the RBD-PO and RPO compared to the coconut oil-fed hamsters. Plasma triglyceride (TG) concentrations were significantly lower in hamsters fed RBD-PO (-32%) and the reconstituted RBD-PO (-31%) compared to the coconut oil-fed hamsters. The plasma gamma-tocopherol concentrations were higher

  14. History and development of plant sterol and stanol esters for cholesterol-lowering purposes.

    PubMed

    Thompson, Gilbert R; Grundy, Scott M

    2005-07-01

    Plant stanol esters provide a novel approach to lowering plasma low-density lipoprotein (LDL) cholesterol by dietary means. Their development was preceded by a long period of research into the cholesterol-lowering properties of plant sterols and, recently, plant stanols. Both classes of compound competitively inhibit the absorption of cholesterol and thus lower its level in plasma. Initial impressions were that stanols were more effective and safer than sterols, but the negative outcome of a study led to the recognition that the lipid solubility of free stanols was very limited. This was overcome by esterifying them with fatty acids, with the resultant stanol esters being freely soluble in fat spreads. This led to the launch of Benecol (margarine; Raisio Group, Raisio, Finland) in 1995. The coincident publication of the year-long North Karelia study conclusively demonstrated the long-term LDL-lowering efficacy of plant stanol esters. Variables that might influence the efficacy of stanol esters include dose, frequency of administration, food vehicle in which the stanol ester is incorporated, and background diet. The effective dose is 1 to 3 g/day, expressed as free stanol, which, in placebo-controlled studies, decreased LDL cholesterol by 6% to 15%. This effect is maintained, appears to be similar with once-daily or divided dosage, and is independent of the fat content of the food vehicle. Short-term studies suggest that equivalent amounts of plant sterol and stanol esters are similarly effective in lowering LDL, the main difference being that plasma plant sterol levels increase on plant sterols and decrease on plant stanols. The clinical significance of these changes remains to be determined.

  15. Pharmacogenomics and pharmacogenetics of cholesterol-lowering therapy.

    PubMed

    Schmitz, Gerd; Drobnik, Wolfgang

    2003-04-01

    Cholesterol-lowering therapy is the central approach in the primary and secondary prevention of cardiovascular disease, the leading cause of death in industrialized countries. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are currently the most potent and widely used cholesterol-lowering drugs. Large-scale clinical trials unequivocally demonstrated the efficacy of statin treatment in reducing the risk of cardiovascular events. In general, HMG-CoA reductase inhibitors are well tolerated, although in a minority of patients severe adverse effects like myopathy or rhabdomyolysis may develop. The incidence of this potentially life-threatening side effects increases with co-adminstration of drugs that are metabolized via the same pharmacokinetic pathways or at high-dose statin therapy. The recent focus on the pleiotropic effects of statins that are more frequently observed at higher doses and the conclusion drawn from the large statin trials that low-density lipoprotein (LDL)-cholesterol is "the lower the better", may need careful consideration in individuals at risk of adverse drug reactions. On the other hand, not all patients respond to statin therapy with a reduction in coronary heart disease (CHD) risk. It is therefore of interest to develop diagnostic test systems, which would allow to identify patients at increased risk of adverse drug reactions or patients with a lack of therapeutic effect. Beside exogenous factors, genetic variability determines the response of an individual to drug therapy and the analysis of genetic variants affecting pharmacokinetic or pharmacodynamic aspects of drug therapy is the subject of pharmacogenomics. This review summarizes current knowledge of the pharmacology and the pharmacogenomics of statin therapy.

  16. Consumption of olive oil has opposite effects on plasma total cholesterol and sphingomyelin concentrations in rats.

    PubMed

    Geelen, M J; Beynen, A C

    2000-05-01

    The hypothesis that olive-oil consumption alters plasma sphingomyelin concentrations and hepatic sphingomyelin metabolism was tested. Rats were fed on purified, high-cholesterol diets with either coconut fat or olive-oil (180 g/kg). In accordance with previous work, olive-oil v. coconut-fat consumption significantly elevated hepatic and total plasma cholesterol concentrations. During the course of the experiment, the concentration of plasma sphingomyelin rose in the coconut-fat group and remained constant in the olive-oil group. When compared with the coconut-fat-fed group, the plasma sphingomyelin levels were significantly lower in the olive-oil-fed group after 14 and 21 d of treatment. Dietary olive oil raised the amounts of cholesterol and sphingomyelin in the VLDL density region, and this change was associated with a reduction in the cholesterol and sphingomyelin contents of the LDL and HDL density ranges. Olive-oil consumption reduced the activity of serine palmitoyltransferase, while the activities of phosphatidylcholine:ceramide cholinephosphotransferase and phosphatidylethanolamine:ceramide ethanolaminephosphotransferase were left unchanged. Dietary olive oil also enhanced the activity of acidic sphingomyelinase, but not that of neutral sphingomyelinase. The present data indicate that dietary olive oil v. coconut fat has opposite effects on total plasma cholesterol and sphingomyelin concentrations. The lower plasma sphingomyelin levels observed in olive-oil-fed, as compared with coconut-fat-fed rats, may be explained by a simultaneous elevation and reduction in sphingomyelin catabolism and synthesis respectively, as based on the measured enzyme activities.

  17. Vegetarians have higher plasma alpha-tocopherol relative to cholesterol than do nonvegetarians.

    PubMed

    Pronczuk, A; Kipervarg, Y; Hayes, K C

    1992-02-01

    Biological antioxidants are thought to play a protective role in certain disease processes, including atherosclerosis. To compare the relative antioxidant/atherogenic risk between vegetarians (presumed lower risk) and omnivores (higher risk), the alpha-tocopherol, total cholesterol and fatty acid (FA) profiles were determined in the plasma of 79 vegetarians (28 males, 51 females) and 79 age- and sex-matched nonvegetarians. In the vegetarian group, mean (+/- SEM) plasma alpha-tocopherol was 714 +/- 46 micrograms/dl for males and 725 +/- 24 for females; corresponding cholesterol values were 122 +/- 5 mg/dl and 138 +/- 3, respectively, which were significantly lower than the respective control values (928 +/- 38; 883 +/- 23 and 206 +/- 6; 188 +/- 4). However, when plasma tocopherol was expressed in terms of cholesterol, the tocopherol: cholesterol molar ratio was significantly enhanced for both male (27%) and female (11%) vegetarians. Vegetarians also had a lower atherosclerosis risk based on their plasma FA profile (higher linoleic:oleic acid ratio) which correlated well (r = 0.72; p less than 0.001) with plasma alpha-tocopherol:cholesterol molar ratio. Since the bulk of tocopherol is transported in low-density lipoprotein, this lipoprotein in vegetarians may be better protected against lipid peroxidation, a process believed to be important in the pathogenesis of atherosclerosis.

  18. Effects of lowering LDL cholesterol on progression of kidney disease.

    PubMed

    Haynes, Richard; Lewis, David; Emberson, Jonathan; Reith, Christina; Agodoa, Lawrence; Cass, Alan; Craig, Jonathan C; de Zeeuw, Dick; Feldt-Rasmussen, Bo; Fellström, Bengt; Levin, Adeera; Wheeler, David C; Walker, Rob; Herrington, William G; Baigent, Colin; Landray, Martin J

    2014-08-01

    Lowering LDL cholesterol reduces the risk of developing atherosclerotic events in CKD, but the effects of such treatment on progression of kidney disease remain uncertain. Here, 6245 participants with CKD (not on dialysis) were randomly assigned to simvastatin (20 mg) plus ezetimibe (10 mg) daily or matching placebo. The main prespecified renal outcome was ESRD (defined as the initiation of maintenance dialysis or kidney transplantation). During 4.8 years of follow-up, allocation to simvastatin plus ezetimibe resulted in an average LDL cholesterol difference (SEM) of 0.96 (0.02) mmol/L compared with placebo. There was a nonsignificant 3% reduction in the incidence of ESRD (1057 [33.9%] cases with simvastatin plus ezetimibe versus 1084 [34.6%] cases with placebo; rate ratio, 0.97; 95% confidence interval [95% CI], 0.89 to 1.05; P=0.41). Similarly, allocation to simvastatin plus ezetimibe had no significant effect on the prespecified tertiary outcomes of ESRD or death (1477 [47.4%] events with treatment versus 1513 [48.3%] events with placebo; rate ratio, 0.97; 95% CI, 0.90 to 1.04; P=0.34) or ESRD or doubling of baseline creatinine (1189 [38.2%] events with treatment versus 1257 [40.2%] events with placebo; rate ratio, 0.93; 95% CI, 0.86 to 1.01; P=0.09). Exploratory analyses also showed no significant effect on the rate of change in eGFR. Lowering LDL cholesterol by 1 mmol/L did not slow kidney disease progression within 5 years in a wide range of patients with CKD.

  19. Mechanisms of cholesterol and saturated fatty acid lowering by Quillaja saponaria extract, studied by in vitro digestion model.

    PubMed

    Vinarova, Liliya; Vinarov, Zahari; Damyanova, Borislava; Tcholakova, Slavka; Denkov, Nikolai; Stoyanov, Simeon

    2015-04-01

    Quillaja saponin extracts are known to reduce plasma cholesterol levels in humans. Here we study the mechanism of this effect with Quillaja Dry saponin extract (QD). In vitro model of triglyceride lipolysis is used to quantify the effect of QD on the solubilization of cholesterol and of the lipolysis products (fatty acids and monoglycerides) in the dietary mixed micelles (DMM). We found that QD extract decreases significantly both the cholesterol (from 80% to 20%) and saturated fatty acids (SFA, from 70% to 10%) solubilised in DMM. Series of dedicated experiments prove that QD may act by two mechanisms: (1) direct precipitation of cholesterol and (2) displacement of cholesterol from the DMM. Both mechanisms lead to increased cholesterol precipitation and, thus, render cholesterol bio-inaccessible. We prove also that the saponin molecules are not the active component of QD, because highly purified Quillaja extract with very similar saponin composition does not exhibit cholesterol-lowering or SFA-lowering effect. The effect of QD extract on cholesterol solubilisation is most probably caused by the high-molecular weight polyphenol molecules, present in this extract. The reduced SFA solubilisation is caused by Ca(2+) ions of relatively high concentration (1.25 wt%), also present in QD extract, which precipitate the fatty acids into calcium soaps. PMID:25773645

  20. Metabolism of low-density lipoprotein free cholesterol by human plasma lecithin-cholesterol acyltransferase

    SciTech Connect

    Fielding, P.E.; Miida, Takashi; Fielding, C.J. )

    1991-09-03

    The metabolism of cholesterol derived from ({sup 3}H) cholesterol-labeled low-density lipoprotein (LDL) was determined in human blood plasma. LDL-derived free cholesterol first appeared in large {alpha}-migrating HDL (HDL{sub 2}) and was then transferred to small {alpha}-HDL (HDL{sub 3}) for esterification. The major part of such esters was retained within HDL of increasing size in the course of lecithin-cholesterol acyltransferase (LCAT) activity; the balance was recovered in LDL. Transfer of preformed cholesteryl esters within HDL contributed little to the labeled cholesteryl ester accumulating HDL{sub 2}. When cholesterol for esterification was derived instead from cell membranes, a significantly smaller proportion of this cholesteryl ester was subsequently recovered in LDL. These data suggest compartmentation of cholesteryl esters within plasma that have been formed from cell membrane or LDL free cholesterol, and the role for HDL{sub 2} as a relatively unreactive sink for LCAT-derived cholesteryl esters.

  1. Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice.

    PubMed

    Thacker, Seth G; Rousset, Xavier; Esmail, Safiya; Zarzour, Abdalrahman; Jin, Xueting; Collins, Heidi L; Sampson, Maureen; Stonik, John; Demosky, Stephen; Malide, Daniela A; Freeman, Lita; Vaisman, Boris L; Kruth, Howard S; Adelman, Steven J; Remaley, Alan T

    2015-07-01

    LCAT, a plasma enzyme that esterifies cholesterol, has been proposed to play an antiatherogenic role, but animal and epidemiologic studies have yielded conflicting results. To gain insight into LCAT and the role of free cholesterol (FC) in atherosclerosis, we examined the effect of LCAT over- and underexpression in diet-induced atherosclerosis in scavenger receptor class B member I-deficient [Scarab(-/-)] mice, which have a secondary defect in cholesterol esterification. Scarab(-/-)×LCAT-null [Lcat(-/-)] mice had a decrease in HDL-cholesterol and a high plasma ratio of FC/total cholesterol (TC) (0.88 ± 0.033) and a marked increase in VLDL-cholesterol (VLDL-C) on a high-fat diet. Scarab(-/-)×LCAT-transgenic (Tg) mice had lower levels of VLDL-C and a normal plasma FC/TC ratio (0.28 ± 0.005). Plasma from Scarab(-/-)×LCAT-Tg mice also showed an increase in cholesterol esterification during in vitro cholesterol efflux, but increased esterification did not appear to affect the overall rate of cholesterol efflux or hepatic uptake of cholesterol. Scarab(-/-)×LCAT-Tg mice also displayed a 51% decrease in aortic sinus atherosclerosis compared with Scarab(-/-) mice (P < 0.05). In summary, we demonstrate that increased cholesterol esterification by LCAT is atheroprotective, most likely through its ability to increase HDL levels and decrease pro-atherogenic apoB-containing lipoprotein particles. PMID:25964513

  2. Global marketing of cholesterol-lowering drugs as therapy.

    PubMed

    Elimimian, Jonathan U; Gilmore, James M; Singletary, Tony J

    2006-01-01

    Pharmaceutical marketing services (PMS) are a key component of pharmaceutical companies' marketing strategies in that they create links between the pharmaceutical company and the physician. They are is also a link between physician and patients locally and globally. PMS discussed in this paper provide various services from tangible to intangible products in order to increase the physicians and pharmacists prescribing activities of their treatment modalities. Given the high cost of recruiting, training, and supporting PMS global marketing efforts, it is important for PMS channels to understand the significance of pharmaceutical multinational companies to ascribe to prescription drug services provided in Thailand. This created the unique marketing environment for the pharmaceutical companies. This study examines whether there is a gap in the existing cholesterol-lowering medication prescribed by physicians in Thailand and the newly introduced brand to the U.S. market. The degree of the new product adoption is analyzed through physician prescription frequency and records. Results of the study indicate there is significant improvement in the health conditions of the users of the new cholesterol medication among Thailand patients. Physicians in Thailand were, however, faced with competing brands in the market due to aggressiveness of advertising and promotion by multinational pharmaceutical marketing and manufacturers Associations. Perceived value and benefit to users were significant outcome of the study. More diagnostic and prescriptive research is recommended to cover Southeast Asia and other parts of the developing countries.

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

    PubMed

    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.

  4. Co-administration of berberine and plant stanols synergistically reduces plasma cholesterol in rats.

    PubMed

    Jia, Xiaoming; Chen, Yanfeng; Zidichouski, Jeffrey; Zhang, Junzeng; Sun, Changhao; Wang, Yanwen

    2008-11-01

    The objective of the present study was to determine the beneficial effects and the safety of oral administration of the combination of berberine (BBR) and plant stanols (PS) on plasma lipid profiles in male Sprague-Dawley rats. Four groups of animals were fed a cornstarch-casein-sucrose-based high-cholesterol (2%, w:w) and high-fat (27.5%) diet. Three treatment groups were supplemented with either BBR (100mgkg(-1)bodyweightd(-1)), PS (1% in diet, w:w), or the combination of both (BBRPS). After 6 wk, animals were sacrificed and followed immediately with the collection of blood and organ samples. Lipid analysis revealed that PS lowered plasma total cholesterol (T-C) by 18% (p=0.067) and non-HDL-cholesterol (non-HDL-C) by 29% (p=0.013) as compared with the control, while BBR had no effect on both T-C and non-HDL-C. The combination treatment of BBRPS reduced plasma T-C by 41% (p=0.0002) and non-HDL-C by 59% (p<0.0001) compared to the control group. BBR reduced plasma TG levels by 31% at a marginal significance relative to the control (p=0.054), whereas PS had no effect. BBRPS showed an additive effect of BBR and PS on plasma TAG. PS and BBRPS both decreased liver cholesterol (p=0.0027 and 0.0002, respectively). BBR and PS, either alone or in combination, did not show any toxic effects as assessed by plasma concentration of hepatic biochemical parameters. These results demonstrate that BBR and PS, when combined, synergistically lower plasma cholesterol levels and significantly reduce liver cholesterol, without the observation of any toxic effects.

  5. Linkage between cholesterol 7alpha-hydroxylase and high plasma low-density lipoprotein cholesterol concentrations.

    PubMed Central

    Wang, J; Freeman, D J; Grundy, S M; Levine, D M; Guerra, R; Cohen, J C

    1998-01-01

    Interindividual differences in plasma low-density lipoprotein cholesterol (LDL-C) levels reflect both environmental variation and genetic polymorphism, but the specific genes involved and their relative contributions to the variance in LDL-C are not known. In this study we investigated the relationship between plasma LDL-C concentrations and three genes with pivotal roles in LDL metabolism: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and cholesterol 7alpha-hydroxylase (CYP7). Analysis of 150 nuclear families indicated statistically significant linkage between plasma LDL-C concentrations and CYP7, but not LDLR or APOB. Further sibling pair analyses using individuals with high plasma LDL-C concentrations as probands indicated that the CYP7 locus was linked to high plasma LDL-C, but not to low plasma LDL-C concentrations. This finding was replicated in an independent sample. DNA sequencing revealed two linked polymorphisms in the 5' flanking region of CYP7. The allele defined by these polymorphisms was associated with increased plasma LDL-C concentrations, both in sibling pairs and in unrelated individuals. Taken together, these findings indicate that polymorphism in CYP7 contributes to heritable variation in plasma LDL-C concentrations. Common polymorphisms in LDLR and APOB account for little of the heritable variation in plasma LDL-C concentrations in the general population. PMID:9502769

  6. Relationship of drinking water disinfectants to plasma cholesterol and thyroid hormone levels in experimental studies

    SciTech Connect

    Revis, N.W.; McCauley, P.; Bull, R.; Holdsworth, G.

    1986-03-01

    The effects of drinking water containing 2 or 15 ppm chlorine (pH 6.5 and 8.5), chlorine dioxide, and monochloramine on thyroid function and plasma cholesterol were studied because previous investigators have reported cardiovascular abnormalities in experimental animals exposed to chlorinated water. Plasma thyroxine (T4) levels, as compared to controls, were significantly decreased in pigeons fed a normal or high-cholesterol diet and drinking water containing these drinking water disinfectants at a concentration of 15 ppm (the exception was chlorine at pH 6.5) for 3 months. In most of the treatment groups, T4 levels were significantly lower following the exposure to drinking water containing the 2 ppm dose. Increase in plasma cholesterol were frequently observed in the groups with lower T4 levels. This association was most evident in pigeons fed the high-cholesterol diet and exposed to these disinfectants at a dose of 15 ppm. The factor(s) associated with the effect of these disinfectants on plasma T4 and cholesterol is not known. The authors suggest however that these effects are probably mediated by products formed when these disinfectants react with organic matter in the upper gastrointestinal tract.

  7. Supplementation of hydroxypropyl methylcellulose into yeast leavened all-whole grain barley bread potentiates cholesterol-lowering effect.

    PubMed

    Kim, Hyunsook; Turowski, Maciej; Anderson, W H Kerr; Young, Scott A; Kim, Yookyung; Yokoyama, Wallace

    2011-07-27

    We investigated in Syrian Golden hamsters the biological impact and its underlying mechanism of single whole grain breads supplemented with 2-3% hydroxypropyl methylcellulose (HPMC), a semisynthetic viscous soluble dietary fiber (SDF) as a substitute for gluten. Hamsters were fed high-fat diets supplemented with 48-65% (w/w) differently ground, freeze-dried single grain breads including whole grain wheat, barley, barley supplemented with HPMC, debranned oat, and oat supplemented with HPMC which were compared to a diet containing microcrystalline cellulose (control). All single grain breads significantly lowered plasma LDL-cholesterol concentrations compared to the control. Enrichment with HPMC further lowered plasma and hepatic cholesterol concentrations. Despite the reduced molecular weight of naturally occurring soluble (1--->3),(1--->4)-β-d-glucan (β-glucan) caused by the bread-making process, whole grain barley breads downregulated hepatic expression of CYP7A1 and HMG-CoAR genes that are responsible for bile acid and cholesterol synthesis, suggesting a possible role of bioactive compounds such as short-chain fatty acids and phenolic compounds from barley bread. Barley bread enriched with HPMC downregulated expression of ABCG5 gene. Taken together, it appears that distinctive modulation of synthesis and excretion of hepatic cholesterol and bile acid contributes to the cholesterol-lowering properties of whole grain barley breads and breads enriched with HPMC. These data suggests that alternative whole grain breads supplemented with HPMC may provide consumers with a staple food that can assist in cholesterol management.

  8. The cholesterol lowering property of coriander seeds (Coriandrum sativum): mechanism of action.

    PubMed

    Dhanapakiam, P; Joseph, J Mini; Ramaswamy, V K; Moorthi, M; Kumar, A Senthil

    2008-01-01

    Coriandrum sativum (Coriander) has been documented as a traditional treatment for cholesterol and diabetes patients. In the present study, coriander seeds incorporated into diet and the effect of the administration of coriander seeds on the metabolism of lipids was studied in rats, fed with high fat diet and added cholesterol. The seeds had a significant hypolipidemic action. In the experimental group of rats (tissue) the level of total cholesterol and triglycerides increased significantly There was significant increase in beta-hydroxy, beta-methyl glutaryl CoA reductase and plasma lecithin cholesterol acyl transferase activity were noted in the experimental group. The level of low density lipoprotein (LDL) + very low density lipoprotein (VLDL) cholesterol decreased while that of high density lipoprotein (HDL) cholesterol increased in the experimental group compared to the control group. The increased activity of plasma LCAT enhanced degradation of cholesterol to fecal bile acids and neutral sterols appeared to account for its hypocholesterolemic effect.

  9. Cholesterol-lowering effects and mechanisms in view of bile acid pathway of resveratrol and resveratrol-glucuronides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Resveratrol (Res) was previously reported to be capable of lowering plasma TC and LDL-C. The mechanism behind Res is not clearly understood, although it is presumed to have an effect on bile acid metabolism in the liver: a significant way in eliminating cholesterol from the body. As one of the major...

  10. Dietary cholesterol and the plasma lipids and lipoproteins in the Tarahumara Indians: a people habituated to a low cholesterol diet after weaning.

    PubMed

    McMurry, M P; Connor, W E; Cerqueira, M T

    1982-04-01

    Eight Tarahumara Indian men participated in a metabolic study to measure the responsiveness of their plasma cholesterol levels to dietary cholesterol. They were fed isocaloric cholesterol-free and high cholesterol diets containing 20% fat, 15% protein, and 65% carbohydrate calories. On admission to the study, the Tarahumaras had a low mean plasma cholesterol concentration (120 mg/dl), reflecting their habitual low cholesterol diet. After 3 wk of a cholesterol-free diet their cholesterol levels were 113 mg/dl. The men were then fed a high cholesterol diet (1000 mg/day) which increased the mean total plasma cholesterol to 147 mg/dl (p less than 0.01) and also increased the low-density lipoprotein cholesterol concentration. Tarahumaras, habituated to a low cholesterol diet after weaning, had the typical hypercholesterolemic response to a high cholesterol diet that has been previously observed in subjects whose lifelong diet was high in cholesterol content.

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

    SciTech Connect

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

    1986-03-01

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

  12. Cholesterol-lowering potential in human subjects of fat from pigs fed rapeseed oil.

    PubMed

    Sandström, B; Bügel, S; Lauridsen, C; Nielsen, F; Jensen, C; Skibsted, L H

    2000-08-01

    The possibility of achieving blood-lipid-lowering characteristics of pig fat by increasing the content of unsaturated fat in pig feed was evaluated. Three pig feeding regimens were applied: basal feed (no added fat or vitamin E), basal feed + rapeseed oil (60 g/kg feed), and basal feed + rapeseed oil (60 g/kg) + vitamin E (200 mg/kg). Meat and meat products from the three pig groups were incorporated into diets providing 86 g pig fat/10 MJ. The diets were served to twelve healthy human male subjects for 3 weeks each in a randomised crossover design. The diets prepared from pigs fed rapeseed oil had a lower content of saturated fatty acids (approximately 9 v. 11% of energy) and a higher content of polyunsaturated fatty acids (approximately 6 v. 4% of energy) than the diet prepared from pigs fed the basal feed. Diets based on fat from pigs fed the rapeseed oil resulted in significantly lower (approximately 4%, P = 0.019) total serum cholesterol concentration compared with the diet from pigs fed the basal feed. No differences were observed in LDL-, HDL- or VLDL-cholesterol, or in triacylglycerol or VLDL-triacylglycerol concentrations. Addition of vitamin E to the pig feed resulted in only a minor increase in vitamin E content in the human subjects' diet and the vitamin E content was low in all three pig diets. Plasma vitamin E concentration in the human subjects at the end of the period with diets from pigs fed rapeseed oil without vitamin E was significantly lower (P = 0.04) than in the other two diet periods. In conclusion, an increased content of rapeseed oil in pig feed changes the fatty acid composition of the pig fat in a way that has a potential to reduce blood cholesterol concentrations in human subjects. However, intake of pig fat with a higher content of unsaturated fatty acids needs to be matched by a higher dietary intake of vitamin E.

  13. Phytosterol intake and dietary fat reduction are independent and additive in their ability to reduce plasma LDL cholesterol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The plasma LDL-cholesterol-lowering effect of plant sterols (PS) appears to be independent of background diet, but definitive proof is lacking. The effect of background diet on plasma concentrations of PS has not been reported. We determined the effects of manipulating dietary contents of PS and f...

  14. Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice[S

    PubMed Central

    Thacker, Seth G.; Rousset, Xavier; Esmail, Safiya; Zarzour, Abdalrahman; Jin, Xueting; Collins, Heidi L.; Sampson, Maureen; Stonik, John; Demosky, Stephen; Malide, Daniela A.; Freeman, Lita; Vaisman, Boris L.; Kruth, Howard S.; Adelman, Steven J.; Remaley, Alan T.

    2015-01-01

    LCAT, a plasma enzyme that esterifies cholesterol, has been proposed to play an antiatherogenic role, but animal and epidemiologic studies have yielded conflicting results. To gain insight into LCAT and the role of free cholesterol (FC) in atherosclerosis, we examined the effect of LCAT over- and underexpression in diet-induced atherosclerosis in scavenger receptor class B member I-deficient [Scarab(−/−)] mice, which have a secondary defect in cholesterol esterification. Scarab(−/−)×LCAT-null [Lcat(−/−)] mice had a decrease in HDL-cholesterol and a high plasma ratio of FC/total cholesterol (TC) (0.88 ± 0.033) and a marked increase in VLDL-cholesterol (VLDL-C) on a high-fat diet. Scarab(−/−)×LCAT-transgenic (Tg) mice had lower levels of VLDL-C and a normal plasma FC/TC ratio (0.28 ± 0.005). Plasma from Scarab(−/−)×LCAT-Tg mice also showed an increase in cholesterol esterification during in vitro cholesterol efflux, but increased esterification did not appear to affect the overall rate of cholesterol efflux or hepatic uptake of cholesterol. Scarab(−/−)×LCAT-Tg mice also displayed a 51% decrease in aortic sinus atherosclerosis compared with Scarab(−/−) mice (P < 0.05). In summary, we demonstrate that increased cholesterol esterification by LCAT is atheroprotective, most likely through its ability to increase HDL levels and decrease pro-atherogenic apoB-containing lipoprotein particles. PMID:25964513

  15. 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.

    PubMed

    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

  16. [PCSK9 inhibitors: new treatment to lower cholesterol].

    PubMed

    Gencer, Baris; Rodondi, Nicolas; Mach, François

    2016-03-01

    The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors appear to represent an important development in the management of hypercholesterolemia. US Food and Drug Administration and European Medicines Agency approved alirocumab and evolocumab, injected drugs administered subcutaneously every 2 or 4 weeks, for patients with hypercholesterolemia, such as those who not reached the cholesterol targets or those with intolerance to statin, especially in secondary prevention or familial hypercholesterolemia. This decision is based on several clinical trials suggesting that these drugs have a powerful effect on levels of LDL-cholesterol with an acceptable safety compared to placebo. Large clinical studies are currently performed to assess the impact of PCSK9 inhibitors on major adverse cardiovascular events in secondary prevention.

  17. [PCSK9 inhibitors: new treatment to lower cholesterol].

    PubMed

    Gencer, Baris; Rodondi, Nicolas; Mach, François

    2016-03-01

    The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors appear to represent an important development in the management of hypercholesterolemia. US Food and Drug Administration and European Medicines Agency approved alirocumab and evolocumab, injected drugs administered subcutaneously every 2 or 4 weeks, for patients with hypercholesterolemia, such as those who not reached the cholesterol targets or those with intolerance to statin, especially in secondary prevention or familial hypercholesterolemia. This decision is based on several clinical trials suggesting that these drugs have a powerful effect on levels of LDL-cholesterol with an acceptable safety compared to placebo. Large clinical studies are currently performed to assess the impact of PCSK9 inhibitors on major adverse cardiovascular events in secondary prevention. PMID:27089600

  18. Randomised controlled trial of the effect of long-term selenium supplementation on plasma cholesterol in an elderly Danish population.

    PubMed

    Cold, Frederik; Winther, Kristian H; Pastor-Barriuso, Roberto; Rayman, Margaret P; Guallar, Eliseo; Nybo, Mads; Griffin, Bruce A; Stranges, Saverio; Cold, Søren

    2015-12-14

    Although cross-sectional studies have shown a positive association between Se and cholesterol concentrations, a recent randomised controlled trial in 501 elderly UK individuals of relatively low-Se status found that Se supplementation for 6 months lowered total plasma cholesterol. The Danish PRECISE (PREvention of Cancer by Intervention with Selenium) pilot study (ClinicalTrials.gov ID: NCT01819649) was a 5-year randomised, double-blinded, placebo-controlled trial with four groups (allocation ratio 1:1:1:1). Men and women aged 60-74 years (n 491) were randomised to 100 (n 124), 200 (n 122) or 300 (n 119) μg Se-enriched yeast or matching placebo-yeast tablets (n 126) daily for 5 years. A total of 468 participants continued the study for 6 months and 361 participants, equally distributed across treatment groups, continued for 5 years. Plasma samples were analysed for total and HDL-cholesterol and for total Se concentrations at baseline, 6 months and 5 years. The effect of different doses of Se supplementation on plasma lipid and Se concentrations was estimated by using linear mixed models. Plasma Se concentration increased significantly and dose-dependently in the intervention groups after 6 months and 5 years. Total cholesterol decreased significantly both in the intervention groups and in the placebo group after 6 months and 5 years, with small and nonsignificant differences in changes in plasma concentration of total cholesterol, HDL-cholesterol, non-HDL-cholesterol and total:HDL-cholesterol ratio between intervention and placebo groups. The effect of long-term supplementation with Se on plasma cholesterol concentrations or its sub-fractions did not differ significantly from placebo in this elderly population. PMID:26420334

  19. Randomised controlled trial of the effect of long-term selenium supplementation on plasma cholesterol in an elderly Danish population.

    PubMed

    Cold, Frederik; Winther, Kristian H; Pastor-Barriuso, Roberto; Rayman, Margaret P; Guallar, Eliseo; Nybo, Mads; Griffin, Bruce A; Stranges, Saverio; Cold, Søren

    2015-12-14

    Although cross-sectional studies have shown a positive association between Se and cholesterol concentrations, a recent randomised controlled trial in 501 elderly UK individuals of relatively low-Se status found that Se supplementation for 6 months lowered total plasma cholesterol. The Danish PRECISE (PREvention of Cancer by Intervention with Selenium) pilot study (ClinicalTrials.gov ID: NCT01819649) was a 5-year randomised, double-blinded, placebo-controlled trial with four groups (allocation ratio 1:1:1:1). Men and women aged 60-74 years (n 491) were randomised to 100 (n 124), 200 (n 122) or 300 (n 119) μg Se-enriched yeast or matching placebo-yeast tablets (n 126) daily for 5 years. A total of 468 participants continued the study for 6 months and 361 participants, equally distributed across treatment groups, continued for 5 years. Plasma samples were analysed for total and HDL-cholesterol and for total Se concentrations at baseline, 6 months and 5 years. The effect of different doses of Se supplementation on plasma lipid and Se concentrations was estimated by using linear mixed models. Plasma Se concentration increased significantly and dose-dependently in the intervention groups after 6 months and 5 years. Total cholesterol decreased significantly both in the intervention groups and in the placebo group after 6 months and 5 years, with small and nonsignificant differences in changes in plasma concentration of total cholesterol, HDL-cholesterol, non-HDL-cholesterol and total:HDL-cholesterol ratio between intervention and placebo groups. The effect of long-term supplementation with Se on plasma cholesterol concentrations or its sub-fractions did not differ significantly from placebo in this elderly population.

  20. Novel method for reducing plasma cholesterol: a ligand replacement therapy

    PubMed Central

    Anantharamaiah, GM; Goldberg, Dennis

    2015-01-01

    Despite wide use of statins, significant cardiovascular disease risk persists. High-density lipoprotein based therapy has not yielded any positive results in combating this disease. Newer methods to rapidly decrease plasma cholesterol are much needed. While apolipoprotein B is a ligand for low-density lipoprotein receptor, which clears low-density lipoprotein cholesterol in a highly regulated pathway, apolipoprotein E (apoE) is a ligand for clearing other apolipoprotein B containing atherogenic lipoproteins via an alternate receptor pathway, especially the heparin sulfate proteoglycans on the liver cell surface. We describe here a novel method that replaces apoE as a ligand to clear all of the atherogenic lipoproteins via the heparin sulfate proteoglycans pathway. This ligand replacement apoE mimetic peptide therapy, having been designated as an orphan drug by the US FDA, is in clinical trials. PMID:25937835

  1. Individual Variation in the Effects of Dietary Cholesterol on Plasma Lipoproteins and Cellular Cholesterol Homeostasis in Man

    PubMed Central

    Mistry, P.; Miller, N. E.; Laker, M.; Hazzard, W. R.; Lewis, B.

    1981-01-01

    The effects of dietary cholesterol on plasma lipoproteins and cholesterol homeostasis in blood mononuclear cells have been examined in healthy adults. Addition of 1,500 mg of cholesterol to the daily diet of 37 subjects for 14 d was associated with a wide range of response of plasma total cholesterol concentration (from −6 to +75 mg/dl; mean change, +29 mg/dl; P < 0.001). Increases in plasma cholesterol reflected increased cholesterol concentrations in intermediate density lipoprotein (IDL; 1.006-1.019 g/ml), low density lipoprotein (LDL; 1.019-1.063 g/ml), and the HDL2 subclass (1.063-1.125 g/ml) of high density lipoprotein, which on average accounted for 20, 58, and 22%, respectively, of the total increment. Similar responses occurred in 14 other subjects given 750 mg cholesterol per day for 28 d. Plasma apolipoprotein B concentrations in IDL and LDL also increased. These effects on plasma lipoproteins were accompanied by three changes in freshly isolated blood mononuclear cells: (a) an increase in cell cholesterol content (mean change, +17%; P < 0.01); (b) suppression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity (−32%; P < 0.001); and (c) reduction of LDL receptor activity (−74%; P < 0.01), quantified as the rate of degradation of 125I-LDL to noniodide trichloroacetic acid-soluble material. These results provide the first direct evidence for the modulation of LDL receptor activity and HMG CoA reductase activity in a peripheral cell type in response to a dietary perturbation of human lipoprotein metabolism. The percentage increase in LDL cholesterol was negatively correlated with the percentage decrease in HMG CoA reductase activity (r = −0.49, P < 0.01). An additional negative correlation existed between the increment in plasma cholesterol concentration and the capacity of cells to degrade 125I-LDL after derepression by preincubation for 72 h in lipoprotein-deficient medium (r = −0.74, P < 0.001). Thus, differences between

  2. Degradation of plasma membrane phosphatidylcholine appears not to affect the cellular cholesterol distribution.

    PubMed

    Pörn, M I; Ares, M P; Slotte, J P

    1993-08-01

    To clarify the role of possible cholesterol/phosphatidylcholine interactions in cellular cholesterol distribution, we have used a phosphatidylcholine-specific phospholipase C from Bacillus cereus to degrade the cell surface phosphatidylcholine of cultured human fibroblasts. Of cellular phosphatidylcholine, approximately 15% was susceptible to degradation by the phospholipase. In spite of the dramatic redistribution of cellular cholesterol that can be observed after sphingomyelin depletion, the degradation of cell surface phosphatidylcholine did not affect the distribution of cholesterol in fibroblasts. In cholesterol-depleted cells as well as in cholesterol-loaded cells, the size of the cell surface cholesterol pool (susceptible to cholesterol oxidase) remained unchanged after phosphatidylcholine degradation. The rate of cholesterol esterification with [3H]oleic acid and the rate of [3H]cholesterol efflux from fibroblasts to high density lipoproteins also remained unchanged after degradation of plasma membrane phosphatidylcholine. An increase in the level of [3H]cholesterol efflux to high density lipoproteins was observed after degradation of plasma membrane sphingomyelin with exogenous sphingomyelinase, in-contrast to earlier reports, where no such effect was observed. The results suggest that interactions between cholesterol and phosphatidylcholine in the fibroblast plasma membranes are less important than cholesterol/sphingomyelin interactions for the asymmetric distribution of cellular cholesterol.

  3. The mechanism of lowering cholesterol absorption by calcium studied by using an in vitro digestion model.

    PubMed

    Vinarova, Liliya; Vinarov, Zahari; Tcholakova, Slavka; Denkov, Nikolai D; Stoyanov, Simeon; Lips, Alex

    2016-01-01

    Studies in humans show that a calcium-enriched diet leads to lower cholesterol in blood serum. This phenomenon is usually explained in the literature with a reduced cholesterol absorption in the small intestine. Our study aims to clarify the effect of calcium on the solubilisation of cholesterol and fatty acid in the dietary mixed micelles (DMM), viz. on the bioaccessibility of these lipophilic substances in the gut. We use an in vitro digestion model which mimics very closely the intestinal pH-profile and the composition of the intestinal fluids. We quantified the effects of Ca(2+) concentration on the lipid solubilization for fats and oils with different saturated/unsaturated fatty acid (FA) contents. We found that the increase of calcium significantly decreases the solubilization of cholesterol, FA and MG. Most importantly, we observe a clear positive correlation between the amounts of solubilized cholesterol, on one side, and solubilized free fatty acids and monoglycerides, on the other side. The main conclusion is that Ca(2+) ions strongly affect the bioaccessibility of both cholesterol and saturated FA. Therefore, calcium may decrease the serum cholesterol via two complementary mechanisms: (1) fatty acid precipitation by calcium ions reduces the solubilisation capacity of the DMM, thus decreasing the levels of solubilised (bioaccessible) cholesterol; (2) the observed strong decrease of the bioaccessible saturated FA, in its own turn, may suppress the cholesterol synthesis in the liver. PMID:26481461

  4. The mechanism of lowering cholesterol absorption by calcium studied by using an in vitro digestion model.

    PubMed

    Vinarova, Liliya; Vinarov, Zahari; Tcholakova, Slavka; Denkov, Nikolai D; Stoyanov, Simeon; Lips, Alex

    2016-01-01

    Studies in humans show that a calcium-enriched diet leads to lower cholesterol in blood serum. This phenomenon is usually explained in the literature with a reduced cholesterol absorption in the small intestine. Our study aims to clarify the effect of calcium on the solubilisation of cholesterol and fatty acid in the dietary mixed micelles (DMM), viz. on the bioaccessibility of these lipophilic substances in the gut. We use an in vitro digestion model which mimics very closely the intestinal pH-profile and the composition of the intestinal fluids. We quantified the effects of Ca(2+) concentration on the lipid solubilization for fats and oils with different saturated/unsaturated fatty acid (FA) contents. We found that the increase of calcium significantly decreases the solubilization of cholesterol, FA and MG. Most importantly, we observe a clear positive correlation between the amounts of solubilized cholesterol, on one side, and solubilized free fatty acids and monoglycerides, on the other side. The main conclusion is that Ca(2+) ions strongly affect the bioaccessibility of both cholesterol and saturated FA. Therefore, calcium may decrease the serum cholesterol via two complementary mechanisms: (1) fatty acid precipitation by calcium ions reduces the solubilisation capacity of the DMM, thus decreasing the levels of solubilised (bioaccessible) cholesterol; (2) the observed strong decrease of the bioaccessible saturated FA, in its own turn, may suppress the cholesterol synthesis in the liver.

  5. Nitric oxide, cholesterol oxides and endothelium-dependent vasodilation in plasma of patients with essential hypertension.

    PubMed

    Moriel, P; Sevanian, A; Ajzen, S; Zanella, M T; Plavnik, F L; Rubbo, H; Abdalla, D S P

    2002-11-01

    The objective of the present study was to identify disturbances of nitric oxide radical (.NO) metabolism and the formation of cholesterol oxidation products in human essential hypertension. The concentrations of.NO derivatives (nitrite, nitrate, S-nitrosothiols and nitrotyrosine), water and lipid-soluble antioxidants and cholesterol oxides were measured in plasma of 11 patients with mild essential hypertension (H: 57.8 +/- 9.7 years; blood pressure, 148.3 +/- 24.8/90.8 +/- 10.2 mmHg) and in 11 healthy subjects (N: 48.4 +/- 7.0 years; blood pressure, 119.4 +/- 9.4/75.0 +/- 8.0 mmHg). Nitrite, nitrate and S-nitrosothiols were measured by chemiluminescence and nitrotyrosine was determined by ELISA. Antioxidants were determined by reverse-phase HPLC and cholesterol oxides by gas chromatography. Hypertensive patients had reduced endothelium-dependent vasodilation in response to reactive hyperemia (H: 9.3 and N: 15.1% increase of diameter 90 s after hyperemia), and lower levels of ascorbate (H: 29.2 +/- 26.0, N: 54.2 +/- 24.9 micro M), urate (H: 108.5 +/- 18.9, N: 156.4 +/- 26.3 micro M), beta-carotene (H: 1.1 +/- 0.8, N: 2.5 +/- 1.2 nmol/mg cholesterol), and lycopene (H: 0.4 +/- 0.2, N: 0.7 +/- 0.2 nmol/mg cholesterol), in plasma, compared to normotensive subjects. The content of 7-ketocholesterol, 5alpha-cholestane-3beta,5,6beta-triol and 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol in LDL, and the concentration of endothelin-1 (H: 0.9 +/- 0.2, N: 0.7 +/- 0.1 ng/ml) in plasma were increased in hypertensive patients. No differences were found for.NO derivatives between groups. These data suggest that an increase in cholesterol oxidation is associated with endothelium dysfunction in essential hypertension and oxidative stress, although.NO metabolite levels in plasma are not modified in the presence of elevated cholesterol oxides. PMID:12426629

  6. Cholesterol-Lowering Effects of Probiotics and Prebiotics: A Review of in Vivo and in Vitro Findings

    PubMed Central

    Ooi, Lay-Gaik; Liong, Min-Tze

    2010-01-01

    Probiotics are live microorganisms that promote health benefits upon consumption, while prebiotics are nondigestible food ingredients that selectively stimulate the growth of beneficial microorganisms in the gastrointestinal tract. Probiotics and/or prebiotics could be used as alternative supplements to exert health benefits, including cholesterol-lowering effects on humans. Past in vivo studies showed that the administration of probiotics and/or prebiotics are effective in improving lipid profiles, including the reduction of serum/plasma total cholesterol, LDL-cholesterol and triglycerides or increment of HDL-cholesterol. However, other past studies have also shown that probiotics and prebiotics had insignificant effects on lipid profiles, disputing the hypocholesterolemic claim. Additionally, little information is available on the effective dosage of probiotics and prebiotics needed to exert hypocholesterolemic effects. Probiotics and prebiotics have been suggested to reduce cholesterol via various mechanisms. However, more clinical evidence is needed to strengthen these proposals. Safety issues regarding probiotics and/or prebiotics have also been raised despite their long history of safe use. Although probiotic-mediated infections are rare, several cases of systemic infections caused by probiotics have been reported and the issue of antibiotic resistance has sparked much debate. Prebiotics, classified as food ingredients, are generally considered safe, but overconsumption could cause intestinal discomfort. Conscientious prescription of probiotics and/or prebiotics is crucial, especially when administering to specific high risk groups such as infants, the elderly and the immuno-compromised. PMID:20640165

  7. Cholesterol-lowering effects of probiotics and prebiotics: a review of in vivo and in vitro findings.

    PubMed

    Ooi, Lay-Gaik; Liong, Min-Tze

    2010-06-17

    Probiotics are live microorganisms that promote health benefits upon consumption, while prebiotics are nondigestible food ingredients that selectively stimulate the growth of beneficial microorganisms in the gastrointestinal tract. Probiotics and/or prebiotics could be used as alternative supplements to exert health benefits, including cholesterol-lowering effects on humans. Past in vivo studies showed that the administration of probiotics and/or prebiotics are effective in improving lipid profiles, including the reduction of serum/plasma total cholesterol, LDL-cholesterol and triglycerides or increment of HDL-cholesterol. However, other past studies have also shown that probiotics and prebiotics had insignificant effects on lipid profiles, disputing the hypocholesterolemic claim. Additionally, little information is available on the effective dosage of probiotics and prebiotics needed to exert hypocholesterolemic effects. Probiotics and prebiotics have been suggested to reduce cholesterol via various mechanisms. However, more clinical evidence is needed to strengthen these proposals. Safety issues regarding probiotics and/or prebiotics have also been raised despite their long history of safe use. Although probiotic-mediated infections are rare, several cases of systemic infections caused by probiotics have been reported and the issue of antibiotic resistance has sparked much debate. Prebiotics, classified as food ingredients, are generally considered safe, but overconsumption could cause intestinal discomfort. Conscientious prescription of probiotics and/or prebiotics is crucial, especially when administering to specific high risk groups such as infants, the elderly and the immuno-compromised.

  8. Cholesterol-lowering properties of Ganoderma lucidum in vitro, ex vivo, and in hamsters and minipigs

    PubMed Central

    Berger, A; Rein, D; Kratky, E; Monnard, I; Hajjaj, H; Meirim, I; Piguet-Welsch, C; Hauser, J; Mace, K; Niederberger, P

    2004-01-01

    Introduction There has been renewed interest in mushroom medicinal properties. We studied cholesterol lowering properties of Ganoderma lucidum (Gl), a renowned medicinal species. Results Organic fractions containing oxygenated lanosterol derivatives inhibited cholesterol synthesis in T9A4 hepatocytes. In hamsters, 5% Gl did not effect LDL; but decreased total cholesterol (TC) 9.8%, and HDL 11.2%. Gl (2.5 and 5%) had effects on several fecal neutral sterols and bile acids. Both Gl doses reduced hepatic microsomal ex-vivo HMG-CoA reductase activity. In minipigs, 2.5 Gl decreased TC, LDL- and HDL cholesterol 20, 27, and 18%, respectively (P < 0.05); increased fecal cholestanol and coprostanol; and decreased cholate. Conclusions Overall, Gl has potential to reduce LDL cholesterol in vivo through various mechanisms. Next steps are to: fully characterize bioactive components in lipid soluble/insoluble fractions; evaluate bioactivity of isolated fractions; and examine human cholesterol lowering properties. Innovative new cholesterol-lowering foods and medicines containing Gl are envisioned. PMID:14969592

  9. Effects of Adiposity on Plasma Lipid Response to Reductions in Dietary Saturated Fatty Acids and Cholesterol1

    PubMed Central

    Flock, Michael R.; Green, Michael H.; Kris-Etherton, Penny M.

    2011-01-01

    Dietary SFA and cholesterol are major targets for reducing plasma total and LDL cholesterol as a strategy to decrease cardiovascular disease risk. However, many studies show that excess adiposity attenuates the expected lipid and lipoprotein response to a plasma cholesterol–lowering diet. Diets low in SFA and cholesterol are less effective in improving the lipid profile in obese individuals and in patients with metabolic syndrome. In contrast, lean persons are more responsive to reductions in dietary SFA and cholesterol. Multiple mechanisms likely contribute to the altered plasma lipid responses to dietary changes in individuals with excess adiposity. The greater rate of hepatic cholesterol synthesis in obese individuals suppresses the expression of hepatic LDL receptors (LDLR), thereby reducing hepatic LDL uptake. Insulin resistance develops as a result of adipose-tissue induced inflammation, causing significant changes in enzymes necessary for normal lipid metabolism. In addition, the LDLR-mediated uptake in obesity is attenuated by alterations in neuroendocrine regulation of hormonal secretions (e.g. growth hormone, thyroid hormone, and cortisol) as well as the unique gut microbiota, the latter of which appears to affect lipid absorption. Reducing adipose tissue mass, especially from the abdominal region, is an effective strategy to improve the lipid response to dietary interventions by reducing inflammation, enhancing insulin sensitivity, and improving LDLR binding. Thus, normalizing adipose tissue mass is an important goal for maximizing the diet response to a plasma cholesterol–lowering diet. PMID:22332058

  10. [The mechanisms of blood LDL-cholesterol lowering by phytosterols--a review].

    PubMed

    Włodarek, Dariusz

    2007-01-01

    Daily cholesterol consumption in western countries reaches as much as 400 mg. According to the health recommendations the daily intake should not exceed 300 mg and in the case of people with cardiovascular disease it should be less than 200 mg. For 50 years it is known that phytosterols can decrease the level of cholesterol in blood. One of the mechanisms is based on the fact that phytosterols stop absorption of cholesterol in digestive tract, which results in the decrease of the concentration of cholesterol in blood. The second mechanism is based on the fact that cholesterol is pumped back out of enterocytes into the lumen of small intestine by ABC transporter and phytosterols increase this process. The above merftioned mechanisms are different than the way statins can lower cholesterol level and they are commonly used as hipocholesterolemic medicine. Because different mechanisms are implemented both statins and fitosterols can be used in therapy of hipercholeserolemia. The people taking statins who still have increased level of total cholesterol and LDL-cholesterol in blood can include phytosterols in their diet what can lead to the decrease of its level.

  11. Sphingolipid domains in the plasma membranes of fibroblasts are not enriched with cholesterol

    SciTech Connect

    Frisz, Jessica F.; Klitzing, Haley A.; Lou, Kaiyan; Hutcheon, Ian D.; Weber, Peter K.; Zimmerberg, Joshua; Kraft, Mary L.

    2013-04-22

    The plasma membranes of mammalian cells are widely expected to contain domains that are enriched with cholesterol and sphingolipids. In this work, we have used high-resolution secondary ion mass spectrometry to directly map the distributions of isotope-labeled cholesterol and sphingolipids in the plasma membranes of intact fibroblast cells. Although acute cholesterol depletion reduced sphingolipid domain abundance, cholesterol was evenly distributed throughout the plasma membrane and was not enriched within the sphingolipid domains. As a result, we rule out favorable cholesterol-sphingolipid interactions as dictating plasma membrane organization in fibroblast cells. Because the sphingolipid domains are disrupted by drugs that depolymerize the cells actin cytoskeleton, cholesterol must instead affect the sphingolipid organization via an indirect mechanism that involves the cytoskeleton.

  12. Sphingolipid domains in the plasma membranes of fibroblasts are not enriched with cholesterol

    DOE PAGES

    Frisz, Jessica F.; Klitzing, Haley A.; Lou, Kaiyan; Hutcheon, Ian D.; Weber, Peter K.; Zimmerberg, Joshua; Kraft, Mary L.

    2013-04-22

    The plasma membranes of mammalian cells are widely expected to contain domains that are enriched with cholesterol and sphingolipids. In this work, we have used high-resolution secondary ion mass spectrometry to directly map the distributions of isotope-labeled cholesterol and sphingolipids in the plasma membranes of intact fibroblast cells. Although acute cholesterol depletion reduced sphingolipid domain abundance, cholesterol was evenly distributed throughout the plasma membrane and was not enriched within the sphingolipid domains. As a result, we rule out favorable cholesterol-sphingolipid interactions as dictating plasma membrane organization in fibroblast cells. Because the sphingolipid domains are disrupted by drugs that depolymerize themore » cells actin cytoskeleton, cholesterol must instead affect the sphingolipid organization via an indirect mechanism that involves the cytoskeleton.« less

  13. Sphingolipid Domains in the Plasma Membranes of Fibroblasts Are Not Enriched with Cholesterol*

    PubMed Central

    Frisz, Jessica F.; Klitzing, Haley A.; Lou, Kaiyan; Hutcheon, Ian D.; Weber, Peter K.; Zimmerberg, Joshua; Kraft, Mary L.

    2013-01-01

    The plasma membranes of mammalian cells are widely expected to contain domains that are enriched with cholesterol and sphingolipids. In this work, we have used high-resolution secondary ion mass spectrometry to directly map the distributions of isotope-labeled cholesterol and sphingolipids in the plasma membranes of intact fibroblast cells. Although acute cholesterol depletion reduced sphingolipid domain abundance, cholesterol was evenly distributed throughout the plasma membrane and was not enriched within the sphingolipid domains. Thus, we rule out favorable cholesterol-sphingolipid interactions as dictating plasma membrane organization in fibroblast cells. Because the sphingolipid domains are disrupted by drugs that depolymerize the cells actin cytoskeleton, cholesterol must instead affect the sphingolipid organization via an indirect mechanism that involves the cytoskeleton. PMID:23609440

  14. Adding monounsaturated fatty acids to a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia

    PubMed Central

    Jenkins, David J.A.; Chiavaroli, Laura; Wong, Julia M.W.; Kendall, Cyril; Lewis, Gary F.; Vidgen, Edward; Connelly, Philip W.; Leiter, Lawrence A.; Josse, Robert G.; Lamarche, Benoît

    2010-01-01

    Background Higher intake of monounsaturated fat may raise high-density lipoprotein (HDL) cholesterol without raising low-density lipoprotein (LDL) cholesterol. We tested whether increasing the monounsaturated fat content of a diet proven effective for lowering LDL cholesterol (dietary portfolio) also modified other risk factors for cardiovascular disease, specifically by increasing HDL cholesterol, lowering serum triglyceride and further reducing the ratio of total to HDL cholesterol. Methods Twenty-four patients with hyperlipidemia consumed a therapeutic diet very low in saturated fat for one month and were then randomly assigned to a dietary portfolio low or high in monounsaturated fatty acid for another month. We supplied participants’ food for the two-month period. Calorie intake was based on Harris–Benedict estimates for energy requirements. Results For patients who consumed the dietary portfolio high in monounsaturated fat, HDL cholesterol rose, whereas for those consuming the dietary portfolio low in monounsaturated fat, HDL cholesterol did not change. The 12.5% treatment difference was significant (0.12 mmol/L, 95% confidence interval [CI] 0.05 to 0.21, p = 0.003). The ratio of total to HDL cholesterol was reduced by 6.5% with the diet high in monounsaturated fat relative to the diet low in monounsaturated fat (−0.28, 95% CI −0.59 to −0.04, p = 0.025). Patients consuming the diet high in monounsaturated fat also had significantly higher concentrations of apolipoprotein AI, and their C-reactive protein was significantly lower. No treatment differences were seen for triglycerides, other lipids or body weight, and mean weight loss was similar for the diets high in monounsaturated fat (−0.8 kg) and low in monounsaturated fat (−1.2 kg). Interpretation Monounsaturated fat increased the effectiveness of a cholesterol-lowering dietary portfolio, despite statin-like reductions in LDL cholesterol. The potential benefits for cardiovascular risk were

  15. Higher Plasma LDL-Cholesterol is Associated with Preserved Executive and Fine Motor Functions in Parkinson’s Disease

    PubMed Central

    Sterling, Nicholas W.; Lichtenstein, Maya; Lee, Eun-Young; Lewis, Mechelle M.; Evans, Alicia; Eslinger, Paul J.; Du, Guangwei; Gao, Xiang; Chen, Honglei; Kong, Lan; Huang, Xuemei

    2016-01-01

    Plasma low density lipoprotein (LDL) cholesterol has been associated both with risk of Parkinson’s disease (PD) and with age-related changes in cognitive function. This prospective study examined the relationship between baseline plasma LDL-cholesterol and cognitive changes in PD and matched Controls. Fasting plasma LDL-cholesterol levels were obtained at baseline from 64 non-demented PD subjects (62.7 ± 7.9 y) and 64 Controls (61.3 ± 6.8 y). Subjects underwent comprehensive neuropsychological testing at baseline, 18-, and 36-months. Linear mixed-effects modeling was used to assess the relationships between baseline LDL-cholesterol levels and longitudinal cognitive changes. At baseline, PD patients had lower scores of fine motor (p<0.0001), executive set shifting (p=0.018), and mental processing speed (p=0.049) compared to Controls. Longitudinally, Controls demonstrated improved fine motor and memory test scores (p=0.044, and p=0.003), whereas PD patients demonstrated significantly accelerated loss in fine motor skill (p=0.002) compared to Controls. Within the PD group, however, higher LDL-cholesterol levels were associated with improved executive set shifting (β=0.003, p<0.001) and fine motor scores (β=0.002, p=0.030) over time. These associations were absent in Controls (p>0.7). The cholesterol - executive set shifting association differed significantly between PDs and Controls (interaction p=0.005), whereas the cholesterol - fine motor association difference did not reach significance (interaction, p=0.104). In summary, higher plasma LDL-cholesterol levels were associated with better executive function and fine motor performance over time in PD, both of which may reflect an effect on nigrostriatal mediation. Confirmation of these results and elucidation of involved mechanisms are warranted, and might lead to feasible therapeutic strategies. PMID:27330838

  16. Higher Plasma LDL-Cholesterol is Associated with Preserved Executive and Fine Motor Functions in Parkinson's Disease.

    PubMed

    Sterling, Nicholas W; Lichtenstein, Maya; Lee, Eun-Young; Lewis, Mechelle M; Evans, Alicia; Eslinger, Paul J; Du, Guangwei; Gao, Xiang; Chen, Honglei; Kong, Lan; Huang, Xuemei

    2016-05-01

    Plasma low density lipoprotein (LDL) cholesterol has been associated both with risk of Parkinson's disease (PD) and with age-related changes in cognitive function. This prospective study examined the relationship between baseline plasma LDL-cholesterol and cognitive changes in PD and matched Controls. Fasting plasma LDL-cholesterol levels were obtained at baseline from 64 non-demented PD subjects (62.7 ± 7.9 y) and 64 Controls (61.3 ± 6.8 y). Subjects underwent comprehensive neuropsychological testing at baseline, 18-, and 36-months. Linear mixed-effects modeling was used to assess the relationships between baseline LDL-cholesterol levels and longitudinal cognitive changes. At baseline, PD patients had lower scores of fine motor (p<0.0001), executive set shifting (p=0.018), and mental processing speed (p=0.049) compared to Controls. Longitudinally, Controls demonstrated improved fine motor and memory test scores (p=0.044, and p=0.003), whereas PD patients demonstrated significantly accelerated loss in fine motor skill (p=0.002) compared to Controls. Within the PD group, however, higher LDL-cholesterol levels were associated with improved executive set shifting (β=0.003, p<0.001) and fine motor scores (β=0.002, p=0.030) over time. These associations were absent in Controls (p>0.7). The cholesterol - executive set shifting association differed significantly between PDs and Controls (interaction p=0.005), whereas the cholesterol - fine motor association difference did not reach significance (interaction, p=0.104). In summary, higher plasma LDL-cholesterol levels were associated with better executive function and fine motor performance over time in PD, both of which may reflect an effect on nigrostriatal mediation. Confirmation of these results and elucidation of involved mechanisms are warranted, and might lead to feasible therapeutic strategies. PMID:27330838

  17. Higher Plasma LDL-Cholesterol is Associated with Preserved Executive and Fine Motor Functions in Parkinson's Disease.

    PubMed

    Sterling, Nicholas W; Lichtenstein, Maya; Lee, Eun-Young; Lewis, Mechelle M; Evans, Alicia; Eslinger, Paul J; Du, Guangwei; Gao, Xiang; Chen, Honglei; Kong, Lan; Huang, Xuemei

    2016-05-01

    Plasma low density lipoprotein (LDL) cholesterol has been associated both with risk of Parkinson's disease (PD) and with age-related changes in cognitive function. This prospective study examined the relationship between baseline plasma LDL-cholesterol and cognitive changes in PD and matched Controls. Fasting plasma LDL-cholesterol levels were obtained at baseline from 64 non-demented PD subjects (62.7 ± 7.9 y) and 64 Controls (61.3 ± 6.8 y). Subjects underwent comprehensive neuropsychological testing at baseline, 18-, and 36-months. Linear mixed-effects modeling was used to assess the relationships between baseline LDL-cholesterol levels and longitudinal cognitive changes. At baseline, PD patients had lower scores of fine motor (p<0.0001), executive set shifting (p=0.018), and mental processing speed (p=0.049) compared to Controls. Longitudinally, Controls demonstrated improved fine motor and memory test scores (p=0.044, and p=0.003), whereas PD patients demonstrated significantly accelerated loss in fine motor skill (p=0.002) compared to Controls. Within the PD group, however, higher LDL-cholesterol levels were associated with improved executive set shifting (β=0.003, p<0.001) and fine motor scores (β=0.002, p=0.030) over time. These associations were absent in Controls (p>0.7). The cholesterol - executive set shifting association differed significantly between PDs and Controls (interaction p=0.005), whereas the cholesterol - fine motor association difference did not reach significance (interaction, p=0.104). In summary, higher plasma LDL-cholesterol levels were associated with better executive function and fine motor performance over time in PD, both of which may reflect an effect on nigrostriatal mediation. Confirmation of these results and elucidation of involved mechanisms are warranted, and might lead to feasible therapeutic strategies.

  18. Lower Low-Density Lipoprotein Cholesterol Levels Are Associated with Severe Dengue Outcome.

    PubMed

    Biswas, Hope H; Gordon, Aubree; Nuñez, Andrea; Perez, Maria Angeles; Balmaseda, Angel; Harris, Eva

    2015-01-01

    Dengue virus (DENV) is a flavivirus of worldwide importance, with approximately 4 billion people across 128 countries at risk of infection, and up to 390 million infections and 96 million clinically apparent cases estimated annually. Previous in vitro studies have shown that lipids and lipoproteins play a role in modifying virus infectivity. However, the relationship between development of severe dengue and total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, is unclear. We analyzed data from 789 laboratory-confirmed dengue cases and 447 other febrile illnesses (OFI) in a prospective pediatric hospital-based study in Managua, Nicaragua between August 2005 and January 2013, using three different classifications of dengue severity: World Health Organization (WHO) 1997, WHO 2009, and standardized intervention categories. Total serum cholesterol and LDL-C levels decreased over the course of illness and were generally lower with increasing dengue severity, regardless of classification scheme. Greater decreases in LDL-C than HDL-C were observed among dengue-positive patients compared to patients with OFI and among severe dengue compared to mild dengue cases. Furthermore, daily cholesterol levels declined with daily albumin blood levels. To examine the effect of cholesterol at presentation on subsequent risk of development of severe dengue, relative risks and 95% confidence intervals were calculated using multivariable modified Poisson models. We found that lower total serum cholesterol and LDL-C levels at presentation were associated with subsequent risk of developing dengue hemorrhagic fever/dengue shock syndrome using the WHO 1997 dengue severity classification, and thus that the reduction in LDL-C is likely driving the decreases observed in total serum cholesterol levels among dengue-positive patients. Our results suggest that cholesterol blood levels are important correlates of dengue

  19. Red yeast rice lowers cholesterol in physicians - a double blind, placebo controlled randomized trial

    PubMed Central

    2013-01-01

    Background In recent years, red yeast rice (RYR) supplements have been marketed aggressively as a natural way to lower cholesterol; however, the large majority of commercially available products have not been studied according to current research standards. Methods In a double blind placebo controlled randomized trial, 52 physicians and their spouses with a total cholesterol level of > 200 mg/dL were randomly allocated to receive a RYR extract or placebo for 8 weeks. As a primary outcome measure, we compared the before-after difference in lipid levels between both groups. As secondary outcome measures we looked at side-effects, CK elevation and a change in cardiovascular risk. Results LDL (low density lipoprotein) cholesterol was lowered with 36 mg/dL (22%) and total cholesterol with 37 mg/dL (15%) in the intervention group. This result was statistically significant as compared to the control group, in which no reduction in total cholesterol and LDL was observed (p < 0.001). There was no marked difference in CK (creatine kinase)-elevation or reported side-effects between study groups. In 5/31 participants in the intervention group, the lipid lowering effect resulted in lower cardiovascular risk as measured with SCORE (Systematic COronary Risk Evaluation). Conclusions The RYR formulation under study was effective in lowering cholesterol and LDL cholesterol in this study population. RYR therapy may be an attractive and relatively well studied alternative in patients who are intolerant for statins or who have objections against pharmacological lipid lowering. However, consumers need to be warned that the actual content of commercially available preparations is not assured by governmental regulations, which raises effectiveness and safety issues. Trial registration Clinicaltrials.gov, nr: NCT01558050 PMID:23866314

  20. Cholesterol Lowering Effect of Plant Stanol Ester Yoghurt Drinks with Added Camelina Oil

    PubMed Central

    Salo, Pia; Kuusisto, Päivi

    2016-01-01

    The aim of this study was to investigate the effects of yoghurt minidrinks containing two doses of plant stanol ester either with or without added camelina oil on the serum cholesterol levels in moderately hypercholesterolemic subjects. In this randomised, double-blind, parallel group study, 143 subjects consumed a 65 mL minidrink together with a meal daily for four weeks. The minidrink contained 1.6 or 2.0 grams of plant stanols with or without 2 grams of alpha-linolenic acid-rich camelina oil. The placebo minidrink did not contain plant stanols or camelina oil. All plant stanol treated groups showed statistically significant total, LDL, and non-HDL cholesterol lowering relative to baseline and relative to placebo. Compared to placebo, LDL cholesterol was lowered by 9.4% (p < 0.01) and 8.1% (p < 0.01) with 1.6 g and 2 g plant stanols, respectively. With addition of Camelina oil, 1.6 g plant stanols resulted in 11.0% (p < 0.01) and 2 g plant stanols in 8.4% (p < 0.01) reduction in LDL cholesterol compared to placebo. In conclusion, yoghurt minidrinks with plant stanol ester reduced serum LDL cholesterol significantly and addition of a small amount of camelina oil did not significantly enhance the cholesterol lowering effect. This trial was registered with ClinicalTrials.gov NCT02628990. PMID:26998355

  1. Transport of cholesterol from the endoplasmic reticulum to the plasma membrane

    PubMed Central

    1985-01-01

    We have studied the transport of newly synthesized cholesterol from the endoplasmic reticulum to the plasma membrane in Chinese hamster ovary cells using a cell fractionation assay. We found that transport is dependent on metabolic energy, but that the maintenance of the high differential concentration of cholesterol in the plasma membrane is not an energy-requiring process. We have tested a variety of inhibitors for their effect on cholesterol transport and found that cytochalasin B, colchicine, monensin, cycloheximide, and NH4Cl did not have any effect. The cholesterol transport process shows a sharp temperature dependence; it ceases at 15 degrees C, whereas cholesterol synthesis continues. When synthesis occurs at 15 degrees C, the newly synthesized cholesterol accumulates in the endoplasmic reticulum and in a low density, lipid-rich vesicle fraction. These results suggest that cholesterol is transported via a vesicular system. PMID:4040520

  2. Detection of cholesterol-rich microdomains in the inner leaflet of the plasma membrane

    SciTech Connect

    Hayashi, Masami; Shimada, Yukiko; Inomata, Mitsushi; Ohno-Iwashita, Yoshiko . E-mail: iwashita@tmig.or.jp

    2006-12-22

    The C-terminal domain (D4) of perfringolysin O binds selectively to cholesterol in cholesterol-rich microdomains. To address the issue of whether cholesterol-rich microdomains exist in the inner leaflet of the plasma membrane, we expressed D4 as a fusion protein with EGFP in MEF cells. More than half of the EGFP-D4 expressed in stable cell clones was bound to membranes in raft fractions. Depletion of membrane cholesterol with {beta}-cyclodextrin reduced the amount of EGFP-D4 localized in raft fractions, confirming EGFP-D4 binding to cholesterol-rich microdomains. Subfractionation of the raft fractions showed most of the EGFP-D4 bound to the plasma membrane rather than to intracellular membranes. Taken together, these results strongly suggest the existence of cholesterol-rich microdomains in the inner leaflet of the plasma membrane.

  3. Effects of lactic acid bacteria isolated from fermented mustard on lowering cholesterol

    PubMed Central

    Wang, Shu Chen; Chang, Chen Kai; Chan, Shu Chang; Shieh, Jiunn Shiuh; Chiu, Chih Kwang; Duh, Pin-Der

    2014-01-01

    Objective To evaluate the ability of lactic acid bacteria (LAB) strains isolated from fermented mustard to lower the cholesterol in vitro. Methods The ability of 50 LAB strains isolated from fermented mustard on lowering cholesterol in vitro was determined by modified o-phtshalaldehyde method. The LAB isolates were analyzed for their resistance to acid and bile salt. Strains with lowering cholesterol activity, were determined adherence to Caco-2 cells. Results Strain B0007, B0006 and B0022 assimilated more cholesterol than BCRC10474 and BCRC 17010. The isolated strains showed tolerance to pH 3.0 for 3 h despite variations in the degree of viability and bile-tolerant strains, with more than 108 CFU/mL after incubation for 24 h at 1% oxigall in MRS. In addition, strain B0007 and B0022 identified as Lactobacillus plantarum with 16S rDNA sequences were able to adhere to the Caco-2 cell lines. Conclusions These strains B0007 and B0022 may be potential functional sources for cholesterol-lowering activities as well as adhering to Caco-2 cell lines. PMID:25183271

  4. Hemagglutinin clusters in the plasma membrane are not enriched with cholesterol and sphingolipids.

    PubMed

    Wilson, Robert L; Frisz, Jessica F; Klitzing, Haley A; Zimmerberg, Joshua; Weber, Peter K; Kraft, Mary L

    2015-04-01

    The clusters of the influenza envelope protein, hemagglutinin, within the plasma membrane are hypothesized to be enriched with cholesterol and sphingolipids. Here, we directly tested this hypothesis by using high-resolution secondary ion mass spectrometry to image the distributions of antibody-labeled hemagglutinin and isotope-labeled cholesterol and sphingolipids in the plasma membranes of fibroblast cells that stably express hemagglutinin. We found that the hemagglutinin clusters were neither enriched with cholesterol nor colocalized with sphingolipid domains. Thus, hemagglutinin clustering and localization in the plasma membrane is not controlled by cohesive interactions between hemagglutinin and liquid-ordered domains enriched with cholesterol and sphingolipids, or from specific binding interactions between hemagglutinin, cholesterol, and/or the majority of sphingolipid species in the plasma membrane. PMID:25863057

  5. Hemagglutinin Clusters in the Plasma Membrane Are Not Enriched with Cholesterol and Sphingolipids

    PubMed Central

    Wilson, Robert L.; Frisz, Jessica F.; Klitzing, Haley A.; Zimmerberg, Joshua; Weber, Peter K.; Kraft, Mary L.

    2015-01-01

    The clusters of the influenza envelope protein, hemagglutinin, within the plasma membrane are hypothesized to be enriched with cholesterol and sphingolipids. Here, we directly tested this hypothesis by using high-resolution secondary ion mass spectrometry to image the distributions of antibody-labeled hemagglutinin and isotope-labeled cholesterol and sphingolipids in the plasma membranes of fibroblast cells that stably express hemagglutinin. We found that the hemagglutinin clusters were neither enriched with cholesterol nor colocalized with sphingolipid domains. Thus, hemagglutinin clustering and localization in the plasma membrane is not controlled by cohesive interactions between hemagglutinin and liquid-ordered domains enriched with cholesterol and sphingolipids, or from specific binding interactions between hemagglutinin, cholesterol, and/or the majority of sphingolipid species in the plasma membrane. PMID:25863057

  6. 1-[4-[4[(4R,5R)-3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]butyl]-4-aza-1-azoniabicyclo[2.2.2]octane methanesulfonate (SC-435), an ileal apical sodium-codependent bile acid transporter inhibitor alters hepatic cholesterol metabolism and lowers plasma low-density lipoprotein-cholesterol concentrations in guinea pigs.

    PubMed

    West, Kristy L; Ramjiganesh, Tripurasundari; Roy, Suheeta; Keller, Bradley T; Fernandez, Maria Luz

    2002-10-01

    Male Hartley guinea pigs (10/group) were assigned either to a control diet (no drug treatment) or to diets containing 0.4, 2.2, or 7.3 mg/day of an ileal apical sodium-codependent bile acid transporter (ASBT) inhibitor, 1-[4-[4[(4R,5R)-3,3-dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]butyl]-4-aza-1-azoniabicyclo[2.2.2] octane methanesulfonate (SC-435). Based on food consumption, guinea pigs received 0, 0.8, 3.7, or 13.4 mg/kg/day of the ASBT inhibitor. The amount of cholesterol in the four diets was maintained at 0.17%, equivalent to 1200 mg/day in the human situation. Guinea pigs treated with 13.4 mg/kg/day SC-435 had 41% lower total cholesterol and 44% lower low-density lipoprotein (LDL)-cholesterol concentrations compared with control (P < 0.01), whereas no significant differences were observed with either of the lower doses of SC-435. Hepatic cholesterol esters were significantly reduced by 43, 56, and 70% in guinea pigs fed 0.8, 3.7, and 13.4 mg/kg/day of the ASBT inhibitor, respectively (P < 0.01). In addition, the highest dose of the inhibitor resulted in a 42% increase in the number of very low-density lipoprotein (VLDL) triacylglycerol molecules and a larger VLDL diameter compared with controls (P < 0.05). Acyl-CoA cholesterol/acyltransferase activity was 30% lower with the highest dose treatment, whereas cholesterol 7alpha-hydroxylase, the regulatory enzyme of bile acid synthesis, was 30% higher with the highest ASBT inhibitor dose (P < 0.05). Furthermore, bile acid excretion increased 2-fold with the highest dose of SC-435 compared with the control group (P < 0.05). These results suggest that the reduction in total and LDL-cholesterol concentrations by the ASBT inhibitor is a result of alterations in hepatic cholesterol metabolism due to modifications in the enterohepatic circulation of bile acids.

  7. Lathosterol to cholesterol ratio in serum predicts cholesterol lowering response to plant sterol consumption in a dual center, randomized, single-blind placebo controlled trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Benefits of plant sterols (PS) for cholesterol lowering are compromised by large variability in efficacy across individuals. High fractional cholesterol synthesis measured by deuterium incorporation has been associated with non-response to PS consumption; however, prospective studies showing this as...

  8. Subjects with Low Plasma HDL Cholesterol Levels Are Characterized by an Inflammatory and Oxidative Phenotype

    PubMed Central

    Holven, Kirsten B.; Retterstøl, Kjetil; Ueland, Thor; Ulven, Stine M.; Nenseter, Marit S.; Sandvik, Marit; Narverud, Ingunn; Berge, Knut E.; Ose, Leiv; Aukrust, Pål; Halvorsen, Bente

    2013-01-01

    Background Epidemiological studies have shown that low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risk of cardiovascular disease, but the mechanisms for the possible atheroprotective effects of HDL cholesterol have still not been fully clarified, in particular in relation to clinical studies. Objective To examine the inflammatory, anti-oxidative and metabolic phenotype of subjects with low plasma HDL cholesterol levels. Methods and Results Fifteen subjects with low HDL cholesterol levels (eleven males and four females) and 19 subjects with high HDL (three males and 16 females) were recruited. Low HDL cholesterol was defined as ≤10th age/sex specific percentile and high HDL-C was defined as ≥90 age/sex specific percentile. Inflammatory markers in circulation and PBMC gene expression of cholesterol efflux mediators were measured. Our main findings were: (i) subjects with low plasma HDL cholesterol levels were characterized by increased plasma levels of CRP, MMP-9, neopterin, CXCL16 and ICAM-1 as well as low plasma levels of adiponectin, suggesting an inflammatory phenotype; (ii) these individuals also had reduced paraoxonase (PON)1 activity in plasma and PON2 gene expression in peripheral blood mononuclear cells (PBMC) accompanied by increased plasma levels of oxidized LDL suggesting decreased anti-oxidative capacity; and (iii) PBMC from low HDL subjects also had decreased mRNA levels of ABCA1 and ABCG1, suggesting impaired reverse cholesterol transport. Conclusion Subjects with low plasma HDL cholesterol levels are characterized by an inflammatory and oxidative phenotype that could contribute to the increased risk of atherosclerotic disorders in these subjects with low HDL levels. PMID:24244297

  9. Components characterization of total tetraploid jiaogulan (Gynostemma pentaphylla) saponin and its cholesterol-lowering properties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study characterized chemical structures of tetraploid jiaogulan saponins, and investigated their cholesterol-lowering effects and mechanisms in hamsters fed a high-fat diet (HFD). Nine saponins, including five reported for the first time, were obtained from total jiaogulan saponins (TJS) and el...

  10. Focus Group Assessment of Culturally Specific Cholesterol-Lowering Menus for Mexican Americans

    ERIC Educational Resources Information Center

    Shah, M.; Coyle, Y.; Kavanaugh, A.; Adams-Huet, B.; Lipsky, P.E.

    2004-01-01

    This study focus tested the acceptability of a set of six 1400 kcal and six 1800 kcal culturally appropriate cholesterol-lowering menus developed for low-income Mexican-Americans with systemic lupus erythematosus (SLE). The focus group, made up of 11 low-income Mexican-American women without SLE, found the menus to be generally culturally valid,…

  11. In vitro cholesterol-lowering properties of Lactobacillus plantarum AN6 isolated from aji-narezushi.

    PubMed

    Kuda, T; Yazaki, T; Ono, M; Takahashi, H; Kimura, B

    2013-09-01

    Aji-narezushi is a traditional lactic acid-fermented fish. In this study, we screened for lactose-utilizing, acidophilic, bile-resistant and cholesterol-lowering lactic acid bacteria (LAB) from aji-narezushi for use as starter strains for fermented foods, as well as for use as probiotics. Of the 301 LAB isolates, 277 fermented lactose, and among these, 171 grew in de Man, Rogosa and Sharpe broth adjusted to pH 3·5. Thirty-four of the isolates were grown in a broth containing 3% (w/v) bile. All of the isolates were lactobacilli. Seven isolates that demonstrated cholesterol-lowering activity in ethanolic solution were selected. All of the isolates were identified as Lactobacillus plantarum. Lactobacillus plantarum AN6 showed the highest cholesterol-lowering activity. AN6 was more resistant to acid, salt and bile than the type strain NBRC15891(T). One-half of the cholesterol-lowering effect remained after boiling AN6 for 10 min. The Fourier transform infrared (FT-IR) analysis indicated that the content of cell wall polysaccharides in AN6 is higher than ones in the type strain. These results indicate that Lact. plantarum AN6 can be used as a profitable starter organism and probiotic.

  12. Association between cholesterol synthesis/absorption markers and effects of cholesterol lowering by atorvastatin among patients with high risk of coronary heart disease.

    PubMed

    Qi, Yue; Liu, Jing; Ma, Changsheng; Wang, Wei; Liu, Xiaohui; Wang, Miao; Lv, Qiang; Sun, Jiayi; Liu, Jun; Li, Yan; Zhao, Dong

    2013-11-01

    No indices are currently available to facilitate clinicians to identify patients who need either statin monotherapy or statin-ezetimibe combined treatment. We aimed to investigate whether cholesterol synthesis and absorption markers can predict the cholesterol-lowering response to statin. Total 306 statin-naïve patients with high risk of coronary heart disease (CHD) were treated with atorvastatin 20 mg/day for 1 month. Cholesterol synthesis and absorption markers and LDL cholesterol (LDL-C) levels were measured before and after treatment. Atorvastatin decreased LDL-C by 36.8% (range: decrease of 74.5% to increase of 31.9%). Baseline cholesterol synthesis marker lathosterol and cholesterol absorption marker campesterol codetermined the effect of atorvastatin treatment. The effect of cholesterol lowering by atorvastatin was significantly associated with baseline lathosterol levels but modified bidirectionally by baseline campesterol levels. In patients with the highest baseline campesterol levels, atorvastatin treatment decreased cholesterol absorption by 46.1%, which enhanced the effect of LDL-C lowering. Atorvastatin treatment increased cholesterol absorption by 52.3% in those with the lowest baseline campesterol levels, which attenuated the effect of LDL-C reduction. Especially those with the highest lathosterol but the lowest campesterol levels at baseline had significantly less LDL-C reduction than those with the same baseline lathosterol levels but the highest campesterol levels (27.3% versus 42.4%, P = 0.002). These results suggest that combined patterns of cholesterol synthesis/absorption markers, rather than each single marker, are potential predictors of the LDL-C-lowering effects of atorvastatin in high-risk CHD patients.

  13. Recurring exon deletions in the haptoglobin (HP) gene associate with lower blood cholesterol levels

    PubMed Central

    Boettger, Linda M.; Salem, Rany M.; Handsaker, Robert E.; Peloso, Gina; Kathiresan, Sekar; Hirschhorn, Joel; McCarroll, Steven A.

    2016-01-01

    Two exons of the human haptoglobin (HP) gene exhibit copy number variation that affects HP multimerization and underlies one of the first protein polymorphisms identified in humans. The evolutionary origins and medical significance of this polymorphism have been uncertain. Here we show that this variation has likely arisen from the recurring reversion of an ancient hominin-specific duplication of these exons. Though this polymorphism has been largely invisible to genome-wide genetic studies to date, we describe a way to analyze it by imputation from SNP haplotypes and find among 22,288 individuals that these HP exonic deletions associate with reduced LDL and total cholesterol levels. We show that these deletions, and a SNP that affects HP expression, are the likely drivers of the strong but complex association of cholesterol levels to SNPs near HP. Recurring exonic deletions in the haptoglobin gene likely enhance human health by lowering cholesterol levels in the blood. PMID:26901066

  14. [Is the Finnish "healthy margarine" food or medicine? Addition of plant sterols can lower cholesterol levels].

    PubMed

    Wikström, A C

    1998-11-11

    Sine the autumn of 1995, Benecol, a proprietary brand of cholesterol-lowering margarine, has been available in ordinary grocery shops in Finland. The active ingredient is a sitostanol ester. Several studies in humans have shown use of the margarine to result in an approximately 10 per cent reduction in total serum cholesterol, and a 13-15 per cent reduction of LDL-cholesterol. However, further studies are required of its phyto-oestrogenic and endocrine effects, and its effects on growing children, particularly regarding subsequent fertility in boys. Although the margarine is classed as a 'functional food' in Finland, the question arises where the line is to be drawn between medicines and food-stuffs.

  15. Aronia melanocarpa (chokeberry) polyphenol-rich extract improves antioxidant function and reduces total plasma cholesterol in apolipoprotein E knockout mice.

    PubMed

    Kim, Bohkyung; Ku, Chai Siah; Pham, Tho X; Park, Youngki; Martin, Derek A; Xie, Liyang; Taheri, Rod; Lee, Jiyoung; Bolling, Bradley W

    2013-05-01

    We hypothesized that a polyphenol-rich chokeberry extract (CBE) would modulate hepatic lipid metabolism and improve antioxidant function in apolipoprotein E knockout (apoE(-/-)) mice. ApoE(-/-) mice were fed diets containing 15% fat with 0.2% cholesterol alone or supplemented with 0.005% or 0.05% CBE for 4 weeks. CBE polyphenol content was determined by the total phenols, 4-dimethylaminocinnamaldehyde, and ultra high-performance liquid chromatography-mass spectrometry methods. The 0.05% CBE diet provided mice with mean daily doses of 1.2 mg gallic acid equivalents of total phenols, 0.19 mg anthocyanins, 0.17 mg phenolic acids, 0.06 mg proanthocyanidins (as catechin-equivalents), and 0.02 mg flavonols. The 0.05% CBE group had 12% less plasma total cholesterol concentrations than the control. Despite the hypocholesterolemic effect of CBE, hepatic mRNA levels of low-density lipoprotein receptor, hydroxyl-3-methylglutaryl coenzyme A reductase and cholesterol 7α-hydroxylase in CBE-fed mice were not significantly different from controls. Dietary CBE did not alter hepatic lipid content or the hepatic expression of genes involved in lipogenesis and fatty acid β-oxidation such as fatty acid synthase, carnitine palmitoyltransferase 1 and acyl-CoA oxidase. Plasma paraoxonase and catalase activities were significantly increased in mice fed 0.05% CBE. Both CBE diets increased hepatic glutathione peroxidase (GPx) activity but the 0.05% CBE group had 24% less proximal intestine GPx activity relative to controls. Thus, dietary CBE lowered total cholesterol and improved plasma and hepatic antioxidant function at nutritionally-relevant doses in apoE(-/-) mice. Furthermore, the CBE cholesterol-lowering mechanism in apoE(-/-) mice was independent of hepatic expression of genes involved in cholesterol metabolism.

  16. Flaxseed dietary fibers lower cholesterol and increase fecal fat excretion, but magnitude of effect depend on food type

    PubMed Central

    2012-01-01

    Background Dietary fibers have been proposed to play a role in cardiovascular risk as well as body weight management. Flaxseeds are a good source of dietary fibers, and a large proportion of these are water-soluble viscous fibers. Method Here, we examine the effect of flaxseed dietary fibers in different food matrices on blood lipids and fecal excretion of fat and energy in a double-blind randomized crossover study with 17 subjects. Three different 7-d diets were tested: a low-fiber control diet (Control), a diet with flaxseed fiber drink (3/day) (Flax drink), and a diet with flaxseed fiber bread (3/day) (Flax bread). Total fat and energy excretion was measured in feces, blood samples were collected before and after each period, and appetite sensation registered 3 times daily before main meals. Results Compared to control, Flax drink lowered fasting total-cholesterol and LDL-cholesterol by 12 and 15%, respectively, (p < 0.01), whereas Flax bread only produced a reduction of 7 and 9%, respectively (p < 0.05). Fecal fat and energy excretion increased by 50 and 23% with Flax drink consumption compared to control (p < 0.05), but only fecal fat excretion was increased with Flax bread compared to control (p < 0.05). Conclusion Both Flax drink and Flax bread resulted in decreased plasma total and LDL-cholesterol and increased fat excretion, but the food matrix and/or processing may be of importance. Viscous flaxseed dietary fibers may be a useful tool for lowering blood cholesterol and potentially play a role in energy balance. Trial Registration ClinicalTrials.gov: NCT00953004 PMID:22305169

  17. Viscosity rather than quantity of dietary fibre predicts cholesterol-lowering effect in healthy individuals.

    PubMed

    Vuksan, Vladimir; Jenkins, Alexandra L; Rogovik, Alexander L; Fairgrieve, Christopher D; Jovanovski, Elena; Leiter, Lawrence A

    2011-11-01

    The well-documented lipid-lowering effects of fibre may be related to its viscosity, a phenomenon that has been understudied, especially when fibre is given against the background of a typical North American (NA) diet. In this three-arm experiment, we compared the lipid-lowering effect of low-viscosity wheat bran (WB), medium-viscosity psyllium (PSY) and a high-viscosity viscous fibre blend (VFB), as part of a fibre intervention aimed at increasing fibre intake to recommended levels within the context of a NA diet in apparently healthy individuals. Using a randomised cross-over design, twenty-three participants (twelve males and eleven females; age 35 (SD 12) years; LDL-cholesterol (C) 2.9 (SEM 0.6) mmol/l) consuming a typical NA diet received a standard, fibre-enriched cereal, where approximately one-third of the fibre was either a low-viscosity (570 centipoise (cP)) WB, medium-viscosity (14,300 cP) PSY or a high-viscosity (136,300 cP) novel VFB, for 3 weeks separated by washout periods of ≥ 2 weeks. There were no differences among the treatments in the amount of food consumed, total dietary fibre intake, reported physical activity and body weight. Final intake of the WB, PSY and VFB was 10.8, 9.0 and 5.1 g, respectively. Reduction in LDL-C was greater with the VFB compared with the medium-viscosity PSY (-12.6 (SEM 3.5) %, P = 0.002) and low-viscosity WB (-14.6 (SEM 4.2) %, P = 0.003). The magnitude of LDL-C reduction showed a positive association with fibre apparent viscosity (r - 0.41, P = 0.001). Despite the smaller quantity consumed, the high-viscosity fibre lowered LDL-C to a greater extent than lower-viscosity fibres. These data support the inclusion of high-viscosity fibre in the diet to reduce plasma lipids among apparently healthy individuals consuming a typical NA diet.

  18. All cholesterol-lowering interventions are expected to reduce stroke: Confirmatory data from IMPROVE-IT

    PubMed Central

    De Caterina, Raffaele; Salvatore, Tanya; Marchioli, Roberto

    2016-01-01

    The relationship of cholesterol with stroke is much less clear than its relationship with myocardial infarction, thus confounding the interpretation of results with cholesterol-lowering trials (Di Napoli et al., 2002) [1], (De Caterina et al., 2010) [2]). IMPROVE-IT data ((Cannon et al. 2015) [3]), showing a 13.3% reduction in total cholesterol at one year in association with a hazard ratio (HR) of 0.i86 for total stroke during the trial, are very closely aligned with the relative risk of 0.90 predicted based on the totality of lipid lowering interventions ((De Caterina et al., 2016) [4]). We here provide the data from the original trials used to construct this meta-analysis, with the now added additional data from IMPROVE-IT, well-fitting the previously found meta-regression line. These data are important to predict stroke outcomes in currently ongoing trials now testing PCSK9 or cholesterol ester transfer protein inhibitors. PMID:27222850

  19. All cholesterol-lowering interventions are expected to reduce stroke: Confirmatory data from IMPROVE-IT.

    PubMed

    De Caterina, Raffaele; Salvatore, Tanya; Marchioli, Roberto

    2016-06-01

    The relationship of cholesterol with stroke is much less clear than its relationship with myocardial infarction, thus confounding the interpretation of results with cholesterol-lowering trials (Di Napoli et al., 2002) [1], (De Caterina et al., 2010) [2]). IMPROVE-IT data ((Cannon et al. 2015) [3]), showing a 13.3% reduction in total cholesterol at one year in association with a hazard ratio (HR) of 0.i86 for total stroke during the trial, are very closely aligned with the relative risk of 0.90 predicted based on the totality of lipid lowering interventions ((De Caterina et al., 2016) [4]). We here provide the data from the original trials used to construct this meta-analysis, with the now added additional data from IMPROVE-IT, well-fitting the previously found meta-regression line. These data are important to predict stroke outcomes in currently ongoing trials now testing PCSK9 or cholesterol ester transfer protein inhibitors. PMID:27222850

  20. Cholesterol transport from plasma membranes to intracellular membranes is inhibited by 3 beta-[2-(diethylamino)ethoxy]androst-5-en-17-one.

    PubMed

    Härmälä, A S; Pörn, M I; Mattjus, P; Slotte, J P

    1994-03-24

    The compound U1866A (3 beta-[2-(diethylamino)ethoxy]androst-5-en-17-one) has been shown to inhibit the cellular transfer of low-density lipoprotein-derived cholesterol from lysosomes to plasma membranes (Liscum and Faust (1989) J. Biol. Chem. 264, 11796-806). We have in this study examined the effects of U18666A on cholesterol translocation from plasma membranes to intracellular membranes. Translocation of plasma membrane cholesterol was induced by degradation of plasma membrane sphingomyelin. The sphingomyelinase-induced activation of the acyl-CoA cholesterol acyl transferase (ACAT) reaction was completely inhibited in a dose-dependent manner by U18666A, both in cultured human skin fibroblasts and baby hamster kidney cells. Half-maximal inhibition (within 60 min) was obtained with 0.5-1 microgram/ml of U18666A. A time-course study indicated that the onset of inhibition was rapid (within 10-15 min), and reversible if U18666A was removed from the incubation mixture. Using a cholesterol oxidase assay, we observed that the extent of plasma membrane cholesterol translocation in sphingomyelinase-treated HSF cells was significantly lowered in the presence of U18666A (at 3 micrograms/ml). The effect of U18666A on cholesterol translocation was also fully reversible when the drug was withdrawn. In mouse Leydig tumor cells, labeled to constant specific activity with [3H]cholesterol, the compound U18666A inhibited in a dose-dependent manner the cyclic AMP-stimulated secretion of [3H]steroid hormones. The effects seen with compound U18666A appeared to be specific for this molecule, since another hydrophobic amine, imipramine, did not in our experiments affect cholesterol translocation or ACAT activation. Since different cell types display sensitivity to U18666A in various intracellular cholesterol transfer processes, they appear to have a common U18666A-sensitive regulatory mechanism.

  1. Cholesterol transport from plasma membranes to intracellular membranes is inhibited by 3 beta-[2-(diethylamino)ethoxy]androst-5-en-17-one.

    PubMed

    Härmälä, A S; Pörn, M I; Mattjus, P; Slotte, J P

    1994-03-24

    The compound U1866A (3 beta-[2-(diethylamino)ethoxy]androst-5-en-17-one) has been shown to inhibit the cellular transfer of low-density lipoprotein-derived cholesterol from lysosomes to plasma membranes (Liscum and Faust (1989) J. Biol. Chem. 264, 11796-806). We have in this study examined the effects of U18666A on cholesterol translocation from plasma membranes to intracellular membranes. Translocation of plasma membrane cholesterol was induced by degradation of plasma membrane sphingomyelin. The sphingomyelinase-induced activation of the acyl-CoA cholesterol acyl transferase (ACAT) reaction was completely inhibited in a dose-dependent manner by U18666A, both in cultured human skin fibroblasts and baby hamster kidney cells. Half-maximal inhibition (within 60 min) was obtained with 0.5-1 microgram/ml of U18666A. A time-course study indicated that the onset of inhibition was rapid (within 10-15 min), and reversible if U18666A was removed from the incubation mixture. Using a cholesterol oxidase assay, we observed that the extent of plasma membrane cholesterol translocation in sphingomyelinase-treated HSF cells was significantly lowered in the presence of U18666A (at 3 micrograms/ml). The effect of U18666A on cholesterol translocation was also fully reversible when the drug was withdrawn. In mouse Leydig tumor cells, labeled to constant specific activity with [3H]cholesterol, the compound U18666A inhibited in a dose-dependent manner the cyclic AMP-stimulated secretion of [3H]steroid hormones. The effects seen with compound U18666A appeared to be specific for this molecule, since another hydrophobic amine, imipramine, did not in our experiments affect cholesterol translocation or ACAT activation. Since different cell types display sensitivity to U18666A in various intracellular cholesterol transfer processes, they appear to have a common U18666A-sensitive regulatory mechanism. PMID:8130265

  2. Effect of dietary cholesterol with or without saturated fat on plasma lipoprotein cholesterol levels in the laboratory opossum (Monodelphis domestica) model for diet-induced hyperlipidaemia.

    PubMed

    Kushwaha, Rampratap S; VandeBerg, Jane F; VandeBerg, John L

    2004-07-01

    Laboratory opossums (Monodelphis domestica) show extreme genetic variability in their responsiveness to dietary lipids; a great proportion of the genetic variability in responsiveness is due to a single major gene. To determine whether the major gene for dietary response detected by genetic analysis in opossums is responsive to dietary cholesterol or dietary saturated fat, or a combination of both, we used males and females of susceptible and resistant lines of laboratory opossums that were 5 to 7 months old. The animals were challenged with three different experimental diets (high-cholesterol diets with or without high saturated fat from lard or coconut oil) and plasma lipoproteins were measured. Plasma and VLDL+LDL-cholesterol concentrations increased several-fold when the animals were fed the diet containing elevated cholesterol (P<0.001) or elevated cholesterol and fat (P<0.001) and differed between the two lines when they were fed high-cholesterol diets with or without fat (P<0.001). Plasma HDL-cholesterol concentrations were higher (P<0.05) in animals of the resistant line than in the susceptible line when they were fed the basal diet (550 (SEM 30) v. 440 (SEM 20) mg/l) and when they were fed the low-cholesterol and high-fat diet (600 (SEM 30) v. 490 (SEM 30) mg/l). Dietary coconut oil and lard had similar effects on plasma lipoprotein cholesterol concentrations in the susceptible line of opossums. A reduction in dietary cholesterol by 50 % with either the lard or coconut oil blunted the plasma cholesterol response. The results from the present studies suggest that the major gene for dietary response previously detected by genetic analysis in laboratory opossums affects the response to dietary cholesterol but not to saturated fat.

  3. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice.

    PubMed

    Schonewille, Marleen; Freark de Boer, Jan; Mele, Laura; Wolters, Henk; Bloks, Vincent W; Wolters, Justina C; Kuivenhoven, Jan A; Tietge, Uwe J F; Brufau, Gemma; Groen, Albert K

    2016-08-01

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we investigated the effects on cholesterol metabolism in mice in detail. Surprisingly, direct measurement of whole body cholesterol synthesis revealed that cholesterol synthesis was robustly increased in statin-treated mice. Measurement of organ-specific cholesterol synthesis demonstrated that the liver is predominantly responsible for the increase in cholesterol synthesis. Excess synthesized cholesterol did not accumulate in the plasma, as plasma cholesterol decreased. However, statin treatment led to an increase in cholesterol removal via the feces. Interestingly, enhanced cholesterol excretion in response to rosuvastatin and lovastatin treatment was mainly mediated via biliary cholesterol secretion, whereas atorvastatin mainly stimulated cholesterol removal via the transintestinal cholesterol excretion pathway. Moreover, we show that plasma cholesterol precursor levels do not reflect cholesterol synthesis rates during statin treatment in mice. In conclusion, cholesterol synthesis is paradoxically increased upon statin treatment in mice. However, statins potently stimulate the excretion of cholesterol from the body, which sheds new light on possible mechanisms underlying the cholesterol-lowering effects of statins.

  4. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice.

    PubMed

    Schonewille, Marleen; Freark de Boer, Jan; Mele, Laura; Wolters, Henk; Bloks, Vincent W; Wolters, Justina C; Kuivenhoven, Jan A; Tietge, Uwe J F; Brufau, Gemma; Groen, Albert K

    2016-08-01

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we investigated the effects on cholesterol metabolism in mice in detail. Surprisingly, direct measurement of whole body cholesterol synthesis revealed that cholesterol synthesis was robustly increased in statin-treated mice. Measurement of organ-specific cholesterol synthesis demonstrated that the liver is predominantly responsible for the increase in cholesterol synthesis. Excess synthesized cholesterol did not accumulate in the plasma, as plasma cholesterol decreased. However, statin treatment led to an increase in cholesterol removal via the feces. Interestingly, enhanced cholesterol excretion in response to rosuvastatin and lovastatin treatment was mainly mediated via biliary cholesterol secretion, whereas atorvastatin mainly stimulated cholesterol removal via the transintestinal cholesterol excretion pathway. Moreover, we show that plasma cholesterol precursor levels do not reflect cholesterol synthesis rates during statin treatment in mice. In conclusion, cholesterol synthesis is paradoxically increased upon statin treatment in mice. However, statins potently stimulate the excretion of cholesterol from the body, which sheds new light on possible mechanisms underlying the cholesterol-lowering effects of statins. PMID:27313057

  5. Oat β-glucan: physico-chemical characteristics in relation to its blood-glucose and cholesterol-lowering properties.

    PubMed

    Wang, Qi; Ellis, Peter R

    2014-10-01

    The water-soluble, mixed-linkage β-glucan, a form of soluble dietary fibre, is considered the main biologically active component responsible for the capacity of many oat products to lower postprandial glycaemia and fasting plasma cholesterol in human subjects. The present review discusses the physical and chemical properties of oat β-glucan that are considered important predictors of these beneficial metabolic effects. In vitro modelling and animal and human studies have provided compelling evidence showing that the ability of oat β-glucan to increase the viscosity of digesta in the gastrointestinal tract (GIT) is a primary determinant of its blood-glucose and cholesterol-lowering properties. Therefore, the chemical structure, molecular weight (MW), the rate and extent of dissolution and solution rheology of oat β-glucan are key factors in determining the physiological function of oat-containing foods. The structure and properties of oat β-glucan vary between species and varieties of oats, and are also affected by the growing and storage conditions and processing of oat grain. In addition, the extraction and analysis methods may also contribute to the variations in the structure, MW, hydration and solution rheology of β-glucan obtained from different laboratories. Recent work has demonstrated that β-glucan solubility in foods depends on the source of the material and processing conditions; solubility may also be subject to changes during food preparation and storage (such as freezing). In conclusion, both the amount and MW of β-glucan that are solubilised in the GIT need to be considered when assessing the blood-glucose and cholesterol-lowering properties of oat-containing foods.

  6. Dose-dependent LDL-cholesterol lowering effect by plant stanol ester consumption: clinical evidence.

    PubMed

    Laitinen, Kirsi; Gylling, Helena

    2012-10-22

    Elevated serum lipids are linked to cardiovascular diseases calling for effective therapeutic means to reduce particularly LDL-cholesterol (LDL-C) levels. Plant stanols reduce levels of LDL-C by partly blocking cholesterol absorption. Accordingly the consumption of foods with added plant stanols, typically esterified with vegetable oil fatty acids in commercial food products, are recommended for lowering serum cholesterol levels. A daily intake of 1.5 to 2.4 g of plant stanols has been scientifically evaluated to lower LDL-C by 7 to 10% in different populations, ages and with different diseases. Based on earlier studies, a general understanding is that no further reduction may be achieved in intakes in excess of approximately 2.5 g/day. Recent studies however suggest that plant stanols show a continuous dose-response effect in serum LDL-C lowering. This review discusses the evidence for a dose-effect relationship between plant stanol ester consumption and reduction of LDL-C concentrations with daily intakes of plant stanols of 4 g/day or more. We identified five such studies and the overall data demonstrate a linear dose-effect relationship with the most pertinent LDL-Cholesterol lowering outcome, 18%, achieved by a daily intake of 9 to 10 g of plant stanols. Along with reduction in LDL-C, the studies demonstrated a decrease in cholesterol absorption markers, the serum plant sterol to cholesterol ratios, by increasing the dose of plant stanol intake. None of the studies with daily intakes up to 10 g of plant stanols reported adverse clinical or biochemical effects from plant stanols. In a like manner, the magnitude of decrease in serum antioxidant vitamins was not related to the dose of plant stanols consumed and the differences between plant stanol ester consumers and controls were minor and insignificant or nonexisting. Consumption of plant stanols in high doses is feasible as a range of food products are commercially available for consumption including spreads

  7. Synthesis of Silicon and Germanium Containing Heteroaromatic Sulfides as Cholesterol Level Lowering and Vasodilating Agents

    PubMed Central

    Rubina, Kira; Abele, Edgars; Arsenyan, Pavel; Abele, Ramona; Veveris, Maris

    2001-01-01

    Silicon and germanium containing heteroaromatic sulfides have been prepared using phase transfer catalytic (PTC) system thiol / Si or Ge containing alkyl halide / solid KOH / 18- crown-6 / toluene. The target sulfides were isolated in yields up to 92 %. It has been found that 2-{[dimethyl (β-triethylgermylethyl)-silylmethyl]thio}-1-methylimidazole and 2-{[dimethyl(β-triphenylsilylethyl) silyl-methyl]thio}benzothiazole are the most active cholesterol level lowering and vasodilating agents. PMID:18475980

  8. Nonlinear lower hybrid modeling in tokamak plasmas

    SciTech Connect

    Napoli, F.; Schettini, G.; Castaldo, C.; Cesario, R.

    2014-02-12

    We present here new results concerning the nonlinear mechanism underlying the observed spectral broadening produced by parametric instabilities occurring at the edge of tokamak plasmas in present day LHCD (lower hybrid current drive) experiments. Low frequency (LF) ion-sound evanescent modes (quasi-modes) are the main parametric decay channel which drives a nonlinear mode coupling of lower hybrid (LH) waves. The spectrum of the LF fluctuations is calculated here considering the beating of the launched LH wave at the radiofrequency (RF) operating line frequency (pump wave) with the noisy background of the RF power generator. This spectrum is calculated in the frame of the kinetic theory, following a perturbative approach. Numerical solutions of the nonlinear LH wave equation show the evolution of the nonlinear mode coupling in condition of a finite depletion of the pump power. The role of the presence of heavy ions in a Deuterium plasma in mitigating the nonlinear effects is analyzed.

  9. Temperature effect of cholesterol association with synaptosomal plasma membranes of rabbit brain.

    PubMed Central

    Deliconstantinos, G

    1984-01-01

    Association of exogenous cholesterol with rabbit brain synaptosomal plasma membranes follows an exponential path described by the general formula y = a X ebx. The co-operative nature of this association was shown when increasing amounts of unlabelled cholesterol glucoside (up to 0.5 mM) were added to a fixed amount (5 microM) of [14C]cholesterol, when a biphasic curve of the binding of [14C]cholesterol into the membranes was obtained. Arrhenius plots of this association revealed two break points which occur at 25 degrees C and 42 degrees C. The first break apparently corresponds to the transition from the crystalline to the gel phase. The second break may be due to the (continuously) increasing entropy of the system which creates at a certain point difficulties in the binding of cholesterol into the lipid bilayer. PMID:6487274

  10. Effects of Plasma Membrane Cholesterol Level and Cytoskeleton F-Actin on Cell Protrusion Mechanics

    PubMed Central

    Khatibzadeh, Nima; Spector, Alexander A.; Brownell, William E.; Anvari, Bahman

    2013-01-01

    Protrusions are deformations that form at the surface of living cells during biological activities such as cell migration. Using combined optical tweezers and fluorescent microscopy, we quantified the mechanical properties of protrusions in adherent human embryonic kidney cells in response to application of an external force at the cell surface. The mechanical properties of protrusions were analyzed by obtaining the associated force-length plots during protrusion formation, and force relaxation at constant length. Protrusion mechanics were interpretable by a standard linear solid (Kelvin) model, consisting of two stiffness parameters, k0 and k1 (with k0>k1), and a viscous coefficient. While both stiffness parameters contribute to the time-dependant mechanical behavior of the protrusions, k0 and k1 in particular dominated the early and late stages of the protrusion formation and elongation process, respectively. Lowering the membrane cholesterol content by 25% increased the k0 stiffness by 74%, and shortened the protrusion length by almost half. Enhancement of membrane cholesterol content by nearly two-fold increased the protrusion length by 30%, and decreased the k0 stiffness by nearly two-and-half-fold as compared with control cells. Cytoskeleton integrity was found to make a major contribution to protrusion mechanics as evidenced by the effects of F-actin disruption on the resulting mechanical parameters. Viscoelastic behavior of protrusions was further characterized by hysteresis and force relaxation after formation. The results of this study elucidate the coordination of plasma membrane composition and cytoskeleton during protrusion formation. PMID:23451167

  11. Imaging approaches for analysis of cholesterol distribution and dynamics in the plasma membrane.

    PubMed

    Wüstner, Daniel; Modzel, Maciej; Lund, Frederik W; Lomholt, Michael A

    2016-09-01

    Cholesterol is an important lipid component of the plasma membrane (PM) of mammalian cells, where it is involved in control of many physiological processes, such as endocytosis, cell migration, cell signalling and surface ruffling. In an attempt to explain these functions of cholesterol, several models have been put forward about cholesterol's lateral and transbilayer organization in the PM. In this article, we review imaging techniques developed over the last two decades for assessing the distribution and dynamics of cholesterol in the PM of mammalian cells. Particular focus is on fluorescence techniques to study the lateral and inter-leaflet distribution of suitable cholesterol analogues in the PM of living cells. We describe also several methods for determining lateral cholesterol dynamics in the PM including fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS), single particle tracking (SPT) and spot variation FCS coupled to stimulated emission depletion (STED) microscopy. For proper interpretation of such measurements, we provide some background in probe photophysics and diffusion phenomena occurring in cell membranes. In particular, we show the equivalence of the reaction-diffusion approach, as used in FRAP and FCS, and continuous time random walk (CTRW) models, as often invoked in SPT studies. We also discuss mass spectrometry (MS) based imaging of cholesterol in the PM of fixed cells and compare this method with fluorescence imaging of sterols. We conclude that evidence from many experimental techniques converges towards a model of a homogeneous distribution of cholesterol with largely free and unhindered diffusion in both leaflets of the PM. PMID:27016337

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

    PubMed

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

    PubMed

    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

  14. Double Potential Pulse Chronocoulometry for Detection of Plasma Membrane Cholesterol Efflux at Disk Platinum Microelectrodes

    PubMed Central

    West, Richard H.; Lu, Hui; Shaw, Kendrick; Chiel, Hillel J.; Kelley, Thomas J.; Burgess, James D.

    2016-01-01

    A double potential pulse scheme is reported for observation of cholesterol efflux from the plasma membrane of a single neuron cell. Capillary Pt disk microelectrodes having a thin glass insulator allow the 10 μm diameter electrode and cell to be viewed under optical magnification. The electrode, covalently functionalized with cholesterol oxidase, is positioned in contact with the cell surface resulting in enzyme catalyzed cholesterol oxidation and efflux of cholesterol from the plasma membrane at the electrode contact site. Enzymatically generated hydrogen peroxide accumulates at the electrode/cell interface during a 5 s hold-time and is oxidized during application of a potential pulse. A second, replicate potential pulse is applied 0.5 s after the first potential pulse to gauge background charge prior to significant accumulation of hydrogen peroxide. The difference in charge passed between the first and second potential pulse provides a measure of hydrogen peroxide generated by the enzyme and is an indication of the cholesterol efflux. Control experiments for bare Pt microelectrodes in contact with the cell plasma membrane show difference charge signals in the range of about 7–10 pC. Enzyme-modified electrodes in contact with the plasma membrane show signals in the range of 16–26 pC. PMID:27330196

  15. [The new atherogenic plasma index reflects the triglyceride and HDL-cholesterol ratio, the lipoprotein particle size and the cholesterol esterification rate: changes during lipanor therapy].

    PubMed

    Dobiásová, M; Frohlich, J

    2000-03-01

    The new atherogenic plasma index (AIP) is a logarithmic transformation of the ratio of the molar triglyceride (TG) concentration and high density lipoprotein cholesterol (HDL-C). AIP correlates closely with the size of LDL particles (r = 0.8) and esterification rate of plasma cholesterol devoid of apo B lipoproteins (FERHDL), r = 0.9 which are considered at present the most sensitive indicators of the atherogenic plasma profile. AIP was recommended by the authors, based on analysis of results of 11 previous studies (1156 subjects) where FERHDL and plasma lipid parameters were investigated in different groups of people who differed as to the atherogenic risk. The AIP index was moreover used for evaluation of a clinical study comprising 609 patients with hyperlipidaemia, who were treated for three months with ciprofibrate (Lipanor). The mean AIP values of non-risk groups (plasma from umbilical blood, children, healthy women etc.) equalled zero or were lower, while with an increasing atherogenic risk (men, women after the menopause) AIP reached positive values, incl. high positive values in risk groups (plasma of diabetic subjects, patients with HLP, patients with positive angiography, myocardial infarction etc.). In all groups women had lower AIP values as compared with males. In patients after Lipanor therapy the AIP declined (from 0.58 +/- 0.17 to 0.33_0.18 in men, from 0.50 +/- 0.18 to 0.21 +/- 0.19 in women). If we consider AIP values from negative ones to 0.15 as "safe" from the aspect of atherogenicity, before Lipanor treatment these "safe" levels were recorded in 1.5% men and in 5.2% women and after treatment in 32% men and 48% women. The results indicate, that AIP which reflects the plasma lipoprotein profile quantifies the relations between TG and HDL-C and thus can be an objective indicator of the atherogenic risk and effectiveness of treatment and it is useful because it can be assessed in any surgery. PMID:11048517

  16. [Update of planning tables of cholesterol-lowering therapy orientated to achieve LDL therapeutic targets].

    PubMed

    Masana, Luis; Plana, Núria

    2015-01-01

    This is the third update of a planning-table for use in cholesterol-lowering therapy, so as to obtain LDLc objectives. This is an easy to use laptop tool to help choose the best statin or combination therapy (statin plus ezetimibe) depending on the current LDL concentration of the patient, and the LDLc objective to achieve. It is based on a colour code that indicates the drugs that are efficient enough to help patients to achieve their LDL goal. Along with the table, recommendations are given for the best strategy in order to implement the optimal therapy in a maximum of two clinical encounters. PMID:25865752

  17. Evolocumab (Repatha)--a second PCSK9 inhibitor to lower LDL-Cholesterol.

    PubMed

    2015-10-12

    The second FDA-approved PCSK9 inhibitor evolocumab (Repatha) appears to be similar in efficacy and safety to alirocumab (Praluent), but no comparative studies are available. Given by subcutaneous injection every 2 weeks or once monthly, evolocumab can further lower LDL-cholesterol levels by about 60% in patients at high risk for atherosclerotic cardiovascular disease already taking maximal statin therapy. Its effect on cardiovascular outcomes remains to be established. The long-term efficacy and safety of both evolocumab and alirocumab are unknown, and they are expensive. PMID:26445204

  18. [Update of planning tables of cholesterol-lowering therapy orientated to achieve LDL therapeutic targets].

    PubMed

    Masana, Luis; Plana, Núria

    2015-01-01

    This is the third update of a planning-table for use in cholesterol-lowering therapy, so as to obtain LDLc objectives. This is an easy to use laptop tool to help choose the best statin or combination therapy (statin plus ezetimibe) depending on the current LDL concentration of the patient, and the LDLc objective to achieve. It is based on a colour code that indicates the drugs that are efficient enough to help patients to achieve their LDL goal. Along with the table, recommendations are given for the best strategy in order to implement the optimal therapy in a maximum of two clinical encounters.

  19. Evolocumab (Repatha)--a second PCSK9 inhibitor to lower LDL-Cholesterol.

    PubMed

    2015-10-12

    The second FDA-approved PCSK9 inhibitor evolocumab (Repatha) appears to be similar in efficacy and safety to alirocumab (Praluent), but no comparative studies are available. Given by subcutaneous injection every 2 weeks or once monthly, evolocumab can further lower LDL-cholesterol levels by about 60% in patients at high risk for atherosclerotic cardiovascular disease already taking maximal statin therapy. Its effect on cardiovascular outcomes remains to be established. The long-term efficacy and safety of both evolocumab and alirocumab are unknown, and they are expensive.

  20. Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis

    PubMed Central

    Chen, Suet Nee; Cilingiroglu, Mehmet; Todd, Josh; Lombardi, Raffaella; Willerson, James T; Gotto, Antonio M; Ballantyne, Christie M; Marian, AJ

    2009-01-01

    Background Plasma level of high-density lipoprotein-cholesterol (HDL-C), a heritable trait, is an important determinant of susceptibility to atherosclerosis. Non-synonymous and regulatory single nucleotide polymorphisms (SNPs) in genes implicated in HDL-C synthesis and metabolism are likely to influence plasma HDL-C, apolipoprotein A-I (apo A-I) levels and severity of coronary atherosclerosis. Methods We genotyped 784 unrelated Caucasian individuals from two sets of populations (Lipoprotein and Coronary Atherosclerosis Study- LCAS, N = 333 and TexGen, N = 451) for 94 SNPs in 42 candidate genes by 5' nuclease assays. We tested the distribution of the phenotypes by the Shapiro-Wilk normality test. We used Box-Cox regression to analyze associations of the non-normally distributed phenotypes (plasma HDL-C and apo A-I levels) with the genotypes. We included sex, age, body mass index (BMI), diabetes mellitus (DM), and cigarette smoking as covariates. We calculated the q values as indicators of the false positive discovery rate (FDR). Results Plasma HDL-C levels were associated with sex (higher in females), BMI (inversely), smoking (lower in smokers), DM (lower in those with DM) and SNPs in APOA5, APOC2, CETP, LPL and LIPC (each q ≤0.01). Likewise, plasma apo A-I levels, available in the LCAS subset, were associated with SNPs in CETP, APOA5, and APOC2 as well as with BMI, sex and age (all q values ≤0.03). The APOA5 variant S19W was also associated with minimal lumen diameter (MLD) of coronary atherosclerotic lesions, a quantitative index of severity of coronary atherosclerosis (q = 0.018); mean number of coronary artery occlusions (p = 0.034) at the baseline and progression of coronary atherosclerosis, as indicated by the loss of MLD. Conclusion Putatively functional variants of APOA2, APOA5, APOC2, CETP, LPL, LIPC and SOAT2 are independent genetic determinants of plasma HDL-C levels. The non-synonymous S19W SNP in APOA5 is also an independent determinant of plasma

  1. Colesevelam hydrochloride: usefulness of a specifically engineered bile acid sequestrant for lowering LDL-cholesterol.

    PubMed

    Corsini, Alberto; Windler, Eberhard; Farnier, Michel

    2009-02-01

    Several recent meta-analyses of numerous lipid-lowering outcome trials confirm the direct relationship between low-density lipoprotein-cholesterol (LDL-C) lowering and cardiovascular risk reduction. As a consequence, LDL-C goals are continuously being set lower. To achieve lipid lowering, several efficient drugs are available, however, the current pharmacopoeia remains limited for some critical patient situations. Colesevelam hydrochloride is a specifically engineered bile acid sequestrant that features a more favourable tolerability and drug interaction profile than traditional bile acid sequestrants, because of a better affinity and binding capacity to bile acids. In addition, colesevelam retains the nonsystemic mode of action of bile acid sequestrants. Moreover, colesevelam lowers LDL-C by 15-19% and 10-16%, respectively, in monotherapy and in combination to various lipid-lowering drugs, such as statins, ezetimibe and fenofibrates. Along with an efficient and sustainable effect on lipid profiles, colesevelam - as other bile acid sequestrants - has been shown to lower the glycosylated haemoglobin HbA1c by 0.5% on average in patients with type 2 diabetes. Overall, colesevelam represents an interesting add-on treatment to be used in high-risk patients with hypercholesterolaemia for whom standard lipid-lowering therapies are not enough or not well tolerated.

  2. Mechanism of transfer of LDL-derived free cholesterol to HDL subfractions in human plasma

    SciTech Connect

    Miida, T.; Fielding, C.J.; Fielding, P.E. )

    1990-11-01

    The transfer of ({sup 3}H)cholesterol in low-density lipoprotein (LDL) to different high-density lipoprotein (HDL) species in native human plasma was determined by using nondenaturing two-dimensional electrophoresis. Transfer from LDL had a t{sub 1/2} at 37{degree}C of 51 {plus minus} 8 min and an activation energy of 18.0 kCal mol{sup {minus}1}. There was unexpected specificity among HDL species as acceptors of LDL-derived labeled cholesterol. The largest fraction of the major {alpha}-migrating class (HDL{sub 2b}) was the major initial acceptor of LDL-derived cholesterol. Kinetic analysis indicated a rapid secondary transfer from HDL{sub 2b} to smaller {alpha}HDL (particularly HDL{sub 3}) driven enzymatically by the lecithin-cholesterol acyltransferase reaction. Rates of transfer among {alpha}HDL were most rapid from the largest {alpha}HDL fraction (HDL{sub 2b}), suggesting possible protein-mediated facilitation. Simultaneous measurements of the transport of LDL-derived and cell-derived isotopic cholesterol indicated that the former preferably utilized the {alpha}HDL pathyway, with little label in pre-{beta}HDL. The same experiments confirmed earlier data that cell-derived cholesterol is preferentially channeled through pre-{beta}HDL. The authors suggest that the functional heterogeneity of HDL demonstrated here includes the ability to independently process cell- and LDL-derived free cholesterol.

  3. STATINS MORE THAN CHOLESTEROL LOWERING AGENTS IN ALZHEIMER DISEASE: THEIR PLEIOTROPIC FUNCTIONS AS POTENTIAL THERAPEUTIC TARGETS

    PubMed Central

    Barone, Eugenio; Domenico, Fabio Di; Butterfield, D. Allan

    2013-01-01

    Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive impairment, inability to perform activities of daily living and mood changes. Statins, long known to be beneficial in conditions where dyslipidemia occurs by lowering serum cholesterol levels, also have been proposed for use in neurodegenerative conditions, including AD. However, it is not clear that the purported effectiveness of statins in neurodegenerative disorders is directly related to cholesterol-lowering effects of these agents; rather, the pleiotropic functions of statins likely play critical roles. The aim of this review is to provide an overview on the new discoveries about the effects of statin therapy on the oxidative ad nitrosative stress levels as well as on the modulation of the heme oxygenase/biliverdin reductase (HO/BVR) system in the brain. We propose a novel mechanism of action for atorvastatin which, through the activation of HO/BVR-A system, may contribute to the neuroprotective effects thus suggesting a potential therapeutic role in AD and potentially accounting for the observation of decreased AD incidence with persons on statin. PMID:24231510

  4. Intensive Lowering of Low-Density Lipoprotein Cholesterol Levels for Primary Prevention of Coronary Artery Disease

    PubMed Central

    Karalis, Dean G.

    2009-01-01

    Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the United States, and a high concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for CAD. Current guidelines recommend the use of statins to lower LDL-C levels for the primary prevention of CAD based on an individual's risk factor profile and baseline LDL-C level. For moderaterisk individuals, those with 2 or more major risk factors for CAD and a Framingham risk score of 10% to 20%, the recommendation is to use a statin to lower LDL-C levels to less than 130 mg/dL. However, up to 40% of individuals who develop CAD have LDL-C levels lower than this cutoff. In 2004, the National Cholesterol Education Program Adult Treatment Panel III guidelines were updated to include an LDL-C goal of less than 100 mg/dL for individuals at moderately high risk of developing CAD. The guidelines identified several risk factors that when present would favor the use of pharmacological therapy to achieve this more aggressive LDL-C goal. This review evaluates the evidence supporting an LDL-C target of less than 100 mg/dL for moderately high-risk individuals and reviews those risk factors that when present help identify patients who would benefit from achieving this lower LDL-C goal. English-language publications in MEDLINE and references from relevant articles published between January 1, 1980, and November 30, 2008, were reviewed. Main keywords searched were coronary artery disease, hyperlipidemia, statins, cardiac risk factors, inflammatory markers, metabolic syndrome, and coronary artery calcium. PMID:19339653

  5. Effect of frequency of dosing of plant sterols on plasma cholesterol levels and synthesis rate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to compare the effects of plant sterols (PS) consumed as a single dose (single) at breakfast or as three doses consumed with breakfast, lunch and dinner (divided) on plasma lipoprotien levels and cholesterol endogenous fractional synthesis rate (FSR). A randomized, placebo-controll...

  6. Detergent-Mediated Phospholipidation of Plasma Lipoproteins Increases HDL Cholesterophilicity and Cholesterol Efflux Via SR-BI†

    PubMed Central

    Pownall, Henry J.

    2008-01-01

    Cellular cholesterol efflux is an early, obligatory step in reverse cholesterol transport, the putative antiatherogenic mechanism by which human plasma high density lipoproteins (HDL) transport cholesterol from peripheral tissue to the liver for recycling or disposal. HDL-phospholipid content is the essential cholesterol-binding component of lipoproteins and therefore a major determinant of cholesterol efflux. Thus, increased phospholipidation of lipoproteins, particularly HDL, is one strategy for increasing cholesterol efflux. This study validates a simple, new detergent perturbation method for the phospholipidation of plasma lipoproteins; we have quantified the cholesterophilicity of human plasma lipoproteins and the effects of lipoprotein phospholipidation on cholesterophilicity and cellular cholesterol efflux mediated by the class B type I scavenger receptor (SR-BI). We determined that low density lipoproteins (LDL) are more cholesterophilic than HDL and that LDL has a higher affinity for phospholipids than HDL whereas HDL has a higher phospholipid capacity than LDL. Phospholipidation of total human plasma lipoproteins enhances cholesterol efflux, an effect that occurs largely through the preferential phospholipidation of HDL. We conclude that increasing HDL phospholipid increases its cholesterophilicity thereby making it a better acceptor of cellular cholesterol efflux. Phospholipidation of lipoproteins by detergent perturbation is a simple way to increase HDL cholesterophilicity and cholesterol efflux in a way that may be clinically useful. PMID:16981711

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

    PubMed Central

    Bays, Harold E

    2014-01-01

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

  8. Liquid General Anesthetics Lower Critical Temperatures in Plasma Membrane Vesicles

    PubMed Central

    Gray, Ellyn; Karslake, Joshua; Machta, Benjamin B.; Veatch, Sarah L.

    2013-01-01

    A large and diverse array of small hydrophobic molecules induce general anesthesia. Their efficacy as anesthetics has been shown to correlate both with their affinity for a hydrophobic environment and with their potency in inhibiting certain ligand-gated ion channels. In this study we explore the effects that n-alcohols and other liquid anesthetics have on the two-dimensional miscibility critical point observed in cell-derived giant plasma membrane vesicles (GPMVs). We show that anesthetics depress the critical temperature (Tc) of these GPMVs without strongly altering the ratio of the two liquid phases found below Tc. The magnitude of this affect is consistent across n-alcohols when their concentration is rescaled by the median anesthetic concentration (AC50) for tadpole anesthesia, but not when plotted against the overall concentration in solution. At AC50 we see a 4°C downward shift in Tc, much larger than is typically seen in the main chain transition at these anesthetic concentrations. GPMV miscibility critical temperatures are also lowered to a similar extent by propofol, phenylethanol, and isopropanol when added at anesthetic concentrations, but not by tetradecanol or 2,6 diterbutylphenol, two structural analogs of general anesthetics that are hydrophobic but have no anesthetic potency. We propose that liquid general anesthetics provide an experimental tool for lowering critical temperatures in plasma membranes of intact cells, which we predict will reduce lipid-mediated heterogeneity in a way that is complimentary to increasing or decreasing cholesterol. Also, several possible implications of our results are discussed in the context of current models of anesthetic action on ligand-gated ion channels. PMID:24359747

  9. The transport of low density lipoprotein-derived cholesterol to the plasma membrane is defective in NPC1 cells.

    PubMed

    Wojtanik, Kari M; Liscum, Laura

    2003-04-25

    Niemann-Pick disease type C (NPC) is characterized by lysosomal storage of cholesterol and gangliosides, which results from defects in intracellular lipid trafficking. Most studies of NPC1 have focused on its role in intracellular cholesterol movement. Our hypothesis is that NPC1 facilitates the egress of cholesterol from late endosomes, which are where active NPC1 is located. When NPC1 is defective, cholesterol does not exit late endosomes; instead, it is carried along to lysosomal storage bodies, where it accumulates. In this study, we addressed whether cholesterol is transported from endosomes to the plasma membrane before reaching NPC1-containing late endosomes. Our study was conducted in Chinese hamster ovary cell lines that display the classical NPC biochemical phenotype and belong to the NPC1 complementation group. We used three approaches to test whether low density lipoprotein (LDL)-derived cholesterol en route to NPC1-containing organelles passes through the plasma membrane. First, we used cyclodextrins to measure the arrival of LDL cholesterol at the plasma membrane and found that the arrival of LDL cholesterol in a cyclodextrin-accessible pool was significantly delayed in NPC1 cells. Second, the movement of LDL cholesterol to NPC1-containing late endosomes was assessed and found to be normal in Chinese hamster ovary mutant 3-6, which exhibits defective movement of plasma membrane cholesterol to intracellular membranes. Third, we examined the movement of plasma membrane cholesterol to the endoplasmic reticulum and found that this pathway is intact in NPC1 cells, i.e. it does not pass through NPC1-containing late endosomes. Our data suggest that in NPC1 cells LDL cholesterol traffics directly through endosomes to lysosomes, bypassing the plasma membrane, and is trapped there because of dysfunctional NPC1. PMID:12591922

  10. Effect of cigarette smoke and dietary cholesterol on plasma lipoprotein composition

    SciTech Connect

    Hojnacki, J.L.; Mulligan, J.J.; Cluette, J.E.; Kew, R.R.; Stack, D.J.; Huber, G.L.

    1981-01-01

    Pigeons were assigned to four treatment groups: 1) Controls fed a chow diet ad libitum and retained in their cages; 2) Sham pigeons fed a cholesterol-saturated fat diet and exposed to fresh air by the Lorillard smoking machine; 3) Low nicotine-low carbon monoxide (LoLo) animals also fed the cholesterol diet and exposed to low concentrations of cigarette smoke; and 4) High nicotine-high carbon monoxide (HiHi) birds fed the cholesterol diet and subjected to high concentrations of inhalants. Plasma very low density (VLDL), low density (LDL), and high density (HDL) lipoproteins were isolated by density gradient ultracentrifugation. Smoke-related differences appeared in HiHi HDL which contained relatively more free and esterified cholesterol and total lipid, but less total protein than HDL from Sham-smoked pigeons. VLDL from birds exposed to cigarette smoke (LoLo and HiHi) contained relatively more total lipid, but less total protein than VLDL from Sham pigeons. Inhalation smoke produced a marked depression in the HDL2/HDL3 ratio resulting from an increased proportion of the HDL3 subfraction relative to HDL2. Pigeons fed the cholesterol-saturated fat diet circulated HDL with greater free and esterified cholesterol mass than Controls. Diet also altered the type of cholesteryl ester present in HDL with cholesteryl linoleate representing the predominant form in Control pigeons and cholesteryl oleate in cholesterol-fed birds. These results demonstrate that cigarette smoking can mediate alterations in lipoprotein composition independent of changes induced by dietary cholesterol and saturated fat.

  11. Digital Gene-Expression Profiling Analysis of the Cholesterol-Lowering Effects of Alfalfa Saponin Extract on Laying Hens

    PubMed Central

    Guo, Rui; Liang, Minggen; Zhu, Xiaoyan; Wang, Chengzhang

    2014-01-01

    Background To prevent cardiovascular disease, people are advised to limit their intake of dietary cholesterol to less than 300 mg/day. Egg consumption has been seriously reduced because of the high levels of cholesterol. The purpose of the present study was to evaluate the cholesterol-lowering effects of alfalfa saponin extract (ASE) in yolk and the molecular mechanisms underlying these effects using digital gene-expression profiling analysis. Liver and ovary tissues were isolated from laying hens fed with ASE for RNA sequencing. Results The cholesterol content of the yolks of eggs from hens fed 120 mg/kg ASE declined considerably on day 60. Other groups (60, 240, 480 mg/kg ASE group) also showed decreases, but they were not significant. Digital gene expression generated over nine million reads per sample, producing expression data for least 12,384 genes. Among these genes, 110 genes showed greater than normal expression in the liver and 107 genes showed greater than normal expression in the ovary. Cholesterol 7 alpha-hydroxylase (Cyp7a1) and apolipoprotein H (Apoh), which act in the synthesis of bile acid and cholesterol efflux, showed more expression in the livers of hens given dietary ASE supplementation. In the ovary, levels of very low density lipoprotein receptor (Vldlr), apolipoprotein B (Apob), apovitellenin 1 (ApovldlII) and vitellogenin (VtgI, VtgII and VtgIII) in ovary decreased with dietary ASE supplementation. Conclusion Transcriptome analysis revealed that the molecular mechanisms underlying the cholesterol-lowering effects of ASE were partially mediated by enhancement of cholesterol efflux in the liver and this reduced of cholesterol deposition in the ovary. PMID:24886784

  12. Some kinetic properties of plasma lecithin-cholesterol acyltransferase in hyper-alphalipoproteinemia in man

    SciTech Connect

    Nikiforova, A.A.; Alksnis, E.G.; Ivanova, E.M.

    1985-07-01

    The aim of this investigation was to study some kinetic properties of lecithin-cholesterol acyltransferase (LCAT) in the blood plasma of patients with hyper-alpha-lipoproteinemia, enabling the presence of LCAT isozymes in the blood to be detected. The velocity of the LCAT reaction was judged by determining labeled CHE formed from /sup 14/C-nonesterified CH and lecithin of HDL on incubation of the latter with the enzyme. Dependence of the velocity of the LCAT reaction on concentration of substrate (nonesterified HDL cholesterol) in four subjects with hyper-alpha-lipoproteinemia is shown.

  13. A reappraisal of the risks and benefits of treating to target with cholesterol lowering drugs.

    PubMed

    Alla, Venkata M; Agrawal, Vrinda; DeNazareth, Andrew; Mohiuddin, Syed; Ravilla, Sudha; Rendell, Marc

    2013-07-01

    Atherosclerotic cardiovascular disease (CVD) is the number one cause of death globally, and lipid modification, particularly lowering of low density lipoprotein cholesterol (LDLc), is one of the cornerstones of prevention and treatment. However, even after lowering of LDLc to conventional goals, a sizeable number of patients continue to suffer cardiovascular events. More aggressive lowering of LDLc and optimization of other lipid parameters like triglycerides (TG) and high density lipoprotein cholesterol (HDLc) have been proposed as two potential strategies to address this residual risk. These strategies entail use of maximal doses of highly potent HMG CoA reductase inhibitors (statins) and combination therapy with other lipid modifying agents. Though statins in general are fairly well tolerated, adverse events like myopathy are dose related. There are further risks with combination therapy. In this article, we review the adverse effects of lipid modifying agents used alone and in combination and weigh these effects against the evidence demonstrating their efficacy in reducing cardiovascular events, cardiovascular mortality, and all cause mortality. For patients with established CVD, statins are the only group of drugs that have shown consistent reductions in hard outcomes. Though more aggressive lipid lowering with high dose potent statins can reduce rates of non fatal events and need for interventions, the incremental mortality benefits remain unclear, and their use is associated with a higher rate of drug related adverse effects. Myopathy and renal events have been a significant concern with the use of high potency statin drugs, in particular simvastatin and rosuvastatin. For patients who have not reached target LDL levels or have residual lipid abnormalities on maximal doses of statins, the addition of other agents has not been shown to improve clinical outcomes and carries an increased risk of adverse events. The clinical benefits of drugs to raise HDLc remain

  14. African Nutmeg (Monodora Myristica) Lowers Cholesterol and Modulates Lipid Peroxidation in Experimentally Induced Hypercholesterolemic Male Wistar Rats

    PubMed Central

    Onyenibe, Nwozo Sarah; Fowokemi, Kasumu Titilayo; Emmanuel, Oyinloye Babatunji

    2015-01-01

    To evaluate the cholesterol lowering potential and protective ability of aqueous extract of Monodora myristica experimental hypercholesterolemic rats, a short-term study was conducted. Hypercholesterolemia was induced by administering cholesterol orally at a dose of 40 mg/kg/0.3 ml. Plant extracts 100 or 200 mg/kg body weight and Questran 0.26 g/kg were administered five times a week for eight weeks for amelioration. Hypolipidemic effects were evaluated by measuring total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in the serum, while the protective ability was measured by the extent of lipid peroxidation (LPO) as well as enzymatic and non-enzymatic antioxidants levels in post mitochondrial fractions (PMF) of the hepatic and cardiac homogenates. Serum aminotransferases activities were also monitored. Results obtained shows that treatment with M. myristica elicited a significant reduction in serum TC, TG and LDL-C levels while there was concomitant increase in HDL-C of hypercholesterolemic rats. Elevations in serum aminotransferases activities and LPO level were reversed and a significant amelioration was noticed in enzymatic and non-enzymatic antioxidants status in the liver and heart of hypercholesterolemic rats. This study suggests that M. myristica possess cholesterol lowering potentials and protective ability in experimental hypercholesterolemia rat model. PMID:26199582

  15. African Nutmeg (Monodora Myristica) Lowers Cholesterol and Modulates Lipid Peroxidation in Experimentally Induced Hypercholesterolemic Male Wistar Rats.

    PubMed

    Onyenibe, Nwozo Sarah; Fowokemi, Kasumu Titilayo; Emmanuel, Oyinloye Babatunji

    2015-06-01

    To evaluate the cholesterol lowering potential and protective ability of aqueous extract of Monodora myristica experimental hypercholesterolemic rats, a short-term study was conducted. Hypercholesterolemia was induced by administering cholesterol orally at a dose of 40 mg/kg/0.3 ml. Plant extracts 100 or 200 mg/kg body weight and Questran 0.26 g/kg were administered five times a week for eight weeks for amelioration. Hypolipidemic effects were evaluated by measuring total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in the serum, while the protective ability was measured by the extent of lipid peroxidation (LPO) as well as enzymatic and non-enzymatic antioxidants levels in post mitochondrial fractions (PMF) of the hepatic and cardiac homogenates. Serum aminotransferases activities were also monitored. Results obtained shows that treatment with M. myristica elicited a significant reduction in serum TC, TG and LDL-C levels while there was concomitant increase in HDL-C of hypercholesterolemic rats. Elevations in serum aminotransferases activities and LPO level were reversed and a significant amelioration was noticed in enzymatic and non-enzymatic antioxidants status in the liver and heart of hypercholesterolemic rats. This study suggests that M. myristica possess cholesterol lowering potentials and protective ability in experimental hypercholesterolemia rat model. PMID:26199582

  16. Cholesterol Modulates CFTR Confinement in the Plasma Membrane of Primary Epithelial Cells

    PubMed Central

    Abu-Arish, Asmahan; Pandzic, Elvis; Goepp, Julie; Matthes, Elizabeth; Hanrahan, John W.; Wiseman, Paul W.

    2015-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma-membrane anion channel that, when mutated, causes the disease cystic fibrosis. Although CFTR has been detected in a detergent-resistant membrane fraction prepared from airway epithelial cells, suggesting that it may partition into cholesterol-rich membrane microdomains (lipid rafts), its compartmentalization has not been demonstrated in intact cells and the influence of microdomains on CFTR lateral mobility is unknown. We used live-cell imaging, spatial image correlation spectroscopy, and k-space image correlation spectroscopy to examine the aggregation state of CFTR and its dynamics both within and outside microdomains in the plasma membrane of primary human bronchial epithelial cells. These studies were also performed during treatments that augment or deplete membrane cholesterol. We found two populations of CFTR molecules that were distinguishable based on their dynamics at the cell surface. One population showed confinement and had slow dynamics that were highly cholesterol dependent. The other, more abundant population was less confined and diffused more rapidly. Treatments that deplete the membrane of cholesterol caused the confined fraction and average number of CFTR molecules per cluster to decrease. Elevating cholesterol had the opposite effect, increasing channel aggregation and the fraction of channels displaying confinement, consistent with CFTR recruitment into cholesterol-rich microdomains with dimensions below the optical resolution limit. Viral infection caused the nanoscale microdomains to fuse into large platforms and reduced CFTR mobility. To our knowledge, these results provide the first biophysical evidence for multiple CFTR populations and have implications for regulation of their surface expression and channel function. PMID:26153705

  17. The Human ABCG1 Transporter Mobilizes Plasma Membrane and Late Endosomal Non-Sphingomyelin-Associated-Cholesterol for Efflux and Esterification

    PubMed Central

    Neufeld, Edward B.; O’Brien, Katherine; Walts, Avram D.; Stonik, John A.; Malide, Daniela; Combs, Christian A.; Remaley, Alan T.

    2014-01-01

    We have previously shown that GFP-tagged human ABCG1 on the plasma membrane (PM) and in late endosomes (LE) mobilizes sterol on both sides of the membrane lipid bilayer, thereby increasing cellular cholesterol efflux to lipid surfaces. In the present study, we examined ABCG1-induced changes in membrane cholesterol distribution, organization, and mobility. ABCG1-GFP expression increased the amount of mobile, non-sphingomyelin(SM)-associated cholesterol at the PM and LE, but not the amount of SM-associated-cholesterol or SM. ABCG1-mobilized non-SM-associated-cholesterol rapidly cycled between the PM and LE and effluxed from the PM to extracellular acceptors, or, relocated to intracellular sites of esterification. ABCG1 increased detergent-soluble pools of PM and LE cholesterol, generated detergent-resistant, non-SM-associated PM cholesterol, and increased resistance to both amphotericin B-induced (cholesterol-mediated) and lysenin-induced (SM-mediated) cytolysis, consistent with altered organization of both PM cholesterol and SM. ABCG1 itself resided in detergent-soluble membrane domains. We propose that PM and LE ABCG1 residing at the phase boundary between ordered (Lo) and disordered (Ld) membrane lipid domains alters SM and cholesterol organization thereby increasing cholesterol flux between Lo and Ld, and hence, the amount of cholesterol available for removal by acceptors on either side of the membrane bilayer for either efflux or esterification. PMID:25485894

  18. Complementary Cholesterol-Lowering Response of a Phytosterol/α-Lipoic Acid Combination in Obese Zucker Rats.

    PubMed

    Rideout, Todd C; Carrier, Bradley; Wen, Shin; Raslawsky, Amy; Browne, Richard W; Harding, Scott V

    2016-01-01

    To investigate the cholesterol-lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (-55%) than either the PS (-24%) or the αLA (-25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (-47%) or in combination with PS (-54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21-22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (+52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLr protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone.

  19. Cholesterol-lowering probiotics: in vitro selection and in vivo testing of bifidobacteria.

    PubMed

    Bordoni, Alessandra; Amaretti, Alberto; Leonardi, Alan; Boschetti, Elisa; Danesi, Francesca; Matteuzzi, Diego; Roncaglia, Lucia; Raimondi, Stefano; Rossi, Maddalena

    2013-09-01

    Thirty-four strains of bifidobacteria belonging to Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, and Bifidobacterium pseu-docatenulatum were assayed in vitro for the ability to assimilate cholesterol and for bile salt hydrolase (BSH) against glycocholic and taurodeoxycholic acids (GCA and TDCA). Cholesterol assimilation was peculiar characteristic of two strains belonging to the species B. bifidum (B. bifidum MB 107 and B. bifidum MB 109), which removed 81 and 50 mg of cholesterol per gram of biomass, being the median of specific cholesterol absorption by bifidobacteria 19 mg/g. Significant differences in BSH activities were not established among bifidobacterial species. However, the screening resulted in the selection of promising strains able to efficiently deconjugate GCA and TDCA. No relationship was recognized between BSH phenotype and the extent of cholesterol assimilation. On the basis of cholesterol assimilation or BSHGCA and BSHTDCA activities, B. bifidum MB 109 (DSMZ 23731), B. breve MB 113 (DSMZ 23732), and B. animalis subsp. lactis MB 2409 (DSMZ 23733) were combined in a probiotic mixture to be fed to hypercholesterolemic rats. The administration of this probiotic formulation resulted in a significant reduction of total cholesterol and low-density cholesterol (LDL-C), whereas it did not affect high-density cholesterol (HDL-C) and HDL-C/LDL-C ratio.

  20. Relationship between the cholesterol ester transfer protein TaqIB polymorphism and the lipid-lowering effect of atorvastatin in patients with coronary atherosclerotic heart disease.

    PubMed

    Li, J; Zhang, L; Xie, N Z; Deng, B; Lv, L X; Zheng, L Q

    2014-03-24

    This study aimed to investigate the relationship between the cholesterol ester transfer protein (CETP) gene TaqIB polymorphism and the lipid-lowering effect of atorvastatin in patients with coronary atherosclerotic heart disease. Two hundred eighty-eight patients were divided into a control group, an acute coronary syndrome (ACS) group, and a stable coronary heart disease (CHD) group. Blood biochemical indices were determined using the enzyme method, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to study the TaqIB polymorphism of the CETP gene. The ACS and stable CHD groups were treated with atorvastatin, and blood lipid levels were reexamined after three months. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a) were all significantly higher in the ACS and stable CHD groups compared to the control group (P < 0.05 or P < 0.01). After three months of treatment with atorvastatin, plasma levels of TC, LDL-C, triglycerides (TG) (only in patients with genotype B2B2), and lipoprotein(a) (only in patients with genotype B1B2) were all significantly decreased (P < 0.05 or P < 0.01). After treatment, the plasma level of TG was lower in patients with genotype B2B2 compared to patients with genotypes B1B1 or B1B2 (B1 carriers) (P < 0.01). Therefore, the CETP TaqIB polymorphism is associated with the lipid-lowering effect of atorvastatin in patients with CHD.

  1. Cholesterol and triglycerides lowering activities of caraway fruits in normal and streptozotocin diabetic rats.

    PubMed

    Lemhadri, A; Hajji, L; Michel, J-B; Eddouks, M

    2006-07-19

    The purpose of this study was to examine the effect of single and repeated oral administration of the aqueous extract of Carum carvi L. fruits at a dose of (20mg/kg) on lipid metabolism in normal and streptozotocin-induced diabetic rats (STZ). After a single oral administration, Carum carvi extract produced a significant decrease on triglycerides levels in normal rats (p<0.05). In STZ diabetic rats, cholesterol levels were decreased significantly 6h after Carum carvi treatment (p<0.05). On the other hand, repeated oral administration of Carum carvi extract exhibited a significant hypotriglyceridemic and hypocholesterolemic activities in both normal (p<0.01 and <0.001 respectively) and STZ diabetic rats (p<0.001) 15 days after Carum carvi treatment. We conclude that the aqueous extract of Carum carvi (20mg/kg) exhibits a potent lipid lowering activity in both normal and severe hyperglycemic rats after repeated oral administration of Carum carvi aqueous extract.

  2. Cholesterol lowering drug may influence cellular immune response by altering MHC II function[S

    PubMed Central

    Roy, Koushik; Ghosh, Moumita; Pal, Tuhin Kumar; Chakrabarti, Saikat; Roy, Syamal

    2013-01-01

    Major histocompatibility complex class II (MHC II) expressed on the surface of antigen-presenting cells (APCs) displays peptides to CD4+ T cells. Depletion of membrane cholesterol from APCs by methyl β-cyclodextrin treatment compromises peptide-MHC II complex formation coupled with impaired binding of conformational antibody, which binds close to the peptide binding groove of MHC II. Interestingly, the total cell surface of MHC II remains unaltered. These defects can be corrected by restoring membrane cholesterol. In silico docking studies with a three-dimensional model showed the presence of a cholesterol binding site in the transmembrane domain of MHC II (TM-MHC-II). From the binding studies it was clear that cholesterol, indeed, interacts with the TM-MHC-II and alters its conformation. Mutation of cholesterol binding residues (F240, L243, and F246) in the TM-MHC-II decreased the affinity for cholesterol. Furthermore, transfection of CHO cells with full-length mutant MHC II, but not wild-type MHC II, failed to activate antigen-specific T cells coupled with decreased binding of conformation-specific antibodies. Thus, cholesterol-induced conformational change of TM-MHC-II may allosterically modulate the peptide binding groove of MHC II leading to T cell activation. PMID:24038316

  3. Nature's Cholesterol-Lowering Drug: Isolation and Structure Elucidation of Lovastatin from Red Yeast Rice-Containing Dietary Supplements

    ERIC Educational Resources Information Center

    Nazri, Maisarah Mohd; Samat, Farah D.; Kavanagh, Pierce V.; Walsh, John J.

    2012-01-01

    Red yeast rice, produced by fermenting the fungus, "Monascus purpureus", on rice ("Oryza sativa" L. gramineae), is commonly used as a dietary supplement. It contains lovastatin, a member of the statin family of compounds, and is licensed for use as a cholesterol-lowering agent. This experiment involves the isolation and structure elucidation of…

  4. EFFECT OF LOWER TARGETS FOR BLOOD PRESSURE AND LDL CHOLESTEROL ON ATHEROSCLEROSIS IN DIABETES

    PubMed Central

    Howard, Barbara V.; Roman, Mary J.; Fleg, Jerome L.; Galloway, James M.; Henderson, Jeffrey A.; Howard, Wm. James; Lee, Elisa T.; Mete, Mihriye; Poolaw, Bryce; Devereux, Richard B.; Russell, Marie; Silverman, Angela; Stylianou, Mario; Umans, Jason; Wang, Wenyu; Weissman, Neil; Weir, Matthew R.; Wilson, Charlton; Yeh, Fawn; Zhu, Jianhui; Ratner, Robert E.

    2008-01-01

    Context Individuals with diabetes are at greatly increased risk for developing cardiovascular disease (CVD), but more aggressive targets for risk factor control have not been tested. Objective To compare the progression of subclinical atherosclerotic disease in diabetic adults treated to aggressive targets of low-density lipoprotein cholesterol (LDL-C) ≤ 70 mg/dL and blood pressure (BP) ≤ 115/75 mm Hg (aggressive) versus treatment to standard targets of LDL-C ≤ 100 mg/dL and BP ≤ 130/85 mm Hg (standard). Design Randomized, open label, blinded-to-endpoint 3-year trial in individuals with diabetes conducted April 2003-July 2004. Setting Four clinical centers in southwestern Oklahoma; Phoenix, AZ; northeastern Arizona; and South Dakota. Participants 499 American Indian men and women ≥ age 40 with type 2 diabetes and no prior CVD events. Interventions Participants were randomized to aggressive vs. standard treatment. The same treatment algorithms were followed for both groups. Main Outcome Measures Primary endpoint was a composite of progression of atherosclerosis as measured by common carotid artery intimal medial thickness (IMT) and clinical events. Secondary endpoints included other carotid and cardiac ultrasonographic measures. Results LDL-C and systolic BP (SBP) goals for both groups were reached within 12 months and maintained to 36 months. LDL-C and SBP in the last 12 months averaged 72 and 104 mg/dL and 116 and 129 mm Hg in the aggressive and standard groups, respectively. Regression of IMT (-0.017 vs. 0.041 mm, p < .0001) and arterial mass (-0.14 vs. 1.14 mm2, p < .0001) and greater decrease in left ventricular mass (-2.4 vs. -1.3 g/m2.7, p = .05) were observed in the aggressive group. Clinical CVD events were lower than expected and did not differ between groups Conclusions Reducing LDL-C and SBP to lower targets resulted in regression of carotid IMT and greater decrease in left ventricular mass in individuals with type 2 diabetes. Clinical events

  5. Localization of genes for V+LDL plasma cholesterol levels on two diets in the opossum Monodelphis domestica[S

    PubMed Central

    Kammerer, Candace M.; Rainwater, David L.; Gouin, Nicolas; Jasti, Madhuri; Douglas, Kory C.; Dressen, Amy S.; Ganta, Prasanth; VandeBerg, John L.; Samollow, Paul B.

    2010-01-01

    Plasma cholesterol levels among individuals vary considerably in response to diet. However, the genes that influence this response are largely unknown. Non-HDL (V+LDL) cholesterol levels vary dramatically among gray, short-tailed opossums fed an atherogenic diet, and we previously reported that two quantitative trait loci (QTLs) influenced V+LDL cholesterol on two diets. We used hypothesis-free, genome-wide linkage analyses on data from 325 pedigreed opossums and located one QTL for V+LDL cholesterol on the basal diet on opossum chromosome 1q [logarithm of the odds (LOD) = 3.11, genomic P = 0.019] and another QTL for V+LDL on the atherogenic diet (i.e., high levels of cholesterol and fat) on chromosome 8 (LOD = 9.88, genomic P = 5 × 10−9). We then employed a novel strategy involving combined analyses of genomic resources, expression analysis, sequencing, and genotyping to identify candidate genes for the chromosome 8 QTL. A polymorphism in ABCB4 was strongly associated (P = 9 × 10−14) with the plasma V+LDL cholesterol concentrations on the high-cholesterol, high-fat diet. The results of this study indicate that genetic variation in ABCB4, or closely linked genes, is responsible for the dramatic differences among opossums in their V+LDL cholesterol response to an atherogenic diet. PMID:20650928

  6. Cholesterol and F-actin are required for clustering of recycling synaptic vesicle proteins in the presynaptic plasma membrane.

    PubMed

    Dason, Jeffrey S; Smith, Alex J; Marin, Leo; Charlton, Milton P

    2014-02-15

    Synaptic vesicles (SVs) and their proteins must be recycled for sustained synaptic transmission. We tested the hypothesis that SV cholesterol is required for proper sorting of SV proteins during recycling in live presynaptic terminals. We used the reversible block of endocytosis in the Drosophila temperature-sensitive dynamin mutant shibire-ts1 to trap exocytosed SV proteins, and then examined the effect of experimental treatments on the distribution of these proteins within the presynaptic plasma membrane by confocal microscopy. SV proteins synaptotagmin, vglut and csp were clustered following SV trapping in control experiments but dispersed in samples treated with the cholesterol chelator methyl-β-cyclodextrin to extract SV cholesterol. There was accumulation of phosphatidylinositol (4,5)-bisphosphate (PIP2) in presynaptic terminals following SV trapping and this was reduced following SV cholesterol extraction. Reduced PIP2 accumulation was associated with disrupted accumulation of actin in presynaptic terminals. Similar to vesicular cholesterol extraction, disruption of actin by latrunculin A after SV proteins had been trapped on the plasma membrane resulted in the dispersal of SV proteins and prevented recovery of synaptic transmission due to impaired endocytosis following relief of the endocytic block. Our results demonstrate that vesicular cholesterol is required for aggregation of exocytosed SV proteins in the presynaptic plasma membrane and are consistent with a mechanism involving regulation of PIP2 accumulation and local actin polymerization by cholesterol. Thus, alteration of membrane or SV lipids may affect the ability of synapses to undergo sustained synaptic transmission by compromising the recycling of SV proteins.

  7. Association between Plasma PFOA and PFOS Levels and Total Cholesterol in a Middle-Aged Danish Population

    PubMed Central

    Eriksen, Kirsten T.; Raaschou-Nielsen, Ole; McLaughlin, Joseph K.; Lipworth, Loren; Tjønneland, Anne; Overvad, Kim; Sørensen, Mette

    2013-01-01

    Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are used in a variety of consumer products and have been detected worldwide in human blood. Recent studies mainly of highly exposed populations have indicated that PFOA and PFOS may affect serum cholesterol levels, but the magnitude of the effect may be inconsistent across exposure levels. The aim of the present cross-sectional study was to investigate the association between plasma PFOA and PFOS and total cholesterol in a general, middle-aged Danish population. The study population comprised 753 individuals (663 men and 90 women), 50–65 years of age, nested within a Danish cohort of 57,053 participants. Blood samples were taken from all cohort members at enrolment (1993–1997) and stored in a biobank at -150°C. Plasma levels of PFOA and PFOS and serum levels of total cholesterol were measured. The associations between plasma PFOA and PFOS levels and total cholesterol levels were analysed by generalized linear models, both crude and adjusted for potential confounders. We observed statistically significant positive associations between both perfluorinated compounds and total cholesterol, e.g. a 4.4 [95% CI  =  1.1–7.8] higher concentration of total cholesterol (mg/dL) per interquartile range of PFOA plasma level. Sex and prevalent diabetes appeared to modify the association between PFOA and PFOS, respectively, and cholesterol. In conclusion, this study indicated positive associations between plasma PFOA and PFOS levels and total cholesterol in a middle-aged Danish population, although whether the observed pattern of results reflects a causal association is unclear. PMID:23441227

  8. A plasma lipoprotein containing only apolipoprotein E and with gamma mobility on electrophoresis releases cholesterol from cells.

    PubMed Central

    Huang, Y; von Eckardstein, A; Wu, S; Maeda, N; Assmann, G

    1994-01-01

    Previous studies have identified lipid-poor high density lipoproteins with electrophoretic pre-beta mobility as the initial acceptors of cell-derived cholesterol in human plasma. These lipoproteins contain apolipoprotein A-I (apo A-I) as their sole apolipoprotein. In the present study, incubation of human plasma with [3H]cholesterol-laden skin fibroblasts has led to the identification of another lipoprotein that serves as a potent initial acceptor of cell-derived cholesterol. This lipoprotein, which we term gamma-LpE, exhibits gamma mobility on agarose gel electrophoresis. As determined by nondenaturing PAGE and by electron microscopy, the size of the spherical particle ranges between 12 and 16 nm. SDS/PAGE and subsequent immunoblotting identified apoE as its sole apolipoprotein. Plasma from normal and apoA-I-deficient mice, but not from apoE-deficient mice, released [3H]cholesterol from fibroblasts into a gamma-migrating lipoprotein. Cell culture media from hepatoma cells or mouse peritoneal macrophages, both of which contain apoE of cellular origin, also promoted efflux of [3H]cholesterol from fibroblasts into a gamma-migrating fraction. This was not observed with cell culture medium from fibroblasts alone. In conclusion, our results strongly indicate the presence in human plasma of a lipoprotein containing only apoE, gamma-LpE, which is secreted by peripheral cells and is a potent acceptor of cell-derived cholesterol. Images PMID:8127890

  9. Insoluble carob fiber rich in polyphenols lowers total and LDL cholesterol in hypercholesterolemic sujects.

    PubMed

    Ruiz-Roso, Baltasar; Quintela, José C; de la Fuente, Ester; Haya, Javier; Pérez-Olleros, Lourdes

    2010-03-01

    Recently, polyphenols have been found to affect blood lipids in animals in a similar manner as soluble dietary fibre. The aim was to assess whether an insoluble dietary fiber very rich in polyphenols has a beneficial effect on serum lipids in humans. In a double-blind randomized placebo-controlled clinical study with parallel arms, 88 volunteers with hypercholesterolemia were randomly assigned to consume daily either, fiber with insoluble 84% polyphenols 4 g twice a day (n = 43) or placebo (n = 45). Serum total, LDL and HDL cholesterol and triglycerides were assessed at baseline and after 4 weeks. The insoluble polyphenols consumption reduced the total cholesterol by 17.8 +/- 6.1% (p < 0.05), LDL cholesterol by 22.5 +/- 8.9% (p < 0.001), LDL: HDL cholesterol ratio by 26.2 +/- 14.3% (p < 0.001) and triglycerides by 16.3 +/- 23.4% (p < 0.05) at the end of the study compared with baseline. No significant differences were found during the study time in the placebo group for the lipid profile. The consumption of fiber very rich in insoluble polyphenols shows beneficial effects on human blood lipid profile and may be effective in prevention and treatment of hyperlipemia.

  10. Enzymatic assay of total cholesterol in serum or plasma by amperometric measurement of rate of oxygen depletion following saponification.

    PubMed

    Kumar, A; Christian, G D

    1977-01-17

    A method for serum or plasma cholesterol assay involving amperometric measurement of the rate of oxygen depletion in the cholesterol oxidase-catalyzed oxidation of cholesterol is described. The hydrolysis of the serum cholesterol esters is accomplished by saponification of 50 mul of sample with 0.2 ml of ethanolic KOH (1.0 mol/1) containing 0.5% Triton X-100 for 5 min at 75 degrees C. The rate of oxygen consumption in a 25-mul aliquot of this is measured with a Clark electrode in a Beckman Glucose Analyzer and the assay takes about one minute after incubation; results are read digitally on the instrument. The analyzer cell contains 1 ml of 1 M phosphate buffer, pH 7.4, with 100 mg sodium cholate/100 ml and 0.1-0.2 U cholesterol oxidase.

  11. All about Cholesterol

    MedlinePlus

    ... are several kinds of fats in your blood. • LDL cholesterol is sometimes called “bad” cholesterol. It can narrow ... medicine to manage blood fats. They help lower LDL cholesterol. They also help lower your risk for a ...

  12. Rapid on-line determination of cholesterol distribution among plasma lipoproteins after high-performance gel filtration chromatography.

    PubMed

    Kieft, K A; Bocan, T M; Krause, B R

    1991-05-01

    A high-performance gel chromatography (HPGC) system has been developed which allows the unattended on-line determination of lipoprotein cholesterol distribution (VLDL-C, LDL-C, HDL-C), within 40 min, in microliter quantities of plasma using a single, relatively inexpensive column (Superose 6HR). The FAST cholesterol reagent (Sclavo) and a knitted PFTE Kratos reaction coil (Applied Biosystems) were found to provide optimal sensitivity, linearity, resolution, and dispersion characteristics. Validation is provided by comparison to target values for human quality control reference sera, and by comparing the values obtained by HPGC to the beta-quant method (LRC). The utility of the system is illustrated by comparing profiles from seven different species with normal or elevated plasma cholesterol concentrations. This technique allows rapid analysis of samples, regardless of species, without the use of precipitating agents or the ultracentrifuge. It could also be applied for the direct clinical determination of LDL-cholesterol. PMID:2072044

  13. Elaidyl-sulfamide, an oleoylethanolamide-modelled PPARα agonist, reduces body weight gain and plasma cholesterol in rats

    PubMed Central

    Decara, Juan Manuel; Romero-Cuevas, Miguel; Rivera, Patricia; Macias-González, Manuel; Vida, Margarita; Pavón, Francisco J.; Serrano, Antonia; Cano, Carolina; Fresno, Nieves; Pérez-Fernández, Ruth; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2012-01-01

    SUMMARY We have modelled elaidyl-sulfamide (ES), a sulfamoyl analogue of oleoylethanolamide (OEA). ES is a lipid mediator of satiety that works through the peroxisome proliferator-activated receptor alpha (PPARα). We have characterised the pharmacological profile of ES (0.3–3 mg/kg body weight) by means of in silico molecular docking to the PPARα receptor, in vitro transcription through PPARα, and in vitro and in vivo administration to obese rats. ES interacts with the binding site of PPARα in a similar way as OEA does, is capable of activating PPARα and also reduces feeding in a dose-dependent manner when administered to food-deprived rats. When ES was given to obese male rats for 7 days, it reduced feeding and weight gain, lowered plasma cholesterol and reduced the plasmatic activity of transaminases, indicating a clear improvement of hepatic function. This pharmacological profile is associated with the modulation of both cholesterol and lipid metabolism regulatory genes, including the sterol response element-binding proteins SREBF1 and SREBF2, and their regulatory proteins INSIG1 and INSIG2, in liver and white adipose tissues. ES treatment induced the expression of thermogenic regulatory genes, including the uncoupling proteins UCP1, UCP2 and UCP3 in brown adipose tissue and UCP3 in white adipose tissue. However, its chronic administration resulted in hyperglycaemia and insulin resistance, which represent a constraint for its potential clinical development. PMID:22736460

  14. Plasma proteomic analysis of stable coronary artery disease indicates impairment of reverse cholesterol pathway

    PubMed Central

    Basak, Trayambak; Tanwar, Vinay Singh; Bhardwaj, Gourav; Bhardwaj, Nitin; Ahmad, Shadab; Garg, Gaurav; V, Sreenivas; Karthikeyan, Ganesan; Seth, Sandeep; Sengupta, Shantanu

    2016-01-01

    Coronary artery disease (CAD) is one of the largest causes of death worldwide yet the traditional risk factors, although useful in identifying people at high risk, lack the desired predictive accuracy. Techniques like quantitative plasma proteomics holds immense potential to identify newer markers and this study (conducted in three phases) was aimed to identify differentially expressed proteins in stable CAD patients. In the first (discovery) phase, plasma from CAD cases (angiographically proven) and controls were subjected to iTRAQ based proteomic analysis. Proteins found to be differentially expressed were then validated in the second and third (verification and validation) phases in larger number of (n = 546) samples. After multivariate logistic regression adjusting for confounding factors (age, diet, etc.), four proteins involved in the reverse cholesterol pathway (Apo A1, ApoA4, Apo C1 and albumin) along with diabetes and hypertension were found to be significantly associated with CAD and could account for approximately 88% of the cases as revealed by ROC analysis. The maximum odds ratio was found to be 6.70 for albumin (p < 0.0001), followed by Apo AI (5.07, p < 0.0001), Apo CI (4.03, p = 0.001), and Apo AIV (2.63, p = 0.003). Down-regulation of apolipoproteins and albumin implicates the impairment of reverse cholesterol pathway in CAD. PMID:27350024

  15. The ATP-binding cassette transporter-2 (ABCA2) regulates esterification of plasma membrane cholesterol by modulation of sphingolipid metabolism

    PubMed Central

    Davis, Warren

    2015-01-01

    The ATP-binding cassette transporters are a large family (~ 48 genes divided into seven families A–G) of proteins that utilize the energy of ATP-hydrolysis to pump substrates across lipid bilayers against a concentration gradient. The ABC “A” subfamily is comprised of 13 members and transport sterols, phospholipids and bile acids. ABCA2 is the most abundant ABC transporter in human and rodent brain with highest expression in oligodendrocytes, although it is also expressed in neurons. Several groups have studied a possible connection between ABCA2 and Alzheimer’s disease as well as early atherosclerosis. ABCA2 expression levels have been associated with changes in cholesterol and sphingolipid metabolism. In this paper, we hypothesized that ABCA2 expression level may regulate esterification of plasma membrane-derived cholesterol by modulation of sphingolipid metabolism. ABCA2 overexpression in N2a neuroblastoma cells was associated with an altered bilayer distribution of the sphingolipid ceramide that inhibited acylCoA:cholesterol acyltransferase (ACAT) activity and cholesterol esterification. In contrast, depletion of endogenous ABCA2 in the rat schwannoma cell line D6P2T increased esterification of plasma membrane cholesterol following treatment with exogenous bacterial sphingomyelinase. These findings suggest that control of ABCA2 expression level may be a key locus of regulation for esterification of plasma membrane-derived cholesterol through modulation of sphingolipid metabolism. PMID:24201375

  16. Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: a randomized, double blind placebo controlled trial.

    PubMed

    Bundy, Rafe; Walker, Ann F; Middleton, Richard W; Wallis, Carol; Simpson, Hugh C R

    2008-09-01

    Cardiovascular diseases are the chief causes of death in the UK, and are associated with high circulating levels of total cholesterol in the plasma. Artichoke leaf extracts (ALEs) have been reported to reduce plasma lipids levels, including total cholesterol, although high quality data is lacking. The objective of this trial was to assess the effect of ALE on plasma lipid levels and general well-being in otherwise healthy adults with mild to moderate hypercholesterolemia. 131 adults were screened for total plasma cholesterol in the range 6.0-8.0 mmol/l, with 75 suitable volunteers randomised onto the trial. Volunteers consumed 1280 mg of a standardised ALE, or matched placebo, daily for 12 weeks. Plasma total cholesterol decreased in the treatment group by an average of 4.2% (from 7.16 (SD 0.62) mmol/l to 6.86 (SD 0.68) mmol/l) and increased in the control group by an average of 1.9% (6.90 (SD 0.49) mmol/l to 7.03 (0.61) mmol/l), the difference between groups being statistically significant (p=0.025). No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or triglyceride levels. General well-being improved significantly in both the treatment (11%) and control groups (9%) with no significant differences between groups. In conclusion, ALE consumption resulted in a modest but favourable statistically significant difference in total cholesterol after 12 weeks. In comparison with a previous trial, it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response.

  17. An antibody against the C-terminal domain of PCSK9 lowers LDL cholesterol levels in vivo.

    PubMed

    Schiele, Felix; Park, John; Redemann, Norbert; Luippold, Gerd; Nar, Herbert

    2014-02-20

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with autosomal dominant hypercholesterolemia, a state of elevated levels of LDL (low-density lipoprotein) cholesterol. Autosomal dominant hypercholesterolemia can result in severe implications such as stroke and coronary heart disease. The inhibition of PCSK9 function by therapeutic antibodies that block interaction of PCSK9 with the epidermal growth factor-like repeat A domain of LDL receptor (LDLR) was shown to successfully lower LDL cholesterol levels in clinical studies. Here we present data on the identification, structural and biophysical characterization and in vitro and in vivo pharmacology of a PCSK9 antibody (mAb1). The X-ray structure shows that mAb1 binds the module 1 of the C-terminal domain (CTD) of PCSK9. It blocks access to an area bearing several naturally occurring gain-of-function and loss-of-function mutations. Although the antibody does not inhibit binding of PCSK9 to epidermal growth factor-like repeat A, it partially reverses PCSK9-induced reduction of the LDLR and LDL cholesterol uptake in a cellular assay. mAb1 is also effective in lowering serum levels of LDL cholesterol in cynomolgus monkeys in vivo. Complete loss of PCSK9 is associated with insufficient liver regeneration and increased risk of hepatitis C infections. Blocking of the CTD is sufficient to partially inhibit PCSK9 function. Antibodies binding the CTD of PCSK9 may thus be advantageous in patients that do not tolerate complete inhibition of PCSK9.

  18. An adhesion-based method for plasma membrane isolation: evaluating cholesterol extraction from cells and their membranes.

    PubMed

    Bezrukov, Ludmila; Blank, Paul S; Polozov, Ivan V; Zimmerberg, Joshua

    2009-11-15

    A method to isolate large quantities of directly accessible plasma membrane from attached cells is presented. The method is based on the adhesion of cells to an adsorbed layer of polylysine on glass plates, followed by hypotonic lysis with ice-cold distilled water and subsequent washing steps. Optimal conditions for coating glass plates and time for cell attachment were established. No additional chemical or mechanical treatments were used. Contamination of the isolated plasma membrane by cell organelles was less than 5%. The method uses inexpensive, commercially available polylysine and reusable glass plates. Plasma membrane preparations can be made in 15 min. Using this method, we determined that methyl-beta-cyclodextrin differentially extracts cholesterol from fibroblast cells and their plasma membranes and that these differences are temperature dependent. Determination of the cholesterol/phospholipid ratio from intact cells does not reflect methyl-beta-cyclodextrin plasma membrane extraction properties.

  19. CYP7A1-rs3808607 and APOE isoform associate with LDL cholesterol lowering after plant sterol consumption in a randomized clinical trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The benefits of plant sterols (PS) for cholesterol lowering are hampered by large heterogeneity across individuals, potentially due to genetic polymorphisms. We investigated the impact of candidate genetic variations on cholesterol response to PS, in a trial which recruited individuals with high or ...

  20. Ultrafast Diffusion of a Fluorescent Cholesterol Analog in Compartmentalized Plasma Membranes

    PubMed Central

    Hiramoto-Yamaki, Nao; Tanaka, Kenji A K; Suzuki, Kenichi G N; Hirosawa, Koichiro M; Miyahara, Manami S H; Kalay, Ziya; Tanaka, Koichiro; Kasai, Rinshi S; Kusumi, Akihiro; Fujiwara, Takahiro K

    2014-01-01

    Cholesterol distribution and dynamics in the plasma membrane (PM) are poorly understood. The recent development of Bodipy488-conjugated cholesterol molecule (Bdp-Chol) allowed us to study cholesterol behavior in the PM, using single fluorescent-molecule imaging. Surprisingly, in the intact PM, Bdp-Chol diffused at the fastest rate ever found for any molecules in the PM, with a median diffusion coefficient (D) of 3.4 µm2/second, which was ∼10 times greater than that of non-raft phospholipid molecules (0.33 µm2/second), despite Bdp-Chol's probable association with raft domains. Furthermore, Bdp-Chol exhibited no sign of entrapment in time scales longer than 0.5 milliseconds. In the blebbed PM, where actin filaments were largely depleted, Bdp-Chol and Cy3-conjugated dioleoylphosphatidylethanolamine (Cy3-DOPE) diffused at comparable Ds (medians = 5.8 and 6.2 µm2/second, respectively), indicating that the actin-based membrane skeleton reduces the D of Bdp-Chol only by a factor of ∼2 from that in the blebbed PM, whereas it reduces the D of Cy3-DOPE by a factor of ∼20. These results are consistent with the previously proposed model, in which the PM is compartmentalized by the actin-based membrane-skeleton fence and its associated transmembrane picket proteins for the macroscopic diffusion of all of the membrane molecules, and suggest that the probability of Bdp-Chol passing through the compartment boundaries, once it enters the boundary, is ∼10× greater than that of Cy3-DOPE. Since the compartment sizes are greater than those of the putative raft domains, we conclude that raft domains coexist with membrane-skeleton-induced compartments and are contained within them. PMID:24506328

  1. Rapid turn-over of plasma membrane sphingomyelin and cholesterol in baby hamster kidney cells after exposure to sphingomyelinase.

    PubMed

    Slotte, J P; Härmälä, A S; Jansson, C; Pörn, M I

    1990-12-14

    Plasma membrane sphingomyelin in baby hamster kidney (BHK-21) cells was hydrolyzed with sphingomyelinase (Staphylococcus aureus) and the effects on membrane cholesterol translocation and the properties of membrane bound adenylate cyclase and Na+/K(+)-ATPase were determined. Exposure of confluent BHK-21 cells to 0.1 U/ml of sphingomyelinase led to the degradation (at 37 degrees C) of about 60% of cell sphingomyelin. No simultaneous hydrolysis of phosphatidylcholine occurred. The hydrolysis of sphingomyelin subsequently led to the translocation (within 40 min) of about 50-60% of cell [3H]cholesterol from a cholesterol oxidase susceptible pool to an oxidase resistant compartment. The translocation of [3H]cholesterol from the cell surface to intracellular membranes was accompanied by a paralleled increase in [3H]cholesterol ester formation. When cells were first exposed to sphingomyelinase (to degrade sphingomyelin) and then incubated without the enzyme in serum-free media, the mass of cell sphingomyelin decreased initially (by 60%), but then began to increase and reached control levels within 3-4 h. The rapid re-synthesis of sphingomyelin was accompanied by an equally rapid normalization of cell [3H]cholesterol distribution. The re-formation of cell sphingomyelin also led to a decreased content of cellular [3H]cholesterol esters, indicating that unesterified [3H]cholesterol was pulled out of the cholesterol ester cycle and transported to the cell surface. Exposure of BHK-21 cells to sphingomyelinase further led to a dramatically decreased activity of ouabain-sensitive Na+/K(+)-ATPase, whereas forskolin-stimulated adenylate cyclase activity was not affected. The activity of Na+/K(+)-ATPase returned to normal in parallel with the normalization of cell sphingomyelin mass and cholesterol distribution. We conclude that sphingomyelin has profound effects on the steady-state distribution of cell cholesterol, and that manipulations of cell sphingomyelin levels directly and

  2. Rapid turn-over of plasma membrane sphingomyelin and cholesterol in baby hamster kidney cells after exposure to sphingomyelinase.

    PubMed

    Slotte, J P; Härmälä, A S; Jansson, C; Pörn, M I

    1990-12-14

    Plasma membrane sphingomyelin in baby hamster kidney (BHK-21) cells was hydrolyzed with sphingomyelinase (Staphylococcus aureus) and the effects on membrane cholesterol translocation and the properties of membrane bound adenylate cyclase and Na+/K(+)-ATPase were determined. Exposure of confluent BHK-21 cells to 0.1 U/ml of sphingomyelinase led to the degradation (at 37 degrees C) of about 60% of cell sphingomyelin. No simultaneous hydrolysis of phosphatidylcholine occurred. The hydrolysis of sphingomyelin subsequently led to the translocation (within 40 min) of about 50-60% of cell [3H]cholesterol from a cholesterol oxidase susceptible pool to an oxidase resistant compartment. The translocation of [3H]cholesterol from the cell surface to intracellular membranes was accompanied by a paralleled increase in [3H]cholesterol ester formation. When cells were first exposed to sphingomyelinase (to degrade sphingomyelin) and then incubated without the enzyme in serum-free media, the mass of cell sphingomyelin decreased initially (by 60%), but then began to increase and reached control levels within 3-4 h. The rapid re-synthesis of sphingomyelin was accompanied by an equally rapid normalization of cell [3H]cholesterol distribution. The re-formation of cell sphingomyelin also led to a decreased content of cellular [3H]cholesterol esters, indicating that unesterified [3H]cholesterol was pulled out of the cholesterol ester cycle and transported to the cell surface. Exposure of BHK-21 cells to sphingomyelinase further led to a dramatically decreased activity of ouabain-sensitive Na+/K(+)-ATPase, whereas forskolin-stimulated adenylate cyclase activity was not affected. The activity of Na+/K(+)-ATPase returned to normal in parallel with the normalization of cell sphingomyelin mass and cholesterol distribution. We conclude that sphingomyelin has profound effects on the steady-state distribution of cell cholesterol, and that manipulations of cell sphingomyelin levels directly and

  3. Effects of cholesterol on plasma membrane lipid order in MCF-7 cells by two-photon microscopy

    NASA Astrophysics Data System (ADS)

    Zeng, Yixiu; Chen, Jianling; Yang, Hongqin; Wang, Yuhua; Li, Hui; Xie, Shusen

    2014-09-01

    Lipid rafts are cholesterol- and glycosphingolipids- enriched microdomains on plasma membrane surface of mammal cells, involved in a variety of cellular processes. Depleting cholesterol from the plasma membrane by drugs influences the trafficking of lipid raft markers. Optical imaging techniques are powerful tools to study lipid rafts in live cells due to its noninvasive feature. In this study, breast cancer cells MCF-7 were treated with different concentrations of MβCD to deplete cholesterol and an environmentally sensitive fluorescence probe, Laurdan was loaded to image lipid order by two-photon microscopy. The generalized polarization (GP) values were calculated to distinguish the lipid order and disorder phase. GP images and GP distributions of native and cholesterol-depleted MCF-7 cells were obtained. Our results suggest that even at low concentration (0.5 mM) of MβCD, the morphology of the MCF-7 cells changes. Small high GP areas (lipid order phase) decrease more rapidly than low GP areas (lipid disorder phase), indicating that lipid raft structure was altered more severely than nonraft domains. The data demonstrates that cholesterol dramatically affect raft coverage and plasma membrane fluidity in living cells.

  4. Plasma lecithin:cholesterol acyltransferase and carotid intima-media thickness in European individuals at high cardiovascular risk

    PubMed Central

    Calabresi, Laura; Baldassarre, Damiano; Simonelli, Sara; Gomaraschi, Monica; Amato, Mauro; Castelnuovo, Samuela; Frigerio, Beatrice; Ravani, Alessio; Sansaro, Daniela; Kauhanen, Jussi; Rauramaa, Rainer; de Faire, Ulf; Hamsten, Anders; Smit, Andries J.; Mannarino, Elmo; Humphries, Steve E.; Giral, Philippe; Veglia, Fabrizio; Sirtori, Cesare R.; Franceschini, Guido; Tremoli, Elena

    2011-01-01

    Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterification in plasma. LCAT is a major factor in HDL remodeling and metabolism, and it has long been believed to play a critical role in macrophage reverse cholesterol transport (RCT). The effect of LCAT on human atherogenesis is still controversial. In the present study, the plasma LCAT concentration was measured in all subjects (n = 540) not on drug treatment at the time of enrollment in the multicenter, longitudinal, observational IMPROVE study. Mean and maximum intima-media thickness (IMT) of the whole carotid tree was measured by B-mode ultrasonography in all subjects. In the entire cohort, LCAT quartiles were not associated with carotid mean and maximum IMT (P for trend 0.95 and 0.18, respectively), also after adjustment for age, gender, HDL-cholesterol (HDL-C), and triglycerides. No association between carotid IMT and LCAT quartiles was observed in men (P=0.30 and P=0.99 for mean and maximum IMT, respectively), whereas carotid IMT increased with LCAT quartiles in women (P for trend 0.14 and 0.019 for mean and maximum IMT, respectively). The present findings support the concept that LCAT is not required for an efficient reverse cholesterol transport and that a low plasma LCAT concentration and activity is not associated with increased atherosclerosis. PMID:21596929

  5. Whole Soy Flour Incorporated into a Muffin and Consumed at 2 Doses of Soy Protein Does Not Lower LDL Cholesterol in a Randomized, Double-Blind Controlled Trial of Hypercholesterolemic Adults12

    PubMed Central

    Padhi, Emily MT; Blewett, Heather J; Duncan, Alison M; Guzman, Randolph P; Hawke, Aileen; Seetharaman, Koushik; Tsao, Rong; Wolever, Thomas MS; Ramdath, D Dan

    2015-01-01

    Background: Soy protein may reduce coronary heart disease (CHD) risk by lowering LDL cholesterol, but few studies have assessed whether whole soy flour displays a similar effect. Objective: The aim of this study was to assess the dose effect of whole soy flour incorporated into muffins on plasma LDL cholesterol in hypercholesterolemic adults. Methods: Adults aged 30–70 y (n = 243) with elevated LDL cholesterol (≥3.0 and ≤5.0 mmol/L) were stratified by LDL cholesterol and randomly assigned to consume 2 soy muffins containing 25 g soy protein [high-dose soy (HDS)], 1 soy and 1 wheat muffin containing 12.5 g soy protein and 12.5 g whey protein [low-dose soy (LDS)], or 2 wheat muffins containing 25 g whey protein (control) daily for 6 wk while consuming a self-selected diet. Fasting blood samples were collected at weeks 0, 3, and 6 for analysis of plasma lipids [total, LDL, and HDL cholesterol and triglycerides (TGs)], glucose, insulin, C-reactive protein (CRP), and isoflavones. Blood pressures also were measured. Dietary intake was assessed at weeks 0 and 4 with the use of 3 d food records. Treatment effects were assessed with the use of intention-to-treat analysis with multiple imputation and LDL cholesterol as the primary outcome. Results: In total, 213 (87.6%) participants completed the trial. Participants were primarily Caucasian (83%) and mostly female (63%), with a mean ± SD body mass index (in kg/m2) of 28.0 ± 4.6 and systolic and diastolic blood pressures of 122 ± 16 and 77 ± 11 mm Hg, respectively. Despite a dose-dependent increase in plasma isoflavones (P < 0.001), neither HDS nor LDS had a significant effect on LDL cholesterol compared with control (mean ± SEM changes: control, −0.04 ± 0.05 mmol/L; HDS, 0.01 ± 0.05 mmol/L; and LDS, −0.04 ± 0.06 mmol/L). There were no significant treatment effects on total or HDL cholesterol, TGs, CRP, homeostatic model assessment of insulin resistance, blood pressure, or the Framingham 10-y CHD risk score

  6. Phospholipid liposomes acquire apolipoprotein E in atherogenic plasma and block cholesterol loading of cultured macrophages.

    PubMed Central

    Williams, K J; Tall, A R; Bisgaier, C; Brocia, R

    1987-01-01

    A single infusion of phospholipid liposomes promptly and persistently abolished the ability of hypercholesterolemic rabbit plasma to cause cholesteryl ester loading in cultured macrophages. This phospholipid enrichment of plasma caused moderate stimulation of cellular cholesterol efflux and, unexpectedly, almost complete inhibition of cellular uptake of beta-very low density lipoprotein (beta-VLDL), the major cholesteryl ester-rich particle in hypercholesterolemic rabbit plasma. Cell viability and LDL receptor activity were unaffected. Incubation of liposomes with beta-VLDL resulted in transfer of apolipoprotein-E (apoE) to the liposomes; reisolated apoE-phospholipid liposomes then competed efficiently for cellular apoprotein receptors. Thus, a major mechanism by which phospholipid infusions result in diminished accumulation of cholesteryl ester in cultured macrophages is by blocking cellular uptake of beta-VLDL. The liposomes deplete beta-VLDL of apoE, then compete for receptor-mediated uptake. These results suggest a novel mechanism contributing to the known antiatherogenic effect of phospholipid infusions: infused liposomes acquire apoE, then block uptake of atherogenic lipoproteins by arterial wall macrophages. Images PMID:3571495

  7. Oxidized Phospholipids Inhibit the Formation of Cholesterol-Dependent Plasma Membrane Nanoplatforms.

    PubMed

    Brameshuber, Mario; Sevcsik, Eva; Rossboth, Benedikt K; Manner, Christina; Deigner, Hans-Peter; Peksel, Begüm; Péter, Mária; Török, Zsolt; Hermetter, Albin; Schütz, Gerhard J

    2016-01-01

    We previously developed a single-molecule microscopy method termed TOCCSL (thinning out clusters while conserving stoichiometry of labeling), which allows for direct imaging of stable nanoscopic platforms with raft-like properties diffusing in the plasma membrane. As a consensus raft marker, we chose monomeric GFP linked via a glycosylphosphatidylinositol (GPI) anchor to the cell membrane (mGFP-GPI). With this probe, we previously observed cholesterol-dependent homo-association to nanoplatforms diffusing in the plasma membrane of live CHO cells. Here, we report the release of this homo-association upon addition of 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) or 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine, two oxidized phospholipids (oxPLs) that are typically present in oxidatively modified low-density lipoprotein. We found a dose-response relationship for mGFP-GPI nanoplatform disintegration upon addition of POVPC, correlating with the signal of the apoptosis marker Annexin V-Cy3. Similar concentrations of lysolipid showed no effect, indicating that the observed phenomena were not linked to properties of the lipid bilayer itself. Inhibition of acid sphingomyelinase by NB-19 before addition of POVPC completely abolished nanoplatform disintegration by oxPLs. In conclusion, we were able to determine how oxidized lipid species disrupt mGFP-GPI nanoplatforms in the plasma membrane. Our results favor an indirect mechanism involving acid sphingomyelinase activity rather than a direct interaction of oxPLs with nanoplatform constituents.

  8. Epistasis contributes to the genetic buffering of plasma HDL cholesterol in mice

    PubMed Central

    Churchill, Gary A.

    2010-01-01

    Stressful environmental factors, such as a high-fat diet, can induce responses in the expression of genes that act to maintain physiological homeostasis. We observed variation in plasma concentrations of high-density lipoprotein (HDL) cholesterol across inbred mouse strains in response to high dietary fat intake. Several strains, including C57BL/6J, have stable levels of plasma HDL independent of diet, whereas other strains, including DBA2/J, show marked changes in plasma HDL. To explore this phenomenon further, we used publicly available data from a C57BL/6J × DBA/2J intercross to identify genetic factors that associate with HDL under high-fat diet conditions. Our analysis identified an epistatic interaction that plays a role in the buffering of HDL levels in C57BL/6J mice, and we have identified Arl4d as a candidate gene that mediates this effect. Structural modeling further elucidates the interaction of genetic factors that contribute to the robustness of HDL in response to high-fat diet in the C57BL/6J strain. PMID:20858711

  9. Diet rich in high glucoraphanin broccoli reduces plasma LDL cholesterol: Evidence from randomised controlled trials

    PubMed Central

    Armah, Charlotte N; Derdemezis, Christos; Traka, Maria H; Dainty, Jack R; Doleman, Joanne F; Saha, Shikha; Leung, Wing; Potter, John F; Lovegrove, Julie A; Mithen, Richard F

    2015-01-01

    Scope Cruciferous-rich diets have been associated with reduction in plasma LDL-cholesterol (LDL-C), which may be due to the action of isothiocyanates derived from glucosinolates that accumulate in these vegetables. This study tests the hypothesis that a diet rich in high glucoraphanin (HG) broccoli will reduce plasma LDL-C. Methods and results One hundred and thirty volunteers were recruited to two independent double-blind, randomly allocated parallel dietary intervention studies, and were assigned to consume either 400 g standard broccoli or 400 g HG broccoli per week for 12 weeks. Plasma lipids were quantified before and after the intervention. In study 1 (37 volunteers), the HG broccoli diet reduced plasma LDL-C by 7.1% (95% CI: –1.8%, –12.3%, p = 0.011), whereas standard broccoli reduced LDL-C by 1.8% (95% CI +3.9%, –7.5%, ns). In study 2 (93 volunteers), the HG broccoli diet resulted in a reduction of 5.1% (95% CI: –2.1%, –8.1%, p = 0.001), whereas standard broccoli reduced LDL-C by 2.5% (95% CI: +0.8%, –5.7%, ns). When data from the two studies were combined the reduction in LDL-C by the HG broccoli was significantly greater than standard broccoli (p = 0.031). Conclusion Evidence from two independent human studies indicates that consumption of high glucoraphanin broccoli significantly reduces plasma LDL-C. PMID:25851421

  10. Background diet and fat type alters plasma lipoprotein response but not aortic cholesterol accumulation in F1B Golden Syrian hamsters.

    PubMed

    Dillard, Alice; Matthan, Nirupa R; Spartano, Nicole L; Butkowski, Ann E; Lichtenstein, Alice H

    2013-12-01

    Dietary modification alters plasma lipoprotein profiles and atherosclerotic lesion progression in humans and some animal models. Variability in response to diet induced atherosclerosis has been reported in hamsters. Assessed was the interaction between background diet composition and dietary fat type on aortic cholesterol accumulation, lipoprotein profiles, hepatic lipids and selected genes. F1B Golden Syrian hamsters (20/group) were fed (12 weeks) semi-purified or non-purified diets containing either 10 % (w/w) coconut oil or safflower oil and 0.15 % (w/w) cholesterol. The non-purified diets relative to semi-purified diets resulted in significantly higher TC (72 % [percent difference] and 38 %, coconut oil and safflower oil, respectively) and nHDL-C (84 and 61 %, coconut oil and safflower oil, respectively), and lower HDL-C (-47 and -45 %, coconut oil and safflower oil, respectively) concentrations. Plasma triacylglycerol concentrations in the hamsters fed the non-purified coconut oil-supplemented diets were three- to fourfold higher than non-purified safflower oil-supplemented, and both semi-purified diets. With the exception of HDL-C, a significant effect of fat type was observed in TC, nHDL-C and triacylglycerol (all P < 0.05) concentrations. Regardless of diet induced differences in lipoprotein profiles, there was no significant effect on aortic cholesterol accumulation. There was an inverse relationship between plasma nHDL-C and triacylglycerol, and hepatic cholesteryl ester content (P < 0.001). Diet induced differences in hepatic gene transcription (LDL receptor, apoB-100, microsomal transfer protein) were not reflected in protein concentrations. Although hamsters fed non-purified and/or saturated fatty acid-supplemented diets had more atherogenic lipoprotein profiles compared to hamsters fed semi-purified and/or polyunsaturated fatty acid-supplemented diets these differences were not reflected in aortic cholesterol accumulation.

  11. Cholesterol-lowering Action of BNA-based Antisense Oligonucleotides Targeting PCSK9 in Atherogenic Diet-induced Hypercholesterolemic Mice

    PubMed Central

    Yamamoto, Tsuyoshi; Harada-Shiba, Mariko; Nakatani, Moeka; Wada, Shunsuke; Yasuhara, Hidenori; Narukawa, Keisuke; Sasaki, Kiyomi; Shibata, Masa-Aki; Torigoe, Hidetaka; Yamaoka, Tetsuji; Imanishi, Takeshi; Obika, Satoshi

    2012-01-01

    Recent findings in molecular biology implicate the involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) in low-density lipoprotein receptor (LDLR) protein regulation. The cholesterol-lowering potential of anti-PCSK9 antisense oligonucleotides (AONs) modified with bridged nucleic acids (BNA-AONs) including 2′,4′-BNA (also called as locked nucleic acid (LNA)) and 2′,4′-BNANC chemistries were demonstrated both in vitro and in vivo. An in vitro transfection study revealed that all of the BNA-AONs induce dose-dependent reductions in PCSK9 messenger RNA (mRNA) levels concomitantly with increases in LDLR protein levels. BNA-AONs were administered to atherogenic diet-fed C57BL/6J mice twice weekly for 6 weeks; 2′,4′-BNA-AON that targeted murine PCSK9 induced a dose-dependent reduction in hepatic PCSK9 mRNA and LDL cholesterol (LDL-C); the 43% reduction of serum LDL-C was achieved at a dose of 20 mg/kg/injection with only moderate increases in toxicological indicators. In addition, the serum high-density lipoprotein cholesterol (HDL-C) levels increased. These results support antisense inhibition of PCSK9 as a potential therapeutic approach. When compared with 2′,4′-BNA-AON, 2′,4′-BNANC-AON showed an earlier LDL-C–lowering effect and was more tolerable in mice. Our results validate the optimization of 2′,4′-BNANC-based anti-PCSK9 antisense molecules to produce a promising therapeutic agent for the treatment of hypercholesterolemia. PMID:23344002

  12. Screening of Cholesterol-lowering Bifidobacterium from Guizhou Xiang Pigs, and Evaluation of Its Tolerance to Oxygen, Acid, and Bile.

    PubMed

    Zhang, Rujiao; He, Laping; Zhang, Ling; Li, Cuiqin; Zhu, Qiujin

    2016-01-01

    Cardiovascular and cerebrovascular diseases seriously harm human health, and Bifidobacterium is the most beneficial probiotic in the gastrointestinal tract of humans. This work aimed to screen cholesterol-lowering Bifidobacterium from Guizhou Xiang Pig and evaluate its tolerance to oxygen, acid, and bile. Twenty-seven aerotolerant strains with similar colony to Bifidobacterium were isolated through incubation at 37℃ in 20% (v/v) CO2-80% (v/v) atmospheric air by using Mupirocin lithium modified MRS agar medium, modified PTYG with added CaCO3, and modified PTYG supplemented with X-gal. Ten strains with cholesterol-lowering rates above 20% (w/w) were used for further screening. The selected strains' tolerance to acid and bile was then determined. A combination of colony and cell morphology, physiological, and biochemical experiments, as well as 16S rRNA gene-sequence analysis, was performed. Results suggested that BZ25 with excellent characteristics of high cholesterol-removal rate of 36.32% (w/w), as well as tolerance to acid and bile, was identified as Bifidobacterium animalis subsp. lactis. To further evaluate Bifidobacterium BZ25's growth characteristic and tolerance to oxygen, culture experiments were performed in liquid medium and an agar plate. Findings suggested that BZ25 grew well both in environmental 20% (v/v) CO2-80% (v/v) atmospheric air and in 100% atmospheric air because BZ25 reached an absorbance of 1.185 at 600 nm in 100% atmospheric air. Moreover, BZ25 was aerotolerant and can grow in an agar medium under the environmental condition of 100% atmospheric air. This study can lay a preliminary foundation for the potential industrial applications of BZ25. PMID:27499662

  13. Screening of Cholesterol-lowering Bifidobacterium from Guizhou Xiang Pigs, and Evaluation of Its Tolerance to Oxygen, Acid, and Bile

    PubMed Central

    Zhang, Rujiao; He, Laping; Zhang, Ling; Li, Cuiqin; Zhu, Qiujin

    2016-01-01

    Cardiovascular and cerebrovascular diseases seriously harm human health, and Bifidobacterium is the most beneficial probiotic in the gastrointestinal tract of humans. This work aimed to screen cholesterol-lowering Bifidobacterium from Guizhou Xiang Pig and evaluate its tolerance to oxygen, acid, and bile. Twenty-seven aerotolerant strains with similar colony to Bifidobacterium were isolated through incubation at 37℃ in 20% (v/v) CO2-80% (v/v) atmospheric air by using Mupirocin lithium modified MRS agar medium, modified PTYG with added CaCO3, and modified PTYG supplemented with X-gal. Ten strains with cholesterol-lowering rates above 20% (w/w) were used for further screening. The selected strains’ tolerance to acid and bile was then determined. A combination of colony and cell morphology, physiological, and biochemical experiments, as well as 16S rRNA gene-sequence analysis, was performed. Results suggested that BZ25 with excellent characteristics of high cholesterol-removal rate of 36.32% (w/w), as well as tolerance to acid and bile, was identified as Bifidobacterium animalis subsp. lactis. To further evaluate Bifidobacterium BZ25’s growth characteristic and tolerance to oxygen, culture experiments were performed in liquid medium and an agar plate. Findings suggested that BZ25 grew well both in environmental 20% (v/v) CO2-80% (v/v) atmospheric air and in 100% atmospheric air because BZ25 reached an absorbance of 1.185 at 600 nm in 100% atmospheric air. Moreover, BZ25 was aerotolerant and can grow in an agar medium under the environmental condition of 100% atmospheric air. This study can lay a preliminary foundation for the potential industrial applications of BZ25. PMID:27499662

  14. LRP5 and plasma cholesterol levels modulate the canonical Wnt pathway in peripheral blood leukocytes.

    PubMed

    Borrell-Pages, Maria; Carolina Romero, July; Badimon, Lina

    2015-08-01

    Inflammation is triggered after invasion or injury to restore homeostasis. Although the activation of Wnt/β-catenin signaling is one of the first molecular responses to cellular damage, its role in inflammation is still unclear. It was our hypothesis that the low-density lipoprotein (LDL) receptor-related protein 5 (LRP5) and the canonical Wnt signaling pathway are modulators of inflammatory mechanisms. Wild-type (WT) and LRP5(-/-) mice were fed a hypercholesterolemic (HC) diet to trigger dislipidemia and chronic inflammation. Diets were supplemented with plant sterol esters (PSEs) to induce LDL cholesterol lowering and the reduction of inflammation. HC WT mice showed increased serum cholesterol levels that correlated with increased Lrp5 and Wnt/β-catenin gene expression while in the HC LRP5(-/-) mice Wnt/β-catenin pathway was shut down. Functionally, HC induced pro-inflammatory gene expression in LRP5(-/-) mice, suggesting an inhibitory role of the Wnt pathway in inflammation. Dietary PSE administration downregulated serum cholesterol levels in WT and LRP5(-/-) mice. Furthermore, in WT mice PSE increased anti-inflammatory genes expression and inhibited Wnt/β-catenin activation. Hepatic gene expression of Vldlr, Lrp2 and Lrp6 was increased after HC feeding in WT mice but not in LRP5(-/-) mice, suggesting a role for these receptors in the clearance of plasmatic lipoproteins. Finally, an antiatherogenic role for LRP5 was demonstrated as HC LRP5(-/-) mice developed larger aortic atherosclerotic lesions than WT mice. Our results show an anti-inflammatory, pro-survival role for LRP5 and the Wnt signaling pathway in peripheral blood leukocytes.

  15. Intestine-specific MTP and global ACAT2 deficiency lowers acute cholesterol absorption with chylomicrons and HDLs

    PubMed Central

    Boutjdir, Mohamed; Rudel, Lawrence L.; Hussain, M. Mahmood

    2014-01-01

    Intestinal cholesterol absorption involves the chylomicron and HDL pathways and is dependent on microsomal triglyceride transfer protein (MTP) and ABCA1, respectively. Chylomicrons transport free and esterified cholesterol, whereas HDLs transport free cholesterol. ACAT2 esterifies cholesterol for secretion with chylomicrons. We hypothesized that free cholesterol accumulated during ACAT2 deficiency may be secreted with HDLs when chylomicron assembly is blocked. To test this, we studied cholesterol absorption in mice deficient in intestinal MTP, global ACAT2, and both intestinal MTP and global ACAT2. Intestinal MTP ablation significantly increased intestinal triglyceride and cholesterol levels and reduced their transport with chylomicrons. In contrast, global ACAT2 deficiency had no effect on triglyceride absorption but significantly reduced cholesterol absorption with chylomicrons and increased cellular free cholesterol. Their combined deficiency reduced cholesterol secretion with both chylomicrons and HDLs. Thus, contrary to our hypothesis, free cholesterol accumulated in the absence of MTP and ACAT2 is unavailable for secretion with HDLs. Global ACAT2 deficiency causes mild hypertriglyceridemia and reduces hepatosteatosis in mice fed high cholesterol diets by increasing hepatic lipoprotein production by unknown mechanisms. We show that this phenotype is preserved in the absence of intestinal MTP in global ACAT2-deficient mice fed a Western diet. Further, we observed increases in hepatic MTP activity in these mice. Thus, ACAT2 deficiency might increase MTP expression to avoid hepatosteatosis in cholesterol-fed animals. Therefore, ACAT2 inhibition might avert hepatosteatosis associated with high cholesterol diets by increasing hepatic MTP expression and lipoprotein production. PMID:25030663

  16. Plant stanol content remains stable during storage of cholesterol-lowering functional foods.

    PubMed

    Nieminen, V; Laakso, P; Kuusisto, P; Niemelä, J; Laitinen, K

    2016-04-01

    Plant stanols reduce the absorption of both dietary and biliary cholesterol. The aim of this study was to examine the stability of plant stanols in the form of plant stanol esters in spreads and biscuits stored under typical storage conditions. The plant stanol content of two commercial margarine-type spreads, containing 35% and 60% absorbable fat, was 6.5 and 6.4 g/100 g after production and remained unaltered when stored at 6 °C for a shelf life of 18 and 22 weeks, respectively. Comparable results were obtained for plant stanol ester ingredient stored under the same conditions and for plant stanol ester-containing biscuits stored at room temperature for up to 74 weeks. Furthermore, the peroxide value and free fatty acids showed that the quality of the food products remained good. The present study demonstrated that plant stanol esters as an ingredient and when added in food products, are stable whilst stored under the appropriate conditions.

  17. Two-photon Laurdan studies of the ternary lipid mixture DOPC:SM:cholesterol reveal a single liquid phase at sphingomyelin:cholesterol ratios lower than 1.

    PubMed

    Carravilla, Pablo; Nieva, José L; Goñi, Félix M; Requejo-Isidro, Jose; Huarte, Nerea

    2015-03-10

    The ternary lipid mixture DOPC:eggSM:cholesterol in excess water has been studied in the form of giant unilamellar vesicles using two-photon fluorescence microscopy. Previous publications based on single-photon fluorescence microscopy had reported heterogeneous phase behavior (phase coexistence) in the region of the triangular phase diagram corresponding to SM:cholesterol molar ratios <1. We have examined this region by two-photon microscopy of Laurdan-labeled mixtures and have found that, under our conditions, only a single liquid phase exists. We have shown that macroscopic phase separation in the above region can be artifactually induced by one-photon excitation of the fluorescent probes and ensuing photooxidation and is prevented using two-photon excitation. The main effect of increasing the concentration of cholesterol in mixtures containing 30 mol % SM was to increase the rigidity of the disordered domains. Increasing the concentration of SM in mixtures containing 20 mol % cholesterol gradually augmented the rigidity of the ordered domains, while the disordered domains reached minimal order at a SM:cholesterol 2.25:1 molar ratio, which then increased again. Moreover, the detailed measurement of Laurdan generalized polarization across the whole phase diagram allowed the representation, for both the single- and two-phase regions, of the gradual variation of membrane lateral packing along the diagram, which we found to be governed largely by SM:cholesterol interactions.

  18. Peptides identified in soybean protein increase plasma cholesterol in mice on hypercholesterolemic diets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The in vitro micellar cholesterol displacement assay has been used to identify peptides that may potentially reduce cholesterol in vivo. We tested two of these peptides, LPYPR and WGAPSI, derived from soybean protein (SP) that have been reported to displace cholesterol from micelles by feeding them...

  19. Lower Hybrid Drift in Simulations of Hypersonic Plasma

    NASA Astrophysics Data System (ADS)

    Niehoff, D.; Ashour-Abdalla, M.; Niemann, C.; Schriver, D.; Sotnikov, V. I.; Lapenta, G.

    2014-12-01

    It has been shown experimentally that hypersonic plasma (defined as moving with a bulk flow velocity of more than 5 to 10 times the Mach speed) traveling through a magnetic field will create a diamagnetic cavity, or bubble [1]. At the edge of the bubble, opposing field and density gradients can drive the lower hybrid drift instability [2]. We will explore two and a half dimensional (2 space and 3 velocity dimensions) simulations of hypersonic plasma within a parameter regime motivated by the aforementioned diamagnetic bubble experiments, wherein we find oscillations excited near the lower hybrid frequency propagating perpendicular to the bulk motion of the plasma and the background magnetic field. The simulations are run using the implicit PIC code iPIC3D so that we are able to capture dynamics of the plasma below ion scales, but not be forced to resolve all electron scales [3]. [1] Niemann et al, Phys. Plasmas 20, 012108 (2013) [2] Davidson et al, Phys. Fluids, Vol. 20, No. 2, February 1977 [3] S. Markidis et al, Math. Comput. Simul. (2009), doi 10.1016/j.matcom.2009.08.038

  20. Lipid-lowering activity of Cow urine ark in guinea pigs fed with a high cholesterol diet

    PubMed Central

    Manubhai, Chawda Hiren; Rasiklal, Mandavia Divyesh; Natvarlal, Baxi Seema; Kishorbhai, Vadgama Vishalkumar; Rajkishor, Tripathi ‎Chandrabhanu

    2014-01-01

    Objectives: Cow urine ark (CUA), known as “Amrita” as mentioned in Ayurveda, contains‎ anti-hyperglycemic and antioxidant effects. Therefore, we designed the present study to evaluate the lipid ‎lowering activity of CUA and its possible implication in metabolic syndrome.‎ Materials and Methods: Thirty guinea pigs of either sex were divided into five groups: Group 1 and 2 serving as a vehicle ‎and sham control, received normal and high fat diet for 60 days respectively; Group 3, 4 and 5 ‎received high fat diet for 60 days with CUA 0.8 ml/kg, 1.6 ml/kg and rosuvastatin (1.5 mg/kg) on the‎last 30 days of study period, respectively. Serum lipid profile (total cholesterol, triglycerides, LDL-‎C, VLDL-C, HDL-C, total Cholesterol/HDL-C) and serum enzymes (ALT, AST, ALP, LDH and CK-MB) ‎were performed in each group at the beginning and end of the study. Histological study of liver and ‎kidney was done in each group. Results: CUA (0.8 ml/kg) significantly decreased the serum triglycerides and VLDL-C, but CUA (1.6 ml/kg) ‎decreased the total serum Cholesterol, triglycerides and VLDL-C (p < 0.05). Higher dose (1.6 ml/kg) of ‎CUA also increased HDL-C level, significantly (p < 0.05). CUA reduced serum AST, ALP and LDH ‎level, which was statistically significant as well, while it also decreased the accumulation of lipid in hepatocytes as ‎compared to sham control.‎ Conclusions: CUA reduced triglycerides, increased HDL-C and found to be hepatoprotective in ‎animals that are on a high fat diet. PMID:25386398

  1. Blueberry intervention improves vascular reactivity and lowers blood pressure in high-fat-, high-cholesterol-fed rats.

    PubMed

    Rodriguez-Mateos, Ana; Ishisaka, Akari; Mawatari, Kazuaki; Vidal-Diez, Alberto; Spencer, Jeremy P E; Terao, Junji

    2013-05-28

    Growing evidence suggests that intake of flavonoid-containing foods may exert cardiovascular benefits in human subjects. We have investigated the effects of a 10-week blueberry (BB) supplementation on blood pressure (BP) and vascular reactivity in rats fed a high-fat/high-cholesterol diet, known to induce endothelial dysfunction. Rats were randomly assigned to follow a control chow diet, a chow diet supplemented with 2 % (w/w) BB, a high-fat diet (10 % lard; 0·5 % cholesterol) or the high fat plus BB for 10 weeks. Rats supplemented with BB showed significant reductions in systolic BP (SBP) of 11 and 14 %, at weeks 8 and 10, respectively, relative to rats fed the control chow diet (week 8 SBP: 107·5 (SEM 4·7) v. 122·2 (SEM 2·1) mmHg, P= 0·018; week 10 SBP: 115·0 (SEM 3·1) v. 132·7 (SEM 1·5) mmHg, P< 0·0001). Furthermore, SBP was reduced by 14 % in rats fed with the high fat plus 2 % BB diet at week 10, compared to those on the high-fat diet only (SBP: 118·2 (SEM 3·6) v. 139·5 (SEM 4·5) mmHg, P< 0·0001). Aortas harvested from BB-fed animals exhibited significantly reduced contractile responses (to L-phenylephrine) compared to those fed the control chow or high-fat diets. Furthermore, in rats fed with high fat supplemented with BB, aorta relaxation was significantly greater in response to acetylcholine compared to animals fed with the fat diet. These data suggest that BB consumption can lower BP and improve endothelial dysfunction induced by a high fat, high cholesterol containing diet. PMID:23046999

  2. An interaction between the TaqIB polymorphism of cholesterol ester transfer protein and smoking is associated with changes in plasma high-density lipoprotein cholesterol levels in Turks.

    PubMed

    Hodoğlugil, U; Williamson, D W; Huang, Y; Mahley, R W

    2005-08-01

    Low levels of high-density lipoprotein cholesterol (HDL-C) are an independent risk factor for atherosclerosis. We investigated the effects of the TaqIB polymorphism of cholesterol ester transfer protein (CETP) on CETP activity and plasma HDL-C levels in random nondiabetic and self-reported diabetic subjects in a population with very low HDL-C levels. The rare B2B2 genotype was associated with significantly higher HDL-C levels and lower CETP activity in random subjects and with higher HDL-C in diabetic subjects. After stratification of random subjects by smoking status, the common B1B1 genotype was associated with lower HDL-C levels than the B2B2 genotype. Although smoking was associated with lower HDL-C, especially in men, HDL-C levels between smokers and nonsmokers were not different in subjects with the B1B2 or B2B2 genotypes. However, smoking (20+ cigarettes/day) was associated with a marked reduction in HDL-C in the B1B1 subjects. The B1B1/smoking interaction was not reflected in a difference in CETP activity. High triglycerides and elevated body mass index (BMI) lower HDL-C. The B2B2 genotype was associated with the highest HDL-C levels, and these levels were significantly lower in the hypertriglyceridemic subjects (>or=50th percentile). The lowest HDL-C levels were seen in hypertriglyceridemic subjects with the B1B1 genotype. Although BMI (>or=50th vs<50th percentile) did not affect HDL-C in B2B2 subjects, a high BMI was associated with markedly lower HDL-C in B1B1 subjects. Thus, HDL-C levels in Turks may be modulated by an interaction between the CETP TaqIB polymorphism and smoking, as well as an interaction with hypertriglyceridemia and BMI.

  3. The molecular mechanism of the cholesterol-lowering effect of dill and kale: The influence of the food matrix components.

    PubMed

    Danesi, Francesca; Govoni, Marco; D'Antuono, Luigi Filippo; Bordoni, Alessandra

    2016-07-01

    Foods are complex matrices containing many different compounds, all of which contribute to the overall effect of the food itself, although they have different mechanisms of action. While evaluating the effect of bioactive compounds, it is important to consider that the use of a single compound can hide the effects of the other molecules that can act synergistically or antagonistically in the same food. The aim of the present study was to evaluate the influence of food matrix components by comparing two edible plants (dill and kale) with cholesterol-lowering potential and similar contents of their most representative bioactive, quercetin. The molecular effects of the extracts were evaluated in HepG2 cells by measuring the expression of sterol-regulatory element-binding proteins (SREBPs), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and low density lipoprotein receptor (LDLR) at the mRNA and protein level. The results reported here show that both extracts reduced the cellular cholesterol level with a similar trend and magnitude. It is conceivable that the slightly different results are due to the diverse composition of minor bioactive compounds, indicating that only by considering food as a whole is it possible to understand the complex relationship between food, nutrition, and health in a foodomics vision. PMID:27028988

  4. Potential fat-lowering and prebiotic effects of enzymatically treated okara in high-cholesterol-fed Wistar rats.

    PubMed

    Villanueva-Suárez, María-José; Pérez-Cózar, María-Luisa; Mateos-Aparicio, Inmaculada; Redondo-Cuenca, Araceli

    2016-11-01

    This study evaluates the effect of the lipid profile on serum, liver and faeces, and the potential prebiotic effect of diets supplemented with enzymatically treated okara (okara(ET)) in high-cholesterol fed Wistar rats. Triglyceride levels were significantly reduced in the serum (p < 0.01) and liver (p < 0.01) of okara(ET) treated rats. Total lipids, triglycerides and bile acids were significantly higher (p < 0.001) in the faeces of rats fed the okara(ET) diet. The pH of faecal contents from treated okara(ET) rats was lower (p < 0.001), probably due to the significantly higher (p < 0.001) production of short-chain fatty acids (SCFA). Okara(ET), therefore, reduced triglycerides in serum and liver, and increased the excretion of total lipids, triglycerides and bile acids, improving the lipid profile in rats fed with high-cholesterol diets. Okara(ET) fibre can improve intestinal transit by increasing faecal bulk. The decreased pH and increased SCFA production indicated that okara(ET) fibre fermentation occurred, suggesting a potential prebiotic effect.

  5. Modifying plasma low-density lipoprotein and high-density lipoprotein cholesterol: what combinations are available in the future?

    PubMed

    Kastelein, John J P

    2005-11-01

    Despite a growing body of research on the benefit of combination drug therapy for dyslipidemia in the metabolic syndrome or diabetes mellitus, there are insufficient outcome data on the use of combination therapy as well as inadequate data to compare certain combination regimens. The focus of the therapeutic approach in treating the metabolic syndrome has been almost exclusively on low-density lipoprotein (LDL) cholesterol for approximately the past 10 years, and specifically on statin therapy. Although results of epidemiologic studies as well as clinical trials using angiographic and clinical end points confirm the association of LDL cholesterol and risk of coronary artery disease, data are lacking regarding the effects of combination therapy in the management of coronary artery disease. Management of the metabolic syndrome focusing on the modification of plasma LDL as well as high-density lipoprotein cholesterol is reviewed. Future management strategies with the use of novel combination therapy is also discussed. PMID:16291010

  6. Cholesterol-lowering activity of soy-derived glyceollins in the golden Syrian hamster model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hypercholesterolemia is one of the major factors contributing to the risk of cardiovascular disease (CVD), which is the leading cause of death in the developed countries. Consumption of soy foods has been recognized to lower the risk of CVD, and phytochemicals in soy may contribute to the health ben...

  7. Dietary capsanthin, the main carotenoid in paprika (Capsicum annuum), alters plasma high-density lipoprotein-cholesterol levels and hepatic gene expression in rats.

    PubMed

    Aizawa, Koichi; Inakuma, Takahiro

    2009-12-01

    The effects of dietary capsanthin, the main carotenoid in paprika (Capsicum annuum), on lipid metabolism were examined. Young male Wistar rats were fed diets containing paprika powder, paprika organic solvent extract, residue of paprika extract, and purified capsanthin. Administration of purified capsanthin for 2 weeks resulted in a significant increase in plasma HDL-cholesterol (P < 0.05) without detectable differences in plasma total cholesterol and TAG concentrations. A statistically significant correlation (r 0.567; P < 0.001) was found between dietary capsanthin concentrations and plasma HDL-cholesterol concentrations. Animals receiving diets containing two different capsanthin concentrations exhibited dose-dependent increases in plasma HDL-cholesterol (r 0.597; P < 0.005). While capsanthin was absent in the liver of animals fed the basal diet, it increased markedly in capsanthin-fed animals (P < 0.001). Quantitative analyses of hepatic mRNA levels revealed that capsanthin administration resulted in up-regulation of mRNA for apoA5 and lecithin cholesterol acyltransferase (LCAT), without significant differences in other mRNA levels related to HDL-cholesterol metabolism. These results suggest that capsanthin had an HDL-cholesterol-raising effect on plasma, and the potential to increase cholesterol efflux to HDL particles by increasing apoA5 levels and/or enhancement of LCAT activity.

  8. Dietary Conjugated Linoleic Acid Alters Oxidative Stability and Alleviates Plasma Cholesterol Content in Meat of Broiler Chickens

    PubMed Central

    Kumari Ramiah, Suriya; Meng, Goh Yong

    2014-01-01

    This study was conducted to investigate the effects of dietary conjugated linoleic acid (CLA) on fatty acid composition, lipoprotein content, lipid peroxidation, and meat colour of broiler chickens. A total of 180 broiler chickens were allocated to 3 dietary treatments (0, 2.5, and 5% Lutrell) and given a standard broiler starter diet and finisher diet. Body weight of chickens and feed intake were recorded weekly. After slaughter, the breast meat was aged at 4°C for 0, 3, and 6 days. The fatty acid composition was measured in the breast meat. Body weight (BW) and feed efficiency were decreased by dietary CLA level (P < 0.05). Chicken fed with 2.5% Lutrell had the highest feed intake compared to the control (CON) group. The total CLA increased significantly (P < 0.05) in breast meat from birds supplemented with CLA. Propensity for lipid peroxidation was significantly higher after 6 days of meat storage (P < 0.05) and the redness in chicken breast meat was lower in CLA-fed birds (P < 0.05). It is also notable that a 5% Lutrell supplementation decreased the plasma total cholesterol (TC), low density protein (LDL), and HDL (high-density lipoprotein)/LDL ratio in chickens (P < 0.05). PMID:25386625

  9. Parabolic relationship between plasma triacylglycerols and LDL-cholesterol in familial combined hyperlipidaemia: the multiple-type hyperlipidaemia explained?

    PubMed

    Brouwers, Martijn C G J; de Graaf, Jacqueline; van Greevenbroek, Marleen M J; Georgieva, Anna M; van der Kallen, Carla J H; Ter Avest, Ewoud; Stehouwer, Coen D A; Stalenhoef, Anton F; de Bruin, Tjerk W A

    2008-03-01

    FCHL (familial combined hyperlipidaemia) is a highly prevalent genetic lipid disorder that accounts for a substantial number of premature cardiovascular events. To date, FCHL has been complicated by the different lipid phenotypes that are present within one family and one individual patient over time. In the present study, we hypothesized that a parabolic relationship between plasma triacylglycerols (triglycerides) and LDL (low-density lipoprotein)-cholesterol can explain this so-called 'multiple-type hyperlipidaemia' in FCHL. Our hypothesis was tested in two well-documented FCHL cohorts [Maastricht (n=145) and Nijmegen (n=299)] that were followed over a 5-year interval. Three groups were constructed depending on plasma triacylglycerols: group A (individuals with both measurements below 1.5 mmol/l), group B (one measurement below and one measurement above 1.5 mmol/l) and group C (both measurement above 1.5 mmol/l). In both male, but not female, cohorts, a significant positive relationship between plasma triacylglycerols and LDL-cholesterol was observed in group A (P=0.02 for Maastricht cohort and P=0.001 for the Nijmegen cohort), a significant negative relationship in group C (P=0.01 for Maastricht cohort and P=0.02 for the Nijmegen cohort), and a relationship intermediate to group A and C in group B. In contrast, both apoB (apolipoprotein B) levels and the prevalence of cardiovascular disease were related with plasma triacylglycerols in a more linear fashion. In conclusion, a parabolic relationship between plasma triacylglycerols and LDL-cholesterol explains the 'multiple-type hyperlipidaemia' in FCHL. In addition, the linear relationship between triacylglycerols and both apoB levels and the prevalence of cardiovascular disease substantiate the use of apoB instead of LDL-cholesterol in the diagnosis of FCHL and the prediction of cardiovascular disease.

  10. Plasma triglyceride/HDL-cholesterol ratio, insulin resistance, and cardiometabolic risk in young adults

    PubMed Central

    Murguía-Romero, Miguel; Jiménez-Flores, J. Rafael; Sigrist-Flores, Santiago C.; Espinoza-Camacho, Miguel A.; Jiménez-Morales, Mayra; Piña, Enrique; Méndez-Cruz, A. René; Villalobos-Molina, Rafael; Reaven, Gerald M.

    2013-01-01

    Studies in mature adults suggest that the plasma concentration ratio of triglyceride (TG)/HDL-cholesterol (HDL-C) provides a simple way to identify apparently healthy individuals who are insulin resistant (IR) and at increased cardiometabolic risk. This study extends these observations by examining the clinical utility of the TG/HDL-C ratio and the metabolic syndrome (MetS) in 2,244 healthy college students (17–24 years old) of Mexican Mestizo ancestry. The TG/HDL-C ratio separating the 25% with the highest value was used to identify IR and increased cardiometabolic risk. Cardiometabolic risk factors were more adverse in men and women whose TG/HDL-C ratios exceeded 3.5 and 2.5, respectively, and approximately one third were identified as being IR. The MetS identified fewer individuals as being IR, but their risk profile was accentuated. In conclusion, both a higher TG/HDL-C ratio and a diagnosis of the MetS identify young IR individuals with an increased cardiometabolic risk profile. The TG/HDL-C ratio identified a somewhat greater number of “high risk” subjects, whereas the MetS found a group whose risk profile was somewhat magnified. These findings suggest that the TG/HDL-C ratio may serve as a simple and clinically useful approach to identify apparently healthy, young individuals who are IR and at increased cardiometabolic risk. PMID:23863983

  11. Cholesterol-Lowering Potentials of Lactic Acid Bacteria Based on Bile-Salt Hydrolase Activity and Effect of Potent Strains on Cholesterol Metabolism In Vitro and In Vivo

    PubMed Central

    Lin, Pei-Pei; Hsieh, You-Miin; Zhang, Zi-yi; Wu, Hui-Ching; Huang, Chun-Chih

    2014-01-01

    This study collected different probiotic isolates from animal and plant sources to evaluate the bile-salt hydrolase activity of probiotics in vitro. The deconjugation potential of bile acid was determined using high-performance liquid chromatography. HepG2 cells were cultured with probiotic strains with high BSH activity. The triglyceride (TG) and apolipoprotein B (apo B) secretion by HepG2 cells were evaluated. Our results show that the BSH activity and bile-acid deconjugation abilities of Pediococcus acidilactici NBHK002, Bifidobacterium adolescentis NBHK006, Lactobacillus rhamnosus NBHK007, and Lactobacillus acidophilus NBHK008 were higher than those of the other probiotic strains. The cholesterol concentration in cholesterol micelles was reduced within 24 h. NBHK007 reduced the TG secretion by 100% after 48 h of incubation. NBHK002, NBHK006, and NBHK007 could reduce apo B secretion by 33%, 38%, and 39%, respectively, after 24 h of incubation. The product PROBIO S-23 produced a greater decrease in the total concentration of cholesterol, low-density lipoprotein, TG, and thiobarbituric acid reactive substance in the serum or livers of hamsters with hypercholesterolemia compared with that of hamsters fed with a high-fat and high-cholesterol diet. These results show that the three probiotic strains of lactic acid bacteria are better candidates for reducing the risk of cardiovascular disease. PMID:25538960

  12. Creosote Bush (Larrea tridentata) Improves Insulin Sensitivity and Reduces Plasma and Hepatic Lipids in Hamsters Fed a High Fat and Cholesterol Diet.

    PubMed

    Del Vecchyo-Tenorio, Georgina; Rodríguez-Cruz, Maricela; Andrade-Cetto, Adolfo; Cárdenas-Vázquez, René

    2016-01-01

    Creosote bush, Larrea tridentata (Sesse y Moc. Ex DC, Zygophyllaceae) is a shrub found in the deserts of Northern Mexico and Southwestern United States. In traditional medicine, it is used to treat a variety of illnesses including type 2 diabetes. The present study aims to investigate the effects of creosote bush ethanolic extract on plasma and liver parameters associated with the metabolic syndrome in hamsters fed a high fat and cholesterol diet (HFD), comparing them with those induced by ezetimibe (EZ). Seven groups of six hamsters each were formed. Six groups were fed HFD for 2 weeks. The following 2 weeks, the HFD groups received: (1) only HFD, (2) HFD + 3 mg% EZ, (3) HFD + 0.2% creosote bush ethanolic extract, (4) only standard diet (Std Diet), (5) Std Diet + 3 mg% EZ, (6) Std Diet + 0.2% creosote bush ethanolic extract. The beneficial effects of creosote bush ethanolic extract in the HFD hamster model were a reduction of insulin resistance, associated with lower serum insulin and leptin, lower hepatic lipid peroxidation and higher liver antioxidant capacity. Plasma and liver lipids tended or were reduced to values closer to those of animals fed standard diet. A similar effect on lipids was induced by EZ, although with even lower hepatic cholesterol and total lipids concentrations. In general, the change from HFD to standard diet plus ethanolic extract induced the same but deeper changes, including a reduction in plasma glucose and an increase in the percentage of HDL cholesterol. Unlike creosote bush extract, EZ increased food consumption and neutral fecal steroids, with no significant effect on body weight, epididymal fat pads, liver peroxidation or antioxidant capacity. Also EZ did not modify serum insulin and leptin. However, insulin sensitivity improved to values similar to those induced by the extract. This suggests that the mechanism of action of creosote bush ethanolic extract is different to inhibition of cholesterol absorption or increase excretion

  13. Creosote Bush (Larrea tridentata) Improves Insulin Sensitivity and Reduces Plasma and Hepatic Lipids in Hamsters Fed a High Fat and Cholesterol Diet.

    PubMed

    Del Vecchyo-Tenorio, Georgina; Rodríguez-Cruz, Maricela; Andrade-Cetto, Adolfo; Cárdenas-Vázquez, René

    2016-01-01

    Creosote bush, Larrea tridentata (Sesse y Moc. Ex DC, Zygophyllaceae) is a shrub found in the deserts of Northern Mexico and Southwestern United States. In traditional medicine, it is used to treat a variety of illnesses including type 2 diabetes. The present study aims to investigate the effects of creosote bush ethanolic extract on plasma and liver parameters associated with the metabolic syndrome in hamsters fed a high fat and cholesterol diet (HFD), comparing them with those induced by ezetimibe (EZ). Seven groups of six hamsters each were formed. Six groups were fed HFD for 2 weeks. The following 2 weeks, the HFD groups received: (1) only HFD, (2) HFD + 3 mg% EZ, (3) HFD + 0.2% creosote bush ethanolic extract, (4) only standard diet (Std Diet), (5) Std Diet + 3 mg% EZ, (6) Std Diet + 0.2% creosote bush ethanolic extract. The beneficial effects of creosote bush ethanolic extract in the HFD hamster model were a reduction of insulin resistance, associated with lower serum insulin and leptin, lower hepatic lipid peroxidation and higher liver antioxidant capacity. Plasma and liver lipids tended or were reduced to values closer to those of animals fed standard diet. A similar effect on lipids was induced by EZ, although with even lower hepatic cholesterol and total lipids concentrations. In general, the change from HFD to standard diet plus ethanolic extract induced the same but deeper changes, including a reduction in plasma glucose and an increase in the percentage of HDL cholesterol. Unlike creosote bush extract, EZ increased food consumption and neutral fecal steroids, with no significant effect on body weight, epididymal fat pads, liver peroxidation or antioxidant capacity. Also EZ did not modify serum insulin and leptin. However, insulin sensitivity improved to values similar to those induced by the extract. This suggests that the mechanism of action of creosote bush ethanolic extract is different to inhibition of cholesterol absorption or increase excretion

  14. Creosote Bush (Larrea tridentata) Improves Insulin Sensitivity and Reduces Plasma and Hepatic Lipids in Hamsters Fed a High Fat and Cholesterol Diet

    PubMed Central

    Del Vecchyo-Tenorio, Georgina; Rodríguez-Cruz, Maricela; Andrade-Cetto, Adolfo; Cárdenas-Vázquez, René

    2016-01-01

    Creosote bush, Larrea tridentata (Sesse y Moc. Ex DC, Zygophyllaceae) is a shrub found in the deserts of Northern Mexico and Southwestern United States. In traditional medicine, it is used to treat a variety of illnesses including type 2 diabetes. The present study aims to investigate the effects of creosote bush ethanolic extract on plasma and liver parameters associated with the metabolic syndrome in hamsters fed a high fat and cholesterol diet (HFD), comparing them with those induced by ezetimibe (EZ). Seven groups of six hamsters each were formed. Six groups were fed HFD for 2 weeks. The following 2 weeks, the HFD groups received: (1) only HFD, (2) HFD + 3 mg% EZ, (3) HFD + 0.2% creosote bush ethanolic extract, (4) only standard diet (Std Diet), (5) Std Diet + 3 mg% EZ, (6) Std Diet + 0.2% creosote bush ethanolic extract. The beneficial effects of creosote bush ethanolic extract in the HFD hamster model were a reduction of insulin resistance, associated with lower serum insulin and leptin, lower hepatic lipid peroxidation and higher liver antioxidant capacity. Plasma and liver lipids tended or were reduced to values closer to those of animals fed standard diet. A similar effect on lipids was induced by EZ, although with even lower hepatic cholesterol and total lipids concentrations. In general, the change from HFD to standard diet plus ethanolic extract induced the same but deeper changes, including a reduction in plasma glucose and an increase in the percentage of HDL cholesterol. Unlike creosote bush extract, EZ increased food consumption and neutral fecal steroids, with no significant effect on body weight, epididymal fat pads, liver peroxidation or antioxidant capacity. Also EZ did not modify serum insulin and leptin. However, insulin sensitivity improved to values similar to those induced by the extract. This suggests that the mechanism of action of creosote bush ethanolic extract is different to inhibition of cholesterol absorption or increase excretion

  15. Use of Lipid-Lowering Medications and the Likelihood of Achieving Optimal LDL-Cholesterol Goals in Coronary Artery Disease Patients.

    PubMed

    Karalis, Dean G; Victor, Brett; Ahedor, Lilian; Liu, Longjian

    2012-01-01

    Background. In clinical practice, most coronary artery disease patients are not achieving their recommend LDL-cholesterol goal of <70 mg/dL. Methods. We conducted a retrospective analysis of outpatient electronic health records and the most recent lipid profile, lipid-lowering medications and doses were collected. Results. We identified 9950 coronary artery disease patients. Only 37% on a statin alone achieved an LDL-cholesterol of <70 mg/dL, and most were on moderate-to-high-potency statins. The intensity of statin therapy did not improve LDL-cholesterol goal attainment. Among patients on combination therapy, 41% on statin plus ezetimibe and 46% on statin plus niacin achieved an LDL-cholesterol of <70 mg/dL (P = 0.01 and <0.0001 versus statin alone). If patients were switched to a high-potency statin LDL-cholesterol goal attainment of <70 mg/dL would increase to 46% and would increase up to 72% with combination therapy. Conclusions. Most coronary artery disease patients in clinical practice do not attain an LDL-cholesterol of <70 mg/dL, even among patients on high potency statins. The combination of statin plus either ezetimibe or niacin is the most effective regimen to achieve an LDL-cholesterol of <70 mg/dL, however, these drug combinations are used infrequently in clinical practice.

  16. Freeze-dried strawberries lower serum cholesterol and lipid peroxidation in adults with abdominal adiposity and elevated serum lipids.

    PubMed

    Basu, Arpita; Betts, Nancy M; Nguyen, Angel; Newman, Emily D; Fu, Dongxu; Lyons, Timothy J

    2014-06-01

    Dietary flavonoid intake, especially berry flavonoids, has been associated with reduced risks of cardiovascular disease (CVD) in large prospective cohorts. Few clinical studies have examined the effects of dietary berries on CVD risk factors. We examined the hypothesis that freeze-dried strawberries (FDS) improve lipid and lipoprotein profiles and lower biomarkers of inflammation and lipid oxidation in adults with abdominal adiposity and elevated serum lipids. In a randomized dose-response controlled trial, 60 volunteers [5 men and 55 women; aged 49 ± 10 y; BMI: 36 ± 5 kg/m(2) (means ± SDs)] were assigned to consume 1 of the following 4 beverages for 12 wk: 1) low-dose FDS (LD-FDS; 25 g/d); 2) low-dose control (LD-C); 3) high-dose FDS (HD-FDS; 50 g/d); and 4) high-dose control (HD-C). Control beverages were matched for calories and total fiber. Blood draws, anthropometrics, blood pressure, and dietary data were collected at screening (0 wk) and after 12-wk intervention. Dose-response analyses revealed significantly greater decreases in serum total and LDL cholesterol and nuclear magnetic resonance (NMR)-derived small LDL particle concentration in HD-FDS [33 ± 6 mg/dL, 28 ± 7 mg/dL, and 301 ± 78 nmol/L, respectively (means ± SEMs)] vs. LD-FDS (-3 ± 11 mg/dL, -3 ± 9 mg/dL, and -28 ± 124 nmol/L, respectively) over 12 wk (0-12 wk; all P < 0.05). Compared with controls, only the decreases in total and LDL cholesterol in HD-FDS remained significant vs. HD-C (0.7 ± 12 and 1.4 ± 9 mg/dL, respectively) over 12 wk (0-12 wk; all P < 0.05). Both doses of strawberries showed a similar decrease in serum malondialdehyde at 12 wk (LD-FDS: 1.3 ± 0.2 μmol/L; HD-FDS: 1.2 ± 0.1 μmol/L) vs. controls (LD-C: 2.1 ± 0.2 μmol/L; HD-C: 2.3 ± 0.2 μmol/L) (P < 0.05). In general, strawberry intervention did not affect any measures of adiposity, blood pressure, glycemia, and serum concentrations of HDL cholesterol and triglycerides, C-reactive protein, and adhesion molecules

  17. Freeze-Dried Strawberries Lower Serum Cholesterol and Lipid Peroxidation in Adults with Abdominal Adiposity and Elevated Serum Lipids123

    PubMed Central

    Basu, Arpita; Betts, Nancy M.; Nguyen, Angel; Newman, Emily D.; Fu, Dongxu; Lyons, Timothy J.

    2014-01-01

    Dietary flavonoid intake, especially berry flavonoids, has been associated with reduced risks of cardiovascular disease (CVD) in large prospective cohorts. Few clinical studies have examined the effects of dietary berries on CVD risk factors. We examined the hypothesis that freeze-dried strawberries (FDS) improve lipid and lipoprotein profiles and lower biomarkers of inflammation and lipid oxidation in adults with abdominal adiposity and elevated serum lipids. In a randomized dose-response controlled trial, 60 volunteers [5 men and 55 women; aged 49 ± 10 y; BMI: 36 ± 5 kg/m2 (means ± SDs)] were assigned to consume 1 of the following 4 beverages for 12 wk: 1) low-dose FDS (LD-FDS; 25 g/d); 2) low-dose control (LD-C); 3) high-dose FDS (HD-FDS; 50 g/d); and 4) high-dose control (HD-C). Control beverages were matched for calories and total fiber. Blood draws, anthropometrics, blood pressure, and dietary data were collected at screening (0 wk) and after 12-wk intervention. Dose-response analyses revealed significantly greater decreases in serum total and LDL cholesterol and nuclear magnetic resonance (NMR)–derived small LDL particle concentration in HD-FDS [33 ± 6 mg/dL, 28 ± 7 mg/dL, and 301 ± 78 nmol/L, respectively (means ± SEMs)] vs. LD-FDS (−3 ± 11 mg/dL, −3 ± 9 mg/dL, and −28 ± 124 nmol/L, respectively) over 12 wk (0–12 wk; all P < 0.05). Compared with controls, only the decreases in total and LDL cholesterol in HD-FDS remained significant vs. HD-C (0.7 ± 12 and 1.4 ± 9 mg/dL, respectively) over 12 wk (0–12 wk; all P < 0.05). Both doses of strawberries showed a similar decrease in serum malondialdehyde at 12 wk (LD-FDS: 1.3 ± 0.2 μmol/L; HD-FDS: 1.2 ± 0.1 μmol/L) vs. controls (LD-C: 2.1 ± 0.2 μmol/L; HD-C: 2.3 ± 0.2 μmol/L) (P < 0.05). In general, strawberry intervention did not affect any measures of adiposity, blood pressure, glycemia, and serum concentrations of HDL cholesterol and triglycerides, C-reactive protein, and adhesion

  18. On the toroidal plasma rotations induced by lower hybrid waves

    NASA Astrophysics Data System (ADS)

    Guan, Xiaoyin; Qin, Hong; Liu, Jian; Fisch, Nathaniel J.

    2013-02-01

    A theoretical model is developed to explain the plasma rotations induced by lower hybrid waves in Alcator C-Mod. In this model, torodial rotations are driven by the Lorentz force on the bulk-electron flow across flux surfaces, which is a response of the plasma to the resonant-electron flow across flux surfaces induced by the lower hybrid waves. The flow across flux surfaces of the resonant electrons and the bulk electrons are coupled through the radial electric field initiated by the resonant electrons, and the friction between ions and electrons transfers the toroidal momentum to ions from electrons. An improved quasilinear theory with gyrophase dependent distribution function is developed to calculate the perpendicular resonant-electron flow. Toroidal rotations are determined using a set of fluid equations for bulk electrons and ions, which are solved numerically by a finite-difference method. Numerical results agree well with the experimental observations in terms of flow profile and amplitude. The model explains the strong correlation between torodial flow and internal inductance observed experimentally, and predicts both counter-current and co-current flows, depending on the perpendicular wave vectors of the lower hybrid waves.

  19. On the Toroidal Plasma Rotations Induced by Lower Hybrid Waves

    SciTech Connect

    Guan, Xiaoyin; Qin, Hong; Liu, Jian; Fisch, Nathaniel J.

    2012-11-14

    A theoretical model is developed to explain the plasma rotations induced by lower hybrid waves in Alcator C-Mod. In this model, torodial rotations are driven by the Lorentz force on the bulk electron flow across flux surfaces, which is a response of the plasma to the resonant-electron flow across flux surfaces induced by the lower hybrid waves. The flow across flux surfaces of the resonant electrons and the bulk electrons are coupled through the radial electric fi eld initiated by the resonant electrons, and the friction between ions and electrons transfers the toroidal momentum to ions from electrons. An improved quasilinear theory with gyrophase dependent distribution function is developed to calculate the perpendicular resonant-electron flow. Toroidal rotations are determined using a set of fluid equations for bulk electrons and ions, which are solved numerically by a fi nite- difference method. Numerical results agree well with the experimental observations in terms of flow pro file and amplitude. The model explains the strong correlation between torodial flow and internal inductance observed experimentally, and predicts both counter-current and co-current flows, depending on the perpendicular wave vectors of the lower hybrid waves. __________________________________________________

  20. Enhanced placental cholesterol efflux by fetal HDL in Smith–Lemli–Opitz syndrome

    PubMed Central

    Jenkins, Katie T.; Merkens, Louise S.; Tubb, Matthew R.; Myatt, Leslie; Davidson, W. Sean; Steiner, Robert D.; Woollett, Laura A.

    2010-01-01

    Previous studies from this laboratory have shown that maternal-derived cholesterol can be effluxed from trophoblasts to fetal HDL and plasma. We had the opportunity to study for the first time the ability of HDL and plasma from a fetus with the Smith–Lemli–Opitz syndrome (SLOS) to efflux cholesterol from trophoblasts. It was unclear whether cholesterol could be effluxed to fetuses with SLOS since lipoprotein levels are often very low. To answer this question, cord blood was collected from the placentas of an SLOS fetus and unaffected fetuses just after delivery. Plasma cholesterol concentrations were very low in the affected fetus; cholesterol, 7-dehydrocholesterol, and 8-dehydocholesterol concentrations were 14.1, 4.5, and 5.2 mg/dl, respectively. The HDL from the fetal SLOS effluxed ≈50% more cholesterol from a trophoblast cell line, were smaller in size, and had a lower cholesterol to phospholipid ratio as compared to HDL from unaffected fetuses or adults. Plasma from the SLOS fetus effluxed cholesterol to a similar percentage as unaffected fetal plasma or adult plasma, possibly due to fewer HDL particles as demonstrated in previous SLOS patients. These novel data demonstrate that the cholesterol-deficient SLOS fetus is able to obtain cholesterol from trophoblasts at a time when cholesterol is playing a critical role in development, and has implications for design of treatments for cholesterol deficiency syndromes as well as understanding of prenatal cholesterol transport in humans. PMID:18346920

  1. Electron beam driven lower hybrid waves in a dusty plasma

    SciTech Connect

    Prakash, Ved; Vijayshri; Sharma, Suresh C.; Gupta, Ruby

    2013-05-15

    An electron beam propagating through a magnetized dusty plasma drives electrostatic lower hybrid waves to instability via Cerenkov interaction. A dispersion relation and the growth rate of the instability for this process have been derived taking into account the dust charge fluctuations. The frequency and the growth rate of the unstable wave increase with the relative density of negatively charged dust grains. Moreover, the growth rate of the instability increases with beam density and scales as the one-third power of the beam density. In addition, the dependence of the growth rate on the beam velocity is also discussed.

  2. Consumption of wheat aleurone-rich foods increases fasting plasma betaine and modestly decreases fasting homocysteine and LDL-cholesterol in adults.

    PubMed

    Price, Ruth K; Keaveney, Edel M; Hamill, Lesley L; Wallace, Julie M W; Ward, Mary; Ueland, Per M; McNulty, Helene; Strain, J J; Parker, Michael J; Welch, Robert W

    2010-12-01

    There is strong evidence that whole-grain foods protect against heart disease. Although underlying mechanisms and components are unclear, betaine, found at high levels in wheat aleurone, may play a role. We evaluated the effects of a diet high in wheat aleurone on plasma betaine and related measures. In a parallel, single-blinded intervention study, 79 healthy participants (aged 45-65 y, BMI ≥ 25 kg/m(2)) incorporated either aleurone-rich cereal products (27 g/d aleurone) or control products balanced for fiber and macronutrients into their habitual diets for 4 wk. Fasting blood samples were taken at baseline and postintervention (4 wk) from participants. Compared with the control, the aleurone products provided an additional 279 mg/d betaine and resulted in higher plasma betaine (P < 0.001; intervention effect size: 5.2 μmol/L) and lower plasma total homocysteine (tHcy) (P = 0.010; -0.7 μmol/L). Plasma dimethylglycine and methionine, which are products of betaine-mediated homocysteine remethylation, were also higher (P < 0.001; P = 0.027) relative to control. There were no significant effects on plasma choline or B vitamins (folate, riboflavin, and vitamin B-6). However, LDL cholesterol was lower than in the control group (P = 0.037). We conclude that incorporating aleurone-rich products into the habitual diet for 4 wk significantly increases plasma betaine concentrations and lowers tHcy, which is attributable to enhanced betaine-homocysteine methyltransferase-mediated remethylation of homocysteine. Although this supports a role for betaine in the protective effects of whole grains, concomitant decreases in LDL suggest more than one component or mechanism may be responsible.

  3. Generalized lower-hybrid-drift instability. [of plasma

    NASA Technical Reports Server (NTRS)

    Hsia, J. B.; Chiu, S. M.; Hsia, M. F.; Chou, R. L.; Wu, C. S.

    1979-01-01

    The theory of lower-hybrid-drift instability is extended to include a finite value of the component of wave vector parallel to the ambient magnetic field so that the analysis bridges the usual lower-hybrid-drift instability of flute modes and the modified-two-stream instability. The present theory also includes electromagnetic and ambient magnetic field-gradient effects. It is found that in the cold-electron limit the density and magnetic gradients can qualitatively modify the conclusion obtained in the early theory of the modified-two-stream instability. For example, even if the relative drift far exceeds the Alfven speed of the plasma, the instability may still persist. This result is in contrast to that established in the literature. When the electron temperature is finite, the problem is complicated. Numerical solutions are obtained for a number of cases.

  4. Soy protein with or without isoflavones, soy germ and soy germ extract, and daidzein lessen plasma cholesterol levels in golden Syrian hamsters.

    PubMed

    Song, Tongtong; Lee, Sun-Ok; Murphy, Patricia A; Hendrich, Suzanne

    2003-10-01

    Dietary isolated soy protein (ISP, containing approximately equal amounts of daidzein and genistein), ethanol-extracted ISP (ISP (-)), soygerm or soygerm extract (containing large amounts of daidzein and glycitein and little genistein) and the isoflavone, daidzein, were hypothesized to lessen plasma cholesterol in comparison with casein. Sixty male and 60 female golden Syrian hamsters (6-8 weeks of age) were randomly assigned to six treatments fed for 10 weeks. Four of the experimental diets (ISP, daidzein, soygerm, and soygerm extract) contained 1.3 mmol total isoflavones/kg. The ISP (-) diet contained 0.013 mmol isoflavone/kg, whereas the casein diet contained no isoflavones. Hamsters fed ISP, ISP (-), daidzein, soygerm, and soygerm extract had significantly less plasma total cholesterol (by 16%-28%), less non-HDL cholesterol (by 15%-50%) and less non-HDL/HDL cholesterol ratios compared with hamsters fed casein (P < 0.01). For male hamsters, there were no differences among treatments in plasma HDL concentrations. Female hamsters fed ISP (-) had significantly greater HDL levels (P < 0.01) than females fed casein or daidzein. Triglyceride concentration was significantly less in hamsters fed ISP (-) compared with the casein-fed females. Because soy protein with or without isoflavones, soygerm and soygerm extract, and daidzein lessened plasma cholesterol to an approximately equal extent, soy protein alone, varying mixtures of isoflavones, and other extractable components of soy are responsible for cholesterol-lessening effects of soy foods, mainly due to their effects to lessen LDL cholesterol.

  5. Effects of a carbohydrate-restricted diet with and without supplemental soluble fiber on plasma low-density lipoprotein cholesterol and other clinical markers of cardiovascular risk.

    PubMed

    Wood, Richard J; Fernandez, Maria Luz; Sharman, Matthew J; Silvestre, Ricardo; Greene, Christine M; Zern, Tosca L; Shrestha, Sudeep; Judelson, Daniel A; Gomez, Ana L; Kraemer, William J; Volek, Jeff S

    2007-01-01

    Carbohydrate-restricted diets (CRDs) promote weight loss, reductions in plasma triacylglycerol (TAG) levels, and increases in high-density lipoprotein cholesterol (HDL-C) levels but may cause undesirable low-density lipoprotein cholesterol (LDL-C) responses in some people. The objective of the present study was to determine the effect of adding soluble fiber to a CRD on plasma LDL-C and other traditionally measured markers of cardiovascular disease. Using a parallel-arm, double-blind, placebo-controlled design, 30 overweight and obese men (body mass index, 25-35 kg/m(2)) were randomly assigned to supplement a CRD with soluble fiber (Konjac-mannan, 3g/d) (n = 15) or placebo (n = 15). Plasma lipids, anthropometrics, body composition, blood pressure, and nutrient intake were evaluated at baseline and at 6 and 12 weeks. Compliance was excellent as assessed by 7-day weighed dietary records and ketonuria. Both groups experienced decreases in (P < .01) body weight, percent body fat, systolic blood pressure, waist circumference, and plasma glucose levels. After 12 weeks, HDL-C and TAG improved significantly in the fiber (10% and -34%) and placebo (14%, -43%) groups. LDL-C decreased by 17.6% (P < .01) at week 6 and 14.1% (P < .01) at week 12 in the fiber group. Conversely, LDL-C reductions were significant in the placebo group only after 12 weeks (-6.0%, P < .05). We conclude that although clearly effective at lowering LDL-C, adding soluble fiber to a CRD during active and significant weight loss provides no additional benefits to the diet alone. Furthermore, a CRD led to clinically important positive alterations in cardiovascular disease risk factors.

  6. Cooking for Lower Cholesterol

    MedlinePlus

    ... flavor, rather than as a main ingredient. Cook fresh vegetables the heart-healthy way Try cooking vegetables ... delivers helpful articles and the latest news on keeping your heart healthy. Sign up today! Email:* State: ...

  7. Pigs fed cholesterol neonatally have increased cerebrum cholesterol as young adults.

    PubMed

    Boleman, S L; Graf, T L; Mersmann, H J; Su, D R; Krook, L P; Savell, J W; Park, Y W; Pond, W G

    1998-12-01

    Sixty-eight female neonatal pigs selected for seven (Experiment 1) or eight (Experiment 2) generations for high (HG) or low (LG) plasma cholesterol were used to test the hypothesis that neonatal dietary cholesterol fed during the first 4 or 8 wk of postnatal life increases the cholesterol content of the cerebrum in young adulthood following free access to a high-fat (15%), high-cholesterol (0.5%) diet from 8 to 20 or 24 wk of age. Pigs were removed from their dams at 1 d of age and given free access to a sow-milk replacer diet containing 9.5% coconut fat and 0 or 0.5 % cholesterol. All pigs (except four HG and four LG pigs in Experiment 2, which were deprived of cholesterol throughout the study) were fed the high-fat, high-cholesterol diet from 8 wk to termination at 20 or 24 wk of age. Cerebrum weight and cholesterol concentration were higher in pigs fed cholesterol neonatally than in those deprived of cholesterol neonatally in both experiments, but weight and cholesterol concentration were unaffected by genetic line. Cholesterol concentrations in longissimus and semitendinosus muscles and in subcutaneous fat were unaffected by diet or genetic line. We conclude that dietary cholesterol deprivation during the first 4 to 8 wk of life in piglets is associated with lower cholesterol concentration and total content in the young adult cerebrum than in pigs supplemented with cholesterol in early life. These data support previous observations and suggest the possibility of a metabolic need for neonatal dietary cholesterol in normal brain development. PMID:9868199

  8. THE INTAKE OF FIBER MESOCARP PASSIONFRUIT (PASSIFLORA EDULIS) LOWERS LEVELS OF TRIGLYCERIDE AND CHOLESTEROL DECREASING PRINCIPALLY INSULIN AND LEPTIN

    PubMed Central

    Corrêa, E.M.; Medina, L.; Barros-Monteiro, J.; Valle, N.O.; Sales, R.; Magalães, A.; Souza, F.C.A.; Carvalho, T.B.; Lemos, J.R.; Lira, E.F.; Lima, E.S.; Galeno, D.M.L.; Morales, L.; Ortiz, C.; Carvalho, R.P.

    2014-01-01

    Background Diabetes mellitus (DM) is a major risk factor for coronary artery disease, renal failure, retinopathy, and neuropathy. Over the last years, there has been an increasing demand in folk medicine for natural sources that could help in the treatment of chronic diseases, including diabetes. The rind of passion fruit (Passiflora edulis f. Flavicarpa) is traditionally used as a functional food due to its high concentration of soluble and insoluble fiber. Objective The aim of this study was to determine the effect of high-fiber diet albedo of passion fruit on the metabolic and biochemical profile in diabetic rats induced by alloxan (2%). Design The passion fruit mesocarp fiber was dried in an oven with circulating air at 60°C and pulverized. We used 32 adult male rats, divided into 4 groups: Wistar group 1 control (GC), Wistar group 2, 15% fiber (GF15), Wistar group 3, 30% fiber (GF30), Wistar group 4, fiber disolved in water (GFH2O). The ratio of passion fruit was prepared according to the AIN 93M guidelines, varying only the source of dietary fiber. The corresponding diet for each group was offered to the animals for 60 days. Results There was a statically significant decrease in plasma glucose for GFH2O, GF15%, and GF30% groups with 27.0%, 37.4%, and 40.2%, respectively. Conclusion The use of mesocarp fiber of passion fruit at concentrations of 15% and 30% are an important dietary supplement for the treatment of DM due to its potential hypoglycemic effect, and its ability to reduce triglycerides and VLDL-cholesterol levels with a principal reduction of insulin and leptin. PMID:25346913

  9. Single-step fermentative production of the cholesterol-lowering drug pravastatin via reprogramming of Penicillium chrysogenum

    PubMed Central

    Hans, Marcus; Meijrink, Ben; van Scheppingen, Wibo B.; Vollebregt, Aad; Tee, Kang Lan; van der Laan, Jan-Metske; Leys, David; Munro, Andrew W.; van den Berg, Marco A.

    2015-01-01

    The cholesterol-lowering blockbuster drug pravastatin can be produced by stereoselective hydroxylation of the natural product compactin. We report here the metabolic reprogramming of the antibiotics producer Penicillium chrysogenum toward an industrial pravastatin production process. Following the successful introduction of the compactin pathway into the β-lactam–negative P. chrysogenum DS50662, a new cytochrome P450 (P450 or CYP) from Amycolatopsis orientalis (CYP105AS1) was isolated to catalyze the final compactin hydroxylation step. Structural and biochemical characterization of the WT CYP105AS1 reveals that this CYP is an efficient compactin hydroxylase, but that predominant compactin binding modes lead mainly to the ineffective epimer 6-epi-pravastatin. To avoid costly fractionation of the epimer, the enzyme was evolved to invert stereoselectivity, producing the pharmacologically active pravastatin form. Crystal structures of the optimized mutant P450Prava bound to compactin demonstrate how the selected combination of mutations enhance compactin binding and enable positioning of the substrate for stereo-specific oxidation. Expression of P450Prava fused to a redox partner in compactin-producing P. chrysogenum yielded more than 6 g/L pravastatin at a pilot production scale, providing an effective new route to industrial scale production of an important drug. PMID:25691737

  10. 3-Deoxyschweinfurthin B Lowers Cholesterol Levels by Decreasing Synthesis and Increasing Export in Cultured Cancer Cell Lines.

    PubMed

    Kuder, Craig H; Weivoda, Megan M; Zhang, Ying; Zhu, Junjia; Neighbors, Jeffrey D; Wiemer, David F; Hohl, Raymond J

    2015-12-01

    The schweinfurthins have potent antiproliferative activity in multiple glioblastoma multiforme (GBM) cell lines; however, the mechanism by which growth is impeded is not fully understood. Previously, we demonstrated that the schweinfurthins reduce the level of key isoprenoid intermediates in the cholesterol biosynthetic pathway. Herein, we describe the effects of the schweinfurthins on cholesterol homeostasis. Intracellular cholesterol levels are greatly reduced in cells incubated with 3-deoxyschweinfurthin B (3dSB), an analog of the natural product schweinfurthin B. Decreased cholesterol levels are due to decreased cholesterol synthesis and increased cholesterol efflux; both of these cellular actions can be influenced by liver X-receptor (LXR) activation. The effects of 3dSB on ATP-binding cassette transporter 1 levels and other LXR targets are similar to that of 25-hydroxycholesterol, an LXR agonist. Unlike 25-hydroxycholesterol, 3dSB does not act as a direct agonist for LXR α or β. These data suggest that cholesterol homeostasis plays a significant role in the growth inhibitory activity of the schweinfurthins and may elucidate a mechanism that can be targeted in human cancers such as GBM.

  11. Endothelial expression of human ABCA1 in mice increases plasma HDL cholesterol and reduces diet-induced atherosclerosis[S

    PubMed Central

    Vaisman, Boris L.; Demosky, Stephen J.; Stonik, John A.; Ghias, Mona; Knapper, Cathy L.; Sampson, Maureen L.; Dai, Cuilian; Levine, Stewart J.; Remaley, Alan T.

    2012-01-01

    The role of endothelial ABCA1 expression in reverse cholesterol transport (RCT) was examined in transgenic mice, using the endothelial-specific Tie2 promoter. Human ABCA1 (hABCA1) was significantly expressed in endothelial cells (EC) of most tissues except the liver. Increased expression of ABCA1 was not observed in resident peritoneal macrophages. ApoA-I-mediated cholesterol efflux from aortic EC was 2.6-fold higher (P < 0.0001) for cells from transgenic versus control mice. On normal chow diet, Tie2 hABCA1 transgenic mice had a 25% (P < 0.0001) increase in HDL-cholesterol (HDL-C) and more than a 2-fold increase of eNOS mRNA in the aorta (P < 0.04). After 6 months on a high-fat, high-cholesterol (HFHC) diet, transgenic mice compared with controls had a 40% increase in plasma HDL-C (P < 0.003) and close to 40% decrease in aortic lesions (P < 0.02). Aortas from HFHC-fed transgenic mice also showed gene expression changes consistent with decreased inflammation and apoptosis. Beneficial effects of the ABCA1 transgene on HDL-C levels or on atherosclerosis were absent when the transgene was transferred onto ApoE or Abca1 knockout mice. In summary, expression of hABCA1 in EC appears to play a role in decreasing diet-induced atherosclerosis in mice and is associated with increased plasma HDL-C levels and beneficial gene expression changes in EC. PMID:22039582

  12. Genetic variation at the SLCO1B1 gene locus and low density lipoprotein cholesterol lowering response to pravastatin in the elderly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our goal was to determine whether genetic variation at genes affecting statin metabolism or targets of statin therapy would influence low density lipoprotein (LDL) cholesterol lowering with pravastatin, baseline heart disease, or cardiac endpoints on trial. We examined associations of single nucleot...

  13. Effects of Dietary Palmitoleic Acid on Plasma Lipoprotein Profile and Aortic Cholesterol Accumulation Are Similar to Those of Other Unsaturated Fatty Acids in the F1B Golden Syrian Hamster 1–3

    PubMed Central

    Matthan, Nirupa R.; Dillard, Alice; Lecker, Jaime L.; Ip, Blanche; Lichtenstein, Alice H.

    2008-01-01

    The lower susceptibility of palmitoleic acid (16:1) to oxidation compared to PUFA may confer functional advantages with respect to finding acceptable alternatives to partially hydrogenated fats, but limited data are available on its effect on cardiovascular risk factors. This study investigated the effect of diets (10% fat, 0.1% cholesterol, wt:wt) enriched with macadamia [monounsaturated fatty acid (MUFA)16:1], palm (SFA,16:0), canola (MUFA,18:1), or safflower (PUFA,18:2) oils on lipoprotein profiles and aortic cholesterol accumulation in F1B Golden Syrian hamsters (n = 16/group). After 12 wk, 8 hamsters in each group were killed (phase 1). The remaining hamsters fed palm oil were changed to a diet containing coconut oil, while hamsters in the other diet groups continued on their original diets for an additional 6 wk (phase 2). With minor exceptions, the time course and dietary SFA source did not alter the study outcomes. Macadamia oil-fed hamsters had lower non-HDL cholesterol and triglyceride concentrations compared with the palm and coconut oil-fed hamsters and higher HDL-cholesterol compared with the coconut, canola, and safflower oil-fed hamsters. The aortic cholesterol concentration was not affected by dietary fat type. The hepatic cholesterol concentration was higher in the unsaturated compared with the saturated oil-fed hamsters. RBC membrane and aortic cholesteryl ester, triglyceride, and phospholipid fatty acid profiles reflected that of the dietary oil. These data suggest that an oil relatively high in palmitoleic acid does not adversely affect plasma lipoprotein profiles or aortic cholesterol accumulation and was similar to other unsaturated fatty acid-rich oils. PMID:19106316

  14. Effects of dietary palmitoleic acid on plasma lipoprotein profile and aortic cholesterol accumulation are similar to those of other unsaturated fatty acids in the F1B golden Syrian hamster.

    PubMed

    Matthan, Nirupa R; Dillard, Alice; Lecker, Jaime L; Ip, Blanche; Lichtenstein, Alice H

    2009-02-01

    The lower susceptibility of palmitoleic acid (16:1) to oxidation compared to PUFA may confer functional advantages with respect to finding acceptable alternatives to partially hydrogenated fats, but limited data are available on its effect on cardiovascular risk factors. This study investigated the effect of diets (10% fat, 0.1% cholesterol, wt:wt) enriched with macadamia [monounsaturated fatty acid (MUFA)16:1], palm (SFA,16:0), canola (MUFA,18:1), or safflower (PUFA,18:2) oils on lipoprotein profiles and aortic cholesterol accumulation in F1B Golden Syrian hamsters (n = 16/group). After 12 wk, 8 hamsters in each group were killed (phase 1). The remaining hamsters fed palm oil were changed to a diet containing coconut oil, while hamsters in the other diet groups continued on their original diets for an additional 6 wk (phase 2). With minor exceptions, the time course and dietary SFA source did not alter the study outcomes. Macadamia oil-fed hamsters had lower non-HDL cholesterol and triglyceride concentrations compared with the palm and coconut oil-fed hamsters and higher HDL-cholesterol compared with the coconut, canola, and safflower oil-fed hamsters. The aortic cholesterol concentration was not affected by dietary fat type. The hepatic cholesterol concentration was higher in the unsaturated compared with the saturated oil-fed hamsters. RBC membrane and aortic cholesteryl ester, triglyceride, and phospholipid fatty acid profiles reflected that of the dietary oil. These data suggest that an oil relatively high in palmitoleic acid does not adversely affect plasma lipoprotein profiles or aortic cholesterol accumulation and was similar to other unsaturated fatty acid-rich oils. PMID:19106316

  15. Artificial quasi-periodic plasma inhomogeneities in the lower ionosphere

    NASA Astrophysics Data System (ADS)

    Belikovich, V. V.; Benediktov, E. A.; Dmitriev, S. A.; Terina, G. I.

    Experimental results are presented on artificial quasi-periodic plasma inhomogeneities in a standing wave field of high-power shortwave radio transmission, at ionospheric altitudes of 75 to 115 km. A transmitter of an equivalent power of 20 MW periodically emitted for 10 to 20 sec an extraordinary component at frequencies of 5.5-5.75 MHz. Backward-scattered signals, at amplitudes of 40-70 dB below the specular channel level, were observed, and relaxation time fluctuation was noted to be within the range of from tenths of seconds to several seconds. The scattering height of the regular component of the sounding waves decreased as the sounding wave frequency approached the extraordinary component frequency of the disturbing radio emission, in accordance with the spatial synchronism condition (Belikovich et al., 1978). The feasibility of using the method for measurements at lower altitudes was shown.

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

    NASA Astrophysics Data System (ADS)

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

    1984-04-01

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

  17. Effects of statins and cholesterol on memory functions in mice.

    PubMed

    Ghodke, Ravindra M; Tour, Nagesh; Devi, Kshama

    2012-12-01

    Studies on influence of lipid lowering therapies have generated wide controversial results on the role of cholesterol on memory function. However recent studies revealed that cholesterol lowering treatment substantially reduce the risk of dementia. The objectives of this study were to analyze the effect of statins on memory function and to establish the relationship between increase/decrease in cholesterol synthesis, total cholesterol level and memory function in animals. We examined the relationship between biosynthesis of cholesterol and memory function using two statins (lipophilic simvastatin and hydrophilic pravastatin) and high cholesterol diet in mice for 15 days and 4 months. Memory performance was evaluated with two different behavioral tests and various biochemical parameters such as serum cholesterol, whole brain cholesterol, brain 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) activity and brain acetylcholine esterase (AChE) activity. We found that statin treatment for 4 months, but not for 15 days, showed significant improvement in memory function whereas high cholesterol diet showed significant impairment of memory. However long-term statin treatment showed significant decrease in serum cholesterol level as well as brain AChE level. Moreover high cholesterol diet showed significant decrease in memory function with an increase in serum cholesterol level as well as brain AChE level. There is no direct correlation between brain cholesterol level, as well as HMG-CoA activity with memory function regulation. However there is definite link between plasma cholesterol level and AChE level. A long-standing plasma cholesterol alteration may be essential to regulate memory function which in turn might be mediated through AChE modulated pathway.

  18. Replacement of butter on bread by rapeseed oil and rapeseed oil-containing margarine: effects on plasma fatty acid composition and serum cholesterol.

    PubMed

    Seppänen-Laakso, T; Vanhanen, H; Laakso, I; Kohtamäki, H; Viikari, J

    1992-11-01

    The effects of zero-erucic acid rapeseed oil and rapeseed oil-containing margarine on plasma fatty acid composition and serum cholesterol were studied in butter users (n 43). Compliance to the substitution was followed by fatty acid analysis of total plasma and plasma phospholipids. The amount of substitute fats represented, on average, 21% of total fat and 8% of total energy intake. Changes in the relative fatty acid composition of plasma phospholipids indicated further fatty acid metabolism, and were closely related to the serum cholesterol level. The reduction in saturated fatty acids led to a significant increase in the proportion of n-3 and n-6 polyunsaturated fatty acids (PUFA) with the rapeseed oil diet, whereas the margarine caused a significant rise in n-6 PUFA only. The increase in the proportions of the two PUFA families occurred in accordance with their competitive order, most completely with the rapeseed oil diet. When butter was replaced by rapeseed oil, low-density-lipoprotein-cholesterol decreased by an average of 9.1% without a reduction in high-density-lipoprotein-cholesterol. During margarine substitution the reduction was 5.2%, on average. Of the plasma phospholipids, alpha-linolenic acid and the linoleic:stearic acid ratio, but not oleic acid, were the components most significantly correlated with serum cholesterol levels or the decrease in these levels. The results show that rapeseed oil can act primarily as a source of essential fatty acids, rather than that of monoenes, in the diet of butter users.

  19. In vivo measurement of plasma cholesterol and fatty acid synthesis with deuterated water: determination of the average number of deuterium atoms incorporated.

    PubMed

    Diraison, F; Pachiaudi, C; Beylot, M

    1996-07-01

    Fractional lipid synthesis can be measured using the incorporation of deuterium from deuterated water. The calculations require knowledge of the maximum incorporation number (N) of deuterium atoms in the molecules synthesized. For both tissue palmitate and cholesterol, N values have been found to be higher during in vivo versus in vitro experiments. We determined the N values to be used for measuring the fractional synthesis of plasma cholesterol and of palmitate triglycerides (TG). Rats were given drinking water enriched (7% to 10%) with deuterated water, and N was determined from the mass isotopomer distributions of plasma cholesterol and plasma TG palmitate and the deuterium enrichment of plasma water. We found N to be 21 for palmitate and 27 for cholesterol. These values agree with those reported for tissue palmitate and cholesterol in vivo, and are higher than values found in vitro. We also found large deuterium enrichments in plasma glucose and in liver lactate and pyruvate. We suggest that, compared with in vitro studies, in vivo metabolism of these compounds leads to an additional pathway of incorporation of deuterium into lipids through deuterium-labeled acetyl coenzyme A (CoA). This could explain why N values are higher in vivo than in vitro. PMID:8692014

  20. Think Again About Cholesterol Survey.

    PubMed

    Catapano, Alberico L; Wiklund, Olov

    2015-12-01

    Cardiovascular disease (CVD) is still the main cause of death in Europe. Elevated plasma cholesterol, specifically low-density lipoprotein cholesterol (LDL-C), is the main causative risk factor for CVD, most prominently associated with coronary heart disease. A widespread disinformation about cholesterol and CVD is one factor underlying a poor compliance to lipid-lowering therapy. To investigate how cholesterol, CVD and cholesterol reduction is perceived in the population, a survey was commissioned by the European Atherosclerosis Society (EAS). Nearly half of people above 25 years of age are most worried about cancer (45%), compared to just over one in four who are worried about heart disease (27%). A majority believe being overweight (72%), blood pressure (70%) and smoking (67%) most affect heart health, far more than note cholesterol (59%) and family history (39%). The majority of adults recognize that high LDL (or "bad") cholesterol should be a health priority for everyone, including those younger than 40 and those who are not overweight. However, 1 in 4 (25%) incorrectly believe that it does not need to be a concern until someone shows signs or symptoms. Although 89% of adults surveyed agreed it is important for people to know whether or not they have high LDL-C, an overwhelming 92% did not know their LDL-C levels or had never had their cholesterol levels tested. A high 63% had never heard of familial hypercholesterolemia: France had the lowest level of awareness (41%) to Denmark with a high 80%, and the association of the disease with high levels of LDL-C is quite poor (only 36%), with Sweden only at 22% versus a high in Spain of 54%. A large part of the people participating in the survey were quite uncertain about the modality of transmission for familial hypercholesterolemia in the family. All in all, this survey highlights the need for more information among citizens for the role of cholesterol in determining CVD.

  1. Think Again About Cholesterol Survey.

    PubMed

    Catapano, Alberico L; Wiklund, Olov

    2015-12-01

    Cardiovascular disease (CVD) is still the main cause of death in Europe. Elevated plasma cholesterol, specifically low-density lipoprotein cholesterol (LDL-C), is the main causative risk factor for CVD, most prominently associated with coronary heart disease. A widespread disinformation about cholesterol and CVD is one factor underlying a poor compliance to lipid-lowering therapy. To investigate how cholesterol, CVD and cholesterol reduction is perceived in the population, a survey was commissioned by the European Atherosclerosis Society (EAS). Nearly half of people above 25 years of age are most worried about cancer (45%), compared to just over one in four who are worried about heart disease (27%). A majority believe being overweight (72%), blood pressure (70%) and smoking (67%) most affect heart health, far more than note cholesterol (59%) and family history (39%). The majority of adults recognize that high LDL (or "bad") cholesterol should be a health priority for everyone, including those younger than 40 and those who are not overweight. However, 1 in 4 (25%) incorrectly believe that it does not need to be a concern until someone shows signs or symptoms. Although 89% of adults surveyed agreed it is important for people to know whether or not they have high LDL-C, an overwhelming 92% did not know their LDL-C levels or had never had their cholesterol levels tested. A high 63% had never heard of familial hypercholesterolemia: France had the lowest level of awareness (41%) to Denmark with a high 80%, and the association of the disease with high levels of LDL-C is quite poor (only 36%), with Sweden only at 22% versus a high in Spain of 54%. A large part of the people participating in the survey were quite uncertain about the modality of transmission for familial hypercholesterolemia in the family. All in all, this survey highlights the need for more information among citizens for the role of cholesterol in determining CVD. PMID:26671304

  2. Variation in the Phosphoinositide 3-Kinase Gamma Gene Affects Plasma HDL-Cholesterol without Modification of Metabolic or Inflammatory Markers

    PubMed Central

    Kächele, Martin; Hennige, Anita M.; Machann, Jürgen; Hieronimus, Anja; Lamprinou, Apostolia; Machicao, Fausto; Schick, Fritz; Fritsche, Andreas; Stefan, Norbert; Nürnberg, Bernd; Häring, Hans-Ulrich; Staiger, Harald

    2015-01-01

    Objective Phosphoinositide 3-kinase γ (PI3Kγ) is a G-protein-coupled receptor-activated lipid kinase mainly expressed in leukocytes and cells of the cardiovascular system. PI3Kγ plays an important signaling role in inflammatory processes. Since subclinical inflammation is a hallmark of atherosclerosis, obesity-related insulin resistance, and pancreatic β-cell failure, we asked whether common genetic variation in the PI3Kγ gene (PIK3CG) contributes to body fat content/distribution, serum adipokine/cytokine concentrations, alterations in plasma lipid profiles, insulin sensitivity, insulin release, and glucose homeostasis. Study Design Using a tagging single nucleotide polymorphism (SNP) approach, we analyzed genotype-phenotype associations in 2,068 German subjects genotyped for 10 PIK3CG SNPs and characterized by oral glucose tolerance tests. In subgroups, data from hyperinsulinaemic-euglycaemic clamps, magnetic resonance spectroscopy of the liver, whole-body magnetic resonance imaging, and intravenous glucose tolerance tests were available, and peripheral blood mononuclear cells (PBMCs) were used for gene expression analysis. Results After appropriate adjustment, none of the PIK3CG tagging SNPs was significantly associated with body fat content/distribution, adipokine/cytokine concentrations, insulin sensitivity, insulin secretion, or blood glucose concentrations (p>0.0127, all; Bonferroni-corrected α-level: 0.0051). However, six non-linked SNPs displayed at least nominal associations with plasma HDL-cholesterol concentrations, two of them (rs4288294 and rs116697954) reaching the level of study-wide significance (p = 0.0003 and p = 0.0004, respectively). More precisely, rs4288294 and rs116697954 influenced HDL2-, but not HDL3-, cholesterol. With respect to the SNPs’ in vivo functionality, rs4288294 was significantly associated with PIK3CG mRNA expression in PBMCs. Conclusions We could demonstrate that common genetic variation in the PIK3CG locus, possibly

  3. Polysaccharide gel coating of the leaves of Brasenia schreberi lowers plasma cholesterol in hamsters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Brasenia schreberi is an invasive aquatic weed in the U.S. but the plant has economic value in Asia where it is cultivated for food. The young leaves of B. schreberi are coated with gelatinous water-insoluble mucilage. This mucilage is a polysaccharide composed of galactose, mannose, fucose and ot...

  4. Understand Your Risk for High Cholesterol

    MedlinePlus

    ... or trans fats also increases the amount of LDL cholesterol in your blood. If high blood cholesterol runs ... may not be enough to help lower your LDL blood cholesterol. View an animation of cholesterol . More information: Women ...

  5. The influence of natural short photoperiodic and temperature conditions on plasma thyroid hormones and cholesterol in male Syrian hamsters

    NASA Astrophysics Data System (ADS)

    Vaughan, M. K.; Brainard, G. C.; Reiter, R. J.

    1984-09-01

    Adult male Syrian hamsters were subjected to 1, 3, 5, 7 or 11 weeks of either natural winter conditions or rigorously controlled laboratory conditions (LD 10∶14; 22 ± 2‡C). Although both groups of hamsters gained weight over the course of the experiment, hamsters housed indoors were significantly heavier after 5 weeks of treatment compared to their outdoors counterparts. Animals housed under natural conditions exhibited a significant decrease in circulating levels of thyroxine (T4) and a rapid rise in triiodothyronine (T3) levels; the free T4 and free T3 index (FT4I and FT3I) mirrored the changes in circulating levels of the respective hormones. Laboratory-housed animals had a slight rise in T4 and FT4I at 3 weeks followed by a slow steady decline in these values; T3 and FT3I values did not change remarkably in these animals. Plasma cholesterol declined steadily over the course of the experiment in laboratory-maintained animals but increased slightly during the first 5 weeks in animals under natural conditions. Since the photoperiodic conditions were approximately of the same duration in these 2 groups, it is concluded that the major differences in body weight, thyroid hormone values and plasma cholesterol are due to some component (possibly temperature) in the natural environment.

  6. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials

    PubMed Central

    Cholesterol Treatment Trialists' (CTT) Collaboration

    2010-01-01

    Summary Background Lowering of LDL cholesterol with standard statin regimens reduces the risk of occlusive vascular events in a wide range of individuals. We aimed to assess the safety and efficacy of more intensive lowering of LDL cholesterol with statin therapy. Methods We undertook meta-analyses of individual participant data from randomised trials involving at least 1000 participants and at least 2 years' treatment duration of more versus less intensive statin regimens (five trials; 39 612 individuals; median follow-up 5·1 years) and of statin versus control (21 trials; 129 526 individuals; median follow-up 4·8 years). For each type of trial, we calculated not only the average risk reduction, but also the average risk reduction per 1·0 mmol/L LDL cholesterol reduction at 1 year after randomisation. Findings In the trials of more versus less intensive statin therapy, the weighted mean further reduction in LDL cholesterol at 1 year was 0·51 mmol/L. Compared with less intensive regimens, more intensive regimens produced a highly significant 15% (95% CI 11–18; p<0·0001) further reduction in major vascular events, consisting of separately significant reductions in coronary death or non-fatal myocardial infarction of 13% (95% CI 7–19; p<0·0001), in coronary revascularisation of 19% (95% CI 15–24; p<0·0001), and in ischaemic stroke of 16% (95% CI 5–26; p=0·005). Per 1·0 mmol/L reduction in LDL cholesterol, these further reductions in risk were similar to the proportional reductions in the trials of statin versus control. When both types of trial were combined, similar proportional reductions in major vascular events per 1·0 mmol/L LDL cholesterol reduction were found in all types of patient studied (rate ratio [RR] 0·78, 95% CI 0·76–0·80; p<0·0001), including those with LDL cholesterol lower than 2 mmol/L on the less intensive or control regimen. Across all 26 trials, all-cause mortality was reduced by 10% per 1·0 mmol/L LDL reduction (RR

  7. Increasing amounts of dietary myristic acid modify the plasma cholesterol level and hepatic mass of scavenger receptor BI without affecting bile acid biosynthesis in hamsters.

    PubMed

    Loison, Carole; Mendy, François; Serougne, Colette; Lutton, Claude

    2002-01-01

    The purpose of this study was to analyze the effects of increasing amounts of dietary myristic acid (0.03 to 4.2% of the total dietary energy) on the plasma and hepatic cholesterol metabolism. Six groups of hamsters received semi-purified diets containing 0.05% cholesterol and 12.5% lipids and differing only by the nature of the triglycerides (Safflower oil, lard, lard/coconut oil (1:1), milk fat, milk fat/coconut oil (1:1), coconut oil) for 3 weeks. A positive regression between the plasma cholesterol level and the dietary myristic acid level was observed (r = 0.60, P < 0.0001). However, it is noteworthy that the increase in plasma total cholesterol only reflects an increase in the level of HDL-cholesterol. In parallel, the mass SR-BI decreased linearly with the increased level of myristic acid in the diet, whereas the LDL-R did not change. This study shows that increasing amounts of myristic acid (0.03 to 4.2%) do not alter the cholesterol or bile acid metabolism and increase only the HDL-C. PMID:12216956

  8. The effects of unsaturated dietary fats on absorption, excretion, synthesis, and distribution of cholesterol in man

    PubMed Central

    Grundy, Scott M.; Ahrens, E. H.

    1970-01-01

    Cholesterol balance studies were carried out in 11 patients with various types of hyperlipoproteinemia to determine the mechanism by which unsaturated fats lower plasma cholesterol. Unsaturated fats produced no increase in fecal endogenous neutral steroids in 10 of 11 patients and no decrease in absorption of exogenous cholesterol in 5 patients who received cholesterol in the diet. In 8 of 11 patients no changes occurred in excretion of bile acids during the period on unsaturated fat when plasma cholesterol was declining. However, in 3 of 11 patients small but significant increases in bile acid excretion were found during this transitional period; in 2 others increases also occurred after plasma cholesterol had become constant at lower levels on unsaturated fat. Since the majority of patients showed no change in cholesterol or bile acid excretions during the transitional period, we propose that when excretion changes did occur they were probably not the cause of the plasma cholesterol change. Furthermore, turnover data and specific activity curves suggested that cholesterol synthesis was not influenced by exchange of dietary fats. Thus, excluding changes in excretion and synthesis, we conclude that it is most likely that unsaturated fats cause plasma cholesterol to be redistributed into tissue pools. We have also examined the possibility that cholesterol which is redistributed into tissues could be secondarily excreted as neutral steroids or bile acids. In at least 5 of 11 patients excretion patterns were consistent with this explanation. However, we cannot rule out that excretion changes may have been due to alterations in transit time, to changes in bacterial flora, or to transitory changes in absorption or synthesis of cholesterol or bile acids. Our conclusion that unsaturated fats cause a redistribution of cholesterol between plasma and tissue pools points to the necessity in future to explore where cholesterol is stored, to what extent stored cholesterol can

  9. Decrease in plasma high-density lipoprotein cholesterol levels at puberty in boys with delayed adolescence: correlation with plasma testosterone levels

    SciTech Connect

    Kirkland, R.T.; Keenan, B.S.; Probstfield, J.L.; Patsch, W.; Lin, T.L.; Clayton, G.W.; Insull, W. Jr.

    1987-01-23

    A three-phase study tested the hypothesis that the decrease in the high-density lipoprotein cholesterol (HDL-C) level observed in boys at puberty is related to an increase in the plasma testosterone concentration. In phase I, 57 boys aged 10 to 17 years were categorized into four pubertal stages based on clinical parameters and plasma testosterone levels. These four groups showed increasing plasma testosterone values and decreasing HDL-C levels. In phase II, 14 boys with delayed adolescence were treated with testosterone enanthate. Plasma testosterone levels during therapy were in the adult male range. Levels of HDL-C decreased by a mean of 7.4 mg/dL (0.20 mmol/L) and 13.7 mg/dL (0.35 mmol/L), respectively, after the first two doses. In phase III, 13 boys with delayed adolescence demonstrated increasing plasma testosterone levels and decreasing HDL-C levels during spontaneous puberty. Levels of HDL-C and apolipoprotein A-1 were correlated during induced and spontaneous puberty. Testosterone should be considered a significant determinant of plasma HDL-C levels during pubertal development.

  10. Elevated Basal Insulin Secretion in Type 2 Diabetes Caused by Reduced Plasma Membrane Cholesterol

    PubMed Central

    Nagaraj, Vini; Kazim, Abdulla S.; Helgeson, Johan; Lewold, Clemens; Barik, Satadal; Buda, Pawel; Reinbothe, Thomas M.; Wennmalm, Stefan

    2016-01-01

    Elevated basal insulin secretion under fasting conditions together with insufficient stimulated insulin release is an important hallmark of type 2 diabetes, but the mechanisms controlling basal insulin secretion remain unclear. Membrane rafts exist in pancreatic islet cells and spatially organize membrane ion channels and proteins controlling exocytosis, which may contribute to the regulation of insulin secretion. Membrane rafts (cholesterol and sphingolipid containing microdomains) were dramatically reduced in human type 2 diabetic and diabetic Goto-Kakizaki (GK) rat islets when compared with healthy islets. Oxidation of membrane cholesterol markedly reduced microdomain staining intensity in healthy human islets, but was without effect in type 2 diabetic islets. Intriguingly, oxidation of cholesterol affected glucose-stimulated insulin secretion only modestly, whereas basal insulin release was elevated. This was accompanied by increased intracellular Ca2+ spike frequency and Ca2+ influx and explained by enhanced single Ca2+ channel activity. These results suggest that the reduced presence of membrane rafts could contribute to the elevated basal insulin secretion seen in type 2 diabetes. PMID:27533789

  11. Preliminary probiotic and technological characterization of Pediococcus pentosaceus strain KID7 and in vivo assessment of its cholesterol-lowering activity.

    PubMed

    Damodharan, Karthiyaini; Lee, Young Sil; Palaniyandi, Sasikumar A; Yang, Seung Hwan; Suh, Joo-Won

    2015-01-01

    The study was aimed to characterize the probiotic properties of a Pediococcus pentosaceus strain, KID7, by in vitro and in vivo studies. The strain possessed tolerance to oro-gastrointestinal transit, adherence to the Caco-2 cell line, and antimicrobial activity. KID7 exhibited bile salt hydrolase activity and cholesterol-lowering activity, in vitro. In vivo cholesterol-lowering activity of KID7 was studied using atherogenic diet-fed hypercholesterolemic mice. The experimental animals (C57BL/6J mice) were divided into 4 groups viz., normal diet-fed group (NCD), atherogenic diet-fed group (HCD), atherogenic diet- and KID7-fed group (HCD-KID7), and atherogenic diet- and Lactobacillus acidophilus ATCC 43121-fed group (HCD-L.ac) as positive control. Serum total cholesterol (T-CHO) level was significantly decreased by 19.8% in the HCD-KID7 group (P < 0.05), but not in the HCD-L.ac group compared with the HCD group. LDL cholesterol levels in both HCD-KID7 and HCD-L.ac groups were decreased by 35.5 and 38.7%, respectively, compared with HCD group (both, P < 0.05). Glutamyl pyruvic transaminase (GPT) level was significantly lower in the HCD-KID7 and HCD-L.ac groups compared to HCD group and was equivalent to that of the NCD group. Liver T-CHO levels in the HCD-KID7 group were reduced significantly compared with the HCD group (P < 0.05) but not in the HCD-L.ac group. Analysis of expression of genes associated with lipid metabolism in liver showed that low-density lipoprotein receptor (LDLR), cholesterol-7α-hydroxylase (CYP7A1) and apolipoprotein E (APOE) mRNA expression was significantly increase in the HCD-KID7 group compared to the HCD group. Furthermore, KID7 exhibited desired viability under freeze-drying and subsequent storage conditions with a combination of skim milk and galactomannan. P. pentosaceus KID7 could be a potential probiotic strain, which can be used to develop cholesterol-lowering functional food after appropriate human clinical trials. PMID:26300852

  12. Preliminary probiotic and technological characterization of Pediococcus pentosaceus strain KID7 and in vivo assessment of its cholesterol-lowering activity

    PubMed Central

    Damodharan, Karthiyaini; Lee, Young Sil; Palaniyandi, Sasikumar A.; Yang, Seung Hwan; Suh, Joo-Won

    2015-01-01

    The study was aimed to characterize the probiotic properties of a Pediococcus pentosaceus strain, KID7, by in vitro and in vivo studies. The strain possessed tolerance to oro-gastrointestinal transit, adherence to the Caco-2 cell line, and antimicrobial activity. KID7 exhibited bile salt hydrolase activity and cholesterol-lowering activity, in vitro. In vivo cholesterol-lowering activity of KID7 was studied using atherogenic diet-fed hypercholesterolemic mice. The experimental animals (C57BL/6J mice) were divided into 4 groups viz., normal diet-fed group (NCD), atherogenic diet-fed group (HCD), atherogenic diet- and KID7-fed group (HCD-KID7), and atherogenic diet- and Lactobacillus acidophilus ATCC 43121-fed group (HCD-L.ac) as positive control. Serum total cholesterol (T-CHO) level was significantly decreased by 19.8% in the HCD-KID7 group (P < 0.05), but not in the HCD-L.ac group compared with the HCD group. LDL cholesterol levels in both HCD-KID7 and HCD-L.ac groups were decreased by 35.5 and 38.7%, respectively, compared with HCD group (both, P < 0.05). Glutamyl pyruvic transaminase (GPT) level was significantly lower in the HCD-KID7 and HCD-L.ac groups compared to HCD group and was equivalent to that of the NCD group. Liver T-CHO levels in the HCD-KID7 group were reduced significantly compared with the HCD group (P < 0.05) but not in the HCD-L.ac group. Analysis of expression of genes associated with lipid metabolism in liver showed that low-density lipoprotein receptor (LDLR), cholesterol-7α-hydroxylase (CYP7A1) and apolipoprotein E (APOE) mRNA expression was significantly increase in the HCD-KID7 group compared to the HCD group. Furthermore, KID7 exhibited desired viability under freeze-drying and subsequent storage conditions with a combination of skim milk and galactomannan. P. pentosaceus KID7 could be a potential probiotic strain, which can be used to develop cholesterol-lowering functional food after appropriate human clinical trials. PMID:26300852

  13. What's Cholesterol?

    MedlinePlus

    ... Most cholesterol is LDL (low-density lipoprotein) cholesterol. LDL cholesterol is more likely to clog blood vessels because ... Here's a way to remember the difference: the LDL cholesterol is the bad kind, so call it "lousy" ...

  14. The expansion of a collisionless plasma into a plasma of lower density

    SciTech Connect

    Perego, M.; Gunzburger, M. D.; Howell, P. D.; Ockendon, J. R.; Allen, J. E.

    2013-05-15

    This paper considers the asymptotic and numerical solution of a simple model for the expansion of a collisionless plasma into a plasma of lower density. The dependence on the density ratio of qualitative and quantitative features of solutions of the well-known cold-ion model is explored. In the cold-ion limit, we find that a singularity develops in the ion density in finite time unless the density ratio is zero or close to unity. The classical cold-ion model may cease to be valid when such a singularity occurs and we then regularize the model by the finite ion-temperature Vlasov-Poisson system. Numerical evidence suggests the emergence of a multi-modal velocity distribution.

  15. MLL Histone Methylases Regulate Expression of HDLR-SR-B1 in Presence of Estrogen and Control Plasma Cholesterol in Vivo

    PubMed Central

    Ansari, Khairul I.; Kasiri, Sahba; Hussain, Imran; Bobzean, Samara A. Morris; Perrotti, Linda I.

    2013-01-01

    High-density lipoprotein receptors scavenger receptor class B type I [HDLR-SR-B1 (SR-B1)] is a key player in reverse cholesterol transport and maintaining blood cholesterol. We demonstrated that human SR-B1 is transcriptionally activated by 17β-estradiol (E2) in HEPG2 and JAR cells. SR-B1 promoter contains multiple estrogen response elements (ERE half-sites) along with some Sp1 binding sites. Knockdown of estrogen receptor (ER)α and ERβ down-regulated E2-induced SR-B1 expression. ERs were bound to SR-B1 promoter EREs in an E2-dependent manner. Along with ERs, mixed-lineage leukemia (MLL) histone methylases, especially MLL1 and MLL2, play key roles in E2-mediated SR-B1 activation. MLL1 and MLL2 bind to SR-B1 promoter in an E2-dependent manner and control the assembly of transcription pre-initiation complex and RNA polymerase II (RNAPII) recruitment. ERs and MLLs play critical roles in determining the cholesterol uptake by steroidogenic tissues/cells, and their knockdown suppressed the E2-induced cholesterol uptake efficiencies of the cells. Intriguingly, MLL2 knockdown in mice resulted in a 33% increase in plasma cholesterol level and also reduced SR-B1 expression in mice liver, demonstrating its crucial functions in controlling plasma cholesterol in vivo. PMID:23192982

  16. Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

    PubMed Central

    Motoyama, Keiichi; Hirai, Yumi; Nishiyama, Rena; Maeda, Yuki; Higashi, Taishi; Ishitsuka, Yoichi; Kondo, Yuki; Irie, Tetsumi; Era, Takumi

    2015-01-01

    Summary The Niemann–Pick type C disease (NPC) is one of inherited lysosomal storage disorders, emerges the accumulation of unesterified cholesterol in endolysosomes. Currently, 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) has been applied for the treatment of NPC. HP-β-CyD improved hepatosplenomegaly in NPC patients, however, a high dose of HP-β-CyD was necessary. Therefore, the decrease in dose by actively targeted-β-CyD to hepatocytes is expected. In the present study, to deliver β-CyD selectively to hepatocytes, we newly fabricated mono-lactose-appended β-CyD (Lac-β-CyD) and evaluated its cholesterol lowering effects in NPC-like HepG2 cells, cholesterol accumulated HepG2 cells induced by treatment with U18666A. Lac-β-CyD (degree of substitution of lactose (DSL) 1) significantly decreased the intracellular cholesterol content in a concentration-dependent manner. TRITC-Lac-β-CyD was associated with NPC-like HepG2 cells higher than TRITC-β-CyD. In addition, TRITC-Lac-β-CyD was partially localized with endolysosomes after endocytosis. Thus, Lac-β-CyD entered NPC-like HepG2 cells via asialoglycoprotein receptor (ASGPR)-mediated endocytosis and decreased the accumulation of intracellular cholesterol in NPC-like HepG2 cells. These results suggest that Lac-β-CyD may have the potential as a drug for the treatment of hepatosplenomegaly in NPC disease. PMID:26664628

  17. In vitro hypoglycemic and cholesterol lowering effects of dietary fiber prepared from cocoa (Theobroma cacao L.) shells.

    PubMed

    Nsor-Atindana, John; Zhong, Fang; Mothibe, Kebitsamang Joseph

    2012-10-01

    Three dietary fiber (DF) powders; soluble dietary fiber (SDF), insoluble dietary fiber (IDF) and total dietary fiber (TDF) were prepared from cocoa bean shells (CBS) by enzymatic treatment. These DFs were evaluated for their effects on glucose adsorption, glucose diffusion, starch hydrolysis, cholesterol binding, sodium cholate binding and oil binding capacities using in vitro model systems by simulating gastric intestinal conditions. The results showed that SDF generally exhibited significantly (p < 0.05) higher glucose adsorption capacity (GAC), α-amylase inhibition activity, cholesterol and sodium cholate binding capacity, but less significant (>0.05) glucose dialysis retardation index (GDRI) and oil binding capacity, when compared with IDF and TDF which both showed similar effects. Moreover, it was discovered that the three CBS dietary fiber powders contained intrinsic antioxidants (phenolic compounds). The study suggested that CBS could be an alternative cheap source of DF with additional benefits. Thus, CBS fibers could be incorporated as low calorie bulk ingredients in high-fiber diet to reduce calorie and cholesterol levels and control blood glucose level.

  18. Triglycerides, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol in rats exposed to premium motor spirit fumes

    PubMed Central

    Aberare, Ogbevire L.; Okuonghae, Patrick; Mukoro, Nathaniel; Dirisu, John O.; Osazuwa, Favour; Odigie, Elvis; Omoregie, Richard

    2011-01-01

    Background: Deliberate and regular exposure to premium motor spirit fumes is common and could be a risk factor for liver disease in those who are occupationally exposed. A possible association between premium motor spirit fumes and plasma levels of triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol using a rodent model could provide new insights in the pathology of diseases where cellular dysfunction is an established risk factor. Aim: The aim of this study was to evaluate the possible effect of premium motor spirit fumes on lipids and lipoproteins in workers occupationally exposed to premium motor spirit fumes using rodent model. Materials and Methods: Twenty-five Wister albino rats (of both sexes) were used for this study between the 4th of August and 7th of September, 2010. The rats were divided into five groups of five rats each. Group 1 rats were not exposed to premium motor spirit fumes (control group), group 2 rats were exposed for 1 hour daily, group 3 for 3 hours daily, group 4 for 5 hours daily and group 5 for 7 hours daily. The experiment lasted for a period of 4 weeks. Blood samples obtained from all the groups after 4 weeks of exposure were used for the estimation of plasma levels of triglyceride, total cholesterol, high density lipoprotein- cholesterol and low density lipoprotein- cholesterol. Result: Results showed significant increase in means of plasma total cholesterol and low density lipoprotein levels (P<0.05). The mean triglyceride and total body weight were significantly lower (P<0.05) in the exposed group when compared with the unexposed. The plasma level of high density lipoprotein, the ratio of low density lipoprotein to high density lipoprotein and the ratio of total cholesterol to high density lipoprotein did not differ significantly in exposed subjects when compared with the control group. Conclusion: These results showed that frequent exposure to petrol fumes may be highly

  19. LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies.

    PubMed

    Ras, Rouyanne T; Geleijnse, Johanna M; Trautwein, Elke A

    2014-07-28

    Phytosterols (PS, comprising plant sterols and plant stanols) have been proven to lower LDL-cholesterol concentrations. The dose-response relationship for this effect has been evaluated in several meta-analyses by calculating averages for different dose ranges or by applying continuous dose-response functions. Both approaches have advantages and disadvantages. So far, the calculation of averages for different dose ranges has not been done for plant sterols and stanols separately. The objective of the present meta-analysis was to investigate the combined and separate effects of plant sterols and stanols when classified into different dose ranges. Studies were searched and selected based on predefined criteria. Relevant data were extracted. Average LDL-cholesterol effects were calculated when studies were categorised by dose, according to random-effects models while using the variance as weighing factor. This was done for plant sterols and stanols combined and separately. In total, 124 studies (201 strata) were included. Plant sterols and stanols were administered in 129 and fifty-nine strata, respectively; the remaining used a mix of both. The average PS dose was 2.1 (range 0.2-9.0) g/d. PS intakes of 0.6-3.3 g/d were found to gradually reduce LDL-cholesterol concentrations by, on average, 6-12%. When plant sterols and stanols were analysed separately, clear and comparable dose-response relationships were observed. Studies carried out with PS doses exceeding 4 g/d were not pooled, as these were scarce and scattered across a wide range of doses. In conclusion, the LDL-cholesterol-lowering effect of both plant sterols and stanols continues to increase up to intakes of approximately 3 g/d to an average effect of 12%.

  20. A diet rich in leafy vegetable fiber improves cholesterol metabolism in high-cholesterol fed rats.

    PubMed

    Ezz El-Arab, A M

    2009-10-01

    In the present study, the hypocholesterolemic effect of leaf vegetable (Jew's mallow) was studied in high-cholesterol fed rats. The animals were fed diets supplemented with cholesterol (0.25%) for 4 weeks. Leaf vegetable diet produced an important hypocholesterolemic action: it led to a significant lowering (p<0.05) of cholesterol in the plasma and liver, as well as of the atherogenic index and a significant increase (p<0.05) in cecal short chain fatty acids, with respect to the control group. Concurrently, total fecal neutral sterols in the excretion increased (p<0.05) and apparent absorption of dietary cholesterol was significantly depressed (-58%). The consumption of leaf vegetable (Jew's mallow) with a hypercholesterolemic diet improved the lipidemic profile and increased excretion of the total cholesterol end-products. PMID:20387744

  1. A diet rich in leafy vegetable fiber improves cholesterol metabolism in high-cholesterol fed rats.

    PubMed

    Ezz El-Arab, A M

    2009-10-01

    In the present study, the hypocholesterolemic effect of leaf vegetable (Jew's mallow) was studied in high-cholesterol fed rats. The animals were fed diets supplemented with cholesterol (0.25%) for 4 weeks. Leaf vegetable diet produced an important hypocholesterolemic action: it led to a significant lowering (p<0.05) of cholesterol in the plasma and liver, as well as of the atherogenic index and a significant increase (p<0.05) in cecal short chain fatty acids, with respect to the control group. Concurrently, total fecal neutral sterols in the excretion increased (p<0.05) and apparent absorption of dietary cholesterol was significantly depressed (-58%). The consumption of leaf vegetable (Jew's mallow) with a hypercholesterolemic diet improved the lipidemic profile and increased excretion of the total cholesterol end-products.

  2. A randomized crossover study to evaluate LDL-cholesterol lowering effect of a generic product of simvastatin (Unison Company) compared to simvastatin (Zocor) in hypercholesterolemic subjects.

    PubMed

    Assawawitoontip, Surin; Wiwanitkit, Viroj

    2002-06-01

    It is agreed that people with a high blood LDL-cholesterol level will have a higher risk of coronary heart disease (CAD) than those with low blood LDL-cholesterol level. Because of the present National Drug Strategy of Thailand, the promotion of "in-country production" of a generic drug has been established. Simvastatin is one of the drugs in this strategy. In this, the primary report of a randomized crossover study with washout period for a cholesterol lowering effect in a generic product of simvastatin (Unison company) which was compared to the original simvastatin (Zocor) hypercholesterolemic to the subjects were presented. Simvastatin used in this study were derived from two sources. The first group was the original product (Zocor), dosage 10 mg, Lot No IC4/36(N) from Merck Sharp & Dohme Company and the second group was a generic product, dosage 10 mg, Lot No T05/080 and T06/109 from Unison Company. All simvastatin tablets from the first and second sources were inserted into closed capsule of the same shape and called drug A and drug B, respectively. Both the physician in-charge and the subjects in this study were blinded for the content inside the capsule (Double blind). Thirty drug capsules were put into a sachet and distributed to the subject at each visit. The interval between each visit was 4 weeks. All subjects were asked to bring back the residual capsule within the sachet to the researcher at each visit in order to evaluate the subject's compliance. All subjects had physical examination and blood tests at each visit. Furthermore, all subjects were advised to practice diet control and regular in-take of the drug capsule daily after their evening meal. All 48 subjects were randomly allocated into 2 groups. This study was run as a randomized crossover study. After taking the drugs for the first 8 weeks, no statistically significant difference of blood LDL-cholesterol between the first and second group was detected. After a 4 week washout period, crossover

  3. Lipid Lowering Effects of Hydroalcoholic Extract of Anethum graveolens L. and Dill Tablet in High Cholesterol Fed Hamsters.

    PubMed

    Abbasi Oshaghi, Ebrahim; Khodadadi, Iraj; Saidijam, Massoud; Yadegarazari, Reza; Shabab, Nooshin; Tavilani, Heidar; Goodarzi, Mohamad Taghi

    2015-01-01

    Objective. This study was aimed to determine the effect of Anethum graveolens extract and Anethum graveolens (dill) tablet on lipid profile, liver enzymes, and gene expression and enzymatic activity of HMG-CoA reductase in high cholesterol fed hamsters. Materials and Methods. Golden Syrian male hamsters (130 ± 10 g) were randomly divided into 6 groups (n = 6) and received daily the following: group 1 received chow + 2% cholesterol + 0.5% cholic acid (HCD), groups 2 and 3 received HCD diet plus 100 and 200 mg/kg hydroalcoholic extract of dill, respectively, and groups 4 and 5 received HCD diet plus 100 and 200 mg/kg dill tablet, respectively. Group 6 received only chow. After 1 month feeding serum biochemical factors were determined. HMG-CoA reductase mRNA level was measured (real-time PCR) and its activity was determined spectrophotometrically. Results. Compared with hypercholesterolemic group 1, lipid profile, blood glucose, and liver enzymes significantly decreased in all dill tablet or dill extract treated groups (p < 0.05). The changes in HMG-CoA reductase gene expression level and enzyme activity significantly reduced in animals that received 200 mg/kg of extract or tablet. Conclusion. Dill extract and dill tablet showed potential hypocholesterolemic properties in hamsters by inhibition of HMG-CoA reductase activity. PMID:26823981

  4. Molecular mechanisms of protein-cholesterol interactions in plasma membranes: Functional distinction between topological (tilted) and consensus (CARC/CRAC) domains.

    PubMed

    Fantini, Jacques; Di Scala, Coralie; Baier, Carlos J; Barrantes, Francisco J

    2016-09-01

    The molecular mechanisms that control the multiple possible modes of protein association with membrane cholesterol are remarkably convergent. These mechanisms, which include hydrogen bonding, CH-π stacking and dispersion forces, are used by a wide variety of extracellular proteins (e.g. microbial or amyloid) and membrane receptors. Virus fusion peptides penetrate the membrane of host cells with a tilted orientation that is compatible with a transient interaction with cholesterol; this tilted orientation is also characteristic of the process of insertion of amyloid proteins that subsequently form oligomeric pores in the plasma membrane of brain cells. Membrane receptors that are associated with cholesterol generally display linear consensus binding motifs (CARC and CRAC) characterized by a triad of basic (Lys/Arg), aromatic (Tyr/phe) and aliphatic (Leu/Val) amino acid residues. In some cases, the presence of both CARC and CRAC within the same membrane-spanning domain allows the simultaneous binding of two cholesterol molecules, one in each membrane leaflet. In this review the molecular basis and the functional significance of the different modes of protein-cholesterol interactions in plasma membranes are discussed.

  5. Oral green tea catechins transiently lower plasma glucose concentrations in female db/db mice.

    PubMed

    Wein, Silvia; Schrader, Eva; Rimbach, Gerald; Wolffram, Siegfried

    2013-04-01

    Polyphenols, including green tea catechins, are secondary plant compounds often discussed in the context of health-promoting potential. Evidence for such effects is mainly derived from epidemiological and cell culture studies. The aim of the present study was to investigate antidiabetic, antiadipogenic, and anti-inflammatory effects at nonpharmacological doses in an obese diabetic mouse model that exerts early relevant clinical signs of non-insulin-dependent diabetes mellitus. Female db/db mice received a flavonoid-poor diet either without additive, with rosiglitazone (RSG, 0.02 g/kg diet), or with green tea extract (low-dose green tea extract [LGTE] and high-dose green tea extract [HGTE], 0.1 and 1 g/kg diet). Food and water were freely available. The body weight was monitored weekly. Blood was sampled (12-h fasted) from the tail vein on day 28 and analyzed for glucose, cholesterol, triacylglycerol, nonesterified fatty acids, insulin, adiponectin, and soluble intercellular adhesion molecule-1 (sICAM-1). Blood glucose was also analyzed on day 14. Furthermore, sICAM-1 release was investigated in tumor necrosis factor alpha-stimulated EAhy926 cells. After 14 days, fasting glycemia was improved by RSG or HGTE supplementation compared to controls. However, at the end of the study (day 28), only RSG exhibited glucose-lowering effects and induced plasma adiponectin concentrations, paralleled by higher body weight gain and reduced periuterine fat pads compared to controls. However, only GTE treatment reduced sICAM-1 release in vitro and in vivo. Nonpharmacological HGTE supplementation in db/db mice caused (1) no adiponectin-inducing or antiadipogenic effects, (2) reduced sICAM-1 release, thereby potentially exerting anti-inflammatory effects in the progressive diabetic state, and (3) a transient improvement in glycemia.

  6. Oral green tea catechins transiently lower plasma glucose concentrations in female db/db mice.

    PubMed

    Wein, Silvia; Schrader, Eva; Rimbach, Gerald; Wolffram, Siegfried

    2013-04-01

    Polyphenols, including green tea catechins, are secondary plant compounds often discussed in the context of health-promoting potential. Evidence for such effects is mainly derived from epidemiological and cell culture studies. The aim of the present study was to investigate antidiabetic, antiadipogenic, and anti-inflammatory effects at nonpharmacological doses in an obese diabetic mouse model that exerts early relevant clinical signs of non-insulin-dependent diabetes mellitus. Female db/db mice received a flavonoid-poor diet either without additive, with rosiglitazone (RSG, 0.02 g/kg diet), or with green tea extract (low-dose green tea extract [LGTE] and high-dose green tea extract [HGTE], 0.1 and 1 g/kg diet). Food and water were freely available. The body weight was monitored weekly. Blood was sampled (12-h fasted) from the tail vein on day 28 and analyzed for glucose, cholesterol, triacylglycerol, nonesterified fatty acids, insulin, adiponectin, and soluble intercellular adhesion molecule-1 (sICAM-1). Blood glucose was also analyzed on day 14. Furthermore, sICAM-1 release was investigated in tumor necrosis factor alpha-stimulated EAhy926 cells. After 14 days, fasting glycemia was improved by RSG or HGTE supplementation compared to controls. However, at the end of the study (day 28), only RSG exhibited glucose-lowering effects and induced plasma adiponectin concentrations, paralleled by higher body weight gain and reduced periuterine fat pads compared to controls. However, only GTE treatment reduced sICAM-1 release in vitro and in vivo. Nonpharmacological HGTE supplementation in db/db mice caused (1) no adiponectin-inducing or antiadipogenic effects, (2) reduced sICAM-1 release, thereby potentially exerting anti-inflammatory effects in the progressive diabetic state, and (3) a transient improvement in glycemia. PMID:23514230

  7. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12 064 survivors of myocardial infarction: a double-blind randomised trial

    PubMed Central

    Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group

    2010-01-01

    Summary Background Lowering of LDL cholesterol reduces major vascular events, but whether more intensive therapy safely produces extra benefits is uncertain. We aimed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk. Methods We undertook a double-blind randomised trial in 12 064 men and women aged 18–80 years with a history of myocardial infarction. Participants were either currently on or had clear indication for statin therapy, and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4·5 mmol/L if not. Randomisation to either 80 mg or 20 mg simvastatin daily was done centrally using a minimisation algorithm. Participants were assessed at 2, 4, 8, and 12 months after randomisation and then every 6 months until final follow-up. The primary endpoint was major vascular events, defined as coronary death, myocardial infarction, stroke, or arterial revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN74348595. Findings 6031 participants were allocated 80 mg simvastatin daily, and 6033 allocated 20 mg simvastatin daily. During a mean follow-up of 6·7 (SD 1·5) years, allocation to 80 mg simvastatin produced an average 0·35 (SE 0·01) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg. Major vascular events occurred in 1477 (24·5%) participants allocated 80 mg simvastatin versus 1553 (25·7%) of those allocated 20 mg, corresponding to a 6% proportional reduction (risk ratio 0·94, 95% CI 0·88–1·01; p=0·10). There were no apparent differences in numbers of haemorrhagic strokes (24 [0·4%] vs 25 [0·4%]) or deaths attributed to vascular (565 [9·4%] vs 572 [9·5%]) or non-vascular (399 [6·6%] vs 398 [6·6%]) causes. Compared with two (0·03%) cases of myopathy in patients taking 20 mg simvastatin daily, there were 53 (0·9%) cases in the 80 mg group. Interpretation The 6% (SE 3·5%) reduction in major

  8. High Cholesterol: Cholesterol-Lowering Medicines

    MedlinePlus

    ... is called a "drug-drug interaction." Vitamins and herbal supplements can also affect the way your body processes ... over-the-counter and prescription medicines, vitamins and herbal supplements that you are taking. Also, talk to your ...

  9. The ATF6-Met[67]Val substitution is associated with increased plasma cholesterol levels

    PubMed Central

    Meex, Steven J.R.; Weissglas-Volkov, Daphna; van der Kallen, Carla J.H.; Thuerauf, Donna J.; van Greevenbroek, Marleen M.J.; Schalkwijk, Casper G.; Stehouwer, Coen D.A.; Feskens, Edith J.M.; Heldens, Lonneke; Ayoubi, Torik A.; Hofker, Marten H.; Wouters, Bradly G.; Vlietinck, Robert; Sinsheimer, Janet S.; Taskinen, Marja-Riitta; Kuusisto, Johanna; Laakso, Markku; de Bruin, Tjerk W.A.; Pajukanta, Päivi; Glembotski, Christopher C.

    2009-01-01

    Objective Activating Transcription Factor 6 (ATF6) is a sensor of the endoplasmic reticulum stress response and regulates expression of several key lipogenic genes. We utilized a two-stage design to investigate whether ATF6 polymorphisms are associated with lipids in subjects at increased risk for cardiovascular disease (CVD). Methods and Results In stage 1, 13 tag-SNPs were tested for association in Dutch samples ascertained for Familial Combined Hyperlipidemia (FCHL) or increased risk for CVD (CVR). In stage 2, we further investigated the SNP with the strongest association from stage 1, a Methionine/Valine substitution at amino-acid 67, in Finnish FCHL families and in subjects with CVR from METSIM, a Finnish population-based cohort. The combined analysis of both stages reached region-wide significance (P=9×10−4), but this association was not seen in the entire METSIM cohort. Our functional analysis demonstrated that Valine at position 67 augments ATF6 protein and its targets Grp78 and Grp94 as well as increases luciferase expression through Grp78 promoter. Conclusions A common nonsynonymous variant in ATF6 increases ATF6 protein levels and is associated with cholesterol levels in subjects at increased risk for CVD, but this association was not seen in a population-based cohort. Further replication is needed to confirm this variant's role in lipids. PMID:19667116

  10. Identification of four novel genes contributing to familial elevated plasma HDL cholesterol in humans.

    PubMed

    Singaraja, Roshni R; Tietjen, Ian; Hovingh, G Kees; Franchini, Patrick L; Radomski, Chris; Wong, Kenny; vanHeek, Margaret; Stylianou, Ioannis M; Lin, Linus; Wang, Liangsu; Mitnaul, Lyndon; Hubbard, Brian; Winther, Michael; Mattice, Maryanne; Legendre, Annick; Sherrington, Robin; Kastelein, John J; Akinsanya, Karen; Plump, Andrew; Hayden, Michael R

    2014-08-01

    While genetic determinants strongly influence HDL cholesterol (HDLc) levels, most genetic causes underlying variation in HDLc remain unknown. We aimed to identify novel rare mutations with large effects in candidate genes contributing to extreme HDLc in humans, utilizing family-based Mendelian genetics. We performed next-generation sequencing of 456 candidate HDLc-regulating genes in 200 unrelated probands with extremely low (≤10th percentile) or high (≥90th percentile) HDLc. Probands were excluded if known mutations existed in the established HDLc-regulating genes ABCA1, APOA1, LCAT, cholesteryl ester transfer protein (CETP), endothelial lipase (LIPG), and UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 2 (GALNT2). We identified 93 novel coding or splice-site variants in 72 candidate genes. Each variant was genotyped in the proband's family. Family-based association analyses were performed for variants with sufficient power to detect significance at P < 0.05 with a total of 627 family members being assessed. Mutations in the genes glucokinase regulatory protein (GCKR), RNase L (RNASEL), leukocyte immunoglobulin-like receptor 3 (LILRA3), and dynein axonemal heavy chain 10 (DNAH10) segregated with elevated HDLc levels in families, while no mutations associated with low HDLc. Taken together, we have identified mutations in four novel genes that may play a role in regulating HDLc levels in humans. PMID:24891332

  11. About Cholesterol

    MedlinePlus

    ... High Blood Pressure Tools & Resources Stroke More About Cholesterol Updated:Aug 10,2016 It may surprise you ... our bodies to keep us healthy. What is cholesterol and where does it come from? Cholesterol is ...

  12. Heterogeneity of cholesterol homeostasis in man. Response to changes in dietary fat quality and cholesterol quantity.

    PubMed Central

    McNamara, D J; Kolb, R; Parker, T S; Batwin, H; Samuel, P; Brown, C D; Ahrens, E H

    1987-01-01

    Studies were carried out to examine the effects of dietary fat and cholesterol on cholesterol homeostasis in man. 75 12-wk studies were carried out during intake of 35% of calories as either saturated or polyunsaturated fat, first low and then high in dietary cholesterol. Dietary fat and cholesterol intakes, plasma lipid and lipoprotein levels, cholesterol absorption and sterol synthesis in isolated blood mononuclear leukocytes were measured during each diet period. In 69% of the studies the subjects compensated for the increased cholesterol intake by decreasing cholesterol fractional absorption and/or endogenous cholesterol synthesis. When an increase in plasma cholesterol levels was observed there was a failure to suppress endogenous cholesterol synthesis. Plasma cholesterol levels were more sensitive to dietary fat quality than to cholesterol quantity. The results demonstrate that the responses to dietary cholesterol and fat are highly individualized and that most individuals have effective feedback control mechanisms. PMID:3584466

  13. The mouse CCR2 gene is regulated by two promoters that are responsive to plasma cholesterol and peroxisome proliferator-activated receptor {gamma} ligands

    SciTech Connect

    Chen Yiming; Green, Simone R.; Ho, Jessica; Li, Andrew; Almazan, Felizidad; Quehenberger, Oswald . E-mail: oquehenberger@ucsd.edu

    2005-06-24

    We have previously shown that the expression of monocyte CCR2, the receptor for monocyte chemoattractant protein-1, is induced by plasma cholesterol. The present study examines the mechanisms that regulate monocyte CCR2 expression in hypercholesterolemia using a mouse model. Our data demonstrate that in the mouse, CCR2 expression in circulating monocytes is controlled by two promoters P1 and P2. The two distinct transcripts, which encode the same protein, are produced by alternative splicing in the 5'-untranslated region. Both promoters are constitutively active, but only P2 is stimulated by cholesterol. However, both promoters are repressed by peroxisome proliferator-activated receptor {gamma}.

  14. A high-cholesterol, n-3 polyunsaturated fatty acid diet causes different responses in rats and hamsters.

    PubMed

    Lin, Mei-Huei; Lu, Shao-Chun; Huang, Po-Chao; Liu, Young-Chau; Liu, Shyun-Yeu

    2005-01-01

    This study was designed to investigate the response to a high-cholesterol, n-3 polyunsaturated fatty acid (PUFA) or n-6 PUFA diet in rats and hamsters. Animals were fed n-3 or n-6 PUFA with a cholesterol-free diet, or with a diet enriched with cholesterol (0.5%, w/w) for 2 weeks. In rats and hamsters fed a cholesterol-free diet, plasma cholesterol, triglycerides and very-low-density lipoprotein (VLDL)-triglyceride levels in n-3 PUFA group were significantly lower than those in n-6 PUFA group. In contrast, when diets were supplemented with 0.5% cholesterol, the plasma cholesterol- and triglyceride-lowering effect of dietary n-3 PUFA disappeared. In hamsters fed with the atherogenic diet (0.5% dietary cholesterol) for 2 weeks, n-3 PUFA induced hypercholesterolemia more than n-6 PUFA, the increase being in the VLDL and low-density lipoprotein (LDL) fractions. Our data thus indicate that elevation of VLDL- and LDL-cholesterol in hamsters by n-3 PUFA, compared with n-6 PUFA, is dependent on 0.5% dietary cholesterol supplementation. In rats, on the other hand, dietary n-3 PUFA did not induce hypercholesterolemia more than n-6 PUFA when 0.5% cholesterol was supplemented. Although the effects of n-3 PUFA on plasma cholesterol, triglycerides and VLDL-triglycerides were similar in hamsters and rats, the interactive effects of n-3 PUFA and cholesterol on plasma and lipoprotein cholesterol levels differed in the two species. It was also found that plasma triglycerides, cholesterol and lipoprotein cholesterol levels in hamsters are higher than in rats in the presence and absence of dietary cholesterol. In addition, cholesterol feeding induces hypertriglyceridemia and hypercholesterolemia only in hamsters. Moreover, liver triglyceride concentrations increased in rats fed a cholesterol-rich diet and hepatic triglyceride levels of the n-3 PUFA-fed rats were significantly lower than those in the n-6 PUFA-fed rats in the presence and absence of dietary cholesterol. However

  15. Plasma triacylglycerol and HDL cholesterol concentrations confirm self-reported changes in carbohydrate and fat intakes in women in a diet intervention trial.

    PubMed

    Rock, Cheryl L; Flatt, Shirley W; Thomson, Cynthia A; Stefanick, Marcia L; Newman, Vicky A; Jones, Lovell; Natarajan, Loki; Pierce, John P; Chang, R Jeffrey; Witztum, Joseph L

    2004-02-01

    Diet intervention trials are currently testing whether reduced fat intake can reduce the risk and progression of breast cancer. Energy from dietary fat is generally replaced by energy from carbohydrate in these studies, and altering the proportion of energy from dietary carbohydrate and fat has been shown to affect plasma lipid concentrations in controlled feeding studies. The purpose of this study was to examine the effect of increased carbohydrate and reduced fat intakes on plasma lipids in a randomized, controlled trial that is testing the effect of diet modification on risk for recurrence and survival in women previously treated for breast cancer. Plasma concentrations of lipids and related factors were measured at enrollment and 1-y follow-up in 393 women enrolled in the trial. Dietary goals for the intervention group focused on an increase in vegetable, fruit and fiber intakes, and reduced fat intake. Women assigned to the intervention group significantly reduced fat intake (from 28.1 to 21.0% of energy), and significantly increased intakes of carbohydrate (from 56.9 to 65.3% of energy) and fiber (from 21.0 to 29.6 g/d) (P < 0.05). Body weight did not change significantly in either study group. A small but significant increase in fasting plasma triacylglycerol concentration, and decreases in HDL cholesterol and apoprotein-A1 concentrations, were observed in the intervention group (P < 0.05) but not in the comparison group. Changes in total cholesterol, LDL cholesterol, apoprotein-B, lipoprotein (a), and insulin concentrations, and in the LDL cholesterol/HDL cholesterol ratio, were not observed in either group. The lipid responses that were observed in this study provide biological evidence that validates the self-reported change in dietary intakes of fat and carbohydrate in response to the intervention efforts. The degree of change in these lipid concentrations was small and does not suggest increased cardiovascular disease risk.

  16. Association between periodontal disease and plasma levels of cholesterol and triglycerides

    PubMed Central

    Lafaurie, Gloria Inés; Millán, Lina Viviana; Ardila, Carlos Martin; Duque, Andrés; Novoa, Camilo; López, Diego; Contreras, Adolfo

    2013-01-01

    Objective: untreated periodontal disease seems to cause low grade systemic inflammation and blood lipid alteration leading to increased cardiovascular disease risk. To start testing this hypothesis in colombian patients, a multicentre study was conducted including the three main state capitals: bogota, medellin and cali. Methods: in this study 192 (28.4%) advanced and 256 (37.8%) moderate periodontitis patients were investigated for socio-demographic variables, city of precedence, periodontal parameters, smoking, red complex periodontopathic bacteria, serum antibodies against porphyromonas gingivalis and aggregatibacter actinomycetemcomitans and blood lipids including total cholesterol, hdl, ldl and triglycerides (tg). Those parameters were compared to 229 (33.8%) controls having periodontal health or gingivitis. Results: advanced periodontitis had worst periodontal indexes, than moderate periodontitis and controls. Interestingly, higher hdl and tg levels were present in periodontitis. Bmi <30 and smoking were associated with increased hdl, hdl-35, ldl and tg, while glycemia >100 mg/dl associated with hdl, hdl-35 and tg. Tannerella forsythia showed a significant association with hdl-35 in bivariate analysis and serum igg1 against p. Gingivalis associated with hdl-35 and serum igg1 against t. Forsythia associated with tg and serum igg2 against a. Actinomycetemcomitans correlated with levels of hdl y hdl-35. In logistic regression the periodontitis patients from cali presented reduced hdl levels as compared to bogota and medellin patients. Presence of igg1 antibodies against p. Gingivalis and a. Actinomycetemcomitans correlated with reduced hdl levels. Conclusion: this study confirmed that untreated periodontitis generates alteration in serum lipid levels and systemic bacterial exposure against important periodontopathic bacteria could be the biological link. PMID:24892452

  17. Effect of fermented milk containing Lactobacillus acidophilus and Bifidobacterium longum on plasma lipids of women with normal or moderately elevated cholesterol.

    PubMed

    Andrade, Sara; Borges, Nuno

    2009-11-01

    This study aimed to evaluate the effect of milk fermented with Lactobacillus acidophilus 145 and Bifidobacterium longum BB536 on plasma lipids in a sample of adult women. A double-blind, placebo controlled, cross-over study (two periods of four weeks each separated by a 1-week washout period) was performed in 34 women, aged between 18 and 65 years. Group A consumed 125 g fermented milk three times a day for the first 4 weeks while group B consumed regular yoghurt under the same conditions. (Groups A and B switched products for the second treatment period). Women taking the test product with a baseline total cholesterol above 190 mg/dl showed a significant reduction in LDL cholesterol. HDL cholesterol was also reduced by the test product. We conclude that the fermented milk may help to reduce LDL levels in hypercholesterolemic adult women.

  18. Effects of yeast-derived beta-glucans on blood cholesterol and macrophage functionality.

    PubMed

    Vetvicka, Vaclav; Vetvickova, Jana

    2009-03-01

    The objective of this study is to investigate the effects of two different yeast-derived beta-glucans on macrophage functionality and blood cholesterol levels in mice. After establishing their ability to act as a strong stimulator of macrophages, we measured the capacities of the glucans to lower blood cholesterol. Our results showed that consumption of diets containing yeast-derived beta-glucan indicated a dose-dependent decrease in plasma cholesterol levels, with Betamune having a significantly stronger effect than WGP (Whole Glucan Particles). In hypercholesterolemic subjects, the cholesterol- and triglycerides-lowering effects of Betamune were again significantly stronger. The results of this investigation demonstrated that highly purified yeast-derived beta-glucans modify plasma cholesterol levels and other indicators associated with artherogenic progression in mice. The fact that these glucans also strongly stimulated both monocytes and macrophages supports the hypothesis that there could be a macrophage-cholesterol (metabolism) axis involvement in these outcomes.

  19. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials

    PubMed Central

    Cholesterol Treatment Trialists' (CTT) Collaborators

    2012-01-01

    Summary Background Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain. Methods This meta-analysis included individual participant data from 22 trials of statin versus control (n=134 537; mean LDL cholesterol difference 1·08 mmol/L; median follow-up 4·8 years) and five trials of more versus less statin (n=39 612; difference 0·51 mmol/L; 5·1 years). Major vascular events were major coronary events (ie, non-fatal myocardial infarction or coronary death), strokes, or coronary revascularisations. Participants were separated into five categories of baseline 5-year major vascular event risk on control therapy (no statin or low-intensity statin) (<5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, ≥30%); in each, the rate ratio (RR) per 1·0 mmol/L LDL cholesterol reduction was estimated. Findings Reduction of LDL cholesterol with a statin reduced the risk of major vascular events (RR 0·79, 95% CI 0·77–0·81, per 1·0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular and all-cause mortality. The proportional reduction in major vascular events was at least as big in the two lowest risk categories as in the higher risk categories (RR per 1·0 mmol/L reduction from lowest to highest risk: 0·62 [99% CI 0·47–0·81], 0·69 [99% CI 0·60–0·79], 0·79 [99% CI 0·74–0·85], 0·81 [99% CI 0·77–0·86], and 0·79 [99% CI 0·74–0·84]; trend p=0·04), which reflected significant reductions in these two lowest risk categories in major coronary events (RR 0·57, 99% CI 0·36–0·89, p=0·0012, and 0·61, 99% CI 0·50–0·74, p<0·0001) and in coronary revascularisations (RR 0·52, 99% CI 0·35–0·75, and 0·63, 99% CI 0·51–0·79; both p<0·0001). For stroke, the reduction in risk in participants with 5-year risk of major vascular events lower than 10% (RR per 1·0 mmol/L LDL cholesterol

  20. The “Mevalonate hypothesis”: a cholesterol-independent alternative for the etiology of atherosclerosis

    PubMed Central

    2012-01-01

    The “cholesterol hypothesis” is the leading theory to explain the cause of atherosclerosis. The “cholesterol hypothesis” assumes that plasma (LDL) cholesterol is an important causal factor for atherosclerosis. However, data of at least seven placebo controlled randomized prospective trials with various cholesterol lowering drugs show that plasma cholesterol lowering does not necessarily lead to protection against cardiovascular disease. Therefore an alternative hypothesis for the etiology of cardiovascular disease is formulated. This alternative hypothesis, the “mevalonate hypothesis”, assumes that after stimulation of the mevalonate pathway in endothelial cells by inflammatory factors, these cells start producing cholesterol and free radicals. In this hypothesis, only the latter play a role in the etiology of atherosclerosis by contributing to the formation of oxidized cholesterol which is a widely accepted causal factor for atherosclerosis. Regardless of how the mevalonate pathway is activated (by withdrawal of statin drugs, by inflammatory factors or indirectly by reduced intracellular cholesterol levels) in all these cases free radical production is observed as well as cardiovascular disease. Since in the “mevalonate hypothesis” cholesterol is produced at the same time as the free radicals causing atherosclerosis, this hypothesis provides an explanation for the correlation which exists between cardiovascular disease and plasma cholesterol levels. From an evolutionary perspective, concomitant cholesterol production and free radical production in response to inflammatory factors makes sense if one realizes that both activities potentially protect cells and organisms from infection by gram-negative bacteria. In conclusion, data have been collected which suggest that activation of the mevalonate pathway in endothelial cells is likely to be a causal factor for atherosclerosis. This “mevalonate hypothesis” provides a better explanation for results

  1. Association of metabolic and genetic factors with cholesterol esterification rate in HDL plasma and atherogenic index of plasma in a 40 years old Slovak population.

    PubMed

    Rašlová, K; Dobiášová, M; Hubáček, J A; Bencová, D; Siváková, D; Danková, Z; Franeková, J; Jabor, A; Gašparovič, J; Vohnout, B

    2011-01-01

    We assessed association between novel biomarkers of cardiovascular disease and conventional factors in 40 years old subjects (208 men and 266 women) from the general population of Slovakia. FER(HDL) (cholesterol esterification rate in HDL plasma), AIP--Atherogenic Index of Plasma [Log(TG/HDL-C)] as markers of lipoprotein particle size, and CILP2, FTO and MLXIPL polymorphisms, were examined in relation to biomarkers and conventional risk factors. Univariate analyses confirmed correlation between AIP, FER(HDL) and the most of measured parameters. Relations between AIP and CILP2, FTO and MLXIPL were not significant. However, CILP2 was significantly related to FER(HDL) in both genders. In multivariate analysis BMI was the strongest correlate of AIP levels. In multivariate model variability of FER(HDL) was best explained by AIP (R(2) = 0.55) in both genders with still significant effect of CILP2 SNP in men. In a model where AIP was omitted, TG levels explained 43 % of the FER(HDL) variability in men, while in women HDL-C was the major determinant (42 %). In conclusions, FER(HDL) and AIP related to the known markers of cardiovascular risk provide means to express their subtle interactions by one number. Our novel finding of association between CILP2 polymorphism and FER(HDL) supports its role in lipid metabolism.

  2. Resistant starch type 4-enriched diet lowered blood cholesterols and improved body composition in a double blind controlled cross-over intervention.

    PubMed

    Nichenametla, Sailendra N; Weidauer, Lee A; Wey, Howard E; Beare, Tianna M; Specker, Bonny L; Dey, Moul

    2014-06-01

    A metabolic health crisis is evident as cardiovascular diseases (CVD) remain the leading cause of mortality in the United States. Effects of resistant starch type 4 (RS4), a prebiotic fiber, in comprehensive management of metabolic syndrome (MetS) remain unknown. This study examined the effects of a blinded exchange of RS4-enriched flour (30% v/v) with regular/control flour (CF) diet on multiple MetS comorbidities. In a double blind (participants-investigators), placebo-controlled, cluster cross-over intervention (n = 86, age≥18, 2-12 week interventions, 2-week washout) in the United States, individuals were classified as having MetS (With-MetS) or not (No-MetS) following International Diabetes Federation (IDF)-criteria. RS4 consumption compared with CF resulted in 7.2% (p = 0.002) lower mean total cholesterol, 5.5% (p = 0.04) lower non-HDL, and a 12.8% (p < 0.001) lower HDL cholesterol in the With-MetS group. No-MetS individuals had a 2.6% (p = 0.02) smaller waist circumference and 1.5% (p = 0.03) lower percent body fat following RS4 intervention compared to CF. A small but significant 1% increase in fat-free mass was observed in all participants combined (p = 0.02). No significant effect of RS4 was observed for glycemic variables and blood pressures. RS4 consumption improved dyslipidemia and body composition. Incorporation of RS4 in routine diets could offer an effective strategy for public cardio-metabolic health promotion.

  3. A high-cholesterol diet enriched with polyphenols from Oriental plums (Prunus salicina) improves cognitive function and lowers brain cholesterol levels and neurodegenerative-related protein expression in mice.

    PubMed

    Kuo, Ping-Hui; Lin, Ching-I; Chen, Yue-Hwa; Chiu, Wan-Chun; Lin, Shyh-Hsiang

    2015-05-28

    Ageing accompanied by a decline in cognitive performance may be a result of the long-term effects of oxidative stress on neurologic processes. It has been shown that high-cholesterol contents in the blood and brain may lead to the deposition of the β-amyloid (Aβ) protein in the brain, which damages brain cells. The present study was designed to observe the effect of polyphenol-rich Oriental plums on cognitive function and cerebral neurodegeneration-related protein expression in mice that were fed a high-cholesterol diet for 5 months. The study consisted of four groups: the control (Ctrl) group, which was fed the American Institute of Nutrition (AIN)-93M diet; the high cholesterol (HC) group, which was fed the AIN-93M diet with 5% cholesterol; the high cholesterol + low Oriental plum (LOP) group, which was fed the AIN-93M diet with 5% cholesterol and 2% Oriental plum powder; and the high cholesterol + high Oriental plum (HOP) group, which was fed the AIN-93M diet with 5% cholesterol and 5% Oriental plum powder. Measurements of cognitive function were assessed using the Morris water maze, and the mRNA expression of cholesterol hydroxylase (Cyp46), Aβ and β-secretase 1 (BACE1) were analysed. The results showed that cholesterol concentrations in both the blood and the brain were significantly higher in the HC group than in the Ctrl and HOP groups at the end of the trial. The high-cholesterol diet per se produced significant cognitive deficits, which were accompanied by a significantly increased mRNA expression of Cyp46, BACE1, Aβ and 24-hydroxycholesterol in the brain cortex and hippocampus. However, all of these variables were non-significantly increased in the HOP group as compared to the Ctrl group. In conclusion, incorporating polyphenol-enriched Oriental plum into a high-cholesterol diet can ameliorate some of the symptoms of neurodegenerative conditions. PMID:25866056

  4. A high-cholesterol diet enriched with polyphenols from Oriental plums (Prunus salicina) improves cognitive function and lowers brain cholesterol levels and neurodegenerative-related protein expression in mice.

    PubMed

    Kuo, Ping-Hui; Lin, Ching-I; Chen, Yue-Hwa; Chiu, Wan-Chun; Lin, Shyh-Hsiang

    2015-05-28

    Ageing accompanied by a decline in cognitive performance may be a result of the long-term effects of oxidative stress on neurologic processes. It has been shown that high-cholesterol contents in the blood and brain may lead to the deposition of the β-amyloid (Aβ) protein in the brain, which damages brain cells. The present study was designed to observe the effect of polyphenol-rich Oriental plums on cognitive function and cerebral neurodegeneration-related protein expression in mice that were fed a high-cholesterol diet for 5 months. The study consisted of four groups: the control (Ctrl) group, which was fed the American Institute of Nutrition (AIN)-93M diet; the high cholesterol (HC) group, which was fed the AIN-93M diet with 5% cholesterol; the high cholesterol + low Oriental plum (LOP) group, which was fed the AIN-93M diet with 5% cholesterol and 2% Oriental plum powder; and the high cholesterol + high Oriental plum (HOP) group, which was fed the AIN-93M diet with 5% cholesterol and 5% Oriental plum powder. Measurements of cognitive function were assessed using the Morris water maze, and the mRNA expression of cholesterol hydroxylase (Cyp46), Aβ and β-secretase 1 (BACE1) were analysed. The results showed that cholesterol concentrations in both the blood and the brain were significantly higher in the HC group than in the Ctrl and HOP groups at the end of the trial. The high-cholesterol diet per se produced significant cognitive deficits, which were accompanied by a significantly increased mRNA expression of Cyp46, BACE1, Aβ and 24-hydroxycholesterol in the brain cortex and hippocampus. However, all of these variables were non-significantly increased in the HOP group as compared to the Ctrl group. In conclusion, incorporating polyphenol-enriched Oriental plum into a high-cholesterol diet can ameliorate some of the symptoms of neurodegenerative conditions.

  5. Glucuronic acid epimerase is associated with plasma triglyceride and high-density lipoprotein cholesterol levels in Turks.

    PubMed

    Hodoğlugil, Uğur; Williamson, David W; Yu, Yi; Farrer, Lindsay A; Mahley, Robert W

    2011-05-01

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

  6. Investigation of possible lower hybrid emission from the NASA Lewis Bumpy Torus plasma

    NASA Technical Reports Server (NTRS)

    Mallavarpu, R.; Roth, J. R.

    1977-01-01

    Radio frequency emission detected near the lower hybrid frequency of the NASA Lewis Bumpy Torus plasma is studied, using a simple detection system that consists of a spectrum analyzer and a 50-ohm miniature co-axial antenna concentrically located in a re-entrant quartz tube. The frequency shift of a broad emission peak is monitored as a function of the background pressure, electrode voltage, and the strength of the dc magnetic field. Simultaneous measurements of the average plasma density are made with a polarization diplexing microwave interferometer. Information from the experiment is discussed with particular reference to the role of atomic or molecular species of deuterium in the emissions, the strength of the dc magnetic field in the emitting region, the geometric location of the emitting region of the plasma, the lower hybrid plasma density as compared with the average plasma density, and the relation of the ion spoke geometry to the lower hybrid emission.

  7. Excitation of the lower oblique resonance by an artificial plasma jet in the ionosphere

    NASA Astrophysics Data System (ADS)

    Thiel, J.; Storey, L. R. O.; Bauer, O. H.; Jones, D.

    1984-04-01

    Aboard the Porcupine rockets, bursts of noise were detected in the electron whistler range during the operation of a xenon plasma gun on a package ejected from the main payload. These observations can be interpreted in terms of excitation of the lower oblique resonance by instabilities associated with the motion of the xenon ion beam through the ionospheric plasma.

  8. Influence of collisions on parametric instabilities induced by lower hybrid waves in tokamak plasmas

    NASA Astrophysics Data System (ADS)

    Castaldo, C.; Di Siena, A.; Fedele, R.; Napoli, F.; Amicucci, L.; Cesario, R.; Schettini, G.

    2016-01-01

    Parametric instabilities induced at the plasma edge by lower hybrid wave power externally coupled to tokamak plasmas have, via broadening of the antenna spectrum, strong influence on the power deposition and current drive in the core. For modeling the parametric instabilities at the tokamak plasma edge in lower hybrid current drive experiments, the effect of the collisions has been neglected so far. In the present work, a specific collisional parametric dispersion relation, useful to analyze these nonlinear phenomena near the lower hybrid antenna mouth, is derived for the first time, based on a kinetic model. Numerical solutions show that in such cold plasma regions the collisions prevent the onset of the parametric instabilities. This result is important for present lower hybrid current drive experiments, as well as in fusion reactor scenarios.

  9. The Metabolism of Cholestanol, Cholesterol, and Bile Acids in Cerebrotendinous Xanthomatosis

    PubMed Central

    Salen, Gerald; Grundy, Scott M.

    1973-01-01

    The metabolism of cholesterol and its 5-dihydro derivative, cholestanol, was investigated by means of sterol balance and isotope kinetic techniques in 3 subjects with cerebrotendinous xanthomatosis (CTX) and 11 other individuals. All subjects were hospitalized on a metabolic ward and were fed diets practically free of cholesterol and cholestanol. After the intravenous administration of [1,2-3H]cholestanol, the radioactive sterol was transported and esterified in plasma lipoproteins in an identical manner to cholesterol. In these short-term experiments, the specific activity-time curves of plasma cholestanol conformed to two-pool models in both the CTX and control groups. However, cholestanol plasma concentrations, total body miscible pools, and daily synthesis rates were two to five times greater in the CTX than control individuals. The short-term specific activity decay curves of plasma [4-14C]cholesterol also conformed to two-pool models in both groups. However, in the CTX subjects the decay was more rapid, and daily cholesterol synthesis was nearly double that of the control subjects. Plasma concentrations and the sizes of the rapidly turning over pool of exchangeable cholesterol were apparently small in the CTX subjects, and these measurements did not correlate with the large cholesterol deposits found in tendon and tuberous xanthomas. Despite active cholesterol synthesis, bile acid formation was subnormal in the CTX subjects. However, bile acid sequestration was accompanied by a rise in plasma cholestanol levels and greatly augmented fecal cholestanol outputs. In contrast, the administration of clofibrate lowered plasma cholesterol levels 50% and presumably reduced synthesis in the CTX subjects. Plasma cholesterol concentrations and fecal steroid excretion did not change significantly during this therapy. These findings indicate that the excessive tissue deposits of cholesterol and cholestanol that characterize CTX were associated with hyperactive neutral

  10. Monascus fermentation of dioscorea for increasing the production of cholesterol-lowering agent--monacolin K and antiinflammation agent--monascin.

    PubMed

    Lee, Chun-Lin; Wang, Jyh-Jye; Kuo, Shing-Lin; Pan, Tzu-Ming

    2006-10-01

    Monacolin K, an inhibitor for cholesterol synthesis, is the secondary metabolite of Monascus species. The formation of the secondary metabolites of the Monascus species is affected by cultivation environment and method. This research uses sweet potato (Ipomoea batatas), potato (Solanum tuberosum), casava (Manihot esculenta), and dioscorea (Dioscorea batatas) as the substrates and discusses the best substrate to produce monacolin K. The results show that Monascus purpureus NTU 301, with dioscorea as the substrate, can produce monacolin K at 2,584 mg kg(-1), which is 5.37 times to that resulted when rice is used as the substrate. In addition, more amount of yellow pigment can be found in Monascus-fermented dioscorea than in Monascus-fermented rice. The certain composition of yellow pigment is identified as monascin, which has been shown as an antiinflammation agent exhibiting potent inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice in previous studies. Therefore, dioscorea is concluded to be the best substrate for Monascus species to produce the cholesterol-lowering agent-monacolin K and antiinflammation agent-monascin.

  11. A nutrient-dense, high-fiber, fruit-based supplement bar increases HDL cholesterol, particularly large HDL, lowers homocysteine, and raises glutathione in a 2-wk trial.

    PubMed

    Mietus-Snyder, Michele L; Shigenaga, Mark K; Suh, Jung H; Shenvi, Swapna V; Lal, Ashutosh; McHugh, Tara; Olson, Don; Lilienstein, Joshua; Krauss, Ronald M; Gildengoren, Ginny; McCann, Joyce C; Ames, Bruce N

    2012-08-01

    Dietary intake modulates disease risk, but little is known how components within food mixtures affect pathophysiology. A low-calorie, high-fiber, fruit-based nutrient-dense bar of defined composition (e.g., vitamins and minerals, fruit polyphenolics, β-glucan, docosahexaenoic acid) appropriate for deconstruction and mechanistic studies is described and evaluated in a pilot trial. The bar was developed in collaboration with the U.S. Department of Agriculture. Changes in cardiovascular disease and diabetes risk biomarkers were measured after 2 wk twice-daily consumption of the bar, and compared against baseline controls in 25 healthy adults. Plasma HDL-cholesterol (HDL-c) increased 6.2% (P=0.001), due primarily to a 28% increase in large HDL (HDL-L; P<0.0001). Total plasma homocysteine (Hcy) decreased 19% (P=0.017), and glutathione (GSH) increased 20% (P=0.011). The changes in HDL and Hcy are in the direction associated with decreased risk of cardiovascular disease and cognitive decline; increased GSH reflects improved antioxidant defense. Changes in biomarkers linked to insulin resistance and inflammation were not observed. A defined food-based supplement can, within 2 wk, positively impact metabolic biomarkers linked to disease risk. These results lay the groundwork for mechanistic/deconstruction experiments to identify critical bar components and putative synergistic combinations responsible for observed effects.

  12. Influence of total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease: the Copenhagen City Heart Study.

    PubMed Central

    Lindenstrøm, E.; Boysen, G.; Nyboe, J.

    1994-01-01

    OBJECTIVE--To estimate the influence of plasma total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease. DESIGN--The Copenhagen City Heart Study is a prospective observational survey with two cardiovascular examinations at five year intervals. Non-fasting plasma lipids were measured in participants once at each examination, along with other variables. The Cox regression model was used to establish the effect of the factors recorded on cerebrovascular events of mostly, but not exclusively, ischaemic origin. SUBJECTS--19,698 women and men at least 20 years old, randomly selected after age stratification from an area of central Copenhagen. MAIN OUTCOME MEASURES--Initial cases of stroke and transient ischaemic attack recorded from hospital records and death certificates from 1976 through 1988. RESULTS--660 non-haemorrhagic and 33 haemorrhagic events were recorded. Total cholesterol was positively associated with risk of non-haemorrhagic events, but only for levels > 8 mmol/l, corresponding to the upper 5% of the distribution in the study population. For lower plasma cholesterol values the relative risk remained nearly constant. Plasma triglyceride concentration was significantly, positively associated with risk of non-haemorrhagic events. The relative risk corresponding to an increase of 1 mmol/l was 1.12 (95% confidence interval 1.07 to 1.16). There was a negative, log linear association between high density lipoprotein cholesterol and risk of non-haemorrhagic events (0.53 (0.34 to 0.83)). There was no indication that the effects of plasma lipids were different in women and men. CONCLUSIONS--The pattern of the association between plasma cholesterol and risk of ischaemic cerebrovascular disease was not log linear, and the increased risk was confined to the upper 5% of the cholesterol distribution. Further studies should concentrate on the association between plasma cholesterol and verified haemorrhagic stroke. PMID

  13. Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis.

    PubMed

    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 (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. PMID:19936222

  14. The CEPHEUS Pan-Asian survey: high low-density lipoprotein cholesterol goal attainment rate among hypercholesterolaemic patients undergoing lipid-lowering treatment in a Hong Kong regional centre.

    PubMed

    Chan, Raymond H W; Chan, P H; Chan, Kelvin K W; Lam, Simon C C; Hai, Jo Jo; Wong, Michael K L; Tam, Frankie C C; Lam, Linda; Chan, Carmen W S; Lam, Y M; Siu, David C W; Tse, H F; Lee, Stephen W L

    2012-10-01

    OBJECTIVES. To evaluate attainment of low-density lipoprotein cholesterol goals among hypercholesterolaemic patients undergoing lipid-lowering drug treatment in Hong Kong and to identify potential determinants of treatment outcomes. DESIGN. Cross-sectional observational study. SETTING. A single site in Hong Kong, as part of the CEPHEUS Pan-Asian survey. PATIENTS. Subjects with hypercholesterolaemia aged 18 years or above, who had been on lipid-lowering drug treatment for at least 3 months with no dose adjustment for at least 6 weeks. RESULTS. A total of 561 such patients (mean age, 65.3; standard deviation, 9.7 years) were evaluated. Most had major cardiovascular risk factors; 534 (95.2%) of 561 patients had coronary heart disease and 534 (95.4%) of 560 patients had low-density lipoprotein cholesterol goals set at lower than 70 mg/dL. In all, 465 (82.9%) patients attained their respective low-density lipoprotein cholesterol goals. Among 75 patients who had coronary heart disease or equivalent risk, and multiple risk factors with a 10-year coronary heart disease risk of over 20%, 62 (82.7%) attained their respective low-density lipoprotein cholesterol goals. Significant predictors of low-density lipoprotein cholesterol goal attainment included the patient's baseline lipid profile (total cholesterol and low-density lipoprotein cholesterol levels), blood pressure, and drugs (statin/non-statin) used for treatment. CONCLUSIONS. Hypercholesterolaemic patients undergoing lipid-lowering drug treatment in the present Hong Kong study were able to achieve a very high attainment rate for the low-density lipoprotein cholesterol goal, despite the fact that most of them had major cardiovascular risk factors.

  15. The amount of dietary cholesterol changes the mode of effects of (n-3) polyunsaturated fatty acid on lipoprotein cholesterol in hamsters.

    PubMed

    Lin, Mei-Huei; Lu, Shao-Chun; Huang, Po-Chao; Liu, Young-Chau; Liu, Shyun-Yeu

    2004-01-01

    This study was designed to investigate the effects of the interaction between dietary (n-3) polyunsaturated fatty acids (PUFA) and different dietary cholesterol content on plasma and liver cholesterol in hamsters. Male Syrian hamsters consumed diets containing an incremental increase in dietary cholesterol content (0, 0.025, 0.05, 0.1 and 0.2%, w/w) with either (n-3) PUFA (21 g/100 g fatty acids) or (n-6) PUFA (37.4 g/100 g fatty acids) fat for 6 weeks. In hamsters fed the nonatherogenic diet (0 or 0.025% dietary cholesterol), very low density lipoprotein (VLDL)-cholesterol levels in the (n-3) PUFA group were not significantly different from those in the (n-6) PUFA group, and low density lipoprotein (LDL)-cholesterol levels in the (n-3) PUFA group were significantly lower than those in the (n-6) PUFA group. In contrast, in hamsters fed the atherogenic diet (0.1 or 0.2% dietary cholesterol), VLDL- and LDL-cholesterol levels in the (n-3) PUFA group were significantly higher than those in the (n-6) PUFA group, in a dose-dependent manner. When the hamsters were fed with 0, 0.025, 0.05, 0.1 or 0.2% (w/w) dietary cholesterol, high density lipoprotein (HDL) cholesterol concentration was significantly lower in the (n-3) PUFA group than those in the (n-6) PUFA group. Hepatic cholesteryl esters were significantly lower, while hepatic microsomal acyl-coenzyme A:cholesterol acyltransferase activity and VLDL-cholesteryl esters were significantly higher in hamsters fed (n-3) PUFA with the atherogenic diet (0.1 or 0.2% dietary cholesterol) than in those fed (n-6) PUFA with the atherogenic diet. Our results demonstrate that the amount of dietary cholesterol is an important factor in determining the mode and extent of effects of dietary (n-3) PUFA, especially on VLDL- and LDL-cholesterol levels. When dietary cholesterol intake was above 0.1% (w/w), the plasma cholesterol-lowering effect of (n-3) PUFA disappeared, and instead, it showed a cholesterol-increasing effect. However, the

  16. α-Tocopherol Attenuates the Triglyceride- and Cholesterol-Lowering Effects of Rice Bran Tocotrienol in Rats Fed a Western Diet.

    PubMed

    Shibata, Akira; Kawakami, Yuki; Kimura, Toshiyuki; Miyazawa, Teruo; Nakagawa, Kiyotaka

    2016-07-01

    Previous studies demonstrated the ability of tocotrienol (T3) to lower levels of lipids, including cholesterol (Cho) and triglycerides (TG). Although α-tocopherol (α-Toc) reportedly inhibits the hypocholesterolemic effect of T3, there is no information about whether α-Toc influences the TG-lowering effect of T3 in vivo. In this study, we investigated the influence of α-Toc on the antihyperlipidemic effects (Cho- and TG-lowering) of rice bran tocotrienols (RBT3) in F344 rats fed a western diet. α-Toc attenuated both the Cho- and TG-lowering effects of RBT3 in vivo, whereas α-Toc alone exhibited no hypolipidemic effects. RBT3-induced Cpt-1a and Cyp7a1 gene expression was reduced by α-Toc. Furthermore, coadministration of α-Toc decreased liver and adipose tissue concentrations of tocotrienols in F344 rats. These results indicate that α-Toc has almost no antihyperlipidemic effect in vivo, but abrogates the antihyperlipidemic effect of RBT3 by reducing tissue concentrations of tocotrienols and regulating expression of genes involved in lipid metabolism. Understanding the underlying mechanism of the beneficial effects of T3 on lipid metabolism and the interaction with α-Toc will be important for developing T3-based therapeutics.

  17. Lack of Effect of Lowering LDL Cholesterol on Cancer: Meta-Analysis of Individual Data from 175,000 People in 27 Randomised Trials of Statin Therapy

    PubMed Central

    2012-01-01

    Background Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials. Methods and Findings Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py

  18. Investigation of possible lower hybrid emission from the NASA Lewis bumpy torus plasma

    NASA Technical Reports Server (NTRS)

    Mallavarpu, R.; Roth, J. R.

    1977-01-01

    Radio frequency emission has been detected near the power hybrid frequency of a bumpy torus plasma by using a responsive detection system that consists of a spectrum analyzer and a 50 ohm miniature coaxial antenna concentrically located in a re-entrant quartz tube. The frequency shift of a broad emission peak was monitored as a function of background pressure, electrode voltage, and the strength of the dc magnetic field. Simultaneous measurements of the average plasma density were made with a polarization diplexing microwave interferometer. The information derived from the experiment is discussed with particular reference to the following: (1) whether the emissions are dominated by atomic or molecular species of deuterium; (2) the strength of the dc magnetic field in the emitting region; (3) the geometric location of the emitting region of the plasma; (4) comparison of the lower hybrid plasma density with the average plasma density; and (5) relation of ion spoke geometry to lower hybrid emission.

  19. Glucose and low-density lipoprotein cholesterol lowering in elderly patients with type 2 diabetes: focus on combination therapy with colesevelam HCl.

    PubMed

    Marrs, Joel C

    2012-05-01

    The prevalence of type 2 diabetes mellitus is high among the elderly population. Treatment of elderly patients with type 2 diabetes presents challenges because of co-morbidities and the potential increase in the risk of adverse effects. Hyperlipidaemia is also common in the elderly population. Glucose- and lipid-lowering treatment in elderly patients should be individualized on the basis of the patient's life expectancy, health status and cardiovascular risk factors, and evidence-based guideline recommendations. Because elderly patients often have impaired renal and hepatic function, careful considerations must be made when selecting appropriate glucose- and lipid-lowering therapy. There are a number of potential safety issues associated with various glucose- and lipid-lowering therapies that are relevant to elderly patients, including increased risk of heart failure exacerbations, weight loss, increased risk of hypoglycaemia, increased risk of myopathy, and contraindications of some agents in patients with hepatic or renal impairment. The bile acid sequestrant colesevelam HCl is unique compared with other glucose- and lipid-lowering therapies because it is the only product approved by the US Food and Drug Administration, as an adjunct to diet and exercise, to lower both glucose and low-density lipoprotein cholesterol (LDL-C) in adults with type 2 diabetes and primary hyperlipidaemia, respectively. Furthermore, colesevelam has been shown to have similar glucose- and lipid-lowering efficacy in patients aged <65 years and those aged ≥65 years. Colesevelam was not associated with weight gain, was associated with a low incidence of hypoglycaemia, and can be safely combined with a broad range of glucose-lowering agents (metformin, sulfonylureas and insulin) and lipid-lowering statins. Currently, colesevelam is available in tablet form and as a powder for oral suspension formulation; the latter may be of benefit to elderly patients with swallowing difficulties. As

  20. Effects of Pediococcus parvulus 2.6 and its exopolysaccharide on plasma cholesterol levels and inflammatory markers in mice

    PubMed Central

    2012-01-01

    Intake of dietary fibres may reduce the prevalence of physiological risk factors of the metabolic syndrome, such as high plasma lipid levels and low-grade inflammatory state. Dietary fibres are usually of plant origin however microbial exopolysaccharides (EPSs) have analogue structures that could potentially exert similar physiological effects. Pediococcus parvulus 2.6 (Pd 2.6) excretes a ropy EPS and has previously shown probiotic potential. The aim of this work was to evaluate physiological effects of Pd 2.6 and its EPS in vivo. The live Pd 2.6 (both the ropy and non-ropy isogenic variant) and its purified EPS were fed to hypercholesterolemic LDL-receptor deficient mice for 6 weeks to investigate their effects on cholesterol levels and the inflammatory tone of the animals. Both variants of Pd 2.6 survived passage through the mouse gut fulfilling an important criterion of probiotics. The ability to produce EPS was conferring an advantage to survival (faecal recovery of 3.7 (1.9-8.7) vs. 0.21 (0.14-0.34) *108 CFU, P < 0.001, median and 25th and 75th percentiles). The ropy Pd 2.6 decreased the levels of soluble vascular cell adhesion molecule-1 compared to the EPS alone (591 ± 14 vs. 646 ± 13 ng/ml, P < 0.05). An increase in liver weight in mice fed the purified EPS was observed, but with no change in liver lipids. No changes in blood lipids were detected in any group. Further the EPS induced growth of the caecal tissue and increased the amount of caecal content showing bulking properties like that of a dietary fibre. PMID:23234432

  1. Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We measured plasma markers of cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, and cholestanol) in order to compare the effects of maximal doses of rosuvastatin with atorvastatin and investigate the basis for the significant individual variation in lipid lowering response...

  2. Cholesterol (image)

    MedlinePlus

    Cholesterol is a soft, waxy substance that is present in all parts of the body including the ... and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed ...

  3. Development and partial metabolic characterization of a dietary cholesterol-resistant colony of rabbits

    SciTech Connect

    Overturf, M.L.; Smith, S.A.; Hewett-Emmett, D.; Loose-Mitchell, D.S.; Soma, M.R.; Gotto, A.M. Jr.; Morrisett, J.D. )

    1989-02-01

    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 {sup 125}I-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.

  4. Evaluation of plasma cholestane-3β,5α,6β-triol and 7-ketocholesterol in inherited disorders related to cholesterol metabolism.

    PubMed

    Boenzi, Sara; Deodato, Federica; Taurisano, Roberta; Goffredo, Bianca Maria; Rizzo, Cristiano; Dionisi-Vici, Carlo

    2016-03-01

    Oxysterols are intermediates of cholesterol metabolism and are generated from cholesterol via either enzymatic or nonenzymatic pathways under oxidative stress conditions. Cholestan-3β,5α,6β-triol (C-triol) and 7-ketocholesterol (7-KC) have been proposed as new biomarkers for the diagnosis of Niemann-Pick type C (NP-C) disease, representing an alternative tool to the invasive and time-consuming method of fibroblast filipin test. To test the efficacy of plasma oxysterol determination for the diagnosis of NP-C, we systematically screened oxysterol levels in patients affected by different inherited disorders related with cholesterol metabolism, which included Niemann-Pick type B (NP-B) disease, lysosomal acid lipase (LAL) deficiency, Smith-Lemli-Opitz syndrome (SLOS), congenital familial hypercholesterolemia (FH), and sitosterolemia (SITO). As expected, NP-C patients showed significant increase of both C-triol and 7-KC. Strong increase of both oxysterols was observed in NP-B and less pronounced in LAL deficiency. In SLOS, only 7-KC was markedly increased, whereas in both FH and in SITO, oxysterol concentrations were normal. Interestingly, in NP-C alone, we observed that plasma oxysterols correlate negatively with patient's age and positively with serum total bilirubin, suggesting the potential relationship between oxysterol levels and hepatic disease status. Our results indicate that oxysterols are reliable and sensitive biomarkers of NP-C.

  5. The small GTPase Cdc42 interacts with Niemann-Pick C1-like 1 (NPC1L1) and controls its movement from endocytic recycling compartment to plasma membrane in a cholesterol-dependent manner.

    PubMed

    Xie, Chang; Li, Na; Chen, Zheng-Jun; Li, Bo-Liang; Song, Bao-Liang

    2011-10-14

    Niemann-Pick C1-like 1 (NPC1L1) is a multi-transmembrane protein that mediates the absorption of dietary and biliary cholesterol through vesicular endocytosis. The subcellular localization of NPC1L1 is regulated by cholesterol. Cholesterol depletion induces the transport of NPC1L1 to plasma membrane (PM) from endocytic recycling compartment that requires MyoVb·Rab11a·Rab11-FIP2 triple complex, and cholesterol-replenishment renders the internalization of NPC1L1 together with cholesterol. Here, we find that GTP-bound Cdc42 interacts with NPC1L1. Cholesterol depletion regulates the activation of Cdc42 and enhances NPC1L1-Cdc42 interaction. Overexpression of constitutive GTP-bound Cdc42 mutant form or knockdown of Cdc42 inhibits the transport of NPC1L1 to the PM and disturbs the cholesterol-regulated binding of NPC1L1 to Rab11a, MyoVb, and actin. Knockdown of Cdc42 downstream effectors N-WASP or Arp3 also leads to the similar results. In liver-specific Cdc42 knock-out (Cdc42 LKO) mice, NPC1L1 fails to localize to bile canaliculi, and the biliary cholesterol cannot be efficiently reabsorbed. These results indicate that Cdc42 controls the cholesterol-regulated transport and localization of NPC1L1, and plays a role in cholesterol absorption.

  6. The Small GTPase Cdc42 Interacts with Niemann-Pick C1-like 1 (NPC1L1) and Controls Its Movement from Endocytic Recycling Compartment to Plasma Membrane in a Cholesterol-dependent Manner*

    PubMed Central

    Xie, Chang; Li, Na; Chen, Zheng-Jun; Li, Bo-Liang; Song, Bao-Liang

    2011-01-01

    Niemann-Pick C1-like 1 (NPC1L1) is a multi-transmembrane protein that mediates the absorption of dietary and biliary cholesterol through vesicular endocytosis. The subcellular localization of NPC1L1 is regulated by cholesterol. Cholesterol depletion induces the transport of NPC1L1 to plasma membrane (PM) from endocytic recycling compartment that requires MyoVb·Rab11a·Rab11-FIP2 triple complex, and cholesterol-replenishment renders the internalization of NPC1L1 together with cholesterol. Here, we find that GTP-bound Cdc42 interacts with NPC1L1. Cholesterol depletion regulates the activation of Cdc42 and enhances NPC1L1-Cdc42 interaction. Overexpression of constitutive GTP-bound Cdc42 mutant form or knockdown of Cdc42 inhibits the transport of NPC1L1 to the PM and disturbs the cholesterol-regulated binding of NPC1L1 to Rab11a, MyoVb, and actin. Knockdown of Cdc42 downstream effectors N-WASP or Arp3 also leads to the similar results. In liver-specific Cdc42 knock-out (Cdc42 LKO) mice, NPC1L1 fails to localize to bile canaliculi, and the biliary cholesterol cannot be efficiently reabsorbed. These results indicate that Cdc42 controls the cholesterol-regulated transport and localization of NPC1L1, and plays a role in cholesterol absorption. PMID:21844200

  7. Effect of Low-Density Lipoprotein Cholesterol Lowering by Ezetimibe/Simvastatin on Outcome Incidence: Overview, Meta-Analyses, and Meta-Regression Analyses of Randomized Trials.

    PubMed

    Thomopoulos, Costas; Skalis, George; Michalopoulou, Helena; Tsioufis, Costas; Makris, Thomas

    2015-12-01

    This analysis investigated the extent of different outcome reductions from low-density lipoprotein cholesterol (LDL-C) lowering following ezetimibe/simvastatin treatment and the proportionality of outcome to LDL-C reductions. The authors searched PubMed between 1997 and mid-June 2015 (any language) and the Cochrane Library to identify all randomized controlled trials comparing ezetimibe/simvastatin with placebo or less intensive LDL-C lowering. Risk ratios (RR) and 95% confidence intervals (CIs), standardized to 20 mg/dL LDL-C reduction, were calculated for 5 primary outcomes (fatal and nonfatal) and 4 secondary outcomes (non-cardiovascular [CV] death, cancer, myopathy, and hepatopathy). Five ezetimibe/simvastatin RCTs (30 051 individuals) were eligible, 2 comparing ezetimibe/simvastatin vs placebo and 3 vs less intensive treatment. Outcomes reduced almost to the same extent were stroke (RR: -13%, 95% CI: -21% to -3%), coronary heart disease (CHD; RR: -12%, 95% CI: -19% to -5%), and composite of stroke and CHD (RR: -14%, 95% CI: -20% to -8%). Absolute risk reductions: 5 strokes, 10 CHD events, and 16 stroke and CHD events prevented for every 1000 patients treated for 5 years. Residual risk was almost 7× higher than absolute risk reduction for all the above outcomes. All death outcomes were not reduced, and secondary outcomes did not differ between groups. Logarithmic risk ratios were not associated with LDL-C lowering. Our meta-analysis provides evidence that, in patients with different CV disease burden, major CV events are safely reduced by LDL-C lowering with ezetimibe/simvastatin, while raising the hypothesis that the extent of LDL-C lowering might not be accompanied by incremental clinical-event reduction.

  8. Measurements of continuum lowering in solid-density plasmas created from elements and compounds.

    PubMed

    Ciricosta, O; Vinko, S M; Barbrel, B; Rackstraw, D S; Preston, T R; Burian, T; Chalupský, J; Cho, B I; Chung, H-K; Dakovski, G L; Engelhorn, K; Hájková, V; Heimann, P; Holmes, M; Juha, L; Krzywinski, J; Lee, R W; Toleikis, S; Turner, J J; Zastrau, U; Wark, J S

    2016-01-01

    The effect of a dense plasma environment on the energy levels of an embedded ion is usually described in terms of the lowering of its continuum level. For strongly coupled plasmas, the phenomenon is intimately related to the equation of state; hence, an accurate treatment is crucial for most astrophysical and inertial-fusion applications, where the case of plasma mixtures is of particular interest. Here we present an experiment showing that the standard density-dependent analytical models are inadequate to describe solid-density plasmas at the temperatures studied, where the reduction of the binding energies for a given species is unaffected by the different plasma environment (ion density) in either the element or compounds of that species, and can be accurately estimated by calculations only involving the energy levels of an isolated neutral atom. The results have implications for the standard approaches to the equation of state calculations.

  9. Measurements of continuum lowering in solid-density plasmas created from elements and compounds

    PubMed Central

    Ciricosta, O.; Vinko, S. M.; Barbrel, B.; Rackstraw, D. S.; Preston, T. R.; Burian, T.; Chalupský, J.; Cho, B. I.; Chung, H. -K.; Dakovski, G. L.; Engelhorn, K.; Hájková, V.; Heimann, P.; Holmes, M.; Juha, L.; Krzywinski, J.; Lee, R. W.; Toleikis, S.; Turner, J. J.; Zastrau, U.; Wark, J. S.

    2016-01-01

    The effect of a dense plasma environment on the energy levels of an embedded ion is usually described in terms of the lowering of its continuum level. For strongly coupled plasmas, the phenomenon is intimately related to the equation of state; hence, an accurate treatment is crucial for most astrophysical and inertial-fusion applications, where the case of plasma mixtures is of particular interest. Here we present an experiment showing that the standard density-dependent analytical models are inadequate to describe solid-density plasmas at the temperatures studied, where the reduction of the binding energies for a given species is unaffected by the different plasma environment (ion density) in either the element or compounds of that species, and can be accurately estimated by calculations only involving the energy levels of an isolated neutral atom. The results have implications for the standard approaches to the equation of state calculations. PMID:27210741

  10. Measurements of continuum lowering in solid-density plasmas created from elements and compounds

    NASA Astrophysics Data System (ADS)

    Ciricosta, O.; Vinko, S. M.; Barbrel, B.; Rackstraw, D. S.; Preston, T. R.; Burian, T.; Chalupský, J.; Cho, B. I.; Chung, H.-K.; Dakovski, G. L.; Engelhorn, K.; Hájková, V.; Heimann, P.; Holmes, M.; Juha, L.; Krzywinski, J.; Lee, R. W.; Toleikis, S.; Turner, J. J.; Zastrau, U.; Wark, J. S.

    2016-05-01

    The effect of a dense plasma environment on the energy levels of an embedded ion is usually described in terms of the lowering of its continuum level. For strongly coupled plasmas, the phenomenon is intimately related to the equation of state; hence, an accurate treatment is crucial for most astrophysical and inertial-fusion applications, where the case of plasma mixtures is of particular interest. Here we present an experiment showing that the standard density-dependent analytical models are inadequate to describe solid-density plasmas at the temperatures studied, where the reduction of the binding energies for a given species is unaffected by the different plasma environment (ion density) in either the element or compounds of that species, and can be accurately estimated by calculations only involving the energy levels of an isolated neutral atom. The results have implications for the standard approaches to the equation of state calculations.

  11. Measurements of continuum lowering in solid-density plasmas created from elements and compounds.

    PubMed

    Ciricosta, O; Vinko, S M; Barbrel, B; Rackstraw, D S; Preston, T R; Burian, T; Chalupský, J; Cho, B I; Chung, H-K; Dakovski, G L; Engelhorn, K; Hájková, V; Heimann, P; Holmes, M; Juha, L; Krzywinski, J; Lee, R W; Toleikis, S; Turner, J J; Zastrau, U; Wark, J S

    2016-01-01

    The effect of a dense plasma environment on the energy levels of an embedded ion is usually described in terms of the lowering of its continuum level. For strongly coupled plasmas, the phenomenon is intimately related to the equation of state; hence, an accurate treatment is crucial for most astrophysical and inertial-fusion applications, where the case of plasma mixtures is of particular interest. Here we present an experiment showing that the standard density-dependent analytical models are inadequate to describe solid-density plasmas at the temperatures studied, where the reduction of the binding energies for a given species is unaffected by the different plasma environment (ion density) in either the element or compounds of that species, and can be accurately estimated by calculations only involving the energy levels of an isolated neutral atom. The results have implications for the standard approaches to the equation of state calculations. PMID:27210741

  12. Measurements of continuum lowering in solid-density plasmas created from elements and compounds

    DOE PAGES

    Ciricosta, O.; Vinko, S. M.; Barbrel, B.; Rackstraw, D. S.; Preston, T. R.; Burian, T.; Chalupský, J.; Cho, B. I.; Chung, H. -K.; Dakovski, G. L.; et al

    2016-05-23

    The effect of a dense plasma environment on the energy levels of an embedded ion is usually described in terms of the lowering of its continuum level. For strongly coupled plasmas, the phenomenon is intimately related to the equation of state; hence, an accurate treatment is crucial for most astrophysical and inertial-fusion applications, where the case of plasma mixtures is of particular interest. In this study, we present an experiment showing that the standard density-dependent analytical models are inadequate to describe solid-density plasmas at the temperatures studied, where the reduction of the binding energies for a given species is unaffectedmore » by the different plasma environment (ion density) in either the element or compounds of that species, and can be accurately estimated by calculations only involving the energy levels of an isolated neutral atom. Lastly, the results have implications for the standard approaches to the equation of state calculations.« less

  13. Co- and counter-current rotation in Tore Supra lower hybrid current drive plasmas

    NASA Astrophysics Data System (ADS)

    Chouli, B.; Fenzi, C.; Garbet, X.; Bourdelle, C.; Decker, J.; Aniel, T.; Artaud, J.-F.; Basiuk, V.; Clairet, F.; Colledani, G.; Dumont, R.; Elbeze, D.; Gil, C.; Lotte, P.; Sarazin, Y.; the Tore Supra Team

    2014-09-01

    Observations of lower hybrid (LH) radio frequency heating effects on toroidal plasma rotation in L-mode Tore Supra plasmas are reported. A database of more than 50 plasma discharges has been analysed. Core rotation is found to increment in co- or counter-current direction depending on the plasma current (Ip). At low plasma current, the induced rotation is up to +15 km s-1 in the co-current direction, the rotation profile being affected over the whole plasma minor radius. At higher plasma current, an opposite trend is observed, the core plasma rotation incrementing up to -15 km s-1 in the counter-current direction, the profile being affected up to r/a < 0.6 only. At the zero crossing point, which is defined when the plasma rotation profile is not affected by LH power injection, Ip ˜ 0.95 MA. In both low and high Ip cases, rotation increments are found to increase with the injected power. Several mechanisms in competition which can induce co- or counter-current rotation in Tore Supra LHCD plasmas are investigated and typical order of magnitude are discussed. How those effects evolve with plasma parameters and how they compete are important issues addressed in this paper. Rotation increment increase with Ip at fixed LH power is consistent with a dominant standard momentum confinement mechanism related to Ip increase. The co-current change in rotation is consistent with a fast electron ripple loss mechanism, while thermal ripple induced neoclassical friction and absorbed LH wave momentum from resonant electrons are expected to influence the rotation in the counter-current direction. Finally, the numerical simulations show that the radial turbulent momentum transport does impact the rotation behaviour inducing increment in co- or counter-current directions, depending on the plasma current amplitude.

  14. The influence of IMF on the lower ionosphere plasma in high and middle latitudes

    NASA Technical Reports Server (NTRS)

    Bremer, J.

    1989-01-01

    As shown by ground-based absorption measurements, the lower ionospheric plasma is markedly controlled by the structure of the IMF. Whereas in high auroral and subauroral latitudes this effect is very pronounced, in midlatitudes its influence is less important. A comparison of these results with satellite data of the IMF and the solar wind speed confirms the important role of these components, not only during special events but also for the normal state of the ionospheric D region plasma.

  15. Plasma membrane cholesterol level and agonist-induced internalization of δ-opioid receptors; colocalization study with intracellular membrane markers of Rab family.

    PubMed

    Brejchova, Jana; Vosahlikova, Miroslava; Roubalova, Lenka; Parenti, Marco; Mauri, Mario; Chernyavskiy, Oleksandr; Svoboda, Petr

    2016-08-01

    Decrease of cholesterol level in plasma membrane of living HEK293 cells transiently expressing FLAG-δ-OR by β-cyclodextrin (β-CDX) resulted in a slight internalization of δ-OR. Massive internalization of δ-OR induced by specific agonist DADLE was diminished in cholesterol-depleted cells. These results suggest that agonist-induced internalization of δ-OR, which has been traditionally attributed exclusively to clathrin-mediated pathway, proceeds at least partially via membrane domains. Identification of internalized pools of FLAG-δ-OR by colocalization studies with proteins of Rab family indicated the decreased presence of receptors in early endosomes (Rab5), late endosomes and lysosomes (Rab7) and fast recycling vesicles (Rab4). Slow type of recycling (Rab11) was unchanged by cholesterol depletion. As expected, agonist-induced internalization of oxytocin receptors was totally suppressed in β-CDX-treated cells. Determination of average fluorescence lifetime of TMA-DPH, the polar derivative of hydrophobic membrane probe diphenylhexatriene, in live cells by FLIM indicated a significant alteration of the overall PM structure which may be interpreted as an increased "water-accessible space" within PM area. Data obtained by studies of HEK293 cells transiently expressing FLAG-δ-OR by "antibody feeding" method were extended by analysis of the effect of cholesterol depletion on distribution of FLAG-δ-OR in sucrose density gradients prepared from HEK293 cells stably expressing FLAG-δ-OR. Major part of FLAG-δ-OR was co-localized with plasma membrane marker Na,K-ATPase and β-CDX treatment resulted in shift of PM fragments containing both FLAG-δ-OR and Na,K-ATPase to higher density. Thus, the decrease in content of the major lipid constituent of PM resulted in increased density of resulting PM fragments.

  16. Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels.

    PubMed Central

    Cohen, J C; Wang, Z; Grundy, S M; Stoesz, M R; Guerra, R

    1994-01-01

    Genetic factors have been shown to play an important role in determining interindividual variation in plasma HDL-C levels, but the specific genetic determinants of HDL cholesterol (HDL-C) levels have not been elucidated. In this study, the effects of variation in the genomic regions encoding hepatic lipase, apolipoprotein AI/CIII/AIV, and the cholesteryl ester transfer protein on plasma HDL-C levels were examined in 73 normotriglyceridemic, Caucasian nuclear families. Genetic factors accounted for 56.5 +/- 13% of the interindividual variation in plasma HDL-C levels. For each candidate gene, adjusted plasma HDL-C levels of sibling pairs who shared zero, one, or two parental alleles identical-by-descent were compared using sibling-pair linkage analysis. Allelic variation in the genes encoding hepatic lipase and apolipoprotein AI/CIII/AIV accounted for 25 and 22%, respectively, of the total interindividual variation in plasma HDL-C levels. In contrast, none of the variation in plasma HDL-C levels could be accounted for by allelic variation in the cholesteryl ester transfer protein. These findings indicate that a major fraction of the genetically determined variation in plasma HDL-C levels is conferred by allelic variation at the hepatic lipase and the apolipoprotein AI/CIII/AIV gene loci. PMID:7989594

  17. MD-2 binds cholesterol.

    PubMed

    Choi, Soo-Ho; Kim, Jungsu; Gonen, Ayelet; Viriyakosol, Suganya; Miller, Yury I

    2016-02-19

    Cholesterol is a structural component of cellular membranes, which is transported from liver to peripheral cells in the form of cholesterol esters (CE), residing in the hydrophobic core of low-density lipoprotein. Oxidized CE (OxCE) is often found in plasma and in atherosclerotic lesions of subjects with cardiovascular disease. Our earlier studies have demonstrated that OxCE activates inflammatory responses in macrophages via toll-like receptor-4 (TLR4). Here we demonstrate that cholesterol binds to myeloid differentiation-2 (MD-2), a TLR4 ancillary molecule, which is a binding receptor for bacterial lipopolysaccharide (LPS) and is indispensable for LPS-induced TLR4 dimerization and signaling. Cholesterol binding to MD-2 was competed by LPS and by OxCE-modified BSA. Furthermore, soluble MD-2 in human plasma and MD-2 in mouse atherosclerotic lesions carried cholesterol, the finding supporting the biological significance of MD-2 cholesterol binding. These results help understand the molecular basis of TLR4 activation by OxCE and mechanisms of chronic inflammation in atherosclerosis.

  18. Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice.

    PubMed

    Bura, Kanwardeep S; Lord, Caleb; Marshall, Stephanie; McDaniel, Allison; Thomas, Gwyn; Warrier, Manya; Zhang, Jun; Davis, Matthew A; Sawyer, Janet K; Shah, Ramesh; Wilson, Martha D; Dikkers, Arne; Tietge, Uwe J F; Collet, Xavier; Rudel, Lawrence L; Temel, Ryan E; Brown, J Mark

    2013-06-01

    Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the nonbiliary transintestinal cholesterol efflux (TICE) pathway. Scavenger receptor class B type I (SR-BI) plays a critical role in the classic hepatobiliary route of RCT. However, the role of SR-BI in TICE has not been studied. To examine the role of intestinal SR-BI in TICE, sterol balance was measured in control mice and mice transgenically overexpressing SR-BI in the proximal small intestine (SR-BI(hApoCIII-ApoAIV-Tg)). SR-BI(hApoCIII-ApoAIV-Tg) mice had significantly lower plasma cholesterol levels compared with wild-type controls, yet SR-BI(hApoCIII-ApoAIV-Tg) mice had normal fractional cholesterol absorption and fecal neutral sterol excretion. Both in the absence or presence of ezetimibe, intestinal SR-BI overexpression had no impact on the amount of cholesterol excreted in the feces. To specifically study effects of intestinal SR-BI on TICE we crossed SR-BI(hApoCIII-ApoAIV-Tg) mice into a mouse model that preferentially utilized the TICE pathway for RCT (Niemann-Pick C1-like 1 liver transgenic), and likewise found no alterations in cholesterol absorption or fecal sterol excretion. Finally, mice lacking SR-BI in all tissues also exhibited normal cholesterol absorption and fecal cholesterol disposal. Collectively, these results suggest that SR-BI is not rate limiting for intestinal cholesterol absorption or for fecal neutral sterol loss through the TICE pathway.

  19. High density lipoprotein as a source of cholesterol for adrenal steroidogenesis: a study in individuals with low plasma HDL-C.

    PubMed

    Bochem, Andrea E; Holleboom, Adriaan G; Romijn, Johannes A; Hoekstra, Menno; Dallinga-Thie, Geesje M; Motazacker, Mahdi M; Hovingh, G Kees; Kuivenhoven, Jan A; Stroes, Erik S G

    2013-06-01

    Few studies have addressed the delivery of lipoprotein-derived cholesterol to the adrenals for steroid production in humans. While there is evidence against a role for low-density lipoprotein (LDL), it is unresolved whether high density lipoprotein (HDL) contributes to adrenal steroidogenesis. To study this, steroid hormone profiles in urine were assessed in male subjects suffering from functional mutations in ATP binding cassette transporter A1 (ABCA1) (n = 24), lecithin:cholesterol acyltransferase (LCAT) (n = 40), as well as in 11 subjects with low HDL cholesterol (HDL-C) without ABCA1/LCAT mutations. HDL-C levels were 39% lower in the ABCA1, LCAT, and low HDL-C groups compared with controls (all P < 0.001). In all groups with low HDL-C levels, urinary excretion of 17-ketogenic steroids was reduced by 33%, 27%, and 32% compared with controls (all P < 0.04). In seven carriers of either type of mutation, adrenocorticotropic hormone (ACTH) stimulation did not reveal differences from normolipidemic controls. In conclusion, this study shows that basal but not stimulated corticosteroid metabolism is attenuated in subjects with low HDL-C, irrespective of its molecular origin. These findings lend support to a role for HDL as a cholesterol donor for basal adrenal steroidogenesis in humans. PMID:23511897

  20. Higher prevalence of smoking and lower BMI, waist circumference, cholesterol and triacylglyceride levels in Prague's homeless compared to a majority of the Czech population

    PubMed Central

    Kubisová, Dana; Adámková, Věra; Lánská, Věra; Dlouhý, Pavel; Rambousková, Jolana; Anděl, Michal

    2007-01-01

    Background Homeless people have higher morbidity and mortality rates than the general population. Research has shown that cardiovascular disease is the leading cause of death in older homeless adults. This study was undertaken to describe the prevalence of cardiovascular risk factors in the homeless population in Prague. Methods Data was obtained from a cross-sectional study carried out in 2003. Body mass index (BMI), waist circumference (WC), total cholesterol (TC), triacylglycerides (TAG) and smoking habits were assessed. The homeless participants in the study were recruited from a homeless center run by a Prague charitable organization called Naděje ("Hope") and at Prague's main railway station. Most participants were assessed at the Naděje center (134 persons) while the rest were assessed at Prague's Bulovka University Hospital (67 persons). Results A total of 201 homeless (174 males and 27 females) aged 19 – 70 years were examined. Mean values of BMI, WC, TC and TAG in homeless men and women were within normal limits. Compared with the majority of the Czech population, the homeless had significantly lower mean levels of TC and TAG and lower BMI and WC values. When compared to the majority of the Czech population, the incidence of smoking among the homeless was significantly higher. Among smokers in both populations, no differences were found in the number of cigarettes smoked per day. Conclusion Classical cardiovascular risk factors such as TC, TAG, BMI and WC, are significantly lower in Prague's homeless minority than in the majority of the Czech population. However, the prevalence of smoking is much higher in the homeless population. PMID:17411429

  1. Diabetes-induced impairments of the exocytosis process and the effect of gabapentin: the link with cholesterol level in neuronal plasma membranes.

    PubMed

    Trikash, Irene; Gumenyuk, Vitaliy; Kuchmerovska, Tamara

    2015-04-01

    Diabetic neuropathy represents one of the most prevalent complications of diabetes mellitus. The aim of this study was to investigate the effect of diabetes-induced disturbances in neurons on the Ca(2+)-triggered membrane fusion process in cell-free system in relation to plasmalemma cholesterol level. The gabapentin therapy on the exocytosis process was also studied. The diabetes in rats was induced by streptozotocin (60 mg/kg of body weight, i.p.). After 4 weeks of diabetes induction the one group of diabetic rats was treated with gabapentin (50 mg/kg, i.p.) during 1 month. Fusion experiments were performed in the cell-free model system using fluorescent dye octadecylrhodamine B. The [2-(14)C]serotonin preloaded synaptosomes were used for assay of stimulated neurotransmitter release. The synaptosomal plasma membrane cholesterol level in diabetic rats was on 12 % higher than in control and was decreased on 5 % after gabapentin therapy. The rate of synaptic vesicles fusion with plasma membranes in the presence of Ca(2+) and synaptosomal cytosolic proteins was decreased to 14.5 % in diabetic rats as compared to control (23 %) and after gabapentin administration to diabetic rats was raised to 18 %. At diabetes the stimulated synaptosomal serotonin release was increased in 1.7-2 folds and was partially normalized by gabapentin therapy. Together, these findings suggest that elevated cholesterol content in neuronal plasma membranes at diabetes impairs the membrane fusion process in neurons that can induce the development of neuropathy. Diabetes-evoked impairments of the exocytotic process can be attenuated by gabapentin therapy.

  2. Cholesterol and Affective Morbidity

    PubMed Central

    Fiedorowicz, Jess G.; Palagummi, Narasimha M.; Behrendtsen, Ole; Coryell, William H.

    2009-01-01

    Depression and mania have been linked with low cholesterol though there has been limited prospective study of cholesterol and subsequent course of affective illness. We studied the relationship between fasting total cholesterol and subsequent depressive and manic symptoms. A total of 131 participants from a prospective cohort study were identified as having had a fasting total cholesterol evaluation at intake. Participants were predominantly inpatients at index visit and were followed for a median of 20 and up to 25 years. Cholesterol was modeled with age, gender, and index use of a mood stabilizer in linear regression to assess its influence on subsequent depressive symptom burden in participants with unipolar disorder as well as depressive and manic symptom burden in participants with bipolar disorder. Among bipolar participants (N=65), low cholesterol predicted a higher proportion of follow-up weeks with manic, but not depressive symptoms. Cholesterol did not appear to predict depressive symptom burden among participants with unipolar depression (N=66). Lower cholesterol levels may predispose individuals with bipolar disorder to a greater burden of manic symptomatology and may provide some insight into the underlying neurobiology. PMID:19969372

  3. Resveratrol Protects Rabbits Against Cholesterol Diet-Induced Hyperlipidaemia.

    PubMed

    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 < 0.05) decrease in total cholesterol (TC), Low density lipoprotein cholesterol (LDP-c), total triacylglyceroland an increase in high density lipoprotein cholesterol (HDL-c) in 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

  4. Cholesterol and unsaturated fat diets influence lipid and glucose concentrations in rats.

    PubMed

    Adamopoulos, P N; Papamichael, C M; Zampelas, A; Moulopoulos, S D

    1996-03-01

    The present study investigated the effects of dietary cholesterol and monounsaturated and polyunsaturated fatty acids on plasma lipids and glucose concentrations. Four groups of ten male Wistar albino rats were fed diets of different fatty acid composition for 40 days. The control group consumed nonpurified diet (containing fat 3.7 g/100 g diet), and cholesterol, olive oil, and safflower oil groups consumed the nonpurified diet enriched with 14 g fat/100 g diet with egg yolk, olive oil, or safflower oil, respectively. Compared with the control, the diet enriched with cholesterol significantly increased fasting plasma cholesterol (P < 0.01), triacylglycerol (P < 0.01), total lipid (P < 0.01) and glucose (P < 0.05) concentrations; in the olive oil group, cholesterol and triacylglycerol levels were significantly increased compared with control group (P < 0.01 in both instances). In safflower oil group, triacylglycerol levels were also significantly increased (P < 0.05) compared with the controls. After comparing diets providing the same amount of fat (cholesterol, olive oil, and safflower oil groups), higher cholesterol, triacylglycerol and total lipid levels were observed in the cholesterol group than in the olive oil group (P < 0.01, P < 0.05 and P < 0.01, respectively), and safflower oil group (P < 0.01 in all instances). High-density lipoprotein-cholesterol concentrations were significantly lower in the cholesterol group than in the olive oil and safflower oil groups (P < 0.05 in both instances) and fasting plasma glucose levels were higher in the cholesterol than in the olive oil (P < 0.05) and safflower oil groups (P < 0.01). Finally, after comparing lipid and glucose levels in the unsaturated fatty acids-enriched diets, higher plasma cholesterol concentrations were observed in the olive oil than in the safflower oil group (P < 0.05). These data suggest that not only the amount but also the type of dietary fat can influence serum lipid levels.

  5. Lower Hybrid Oscillations in Multicomponent Space Plasmas Subjected to Ion Cyclotron Waves

    NASA Technical Reports Server (NTRS)

    Khazanov, G. V.; Krivorutsky, E. N.; Moore, T. E.; Liemohn, M. W.; Horwitz, J. L.

    1997-01-01

    It is found that in multicomponent plasmas subjected to Alfven or fast magnetosonic waves, such as are observed in regions of the outer plasmasphere and ring current-plasmapause overlap, lower hybrid oscillations are generated. The addition of a minor heavy ion component to a proton-electron plasma significantly lowers the low-frequency electric wave amplitude needed for lower hybrid wave excitation. It is found that the lower hybrid wave energy density level is determined by the nonlinear process of induced scattering by ions and electrons; hydrogen ions in the region of resonant velocities are accelerated; and nonresonant particles are weakly heated due to the induced scattering. For a given example, the light resonant ions have an energy gain factor of 20, leading to the development of a high-energy tail in the H(+) distribution function due to low-frequency waves.

  6. Effect of pharmacological lowering of plasma urate on exercise-induced oxidative stress.

    PubMed

    McAnulty, S R; Hosick, P A; McAnulty, L S; Quindry, J C; Still, L; Hudson, M B; Dibarnardi, A N; Milne, G L; Morrow, J D; Austin, M D

    2007-12-01

    Urate is a metabolic end product of purine metabolism that contributes about 66% of the antioxidant capacity of plasma. The objective of this study was to evaluate the importance of plasma urate as an antioxidant using pharmacological lowering and examining the impact on plasma antioxidant capacity and oxidative stress after intense exercise. Fifteen subjects ran for 45 min at approximately 80% VO2 max under the influence of probenecid (1 g/d) (PRO) or placebo (PLA) in a double-blind, crossover design. Blood samples obtained at baseline, pre-exercise, and immediately post-exercise were analyzed for F2-isoprostanes, lipid hydroperoxides (LHs), ferric-reducing ability of plasma (FRAP), urate, ascorbate (AA), and nitrite. A 2 (group)x2 (time) repeated-measures analysis of variance (ANOVA), one-way ANOVA, Tukey-Kramer multiple comparison tests, and Student's t tests were used for statistical analysis. PRO exhibited lowered urate and FRAP compared with baseline (pplasma markers of exercise-induced oxidative stress were not affected by below-normal physiological concentrations of urate and a diminished antioxidant capacity within the plasma compartment.

  7. Effect on plasma rotation of lower hybrid (LH) waves in Alcator C-Mod

    SciTech Connect

    Lee, J. P.; Barnes, M.; Parker, R. R.; Rice, J. E.; Parra, F. I.; Bonoli, P. T.; Reinke, M. L.

    2014-02-12

    The injection of LH waves for current drive into a tokamak changes the ion toroidal rotation. In Alcator C-Mod, the direction of the steady state rotation change due to LH waves depends on the plasma current and the density. The change in rotation can be estimated by balancing the external torque of lower hybrid waves with the turbulent radial transport of the momentum. For high plasma current, the turbulent pinch and diffusion of the injected counter-current momentum are sufficient to explain the rotation change. However, for low plasma current, the change in the the intrinsic momentum transport (residual stress) for a non-rotating state is required to explain the co-current rotation change. Accordingly, we investigate the intrinsic momentum transport for the non-rotating state when diamagnetic flow and ExB flow cancel each other. The change in the intrinsic momentum transport due to lower hybrid waves is significant when the plasma current is low, which may explain the rotation reversal for low plasma current. The effect of changed q (safety factor) profile by lower hybrid on the intrinsic momentum transport is estimated by gyrokinetics.

  8. Membrane Cholesterol Regulates Lysosome-Plasma Membrane Fusion Events and Modulates Trypanosoma cruzi Invasion of Host Cells

    PubMed Central

    Hissa, Bárbara; Duarte, Jacqueline G.; Kelles, Ludmila F.; Santos, Fabio P.; del Puerto, Helen L.; Gazzinelli-Guimarães, Pedro H.; de Paula, Ana M.; Agero, Ubirajara; Mesquita, Oscar N.; Guatimosim, Cristina; Chiari, Egler; Andrade, Luciana O.

    2012-01-01

    Background Trypomastigotes of Trypanosoma cruzi are able to invade several types of non-phagocytic cells through a lysosomal dependent mechanism. It has been shown that, during invasion, parasites trigger host cell lysosome exocytosis, which initially occurs at the parasite-host contact site. Acid sphingomyelinase released from lysosomes then induces endocytosis and parasite internalization. Lysosomes continue to fuse with the newly formed parasitophorous vacuole until the parasite is completely enclosed by lysosomal membrane, a process indispensable for a stable infection. Previous work has shown that host membrane cholesterol is also important for the T. cruzi invasion process in both professional (macrophages) and non-professional (epithelial) phagocytic cells. However, the mechanism by which cholesterol-enriched microdomains participate in this process has remained unclear. Methodology/Principal Finding In the present work we show that cardiomyocytes treated with MβCD, a drug able to sequester cholesterol from cell membranes, leads to a 50% reduction in invasion by T. cruzi trypomastigotes, as well as a decrease in the number of recently internalized parasites co-localizing with lysosomal markers. Cholesterol depletion from host membranes was accompanied by a decrease in the labeling of host membrane lipid rafts, as well as excessive lysosome exocytic events during the earlier stages of treatment. Precocious lysosomal exocytosis in MβCD treated cells led to a change in lysosomal distribution, with a reduction in the number of these organelles at the cell periphery, and probably compromises the intracellular pool of lysosomes necessary for T. cruzi invasion. Conclusion/Significance Based on these results, we propose that cholesterol depletion leads to unregulated exocytic events, reducing lysosome availability at the cell cortex and consequently compromise T. cruzi entry into host cells. The results also suggest that two different pools of lysosomes are

  9. Men and women--similar but not identical: insights into LDL-lowering therapy in women from the Cholesterol Treatment Trialists Collaboration.

    PubMed

    Kritharides, Leonard; Nicholls, Stephen J

    2015-09-01

    Evaluation of: Fulcher et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet 385(9976), 1397-1405 (2015). A recent publication has explored the role of gender in determining the benefit from statins. Using data on 174,000 patients (including 46,000 women) collected up to 2010, a meta-analysis was performed using individual patient data, separately analyzing results for men and women and adjusting for baseline risk and nongender related risk factors. Over a median duration of follow-up of 4.9 years, statins reduced the risk of major vascular events by 21% for each mmol/l reduction of LDL cholesterol (relative risk: 0.79; 95% CI: 0.77-0.81; p < 0.001), reducing risk by 22% for men and 16% for women. There was no significant overall heterogeneity for the benefit achieved in men versus that achieved in women after adjusting for baseline risk. Baseline risk substantially affected the absolute number of events prevented, but did not affect the proportional benefit attributed to the use of statins. Total mortality was similarly and significantly reduced in men (10%) and women (9%). This study adds to existing literature in confirming that statins have demonstrable benefit in men and women. PMID:26406297

  10. Electrostatic ion cyclotron, beam-plasma, and lower hybrid waves excited by an electron beam

    NASA Technical Reports Server (NTRS)

    Singh, N.; Conrad, J. R.; Schunk, R. W.

    1985-01-01

    It is pointed out that electrostatic ion cyclotron (EIC) waves have been extensively investigated in connection with both space and laboratory plasmas. The present investigation has the objective to study the excitation of low-frequency waves in a multiion plasma by electron beams. The frequencies considered range from below the lowest gyrofrequency of the heaviest ion to about the lower hybrid frequency. It is shown that electron-beam instabilities can produce peaks in the growth rate below the cyclotron frequency of each ion species if nonzero perpendicular wave number effects are included in the ion dynamics. The dispersion relations for neutralized ion Bernstein (NIB) and pure ion Bernstein (PIB) waves are considered along with an instability analysis for a cold plasma and warm electron beam, the electron beam-plasma mode, banded ion cyclotron (EIC) waves with small perpendicular wavelengths, and the growth lengths of the waves.

  11. COST-EFFECTIVENESS OF LOWER TARGETS FOR BLOOD PRESSURE AND LDL CHOLESTEROL IN DIABETES: THE STOP ATHEROSCLEROSIS IN NATIVE DIABETICS STUDY (SANDS)

    PubMed Central

    Wilson, Charlton; Huang, Chun-Chih; Shara, Nawar; Howard, Barbara V.; Fleg, Jerome L.; Henderson, Jeffrey A.; Howard, Wm. James; Huentelman, Heather; Lee, Elisa T.; Mete, Mihriye; Russell, Marie; Galloway, James M.; Silverman, Angela; Stylianou, Mario; Umans, Jason; Weir, Matthew R.; Yeh, Fawn; Ratner, Robert E.

    2010-01-01

    Background The Stop Atherosclerosis in Native Diabetics Study (SANDS) reported cardiovascular benefit of aggressive versus standard treatment targets for both low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) in diabetic individuals. Objective In this analysis, we examined within trial cost-effectiveness of aggressive targets of LDL-C ≤70 mg/dL and systolic blood pressure (SBP) ≤115 mmHg vs. standard targets of LDL-C ≤100 mg/dL and SBP ≤130 mmHg. Design Randomized, open label blinded-to-endpoint 3-year trial. Data Sources SANDS clinical trial database, Quality of Wellbeing (QWB) survey, Centers for Medicare and Medicaid Services, Wholesale Drug Prices. Target Population American Indians ≥ age 40 years with type 2 diabetes and no prior cardiovascular events. Time Horizon April 2003-July 2007. Perspective Health payer. Interventions Participants were randomized to aggressive vs. standard groups with treatment algorithms defined for both. Outcome Measures Incremental cost-effectiveness. Results of Base-Case Analysis Compared with the standard group, the aggressive group had slightly lower costs of medical services ($-116), but a 54% higher cost for BP medication ($1,242) and a 116% higher cost for lipid-lowering medication ($2,863), resulting in an increased cost of $3,988 over 3 years. Those in the aggressively treated group gained 0.0480 quality-adjusted life-years (QALY) over the standard group. Using a 3% discount rate for costs and outcomes, the resulting cost per QALY was $82,589. Results of Sensitivity Analysis Using a 25%, 50%, and 75% reduction in drug costs resulted in a cost per QALY of $61,329, $40,070, and $18,810, respectively. Limitations This study was limited by use of a single ethnic group and by its 3-year duration. Conclusions Within this 3-year study, treatment to lower BP and LDL-C below standard targets was not cost-effective due to the cost of the additional medications required to meet the lower targets. With the

  12. Facts about...Blood Cholesterol. Revised.

    ERIC Educational Resources Information Center

    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…

  13. Cholesterol, inflammasomes, and atherogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasma cholesterol levels have been strongly associated with atherogenesis, underscoring the role of lipid metabolism in defining cardiovascular disease risk. However, atherosclerotic plaque is highly dynamic and contains elements of both the innate and adaptive immune system that respond to the abe...

  14. Interference patterns in the Spacelab 2 plasma wave data: Lower hybrid waves driven by pickup ions

    NASA Technical Reports Server (NTRS)

    Feng, Wei; Gurnett, Donald A.; Cairns, Iver H.

    1993-01-01

    During the Spacelab 2 mission the University of Iowa's Plasma Diagnostics Package (PDP) was released from the shuttle to explore the plasma environment around the shuttle. Wideband spectrograms were obtained from the PDP at frequencies from 0 to 30 kHz and distances up to 400 m from the shuttle. The wideband data frequently showed antenna interference patterns when the PDP was on the downstream side of the shuttle. Analysis of these interference patterns allows a determination of the wavelength, the plasma rest frame frequency, the direction of propagation, the power spectrum, and in some cases the location of the source. We concentrate our analysis on interference patterns due to lower hybrid waves: waves which have rest frame frequencies near the lower hybrid frequency and propagate perpendicular to the magnetic field. The waves have an almost flat dispersion relation with frequencies just above the lower hybrid frequency and relatively short wavelengths (1 - 4 m). The observed lower hybrid waves depend strongly on the position of the PDP relative to the shuttle and the magnetic field direction. Our results confirm previous suggestions that the lower hybrid waves are generated primarily in the vicinity of the shuttle and that they are driven by a charge exchange interaction between the ambient ionosphere and a H2O cloud around the shuttle.

  15. Plasma current start-up using the lower hybrid wave on the TST-2 spherical tokamak

    NASA Astrophysics Data System (ADS)

    Takase, Y.; Ejiri, A.; Inada, T.; Moeller, C. P.; Shinya, T.; Tsujii, N.; Yajima, S.; Furui, H.; Homma, H.; Imamura, K.; Nakamura, K.; Nakamura, K.; Sonehara, M.; Takeuchi, T.; Togashi, H.; Tsuda, S.; Yoshida, Y.

    2015-12-01

    Non-inductive plasma current start-up, ramp-up and sustainment by waves in the lower hybrid wave (LHW) frequency range at 200 MHz were investigated on the TST-2 spherical tokamak (R0 ≤ 0.38 m, a ≤ 0.25 m, Bt0 ≤ 0.3T, Ip ≤ 0.14 MA). Experimental results obtained using three types of antenna were compared. Both the highest plasma current (Ip = 18 kA) and the highest current drive figure of merit ηCD≡n¯eIpR0/PRF=1.4 ×1017 A/W/m2 were achieved using the capacitively-coupled combline (CCC) antenna, designed to excite the LHW with a sharp and highly directional wavenumber spectrum. For Ip greater than about 5 kA, high energy electrons accelerated by the LHW become the dominant carrier of plasma current. The low value of ηCD observed so far are believed to be caused by a rapid loss of energetic electrons and parasitic losses of the LHW energy in the plasma periphery. ηCD is expected to improve by an order of magnitude by increasing the plasma current to improve energetic electron confinement. In addition, edge power losses are expected to be reduced by increasing the toroidal magnetic field to improve wave accessibility to the plasma core, and by launching the LHW from the inboard upper region of the torus to achieve better single-pass absorption.

  16. Experimental Measurements and Density Functional Theory Calculations of Continuum Lowering in Strongly Coupled Plasmas

    NASA Astrophysics Data System (ADS)

    Vinko, Sam

    2014-10-01

    An accurate description of the ionization potential depression (IPD) of ions in plasmas due to their interaction with the environment is a fundamental problem in plasma physics, playing a key role in determining the ionization balance, charge state distribution, opacity and plasma equation of state. Here I present the first experimental investigation of the IPD as a function of ionic charge state in a range of dense Mg, Al and Si plasmas, using the Linac Coherent Light Source X-ray free-electron laser. The measurements show significantly larger IPDs than are predicted by the most commonly used models, such as that of Stewart-Pyatt, or the ion-sphere model of Zimmerman-More. Instead, plasma simulations using finite-temperature density functional theory with excited-state projector augmented-wave potentials show excellent agreement with the experimental results and explain the stronger-than-expected continuum lowering through the electronic structure of the valence states in these strong-coupling conditions, which retain much of their atomic characteristics close to the ion core regions. These results have a profound impact on the understanding and modelling of plasmas over a wide range of warm- and hot-dense matter conditions.

  17. Investigations of lower hybrid wave-plasma coupling by gas puffing in HT-7

    SciTech Connect

    Ding, B. J.; Li, M. H.; Qin, Y. L.; Li, W. K.; Zhang, L. Z.; Shan, J. F.; Liu, F. K.; Wang, M.; Meng, L. G.; Xu, H. D.; Wang, D. X.; Jie, Y. X.; Sun, Y. W.; Shen, B.; Zhang, W.; Wang, X. M.; Wu, J. H.; Gao, X.; Zhang, X. D.; Zhao, Y. P.

    2010-02-15

    Lower hybrid wave (LHW)-plasma coupling experiments in HT-7 [J. K. Xie and HT-7 Group, Proceedings of the 16th International Conference on Fusion Energy, Montreal, 1996 (IAEA, Trieste, 1997), Vol. 1, p. 685] were carried out by means of puffing gas (CD{sub 4} and D{sub 2}) just around the antenna. Both experiments show that wave-plasma coupling is improved by the gas puffing. The maximum distance between the plasma and the antenna is limited to about 8 cm due to the plasma disruption. The variation in the lined averaged density in the different channels gives a possible evidence of the mechanism of the ionization of neutral gas. The effect of the gas flow rate on the wave-plasma coupling shows that an optimized gas flow rate is necessary for good coupling, being consistent with simulation through Brambilla theory qualitatively. Experiments with puffing D{sub 2} show that the improved coupling results from the global density increase and the local gas puffing. Langmuir probe measurements indicate that the gas puffing effectively increases the density and decreases the temperature in scrape of layer. Studies show that the ionization of the puffed gas is affected by both LHW electric field and plasma temperature. Comparison of D{sub 2} and CD{sub 4} puffing shows that D{sub 2} improves coupling better with less effect on core density.

  18. Subacute therapeutic dosing of artemether-lumefantrine and artesunate-amodiaquine combination preserves plasma cholesterol, renal antioxidant status, and organ weights in rats.

    PubMed

    Otuechere, Chiagoziem A; Edewor, Gloria; Kale, Oluwafemi Ezekiel; Ekor, Martins

    2012-01-01

    Recent instances of breakdowns of malaria control programs and the constant emergence of drug-resistant parasites to monotherapies have shored up the use of artemisinin-based combination therapy (ACT) as the malaria therapy of choice. We evaluated a subacute therapeutic dosing of artemether-lumefantrine and artesunate-amodiaquine on plasma cholesterol, renal antioxidants, and organ weights in rats. Sixteen albino rats were grouped into three. Group A (n = 5) served as the control. Groups B (n = 6) and C (n = 5) were administered, twice daily, oral therapeutic doses of artemether-lumefantrine (1.14/6.86 mg/kg/d) and artesunate-amodiaquine (2.86/8.58 mg/kg/d), respectively, for seven days. From our results, ACTs did not significantly (P > 0.05) alter catalase, superoxide dismutase, glutathione S-transferase, myeloperoxidase, and total glutathione levels when compared with the control. Plasma total cholesterol levels also decreased insignificantly (P > 0.05). Organ-system weights were not significantly (P > 0.05) different from control rats. Artesunate-amodiaquine, but not artemether-lumefantrine, significantly increased (P < 0.05) lactate dehydrogenase activity and also afforded a 27.2% decrease in heart weight when compared with control. Also, both ACTs increased (P < 0.05) lipid peroxidation. Overall, artesunate-amodiaquine and artemether-lumefantrine may preserve renal antioxidants and organ weights in vivo. However, caution is required above therapeutic indications or in chronic doses as this may predispose to renal oxidative stress.

  19. An Ester of β-Hydroxybutyrate Regulates Cholesterol Biosynthesis in Rats and a Cholesterol Biomarker in Humans.

    PubMed

    Kemper, Martin F; Srivastava, Shireesh; Todd King, M; Clarke, Kieran; Veech, Richard L; Pawlosky, Robert J

    2015-12-01

    In response to carbohydrate deprivation or prolonged fasting the ketone bodies, β-hydroxybutyrate (βHB) and acetoacetate (AcAc), are produced from the incomplete β-oxidation of fatty acids in the liver. Neither βHB nor AcAc are well utilized for synthesis of sterols or fatty acids in human or rat liver. To study the effects of ketones on cholesterol homeostasis a novel βHB ester (KE) ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) was synthesized and given orally to rats and humans as a partial dietary carbohydrate replacement. Rats maintained on a diet containing 30-energy % as KE with a concomitant reduction in carbohydrate had lower plasma cholesterol and mevalonate (-40 and -27 %, respectively) and in the liver had lower levels of the mevalonate precursors acetoacetyl-CoA and HMG-CoA (-33 and -54 %) compared to controls. Whole liver and membrane LDL-R as well as SREBP-2 protein levels were higher (+24, +67, and +91 %, respectively). When formulated into a beverage for human consumption subjects consuming a KE drink (30-energy %) had elevated plasma βHB which correlated with decreased mevalonate, a liver cholesterol synthesis biomarker. Partial replacement of dietary carbohydrate with KE induced ketosis and altered cholesterol homeostasis in rats. In healthy individuals an elevated plasma βHB correlated with lower plasma mevalonate. PMID:26498829

  20. An Ester of β-Hydroxybutyrate Regulates Cholesterol Biosynthesis in Rats and a Cholesterol Biomarker in Humans.

    PubMed

    Kemper, Martin F; Srivastava, Shireesh; Todd King, M; Clarke, Kieran; Veech, Richard L; Pawlosky, Robert J

    2015-12-01

    In response to carbohydrate deprivation or prolonged fasting the ketone bodies, β-hydroxybutyrate (βHB) and acetoacetate (AcAc), are produced from the incomplete β-oxidation of fatty acids in the liver. Neither βHB nor AcAc are well utilized for synthesis of sterols or fatty acids in human or rat liver. To study the effects of ketones on cholesterol homeostasis a novel βHB ester (KE) ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) was synthesized and given orally to rats and humans as a partial dietary carbohydrate replacement. Rats maintained on a diet containing 30-energy % as KE with a concomitant reduction in carbohydrate had lower plasma cholesterol and mevalonate (-40 and -27 %, respectively) and in the liver had lower levels of the mevalonate precursors acetoacetyl-CoA and HMG-CoA (-33 and -54 %) compared to controls. Whole liver and membrane LDL-R as well as SREBP-2 protein levels were higher (+24, +67, and +91 %, respectively). When formulated into a beverage for human consumption subjects consuming a KE drink (30-energy %) had elevated plasma βHB which correlated with decreased mevalonate, a liver cholesterol synthesis biomarker. Partial replacement of dietary carbohydrate with KE induced ketosis and altered cholesterol homeostasis in rats. In healthy individuals an elevated plasma βHB correlated with lower plasma mevalonate.

  1. Phosphatidylcholine: Greasing the Cholesterol Transport Machinery

    PubMed Central

    Lagace, Thomas A.

    2015-01-01

    Negative feedback regulation of cholesterol metabolism in mammalian cells ensures a proper balance of cholesterol with other membrane lipids, principal among these being the major phospholipid phosphatidylcholine (PC). Processes such as cholesterol biosynthesis and efflux, cholesteryl ester storage in lipid droplets, and uptake of plasma lipoproteins are tuned to the cholesterol/PC ratio. Cholesterol-loaded macrophages in atherosclerotic lesions display increased PC biosynthesis that buffers against elevated cholesterol levels and may also facilitate cholesterol trafficking to enhance cholesterol sensing and efflux. These same mechanisms could play a generic role in homeostatic responses to acute changes in membrane free cholesterol levels. Here, I discuss the established and emerging roles of PC metabolism in promoting intracellular cholesterol trafficking and membrane lipid homeostasis. PMID:27081313

  2. On the instability and energy flux of lower hybrid waves in the Venus plasma mantle

    NASA Technical Reports Server (NTRS)

    Strangeway, R. J.; Crawford, G. K.

    1993-01-01

    Waves generated near the lower hybrid resonance frequency by the modified two stream instability have been invoked as a possible source of energy flux into the topside ionosphere of Venus. These waves are observed above the ionopause in a region known as the plasma mantle. The plasma within the mantle appears to be a mixture of magnetosheath and ionospheric plasmas. Since the magnetosheath electrons and ions have temperatures of several tens of eV, any instability analysis of the modified two stream instability requires the inclusion of finite electron and ion temperatures. Finite temperature effects are likely to reduce the growth rate of the instability. Furthermore, the lower hybrid waves are only quasi-electrostatic, and the energy flux of the waves is mainly carried by parallel Poynting flux. The magnetic field in the mantle is draped over the ionopause. Lower hybrid waves therefore cannot transport any significant wave energy to lower altitudes, and so do not act as a source of additional heat to the topside ionosphere.

  3. Estrogen Decreases Atherosclerosis In Part By Reducing Hepatic Acyl-CoA:Cholesterol Acyltransferase 2 (ACAT2) In Monkeys

    PubMed Central

    Kavanagh, Kylie; Davis, Matthew A.; Zhang, Li; Wilson, Martha D.; Register, Thomas C.; Adams, Michael R.; Rudel, Lawrence L.; Wagner, Janice D.

    2009-01-01

    Objective Estrogens decrease atherosclerosis progression, mediated in part through changes in plasma lipids and lipoproteins. This study aimed to determine estrogen-induced changes in hepatic cholesterol metabolism, plasma lipoproteins, and the relationship of these changes to atherosclerosis extent. Methods and Results Ovariectomized monkeys (n=34) consumed atherogenic diets for 30 months which contained either no hormones (control, n=17) or conjugated equine estrogens (CEE, n=17) at a human dose equivalent of 0.625 mg/d. Hepatic cholesterol content, low-density lipoprotein (LDL) receptor expression, cholesterol 7α-hydroxylase and acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity and expression levels were determined. CEE treatment resulted in lower plasma concentrations of very-low- and intermediate density lipoprotein cholesterol (V+IDLC; p=0.01), smaller LDL particles (p=0.002) and 50% lower hepatic cholesterol content (total, free and esterified; p<0.05 for all). Total ACAT activity was significantly lower (p=0.01), explained primarily by reductions in the activity of ACAT2. Estrogen regulation of enzymatic activity was at the protein level as both ACAT1 and 2 protein, but not mRNA levels, were lower (p=0.02 and <0.0001, respectively). ACAT2 activity was significantly associated with hepatic total cholesterol, plasma V+IDLC cholesterol, and atherosclerosis. Conclusions Atheroprotective effects of estrogen therapy may be related to reduced hepatic secretion of ACAT2-derived cholesteryl esters in plasma lipoproteins. Condensed Abstract Estrogen inhibits atherogenesis. We demonstrate in ovariectorized monkeys that estrogen therapy led to lower hepatic and circulating lipoprotein cholesterol, and lower ACAT2 protein and associated activity levels as compared to controls. Hepatic ACAT2 activity was highly correlated with, and was an independent predictor of coronary artery atherosclerosis extent. PMID:19759374

  4. The influence of Lactobacillus acidophilus and bacitracin on layer performance of chickens and cholesterol content of plasma and egg yolk.

    PubMed

    Abdulrahim, S M; Haddadin, S Y; Hashlamoun, E A; Robinson, R K

    1996-05-01

    1. The influence of Lactobacillus acidophilus alone or in combination with zinc bacitracin on the performance of laying hens was monitored over a period of 4 months. 2. Lactobacillus acidophilus improved egg production, food conversion and reduced the cholesterol concentration in the eggs, but zinc bacitracin had no effect when administered alone. 3. In combination, bacitracin had an adverse effect on the otherwise beneficial activity of the culture. PMID:8773843

  5. How cholesterol regulates endothelial biomechanics

    PubMed Central

    Hong, Zhongkui; Staiculescu, Marius C.; Hampel, Paul; Levitan, Irena; Forgacs, Gabor

    2012-01-01

    As endothelial cells form the barrier between blood flow and surrounding tissue, many of their functions depend on mechanical integrity, in particular those of the plasma membrane. As component and organizer of the plasma membrane, cholesterol is a regulator of cellular mechanical properties. Disruption of cholesterol balance leads to impairment of endothelial functions and eventually to disease. The mechanical properties of the membrane are strongly affected by the cytoskeleton. As Phosphatidylinositol-4,5-bisphosphate (PIP2) is a key mediator between the membrane and cytoskeleton, it also affects cellular biomechanical properties. Typically, PIP2 is concentrated in cholesterol-rich microdomains, such as caveolae and lipid rafts, which are particularly abundant in the endothelial plasma membrane. We investigated the connection between cholesterol and PIP2 by extracting membrane tethers from bovine aortic endothelial cells (BAEC) at different cholesterol levels and PIP2 conditions. Our results suggest that in BAEC the role of PIP2, as a mediator of membrane-cytoskeleton adhesion, is regulated by cholesterol. Our findings confirm the specific role of cholesterol in endothelial cells and may have implications for cholesterol-dependent vascular pathologies. PMID:23162471

  6. Cholesterol as a Causative Factor in Alzheimer Disease: A Debatable Hypothesis

    PubMed Central

    Wood, W. Gibson; Li, Ling; Müller, Walter E.; Eckert, Gunter P.

    2014-01-01

    High serum/plasma cholesterol levels have been suggested as a risk factor for Alzheimer disease (AD). Some reports, mostly retrospective epidemiological studies, have observed a decreased prevalence of AD in patients taking the cholesterol lowering drugs, statins. The strongest evidence causally linking cholesterol to AD is provided by experimental studies showing that adding/reducing cholesterol alters amyloid precursor protein (APP) and amyloid beta-protein (Aβ) levels. However, there are problems with the cholesterol-AD hypothesis. Cholesterol levels in serum/plasma and brain of AD patients do not support cholesterol as a causative factor in AD. Prospective studies on statins and AD have largely failed to show efficacy. Even the experimental data are open to interpretation given that it is well-established that modification of cholesterol levels has effects on multiple proteins, not only APP and Aβ. The purpose of this review, therefore, is to examine the above-mentioned issues and discuss the pros and cons of the cholesterol-AD hypothesis, and the involvement of other lipids in the mevalonate pathway, such as isoprenoids and oxysterols, in AD. PMID:24329875

  7. The Nonlinear Coupling of Alfven and Lower Hybrid Waves in Space Plasma

    NASA Technical Reports Server (NTRS)

    Khazanov, G. V.; Singh, N.; Krivorutsky, E.

    2003-01-01

    Space plasmas support a wide variety of waves, and wave-particle interactions as well as wave-wave interactions which are of crucial importance to magnetospheric and ionospheric plasma behavior. The excitation of lower hybrid waves (LHWs), in particular, is a widely discussed mechanism of interaction between plasma species in space and is one of the unresolved questions of magnetospheric multi-ion plasmas. It is demonstrated that large-amplitude Alfven waves may generate LHWs in the auroral zone and ring current region and in some cases (particularly in the inner magnetosphere) this serves as the Alfven wave saturation mechanism. We present several examples of observational data which illustrate that the proposed mechanism is a plausible candidate to explain certain classes of LHW generation events in the ionosphere and magnetosphere and demonstrate electron and ion energization involving these processes. Furthermore, we will present results from particle-in-cell simulations showing the generation of particle drifts in response to an Alfven wave, resulting in excitation of waves and ion heating in a multi- ion plasma.

  8. Correlation between plasma component levels of cultured fish and resistance to bacterial infection

    USGS Publications Warehouse

    Maita, M.; Satoh, K.-I.; Fukuda, Y.; Lee, H.-K.; Winton, J.R.; Okamoto, N.

    1998-01-01

    Mortalities of yellowtail Seriola quinqueradiata artificially infected with Lactococcus garvieae and of rainbow trout Oncorhynchus mykiss artificially infected with Vibrio anguillarum were compared with the levels of plasma components measured prior to challenge. The levels of plasma total cholesterol, free cholesterol and phospholipid of fish surviving infection were significantly higher in both yellowtail and rainbow trout than those of fish which died during the challenge test. Mortality of yellowtail with plasma total cholesterol levels lower than 250 mg/100 ml was significantly higher than that of fish which had cholesterol levels higher than 275 mg/100 ml (p < 0.05). Rainbow trout whose cholesterol was lower than 520 mg/100 ml suffered a significantly higher mortality due to vibriosis than fish having cholesterol levels higher than 560 mg/100 ml (p < 0.005). These results indicate that low levels of plasma lipid components may be an indicator of lowered disease resistance in cultured fish.

  9. The cholesterol-lowering agent methyl-β-cyclodextrin promotes glucose uptake via GLUT4 in adult muscle fibers and reduces insulin resistance in obese mice.

    PubMed

    Llanos, Paola; Contreras-Ferrat, Ariel; Georgiev, Tihomir; Osorio-Fuentealba, Cesar; Espinosa, Alejandra; Hidalgo, Jorge; Hidalgo, Cecilia; Jaimovich, Enrique

    2015-02-15

    Insulin stimulates glucose uptake in adult skeletal muscle by promoting the translocation of GLUT4 glucose transporters to the transverse tubule (T-tubule) membranes, which have particularly high cholesterol levels. We investigated whether T-tubule cholesterol content affects insulin-induced glucose transport. Feeding mice a high-fat diet (HFD) for 8 wk increased by 30% the T-tubule cholesterol content of triad-enriched vesicular fractions from muscle tissue compared with triads from control mice. Additionally, isolated muscle fibers (flexor digitorum brevis) from HFD-fed mice showed a 40% decrease in insulin-stimulated glucose uptake rates compared with fibers from control mice. In HFD-fed mice, four subcutaneous injections of MβCD, an agent reported to extract membrane cholesterol, improved their defective glucose tolerance test and normalized their high fasting glucose levels. The preincubation of isolated muscle fibers with relatively low concentrations of MβCD increased both basal and insulin-induced glucose uptake in fibers from controls or HFD-fed mice and decreased Akt phosphorylation without altering AMPK-mediated signaling. In fibers from HFD-fed mice, MβCD improved insulin sensitivity even after Akt or CaMK II inhibition and increased membrane GLUT4 content. Indinavir, a GLUT4 antagonist, prevented the stimulatory effects of MβCD on glucose uptake. Addition of MβCD elicited ryanodine receptor-mediated calcium signals in isolated fibers, which were essential for glucose uptake. Our findings suggest that T-tubule cholesterol content exerts a critical regulatory role on insulin-stimulated GLUT4 translocation and glucose transport and that partial cholesterol removal from muscle fibers may represent a useful strategy to counteract insulin resistance.

  10. Low HDL cholesterol, aggression and altered central serotonergic activity.

    PubMed

    Buydens-Branchey, L; Branchey, M; Hudson, J; Fergeson, P

    2000-03-01

    Many studies support a significant relation between low cholesterol levels and poor impulse, aggression and mood control. Evidence exists also for a causal link between low brain serotonin (5-HT) activity and these behaviors. Mechanisms linking cholesterol and hostile or self-destructive behavior are unknown, but it has been suggested that low cholesterol influences 5-HT function. This study was designed to explore the relationship between plasma cholesterol, measures of impulsivity and aggression, and indices of 5-HT function in personality disordered cocaine addicts. Thirty-eight hospitalized male patients (age 36.8+/-7.1) were assessed with the DSM-III-R, the Buss-Durkee Hostility Inventory (BDHI), the Barratt Impulsiveness Scale (BIS) and the Brown-Goodwin Assessment for Life History of Aggression. Fasting basal cholesterol (total, LDL and HDL) was determined 2 weeks after cocaine discontinuation. On the same day 5-HT function was assessed by neuroendocrine (cortisol and prolactin) and psychological (NIMH and 'high' self-rating scales) responses following meta-chlorophenylpiperazine (m-CPP) challenges. Reduced neuroendocrine responses, 'high' feelings and increased 'activation-euphoria' following m-CPP have been interpreted as indicating 5-HT alterations in a variety of psychiatric conditions. Significantly lower levels of HDL cholesterol were found in patients who had a history of aggression (P=0.005). Lower levels of HDL cholesterol were also found to be significantly associated with more intense 'high' and 'activation-euphoria' responses as well as with blunted cortisol responses to m-CPP (P=0.033, P=0.025 and P=0.018, respectively). This study gives further support to existing evidence indicating that in some individuals, the probability of exhibiting impulsive and violent behaviors may be increased when cholesterol is low. It also suggests that low cholesterol and alterations in 5-HT activity may be causally related.

  11. Chlordecone altered hepatic disposition of [{sup 14}C]cholesterol and plasma cholesterol distribution but not SR-BI or ABCG8 proteins in livers of C57BL/6 mice

    SciTech Connect

    Lee, Junga; Scheri, Richard C.; Curtis, Lawrence R.

    2008-06-15

    Organochlorine (OC) insecticides continue to occur in tissues of humans and wildlife throughout the world although they were banned in the United States a few decades ago. Low doses of the OC insecticide chlordecone (CD) alter hepatic disposition of lipophilic xenobiotics and perturb lipid homeostasis in rainbow trout, mice and rats. CD pretreatment altered tissue and hepatic subcellular distribution of exogenous [{sup 14}C]cholesterol (CH) equivalents 4 and 16 h after a bolus intraperitoneal (ip) injection of 5 ml corn oil/kg that contained 10 mg CH/kg. CD pretreatment altered tissue distribution of exogenously administered [{sup 14}C]CH by decreased hepatic and renal accumulation, and increased biliary excretion up to 300%. Biliary excretion of polar [{sup 14}C]CH metabolites was not altered by CD. CD pretreatment decreased subcellular distribution of [{sup 14}C]CH equivalents in hepatic cytosol and microsomes and lipoprotein-rich fraction-to-homogenate ratio. CD pretreatment increased the ratio of [{sup 14}C]CH equivalents in high density lipoprotein (HDL) to that in plasma and reduced [{sup 14}C]CH equivalents in the non-HDL fraction 4 h after a bolus lipid dose. CD pretreatment increased plasma non-HDL total CH by 80% 4 h after a bolus lipid dose. Scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter G8 (ABCG8) proteins were quantified by western blotting in hepatic membranes from control and CD treated mice. Liver membrane contents of SR-BI and ABCG8 proteins were unchanged by CD pretreatment. The data demonstrated that a single dose of CD altered CH homeostasis and lipoprotein metabolism.

  12. Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport

    PubMed Central

    Fernández-Suárez, María E.; Escolà-Gil, Joan C.; Pastor, Oscar; Dávalos, Alberto; Blanco-Vaca, Francisco; Lasunción, Miguel A.; Martínez-Botas, Javier; Gómez-Coronado, Diego

    2016-01-01

    Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17β-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [3H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [3H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages. PMID:27601313

  13. Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport.

    PubMed

    Fernández-Suárez, María E; Escolà-Gil, Joan C; Pastor, Oscar; Dávalos, Alberto; Blanco-Vaca, Francisco; Lasunción, Miguel A; Martínez-Botas, Javier; Gómez-Coronado, Diego

    2016-09-07

    Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17β-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [(3)H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [(3)H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages.

  14. Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport.

    PubMed

    Fernández-Suárez, María E; Escolà-Gil, Joan C; Pastor, Oscar; Dávalos, Alberto; Blanco-Vaca, Francisco; Lasunción, Miguel A; Martínez-Botas, Javier; Gómez-Coronado, Diego

    2016-01-01

    Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17β-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [(3)H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [(3)H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages. PMID:27601313

  15. Human apolipoprotein E allele and docosahexaenoic acid intake modulate peripheral cholesterol homeostasis in mice.

    PubMed

    Pinçon, Anthony; Coulombe, Jean-Denis; Chouinard-Watkins, Raphaël; Plourde, Mélanie

    2016-08-01

    Carrying at least one apolipoprotein E ε4 allele (E4+) is the main genetic risk factor for Alzheimer's disease (AD). Epidemiological studies support that consuming fatty fish rich in docosahexaenoic acid (DHA; 22:6ω3) is protective against development of AD. However, this protective effect seems not to hold in E4+. The involvement of APOE genotype on the relationship between DHA intake and cognitive decline could be mediated through cholesterol. Many studies show a link between cholesterol metabolism and AD progression. In this study, we investigated whether cholesterol metabolism is improved in E3+ and E4+ mice consuming a diet rich in DHA. Plasma cholesterol was 36% lower in E4+ mice compared to E3+ mice fed the control diet (P=.02), and in the liver, there was a significant genotype effect where cholesterol levels were 18% lower in E4+ mice than E3+ mice. The low-density lipoprotein receptor was overexpressed in the liver of E4+ mice. Plasma cholesterol levels were 33% lower after the DHA diet (P=.02) in E3+ mice only, and there was a significant diet effect where cholesterol level was 67% lower in the liver of mice fed DHA. Mice fed the DHA diet also had 62% less lipolysis stimulated lipoprotein receptor expression in the liver compared to mice fed the control diet (P<.0001), but there was no genotype effect. These findings suggest that plasma and liver cholesterol homeostasis and the receptors regulating uptake of cholesterol in the liver are modulated differently and independently by APOE allele and DHA intake.

  16. Cholesterol-lowering properties of oat β-glucan and the promotion of cardiovascular health: did Health Canada make the right call?

    PubMed

    Nwachukwu, Ifeanyi D; Devassy, Jessay G; Aluko, Rotimi E; Jones, Peter J H

    2015-06-01

    In 2010, Health Canada approved a heath claim acknowledging the link between increased oats (Avena sativa)-soluble fibre consumption and a reduction in total serum cholesterol levels. The approval also recognized the relationship between decreased total blood cholesterol concentration and a reduced risk of coronary heart disease. The functional food ingredient believed to be responsible for the hypocholesterolemic property of oats is β-glucan, a highly viscous, soluble fibre composed of d-glucose monomers linked by a combination of β-(1→4) and β-(1→3) glycosidic bonds. Found mainly in the endosperm cell wall of oats, β-glucan is thought to reduce total serum and low-density lipoprotein cholesterol by forming a viscous mass in the small intestine thus limiting intestinal absorption of dietary cholesterol as well as the re-absorption of bile acids. Given the evolution of research information with time as a result of the continual, rapid generation of new research data by laboratories around the world, it became imperative to examine the compatibility of the conclusion reached by Health Canada on the basis of the body of evidence contained in the initial petition submitted in January 2007, with newer post-2006 data. After careful evaluation, this work concludes on the basis of new research information that a dose of 3 g/day oat β-glucan consumed as part of a diet "free of saturated fatty acids" or "low in saturated fatty acids" could help to promote cardiovascular health.

  17. Effects of regional hemoconcentration during LBNP on plasma volume determinations. [Lower Body Negative Pressure

    NASA Technical Reports Server (NTRS)

    Loeppky, J. A.; Kobayashi, Y.; Venters, M. D.; Luft, U. C.

    1979-01-01

    Blood samples were obtained from forearm vein or artery with indwelling cannula (1) before, (2) during the last min, and (3) about 2 min after lower body negative pressure (LBNP) in 16 experiments to determine whether plasma volume (PV) estimates were affected by regional hemoconcentration in the lower body. Total hemoglobin (THb) was estimated with the CO method prior to LBNP. Hemoglobin (Hb) and hematocrit (Hct) values from (2) gave only a 3% (87 ml) loss in PV due to LBNP, assuming no change in THb. However, Hb and Hct values from (3) showed an 11% loss in PV (313 ml). This 72% underestimation of PV loss with (2) must have resulted from the sequestration of blood and subsequent hemoconcentration in the lower body during LBNP. The effects of LBNP on PV should be estimated 1-3 min after exposure, after mixing but before extravascular fluid returns to the circulation.

  18. Do You Know Your Cholesterol Levels?

    MedlinePlus

    ... Health Information Center Do You Know Your Cholesterol Levels? Print-friendly Version (PDF, 6.1 MB) Spanish ... Syndrome? My Family Plan To Lower Blood Cholesterol Levels My Heart Health Card Play It Smart, Take ...

  19. The solid phase synthesis of a protein activator for lecithin-cholesterol acyltransferase corresponding to human plasma apoC-I.

    PubMed Central

    Sigler, G F; Soutar, A K; Smith, L C; Gotto, A M; Sparrow, J T

    1976-01-01

    Apolipoprotein C-I, a protein constituent of the very low density lipoproteins of human plasma, consists of a single chain of 57 amino acids. The total synthesis of a protein corresponding to apolipoprotein C-I in physical properties and compositions was accomplished by solid phase techniques employing a modified polystrene incorporating spacer groups between the point of attachment of the first residue and the polymer matrix. The synthetic apoprotein was shown to activate lecithin:cholesterol acyltransferase to the same extent as the native protein. Comparative lipid-binding studies with dimyristoyl phosphatidylcholine gave complexes for native and synthetic apoprotein which floated at the same density after ultracentrifugation in KBr gradients and had virtually the same lipid:protein ratios. Images PMID:179085

  20. The solid phase synthesis of a protein activator for lecithin-cholesterol acyltransferase corresponding to human plasma apoC-I.

    PubMed

    Sigler, G F; Soutar, A K; Smith, L C; Gotto, A M; Sparrow, J T

    1976-05-01

    Apolipoprotein C-I, a protein constituent of the very low density lipoproteins of human plasma, consists of a single chain of 57 amino acids. The total synthesis of a protein corresponding to apolipoprotein C-I in physical properties and compositions was accomplished by solid phase techniques employing a modified polystrene incorporating spacer groups between the point of attachment of the first residue and the polymer matrix. The synthetic apoprotein was shown to activate lecithin:cholesterol acyltransferase to the same extent as the native protein. Comparative lipid-binding studies with dimyristoyl phosphatidylcholine gave complexes for native and synthetic apoprotein which floated at the same density after ultracentrifugation in KBr gradients and had virtually the same lipid:protein ratios. PMID:179085

  1. Effects of dietary fats on plasma lipids and lipoproteins: an hypothesis for the lipid-lowering effect of unsaturated fatty acids

    PubMed Central

    Spritz, Norton; Mishkel, Maurice A.

    1969-01-01

    Several aspects of the effects of dietary fat on plasma lipids and lipoproteins were investigated in 12 subjects during the long-term feeding of formulas containing 40% of their calories as either saturated or unsaturated fats. The changes in fatty acid composition of plasma lipids, shown previously to occur after prolonged feedings of a dietary fat, required 10-14 days to be complete and were synchronous with the effect of the fat on plasma lipid concentrations. The change in lipid concentration occurred in low but not in high density lipoproteins. The effects on lipid levels of the low density lipoproteins were found to occur with little or no effect on the concentration of the protein moiety of these lipoproteins; as a result, cholesterol- and phospholipid to protein ratios in low density lipoproteins fell during unsaturated fat feeding. The effects of dietary fat on plasma phospholipids were studied in detail: the relative amounts of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and lysophosphatidylcholine were unaffected by the type of dietary fat. However, the molecular species of phosphatidylcholine were markedly affected. More than 90% of the fatty acids at the α-position were saturated during both saturated and unsaturated feedings. In contrast, during unsaturated feedings, linoleate at the β-position outnumbered oleate by approximately 4:1, whereas during saturated feedings these two types of fatty acids were present in nearly equal amounts. This paper also presents the following hypothesis for the lipid-lowering effect of unsaturated dietary fat: since unsaturated fatty acids occupy a greater area than saturated acids, they alter the spatial configuration of the lipids into which they are incorporated; as a result, fewer lipid molecules can be accommodated by the apoprotein of the low-density lipoproteins (LDL), and thus the lipid content of the lipoprotein is lowered. The experimental findings of this study, while not proving this

  2. Excitation of lower hybrid waves by a gyrating ion beam in a negative ion plasma

    SciTech Connect

    Sharma, Jyotsna; Jain, V. K.; Sharma, Suresh C.; Gahlot, Ajay

    2013-03-15

    A gyrating ion beam propagating through a magnetized plasma cylinder containing K{sup +} positive ions, electrons, and SF{sub 6}{sup -} negative ions drives electrostatic lower hybrid waves to instability via Cyclotron interaction. Numerical calculations of the unstable mode frequencies and growth rates of both the unstable positive ion and negative ion modes have been carried out for the existing negative ion plasma parameters. It is found that the unstable mode frequencies of both the modes increase, with the relative density of negative ions. In addition, the growth rates of both the unstable modes also increases with relative density of negative ions. Moreover, the growth rates of both the unstable modes scale as the one-third power of the beam density. The frequencies of both the unstable modes also increase with the magnetic fields. The real part of the unstable wave frequency increases as almost the square root of the beam energy.

  3. Lower hybrid current drive at ITER-relevant high plasma densities

    SciTech Connect

    Cesario, R.; Amicucci, L.; Cardinali, A.; Castaldo, C.; Marinucci, M.; Panaccione, L.; Pericoli-Ridolfini, V.; Tuccillo, A. A.; Tudisco, O.

    2009-11-26

    Recent experiments indicated that a further non-inductive current, besides bootstrap, should be necessary for developing advanced scenario for ITER. The lower hybrid current drive (LHCD) should provide such tool, but its effectiveness was still not proved in operations with ITER-relevant density of the plasma column periphery. Progress of the LH deposition modelling is presented, performed considering the wave physics of the edge, and different ITER-relevant edge parameters. Operations with relatively high edge electron temperatures are expected to reduce the LH{sub ||} spectral broadening and, consequently, enabling the LH power to propagate also in high density plasmas ({sub ||} is the wavenumber component aligned to the confinement magnetic field). New results of FTU experiments are presented, performed by following the aforementioned modeling: they indicate that, for the first time, the LHCD conditions are established by operating at ITER-relevant high edge densities.

  4. The response of plasma density to breaking inertial gravity wave in the lower regions of ionosphere

    SciTech Connect

    Tang, Wenbo Mahalov, Alex

    2014-04-15

    We present a three-dimensional numerical study for the E and lower F region ionosphere coupled with the neutral atmosphere dynamics. This model is developed based on a previous ionospheric model that examines the transport patterns of plasma density given a prescribed neutral atmospheric flow. Inclusion of neutral dynamics in the model allows us to examine the charge-neutral interactions over the full evolution cycle of an inertial gravity wave when the background flow spins up from rest, saturates and eventually breaks. Using Lagrangian analyses, we show the mixing patterns of the ionospheric responses and the formation of ionospheric layers. The corresponding plasma density in this flow develops complex wave structures and small-scale patches during the gravity wave breaking event.

  5. Parenteral lipid emulsions in guinea pigs differentially influence plasma and tissue levels of fatty acids, squalene, cholesterol, and phytosterols.

    PubMed

    Harvey, Kevin; Xu, Zhidong; Walker, Candace; Pavlina, Thomas; McGrath, Sheila; Zaloga, Gary; Siddiqui, Rafat

    2014-08-01

    Lipid emulsions are made by mixing vegetable and/or fish oils with egg yolk and contain different types and amounts of fatty acids and sterols. This study assessed the effects of oral diet, soybean oil (SO)-, fish oil (FO)-, a mixture of olive and soybean oil (OOSO)-, and a mixture of fish, olive, coconut, and soybean oil (FOCS)-based emulsions on plasma triacylglycerols and plasma and tissue fatty acid and sterol content following acute and chronic intravenous administration in the guinea pig. Upon acute administration, peak triacylglycerols were highest with SO and lowest with OOSO. Upon chronic administration, the plasma triglyceride levels did not increase in any group over that of the controls. Fatty acid levels varied greatly between organs of animals on the control diets and organs of animals following acute or chronic lipid administration. Squalene levels increased in plasma following acute administration of OOSO, but plasma squalene levels were similar to control in all emulsion groups following chronic administration. Total plasma phytosterol levels were increased in the SO, OOSO, and FOCS groups following both acute and chronic infusions, whereas phytosterols were not increased following FO infusion. Total phytosterol levels were higher in liver, lung, kidney and adipose tissue following SO and OOSO. Levels were not increased in tissues after FO and FOCS infusion. These results indicate that fatty acid and sterol contents vary greatly among organs and that no one tissue reflects the fatty acid or sterol composition of other tissues, suggesting that different organs regulate these compounds differently.

  6. Effects of Magnetic Shear on Toroidal Rotation in Tokamak Plasmas with Lower Hybrid Current Drive

    NASA Astrophysics Data System (ADS)

    Rice, J. E.; Podpaly, Y. A.; Reinke, M. L.; Mumgaard, R.; Scott, S. D.; Shiraiwa, S.; Wallace, G. M.; Chouli, B.; Fenzi-Bonizec, C.; Nave, M. F. F.; Diamond, P. H.; Gao, C.; Granetz, R. S.; Hughes, J. W.; Parker, R. R.; Bonoli, P. T.; Delgado-Aparicio, L.; Eriksson, L.-G.; Giroud, C.; Greenwald, M. J.; Hubbard, A. E.; Hutchinson, I. H.; Irby, J. H.; Kirov, K.; Mailloux, J.; Marmar, E. S.; Wolfe, S. M.

    2013-09-01

    Application of lower hybrid (LH) current drive in tokamak plasmas can induce both co- and countercurrent directed changes in toroidal rotation, depending on the core q profile. For discharges with q0<1, rotation increments in the countercurrent direction are observed. If the LH-driven current is sufficient to suppress sawteeth and increase q0 above unity, the core toroidal rotation change is in the cocurrent direction. This change in sign of the rotation increment is consistent with a change in sign of the residual stress (the divergence of which constitutes an intrinsic torque that drives the flow) through its dependence on magnetic shear.

  7. Low Maternal Vitamin B12 Status Is Associated with Lower Cord Blood HDL Cholesterol in White Caucasians Living in the UK

    PubMed Central

    Adaikalakoteswari, Antonysunil; Vatish, Manu; Lawson, Alexander; Wood, Catherine; Sivakumar, Kavitha; McTernan, Philip G.; Webster, Craig; Anderson, Neil; Yajnik, Chittaranjan S.; Tripathi, Gyanendra; Saravanan, Ponnusamy

    2015-01-01

    Background and Aims: Studies in South Asian population show that low maternal vitamin B12 associates with insulin resistance and small for gestational age in the offspring. Low vitamin B12 status is attributed to vegetarianism in these populations. It is not known whether low B12 status is associated with metabolic risk of the offspring in whites, where the childhood metabolic disorders are increasing rapidly. Here, we studied whether maternal B12 levels associate with metabolic risk of the offspring at birth. Methods: This is a cross-sectional study of 91 mother-infant pairs (n = 182), of white Caucasian origin living in the UK. Blood samples were collected from white pregnant women at delivery and their newborns (cord blood). Serum vitamin B12, folate, homocysteine as well as the relevant metabolic risk factors were measured. Results: The prevalence of low serum vitamin B12 (<191 ng/L) and folate (<4.6 μg/L) were 40% and 11%, respectively. Maternal B12 was inversely associated with offspring’s Homeostasis Model Assessment 2-Insulin Resistance (HOMA-IR), triglycerides, homocysteine and positively with HDL-cholesterol after adjusting for age and BMI. In regression analysis, after adjusting for likely confounders, maternal B12 is independently associated with neonatal HDL-cholesterol and homocysteine but not triglycerides or HOMA-IR. Conclusions: Our study shows that low B12 status is common in white women and is independently associated with adverse cord blood cholesterol. PMID:25849948

  8. Screening for cholesterol-lowering probiotic based on deoxycholic acid removal pathway and studying its functional mechanisms in vitro.

    PubMed

    Guo, Chun-Feng; Zhang, Lan-Wei; Han, Xue; Yi, Hua-Xi; Li, Jing-Yan; Tuo, Yan-Feng; Zhang, Ying-Chun; Du, Ming; Shan, Yu-Juan; Yang, Lin

    2012-10-01

    Elevated serum cholesterol in humans is generally a risk factor correlated with the development of coronary heart disease (CHD). Reducing deoxycholic acid (DCA) content in the intestine can reduce serum cholesterol levels, which reduce the incidence of CHD. A total of 150 strains of lactic acid bacteria and bifidobacteria were isolated from human fecal samples. The DCA removal ability of these strains was evaluated. Results showed that 9 strains displayed above 10% DCA removal rate. The probiotic potentials of the 9 strains were evaluated. The strain Lactobacillus casei F0822 was screened out due to the stronger adhesion to HT-29 cells and tolerance to bile and acid. DCA removal for this strain resulted from that the S-layer protein locating the cell surface bound DCA. The FTIR spectra showed that the carboxyl group in DCA was the principal group by which DCA was bound to the S-layer protein of L. casei F0822. These findings suggested that L. casei F0822 is a better candidate probiotic strain, which has the potential to reduce human serum cholesterol levels. PMID:22926345

  9. Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis.

    PubMed

    Sallam, Tamer; Jones, Marius C; Gilliland, Thomas; Zhang, Li; Wu, Xiaohui; Eskin, Ascia; Sandhu, Jaspreet; Casero, David; Vallim, Thomas Q de Aguiar; Hong, Cynthia; Katz, Melanie; Lee, Richard; Whitelegge, Julian; Tontonoz, Peter

    2016-06-01

    Liver X receptors (LXRs) are transcriptional regulators of cellular and systemic cholesterol homeostasis. Under conditions of excess cholesterol, LXR activation induces the expression of several genes involved in cholesterol efflux, facilitates cholesterol esterification by promoting fatty acid synthesis, and inhibits cholesterol uptake by the low-density lipoprotein receptor. The fact that sterol content is maintained in a narrow range in most cell types and in the organism as a whole suggests that extensive crosstalk between regulatory pathways must exist. However, the molecular mechanisms that integrate LXRs with other lipid metabolic pathways are incompletely understood. Here we show that ligand activation of LXRs in mouse liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as a mediator of this effect. Hepatic LeXis expression is robustly induced in response to a Western diet (high in fat and cholesterol) or to pharmacological LXR activation. Raising or lowering LeXis levels in the liver affects the expression of genes involved in cholesterol biosynthesis and alters the cholesterol levels in the liver and plasma. LeXis interacts with and affects the DNA interactions of RALY, a heterogeneous ribonucleoprotein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the mouse liver. These findings outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis.

  10. Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis.

    PubMed

    Sallam, Tamer; Jones, Marius C; Gilliland, Thomas; Zhang, Li; Wu, Xiaohui; Eskin, Ascia; Sandhu, Jaspreet; Casero, David; Vallim, Thomas Q de Aguiar; Hong, Cynthia; Katz, Melanie; Lee, Richard; Whitelegge, Julian; Tontonoz, Peter

    2016-06-01

    Liver X receptors (LXRs) are transcriptional regulators of cellular and systemic cholesterol homeostasis. Under conditions of excess cholesterol, LXR activation induces the expression of several genes involved in cholesterol efflux, facilitates cholesterol esterification by promoting fatty acid synthesis, and inhibits cholesterol uptake by the low-density lipoprotein receptor. The fact that sterol content is maintained in a narrow range in most cell types and in the organism as a whole suggests that extensive crosstalk between regulatory pathways must exist. However, the molecular mechanisms that integrate LXRs with other lipid metabolic pathways are incompletely understood. Here we show that ligand activation of LXRs in mouse liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as a mediator of this effect. Hepatic LeXis expression is robustly induced in response to a Western diet (high in fat and cholesterol) or to pharmacological LXR activation. Raising or lowering LeXis levels in the liver affects the expression of genes involved in cholesterol biosynthesis and alters the cholesterol levels in the liver and plasma. LeXis interacts with and affects the DNA interactions of RALY, a heterogeneous ribonucleoprotein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the mouse liver. These findings outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis. PMID:27251289

  11. Ursodeoxycholate stabilizes phospholipid-rich membranes and mimics the effect of cholesterol: investigations on large unilamellar vesicles.

    PubMed

    Güldütuna, S; Deisinger, B; Weiss, A; Freisleben, H J; Zimmer, G; Sipos, P; Leuschner, U

    1997-06-12

    Ursodeoxycholate is used to treat primary biliary cirrhosis and is incorporated into hepatocyte plasma membranes. Its steroid nucleus binds to the apolar domain of the membrane, in a similar position to cholesterol. Therefore the question arises whether ursodeoxycholate has a similar effect on membrane structure and stability as cholesterol. Using differential scanning calorimetry the thermotropic behavior of egg phosphatidylcholine and dimyristoylphosphatidylcholine were studied after incubation with cholesterol or ursodeoxycholate. Large unilamellar vesicles were prepared with cholesterol contents of 0-50%. Following incubation of these vesicles with different amounts of ursodeoxycholate, vesicle stability in a gravitational field was investigated by measuring the phospholipid and cholesterol release. Vesicle size was studied by laser light scattering after incubation with cheno- and ursodeoxycholate, and the release of entrapped carboxyfluorescein was measured by means of fluorescence spectroscopy. Increasing cholesterol diminished the enthalpy of the phase transition in the membrane. Ursodeoxycholate decreased the enthalpy of the phase transition at even lower concentrations. Lipid release from vesicles in a high gravitational field diminished with increasing cholesterol content of the vesicles. Ursodeoxycholate had a comparable effect, which increased as the cholesterol content of the vesicles was decreased. Chenodeoxycholate damaged vesicles, whereas ursodeoxycholate did not. Cholesterol and ursodeoxycholate (below its critical micellar concentration) decreased the carboxyfluorescein release from vesicles induced by chenodeoxycholate. Thus like cholesterol, ursodeoxycholate is incorporated into phospholipid model membranes and reduces the change in enthalpy of the gel to liquid-crystalline phase transition. Like cholesterol ursodeoxycholate also maintains membrane stability and prevents membrane damage induced by mechanical and chemical stress.

  12. Mediation of beta-endorphin by the isoflavone puerarin to lower plasma glucose in streptozotocin-induced diabetic rats.

    PubMed

    Chen, Wang-Chuan; Hayakawa, Satoshi; Yamamoto, Tatsuo; Su, Hui-Chen; Liu, I-Min; Cheng, Juei-Tang

    2004-02-01

    We investigate the mechanism(s) of plasma glucose lowering action of puerarin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Puerarin at the effective dosage to lower higher plasma glucose increased plasma beta-endorphin-like immunoreactivity (BER) in STZ-diabetic rats. Both effects of puerarin were abolished by the pretreatment with prazosin. Also, puerarin enhanced BER release from isolated rat adrenal medulla in a concentration-dependent manner that can be abolished by prazosin. Moreover, bilateral adrenalectomy in STZ-diabetic rats eliminated the actions of puerarin including the plasma glucose lowering effect and plasma BER elevating effect. In addition, naloxone and naloxonazine inhibited the plasma glucose lowering action of puerarin. Unlike in wild-type diabetic mice, puerarin failed to lower the plasma glucose in opioid micro-receptor knockout diabetic mice. In conclusion, our results suggest that puerarin may activate alpha (1)-adrenoceptors on the adrenal gland to enhance the secretion of beta-endorphin to result in a decrease of plasma glucose in STZ-diabetic rats.

  13. Lower Oxytocin Plasma Levels in Borderline Patients with Unresolved Attachment Representations.

    PubMed

    Jobst, Andrea; Padberg, Frank; Mauer, Maria-Christine; Daltrozzo, Tanja; Bauriedl-Schmidt, Christine; Sabass, Lena; Sarubin, Nina; Falkai, Peter; Renneberg, Babette; Zill, Peter; Gander, Manuela; Buchheim, Anna

    2016-01-01

    Interpersonal problems and affective dysregulation are core characteristics of borderline personality disorder (BPD). BPD patients predominantly show unresolved attachment representations. The oxytocin (OT) system is associated with human social attachment and affiliative behavior, and OT dysregulation may be related to distinct attachment characteristics. Here, we investigated whether attachment representations are related to peripheral OT levels in BPD patients. Twenty-one female BPD patients and 20 age-, gender-, and education-matched healthy controls (HCs) were assessed with clinical scales and measures of interpersonal and attachment-related characteristics, including the Adult Attachment Projective Picture System (AAP). Plasma OT concentrations were measured prior to and during social exclusion in a virtual ball tossing game (Cyberball). The majority of BPD patients (63.2%) but no HCs showed unresolved (disorganized) attachment representations. In this subgroup of patients, baseline OT plasma levels were significantly lower than in BPD patients with organized attachment representations. This pilot study extends previous findings of altered OT regulation in BPD as a putative key mechanism underlying interpersonal dysregulation. Our results provide first evidence that altered OT plasma levels are related to disorganized attachment representations in BPD patients.

  14. The Nonlinear Coupling of Alfven and Lower Hybrid Waves in Space Plasma

    NASA Technical Reports Server (NTRS)

    Khazanov, George V.

    2004-01-01

    Space plasmas support a wide variety of waves, and wave-particle interactions as well as wave-wave interactions which are of crucial importance to magnetospheric and ionospheric plasma behavior. The excitation of lower hybrid waves (LHWs) in particular is a widely discussed mechanism of interaction between plasma species in space and is one of the unresolved questions of magnetospheric multi-ion plasmas. It is demonstrated that large-amplitude Alfven waves may generate LHWs in the auroral zone and ring current region and in some cases (particularly in the inner magnetosphere) this serves as the Alfven wave saturation mechanism. We present several examples of observational data which illustrate that the proposed mechanism is a plausible candidate to explain certain classes of LHW generation events in the ionosphere and magnetosphere and demonstrate electron and ion energization involving these processes. We discuss the morphology dynamics and level of LHW activity generated by electromagnetic ion cyclotron (EMIC) waves during the May 2-7 1998 storm period on the global scale. The LHWs were calculated based on a newly developed self-consistent model (Khazanov et. al. 2002) that couples the system of two kinetic equations: one equation describes the ring current (RC) ion dynamic and another equation describes the evolution of EMIC waves. It is found that the LHWs are excited by helium ions due to their mass dependent drift in the electric field of EMIC waves. The level of LHW activity is calculated assuming that the induced scattering process is the main saturation mechanism for these waves. The calculated LHWs electric fields are consistent with the observational data.

  15. Active membrane cholesterol as a physiological effector.

    PubMed

    Lange, Yvonne; Steck, Theodore L

    2016-09-01

    Sterols associate preferentially with plasma membrane sphingolipids and saturated phospholipids to form stoichiometric complexes. Cholesterol in molar excess of the capacity of these polar bilayer lipids has a high accessibility and fugacity; we call this fraction active cholesterol. This review first considers how active cholesterol serves as an upstream regulator of cellular sterol homeostasis. The mechanism appears to utilize the redistribution of active cholesterol down its diffusional gradient to the endoplasmic reticulum and mitochondria, where it binds multiple effectors and directs their feedback activity. We have also reviewed a broad literature in search of a role for active cholesterol (as opposed to bulk cholesterol or lipid domains such as rafts) in the activity of diverse membrane proteins. Several systems provide such evidence, implicating, in particular, caveolin-1, various kinds of ABC-type cholesterol transporters, solute transporters, receptors and ion channels. We suggest that this larger role for active cholesterol warrants close attention and can be tested easily.

  16. Serine palmitoyltransferase (SPT) deficient mice absorb less cholesterol.

    PubMed

    Li, Zhiqiang; Park, Tae-Sik; Li, Yan; Pan, Xiaoyue; Iqbal, Jahangir; Lu, David; Tang, Weiqing; Yu, Liqing; Goldberg, Ira J; Hussain, M Mahmood; Jiang, Xian-Cheng

    2009-04-01

    Serine palmitoyltransferase (SPT) is the key enzyme for the biosynthesis of sphingolipids. It has been reported that oral administration of myriocin (an SPT inhibitor) decreases plasma sphingomyelin (SM) and cholesterol levels, and reduces atherosclerosis in apoE knockout (KO) mice. We studied cholesterol absorption in myriocin-treated WT or apoE KO animals and found that, after myriocin treatment, the mice absorbed significantly less cholesterol than controls, with no observable pathological changes in the small intestine. More importantly, we found that heterozygous Sptlc1 (a subunit of SPT) KO mice also absorbed significantly less cholesterol than controls. To understand the mechanism, we measured protein levels of Niemann-Pick C1-like 1 (NPC1L1), ABCG5, and ABCA1, three key factors involved in intestinal cholesterol absorption. We found that NPC1L1 and ABCA1 were decreased, whereas ABCG5 was increased in the SPT deficient small intestine. SM levels on the apical membrane were also measured and they were significantly decreased in SPT deficient mice, compared with controls. In conclusion, SPT deficiency might reduce intestinal cholesterol absorption by altering NPC1L1 and ABCG5 protein levels in the apical membranes of enterocytes through lowering apical membrane SM levels. This may be also true for ABCA1 which locates on basal membrane of enterocytes. Manipulation of SPT activity could thus provide a novel alternative treatment for dyslipidemia. PMID:19416652

  17. Serine palmitoyltransferase (SPT) deficient mice absorb less cholesterol.

    PubMed

    Li, Zhiqiang; Park, Tae-Sik; Li, Yan; Pan, Xiaoyue; Iqbal, Jahangir; Lu, David; Tang, Weiqing; Yu, Liqing; Goldberg, Ira J; Hussain, M Mahmood; Jiang, Xian-Cheng

    2009-04-01

    Serine palmitoyltransferase (SPT) is the key enzyme for the biosynthesis of sphingolipids. It has been reported that oral administration of myriocin (an SPT inhibitor) decreases plasma sphingomyelin (SM) and cholesterol levels, and reduces atherosclerosis in apoE knockout (KO) mice. We studied cholesterol absorption in myriocin-treated WT or apoE KO animals and found that, after myriocin treatment, the mice absorbed significantly less cholesterol than controls, with no observable pathological changes in the small intestine. More importantly, we found that heterozygous Sptlc1 (a subunit of SPT) KO mice also absorbed significantly less cholesterol than controls. To understand the mechanism, we measured protein levels of Niemann-Pick C1-like 1 (NPC1L1), ABCG5, and ABCA1, three key factors involved in intestinal cholesterol absorption. We found that NPC1L1 and ABCA1 were decreased, whereas ABCG5 was increased in the SPT deficient small intestine. SM levels on the apical membrane were also measured and they were significantly decreased in SPT deficient mice, compared with controls. In conclusion, SPT deficiency might reduce intestinal cholesterol absorption by altering NPC1L1 and ABCG5 protein levels in the apical membranes of enterocytes through lowering apical membrane SM levels. This may be also true for ABCA1 which locates on basal membrane of enterocytes. Manipulation of SPT activity could thus provide a novel alternative treatment for dyslipidemia.

  18. Discovery of XEN445: a potent and selective endothelial lipase inhibitor raises plasma HDL-cholesterol concentration in mice.

    PubMed

    Sun, Shaoyi; Dean, Richard; Jia, Qi; Zenova, Alla; Zhong, Jing; Grayson, Celene; Xie, Clark; Lindgren, Andrea; Samra, Pritpaul; Sojo, Luis; van Heek, Margaret; Lin, Linus; Percival, David; Fu, Jian-Min; Winther, Michael D; Zhang, Zaihui

    2013-12-15

    Endothelial lipase (EL) activity has been implicated in HDL metabolism and in atherosclerotic plaque development; inhibitors are proposed to be efficacious in the treatment of dyslipidemia related cardiovascular disease. We describe here the discovery of a novel class of anthranilic acids EL inhibitors. XEN445 (compound 13) was identified as a potent and selective EL inhibitor, that showed good ADME and PK properties, and demonstrated in vivo efficacy in raising plasma HDLc concentrations in mice. PMID:24211162

  19. The Structural Basis of Cholesterol Activity in Membranes

    SciTech Connect

    Olsen, Brett N.; Bielska, Agata; Lee, Tiffany; Daily, Michael D.; Covey, Douglas F.; Schlesinger, Paul H.; Baker, Nathan A.; Ory, Daniel S.

    2013-10-15

    Although the majority of free cellular cholesterol is present in the plasma membrane, cholesterol homeostasis is principally regulated through sterol-sensing proteins that reside in the cholesterol-poor endoplasmic reticulum (ER). In response to acute cholesterol loading or depletion, there is rapid equilibration between the ER and plasma membrane cholesterol pools, suggesting a biophysical model in which the availability of plasma membrane cholesterol for trafficking to internal membranes modulates ER membrane behavior. Previous studies have predominantly examined cholesterol availability in terms of binding to extramembrane acceptors, but have provided limited insight into the structural changes underlying cholesterol activation. In this study, we use both molecular dynamics simulations and experimental membrane systems to examine the behavior of cholesterol in membrane bilayers. We find that cholesterol depth within the bilayer provides a reasonable structural metric for cholesterol availability and that this is correlated with cholesterol-acceptor binding. Further, the distribution of cholesterol availability in our simulations is continuous rather than divided into distinct available and unavailable pools. This data provide support for a revised cholesterol activation model in which activation is driven not by saturation of membrane-cholesterol interactions but rather by bulk membrane remodeling that reduces membrane-cholesterol affinity.

  20. The Structural Basis of Cholesterol Accessibility in Membranes

    PubMed Central

    Olsen, Brett N.; Bielska, Agata A.; Lee, Tiffany; Daily, Michael D.; Covey, Douglas F.; Schlesinger, Paul H.; Baker, Nathan A.; Ory, Daniel S.

    2013-01-01

    Although the majority of free cellular cholesterol is present in the plasma membrane, cholesterol homeostasis is principally regulated through sterol-sensing proteins that reside in the cholesterol-poor endoplasmic reticulum (ER). In response to acute cholesterol loading or depletion, there is rapid equilibration between the ER and plasma membrane cholesterol pools, suggesting a biophysical model in which the availability of plasma membrane cholesterol for trafficking to internal membranes modulates ER membrane behavior. Previous studies have predominantly examined cholesterol availability in terms of binding to extramembrane acceptors, but have provided limited insight into the structural changes underlying cholesterol activation. In this study, we use both molecular dynamics simulations and experimental membrane systems to examine the behavior of cholesterol in membrane bilayers. We find that cholesterol depth within the bilayer provides a reasonable structural metric for cholesterol availability and that this is correlated with cholesterol-acceptor binding. Further, the distribution of cholesterol availability in our simulations is continuous rather than divided into distinct available and unavailable pools. This data provide support for a revised cholesterol activation model in which activation is driven not by saturation of membrane-cholesterol interactions but rather by bulk membrane remodeling that reduces membrane-cholesterol affinity. PMID:24138860

  1. Reverse transport of cholesterol is the reason for resistance to development of atherosclerosis in Prague Hereditary Hypercholesterolemic (PHHC) rat.

    PubMed

    Schmiedtova, M; Heczkova, M; Kovar, J; Kralova Lesna, I; Poledne, R

    2014-01-01

    The Prague Hereditary Hypercholesterolemic (PHHC) rat is a model of hypercholesterolemia. In previous experiments, it was found to be completely resistant to the development of atherosclerosis. It was assumed that the reverse transport of cholesterol (RCT) might be the reason for this resistance. In this study, RCT was measured in vivo by cholesterol efflux from macrophages to plasma, using previously established methods for RCT in mice (Rader 2003), optimized for measurements in rats. Primary cell culture of macrophages was labeled with (14)C-cholesterol and then injected intraperitoneally into rats. Plasma and feces were collected at 24 and 48 h. The plasma (14)C-cholesterol levels at both 24 and 48 h were significantly higher in male PHHC rats compared to control Wistar rats. The PHHC rats excreted less (14)C-cholesterol in feces in 24 and 48 h compared to Wistar rats. The largest pool of (14)C-cholesterol was found in the adipose tissue of PHHC rats and in contrast lower levels of (14)C-cholesterol were measured in the liver and muscle tissues of PHHC rats compared with Wistar rats. Increasing release of (14)C-cholesterol efflux from macrophages demonstrates accelerated RTC and leads to prevention of atherogenesis in PHHC rats.

  2. Women and Cholesterol

    MedlinePlus

    ... Blood Pressure Tools & Resources Stroke More Women and Cholesterol Updated:Apr 1,2016 The female sex hormone ... Glossary Related Sites Nutrition Center My Life Check Cholesterol • Home • About Cholesterol • Why Cholesterol Matters • Understand Your ...

  3. Cholesterol IQ Quiz

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Cholesterol IQ Quiz Updated:Feb 2,2015 Begin the quiz Cholesterol • Home • About Cholesterol Introduction Good vs. Bad Cholesterol ...

  4. Effects of feeding different postbiotic metabolite combinations produced by Lactobacillus plantarum strains on egg quality and production performance, faecal parameters and plasma cholesterol in laying hens

    PubMed Central

    2014-01-01

    Background Probiotics are beneficial bacteria that are able to colonize the host digestive system, increasing the natural flora and preventing colonization of pathogenic organisms and thus, securing optimal utility of the feed. However, commercial probiotic often do not meet the expected standards and the viability of the efficacy of these strains remains questionable. Another major issue has been highlighted in relation to the application of antibiotic resistant probiotics, the antibiotic resistant gene can be transferred between organisms. Recently, postbiotic metabolites produced from microbes have been extensively studied as feed additive in order to substitute in-feed antibiotics. Results No significant difference (P > 0.05) was found among the treatment groups on overall feed intake, egg weight, egg mass and feed conversion efficiency. COM456 had a significant reduction (P < 0.05) in faecal pH compared to the other groups at 28 weeks of age onwards. COM456 had significant higher (P < 0.05) level of lactic acid bacteria counts from 30 weeks of age onwards, followed by COM246 and COM345 at 32 and 34 weeks of age, respectively. Significant reduction of faecal Enterobacteriaceae (P < 0.05) were observed in COM246 and COM456 from 30 weeks of age onwards. The lowest levels (P < 0.05) of plasma and egg yolk cholesterol were observed in COM456, followed by COM345 and COM246. There was no significant difference in terms of yolk weight between the treatment groups. Significant higher (P < 0.05) content of C18:3, C20:2 and C22:6 were found in treatments supplemented with metabolite combinations as compared with the control group. Conclusions The present study demonstrated the positive effects of metabolite combinations supplementation in laying hens. Increase in hen-day egg production was observed in all treatments supplemented with metabolite combinations. In addition, the metabolite combinations, COM456 had reduced the faecal pH and faecal

  5. Nitric oxide-mediated endothlium-dependent vasodilation is impaired with borderline high-LDL cholesterol.

    PubMed

    Diehl, Kyle J; Stauffer, Brian L; Greiner, Jared J; Weil, Brian R; DeSouza, Christopher A

    2012-02-01

    The experimental aims of this study were to determine: (1) whether nitric oxide-mediated endothelium-dependent vasodilation is blunted in adult humans with borderline high plasma low-density lipoprotein (LDL)-cholesterol compared with adults with optimal/near optimal LDL-cholesterol levels; and, if so: (2) whether the magnitude of impairment in adults with borderline high LDL-cholesterol is similar to adults with high LDL-cholesterol. Forearm blood flow responses to intraarterial infusions of acetylcholine and sodium nitroprusside were measured in 50 middle-aged (43-64 year) adults: 20 in the optimal/near optimal LDL-cholesterol range (<130 mg/dL); 20 with borderline high LDL-cholesterol (130-159 mg/dL); and 10 with high LDL-cholesterol ($160 mg/dL). In addition, blood flow responses to acetylcholine were determined in the absence and presence of the endothelial nitric oxide synthase inhibitor N(G) -monomethyl-L-arginine (L-NMMA). Vasodilation to acetylcholine was ~20% lower (p < 0.05) in the borderline high (from 4.3 ± 0.2 to 12.3 ± 0.8 mL/100 mL tissue/min) and high (from 4.3 ± 0.3 to 12.0 ± 0.5 mL/100 mL tissue/min) LDL-cholesterol groups compared with the optimal/near optimal (from 4.4 ± 0.2 to 14.5 ± 0.5 mL/100 mL tissue/min) LDL-cholesterol group. L-NMMA significantly reduced (~30%) the vasodilator response to acetylcholine in the optimal/near optimal LDL-cholesterol group but not the borderline high or high LDL-cholesterol groups. Borderline high LDL-cholesterol is associated with impaired nitric oxide-mediated endothelium-dependent vasodilation.

  6. Toroidal rotation of multiple species of ions in tokamak plasma driven by lower-hybrid-waves

    NASA Astrophysics Data System (ADS)

    Zuo, Yang; Wang, Shaojie; Pan, Chengkang

    2012-10-01

    A numerical simulation is carried out to investigate the toroidal rotation of multiple species of ions and the radial electric field in a tokamak plasma driven by the lower-hybrid-wave (LHW). The theoretical model is based on the neoclassical transport theory associated with the anomalous transport model. Three species of ions (primary ion and two species of impurity ions) are taken into consideration. The predicted toroidal velocity of the trace impurities during the LHW injection agrees reasonably well with the experimental observation. It is shown that the toroidal rotation velocities of the trace impurity ions and the primary ions are close, therefore the trace impurity ions are representative of the primary ions in the toroidal rotation driven by the LHW.

  7. Toroidal rotation of multiple species of ions in tokamak plasma driven by lower-hybrid-waves

    SciTech Connect

    Zuo Yang; Wang Shaojie; Pan Chengkang

    2012-10-15

    A numerical simulation is carried out to investigate the toroidal rotation of multiple species of ions and the radial electric field in a tokamak plasma driven by the lower-hybrid-wave (LHW). The theoretical model is based on the neoclassical transport theory associated with the anomalous transport model. Three species of ions (primary ion and two species of impurity ions) are taken into consideration. The predicted toroidal velocity of the trace impurities during the LHW injection agrees reasonably well with the experimental observation. It is shown that the toroidal rotation velocities of the trace impurity ions and the primary ions are close, therefore the trace impurity ions are representative of the primary ions in the toroidal rotation driven by the LHW.

  8. Papain-hydrolyzed pork meat reduces serum cholesterol level and premature atherosclerosis in dietary-induced hypercholesterolemic rabbits.

    PubMed

    Katsuda, S; Ito, M; Waseda, Y; Morimatsu, F; Taguichi, Y; Hasegawa, M; Takaichi, S; Yamada, R; Furukawa, Y; Shimizu, T

    2000-08-01

    The effects of the low-molecular-weight fraction of papain-hydrolyzed pork meat (LMF) on the plasma cholesterol level and the generation of atherosclerosis were studied in rabbits fed a cholesterol-enriched diet. In LMF-fed rabbits, the plasma and liver cholesterol concentrations were both significantly lower (p<0.0 1) than in rabbits fed untreated pork meat (PM). Similarly, the cholesterol concentrations of the chylomicron and VLDL fractions were significantly lower in LMF-fed rabbits than in rabbits fed PM. Deposition of lipid in transverse sections of the aortic arch was significantly less in rabbits fed LMF than in those fed PM. Electron microscopic studies revealed preventive effects against premature atherosclerotic lesions in the aorta of rabbits fed LME These results indicate that LMF has a hypocholesterolemic action and preventive effects against premature atherosclerosis. PMID:11185655

  9. Persimmon fruit tannin-rich fiber reduces cholesterol levels in humans.

    PubMed

    Gato, Nobuki; Kadowaki, Akio; Hashimoto, Natsumi; Yokoyama, Shin-ichiro; Matsumoto, Kenji

    2013-01-01

    Bile acid-binding agents are known to lower blood cholesterol levels and have been clinically used for the treatment of hypercholesterolemia. We previously showed that tannin-rich fiber from young persimmon (Diospyros kaki) fruits had bile acid-binding properties. In this study, we performed a randomized, double-blind, placebo-controlled trial to investigate the hypocholesterolemic effects of tannin-rich fiber in humans. The subjects (n = 40, plasma total cholesterol levels 180-259 mg/dl) were divided into 3 groups and ingested cookie bars containing 0 g (placebo group, n = 14), 3 g (low-dose group, n = 13), or 5 g (high-dose group, n = 13) of tannin-rich fiber 3 times daily before meals for 12 weeks. Plasma total cholesterol levels decreased significantly in the low-dose (12 weeks, p < 0.005) and high-dose (6 weeks, p < 0.05; 12 weeks, p < 0.001) groups. In addition, plasma low-density lipoprotein cholesterol levels decreased significantly in the high-dose group (6 weeks, p < 0.05; 12 weeks, p < 0.001). These improvements were not accompanied by changes in plasma high-density lipoprotein cholesterol or plasma triglyceride levels. Our findings indicate that tannin-rich fiber from young persimmon fruits is a useful food material for treating hypercholesterolemia. PMID:23171573

  10. The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans.

    PubMed Central

    Walford, R L; Harris, S B; Gunion, M W

    1992-01-01

    Biosphere 2 is a 3.15-acre space containing an ecosystem that is energetically open (sunlight, electric power, and heat) but materially closed, with air, water, and organic material being recycled. Since September 1991, eight subjects (four women and four men) have been sealed inside, living on food crops grown within. Their diet, low in calories (average, 1780 kcal/day; 1 kcal = 4.184 kJ), low in fat (10% of calories), and nutrient-dense, conforms to that which in numerous animal experiments has promoted health, retarded aging, and extended maximum life span. We report here medical data on the eight subjects, comparing preclosure data with data through 6 months of closure. Significant changes included: (i) weight, 74 to 62 kg (men) and 61 to 54 kg (women); (ii) mean systolic/diastolic blood pressure (eight subjects), 109/74 to 89/58 mmHg (1 mmHg = 133 Pa); (iii) total serum cholesterol, from 191 +/- 11 to 123 +/- 9 mg/dl (mean +/- SD; 36% mean reduction), and high density lipoprotein, from 62 +/- 8 to 38 +/- 5 (risk ratio unchanged); (iv) triglyceride, 139 to 96 mg/dl (men) and 78 to 114 mg/dl (women); (v) fasting glucose, 92 to 74 mg/dl; (vi) leukocyte count, 6.7 to 4.7 x 10(9) cells per liter. We conclude that drastic reductions in cholesterol and blood pressure may be instituted in normal individuals in Western countries by application of a carefully chosen diet and that a low-calorie nutrient-dense regime shows physiologic features in humans similar to those in other animal species. PMID:1454844

  11. Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol

    PubMed Central

    Laaksonen, Reijo; Ekroos, Kim; Sysi-Aho, Marko; Hilvo, Mika; Vihervaara, Terhi; Kauhanen, Dimple; Suoniemi, Matti; Hurme, Reini; März, Winfried; Scharnagl, Hubert; Stojakovic, Tatjana; Vlachopoulou, Efthymia; Lokki, Marja-Liisa; Nieminen, Markku S.; Klingenberg, Roland; Matter, Christian M.; Hornemann, Thorsten; Jüni, Peter; Rodondi, Nicolas; Räber, Lorenz; Windecker, Stephan; Gencer, Baris; Pedersen, Eva Ringdal; Tell, Grethe S.; Nygård, Ottar; Mach, Francois; Sinisalo, Juha; Lüscher, Thomas F.

    2016-01-01

    Aims The aim was to study the prognostic value of plasma ceramides (Cer) as cardiovascular death (CV death) markers in three independent coronary artery disease (CAD) cohorts. Methods and results Corogene study is a prospective Finnish cohort including stable CAD patients (n = 160). Multiple lipid biomarkers and C-reactive protein were measured in addition to plasma Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), and Cer(d18:1/24:1). Subsequently, the association between high-risk ceramides and CV mortality was investigated in the prospective Special Program University Medicine—Inflammation in Acute Coronary Syndromes (SPUM-ACS) cohort (n = 1637), conducted in four Swiss university hospitals. Finally, the results were validated in Bergen Coronary Angiography Cohort (BECAC), a prospective Norwegian cohort study of stable CAD patients. Ceramides, especially when used in ratios, were significantly associated with CV death in all studies, independent of other lipid markers and C-reactive protein. Adjusted odds ratios per standard deviation for the Cer(d18:1/16:0)/Cer(d18:1/24:0) ratio were 4.49 (95% CI, 2.24–8.98), 1.64 (1.29–2.08), and 1.77 (1.41–2.23) in the Corogene, SPUM-ACS, and BECAC studies, respectively. The Cer(d18:1/16:0)/Cer(d18:1/24:0) ratio improved the predictive value of the GRACE score (net reclassification improvement, NRI = 0.17 and ΔAUC = 0.09) in ACS and the predictive value of the Marschner score in stable CAD (NRI = 0.15 and ΔAUC = 0.02). Conclusions Distinct plasma ceramide ratios are significant predictors of CV death both in patients with stable CAD and ACS, over and above currently used lipid markers. This may improve the identification of high-risk patients in need of more aggressive therapeutic interventions. PMID:27125947

  12. Localization of cholesterol in sphingomyelinase-treated fibroblasts.

    PubMed Central

    Pörn, M I; Slotte, J P

    1995-01-01

    The distribution of cellular unesterified cholesterol was studied in fibroblasts, which had been depleted of plasma membrane sphingomyelin by exposure to exogenous sphingomyelinase. This treatment has previously been shown to induce an increase in cholesterol esterification, a decrease in the biosynthesis of cholesterol, and a decreased susceptibility of cell cholesterol to oxidation with cholesterol oxidase. When the cellular localization of cholesterol was studied with fluorescent filipin staining, sphingomyelin depletion did not cause any visible changes in the filipin-cholesterol staining pattern, suggesting that the major part of cellular cholesterol was retained in the plasma membrane after sphingomyelinase treatment. After the oxidation of cell-surface cholesterol with cholesterol oxidase, the plasma membrane was no longer stained by filipin, but the plasma membrane cholesterol of sphingomyelin-depleted cells appeared to be resistant to oxidation with cholesterol oxidase when sphingomyelinase was used as an oxidation-promoting agent. However, the use of hypotonic buffer or phosphatidylcholine-specific phospholipase C together with cholesterol oxidase resulted in a complete oxidation of the cell-surface cholesterol in sphingomyelin-depleted cells, as evidenced by the filipin-cholesterol staining pattern. Similar results were obtained when [3H]cholesterol-labelled fibroblasts were used for determination of the susceptibility to cholesterol oxidation. The kinetics of [3H]cholesterol oxidation in sphingomyelin-depleted cells with cholesterol oxidase in hypotonic buffer indicated that approximately 85% of the cellular cholesterol still resided in the plasma membrane after sphingomyelin depletion. These results are contradictory to earlier reports on sphingomyelinase-induced changes in cellular cholesterol distribution and suggest that minor changes in the kinetics of cholesterol transport from the plasma membrane to the endoplasmic reticulum may be responsible

  13. Localization of cholesterol in sphingomyelinase-treated fibroblasts.

    PubMed

    Pörn, M I; Slotte, J P

    1995-05-15

    The distribution of cellular unesterified cholesterol was studied in fibroblasts, which had been depleted of plasma membrane sphingomyelin by exposure to exogenous sphingomyelinase. This treatment has previously been shown to induce an increase in cholesterol esterification, a decrease in the biosynthesis of cholesterol, and a decreased susceptibility of cell cholesterol to oxidation with cholesterol oxidase. When the cellular localization of cholesterol was studied with fluorescent filipin staining, sphingomyelin depletion did not cause any visible changes in the filipin-cholesterol staining pattern, suggesting that the major part of cellular cholesterol was retained in the plasma membrane after sphingomyelinase treatment. After the oxidation of cell-surface cholesterol with cholesterol oxidase, the plasma membrane was no longer stained by filipin, but the plasma membrane cholesterol of sphingomyelin-depleted cells appeared to be resistant to oxidation with cholesterol oxidase when sphingomyelinase was used as an oxidation-promoting agent. However, the use of hypotonic buffer or phosphatidylcholine-specific phospholipase C together with cholesterol oxidase resulted in a complete oxidation of the cell-surface cholesterol in sphingomyelin-depleted cells, as evidenced by the filipin-cholesterol staining pattern. Similar results were obtained when [3H]cholesterol-labelled fibroblasts were used for determination of the susceptibility to cholesterol oxidation. The kinetics of [3H]cholesterol oxidation in sphingomyelin-depleted cells with cholesterol oxidase in hypotonic buffer indicated that approximately 85% of the cellular cholesterol still resided in the plasma membrane after sphingomyelin depletion. These results are contradictory to earlier reports on sphingomyelinase-induced changes in cellular cholesterol distribution and suggest that minor changes in the kinetics of cholesterol transport from the plasma membrane to the endoplasmic reticulum may be responsible

  14. Impaired Cholesterol Efflux Capacity of High-Density Lipoprotein Isolated From Interstitial Fluid in Type 2 Diabetes Mellitus—Brief Report

    PubMed Central

    Tietge, Uwe J.F.; Dikkers, Arne; Parini, Paolo; Angelin, Bo; Rudling, Mats

    2016-01-01

    Objective— Patients with type 2 diabetes mellitus (T2D) have an increased risk of cardiovascular disease, the mechanism of which is incompletely understood. Their high-density lipoprotein (HDL) particles in plasma have been reported to have impaired cholesterol efflux capacity. However, the efflux capacity of HDL from interstitial fluid (IF), the starting point for reverse cholesterol transport, has not been studied. We here investigated the cholesterol efflux capacity of HDL from IF and plasma from T2D patients and healthy controls. Approach and Results— HDL was isolated from IF and peripheral plasma from 35 T2D patients and 35 age- and sex-matched healthy controls. Cholesterol efflux to HDL was determined in vitro, normalized for HDL cholesterol, using cholesterol-loaded macrophages. Efflux capacity of plasma HDL was 10% lower in T2D patients than in healthy controls, in line with previous observations. This difference was much more pronounced for HDL from IF, where efflux capacity was reduced by 28% in T2D. Somewhat surprisingly, the efflux capacity of HDL from IF was lower than that of plasma HDL, by 15% and 32% in controls and T2D patients, respectively. Conclusion— These data demonstrate that (1) HDL from IF has a lower cholesterol efflux capacity than plasma HDL and (2) the efflux capacity of HDL from IF is severely impaired in T2D when compared with controls. Because IF comprises the compartment where reverse cholesterol transport is initiated, the marked reduction in cholesterol efflux capacity of IF-HDL from T2D patients may play an important role for their increased risk to develop atherosclerosis. PMID:27034474

  15. Inhibition of cholesterol synthesis by atorvastatin in homozygous familial hypercholesterolaemia.

    PubMed

    Raal, F J; Pappu, A S; Illingworth, D R; Pilcher, G J; Marais, A D; Firth, J C; Kotze, M J; Heinonen, T M; Black, D M

    2000-06-01

    Patients with homozygous familial hypercholesterolaemia (HoFH) have markedly elevated low density lipoprotein (LDL) cholesterol levels that are refractory to standard doses of lipid-lowering drug therapy. In the present study we evaluated the effect of atorvastatin on steady state concentrations of plasma lipids and mevalonic acid (MVA), as well as on 24-h urinary excretion of MVA in patients with well characterized HoFH. Thirty-five HoFH patients (18 males; 17 females) received 40 mg and then 80 mg atorvastatin/day. The dose of atorvastatin was increased further to 120 mg/day in 20 subjects and to 160 mg/day in 13 subjects who had not achieved LDL cholesterol goal, or in whom the dose of atorvastatin had not exceeded 2.5 mg/kg body wt per day. LDL cholesterol levels were reduced by 17% at the 40 mg/day and by 28% at the 80 mg/day dosage (P<0.01). Reduction in LDL cholesterol in the five receptor negative patients was similar to that achieved in the 30 patients with residual LDL receptor activity. Plasma MVA and 24-h urinary excretion of MVA, as markers of in vivo cholesterol synthesis, were elevated at baseline and decreased markedly with treatment. Urinary MVA excretion decreased by 57% at the 40 mg/day dose and by 63% at the 80 mg/day dosage (P<0. 01). There was a correlation between reduction in LDL cholesterol and reduction in urinary MVA excretion; those patients with the highest basal levels of MVA excretion and thus the highest rates of cholesterol synthesis having the greatest reduction in LDL cholesterol (r=0.38; P=0.02). Increasing the dose of atorvastatin to 120 and 160 mg/day did not result in any further reduction in LDL cholesterol or urinary MVA excretion suggesting a plateau effect with no further inhibition of cholesterol synthesis at doses of atorvastatin greater than 80 mg/day. PMID:10856535

  16. Cholesterol's location in lipid bilayers

    DOE PAGES

    Marquardt, Drew; Kučerka, Norbert; Wassall, Stephen R.; Harroun, Thad A.; Katsaras, John

    2016-04-04

    It is well known that cholesterol modifies the physical properties of lipid bilayers. For example, the much studied liquid-ordered Lo phase contains rapidly diffusing lipids with their acyl chains in the all trans configuration, similar to gel phase bilayers. Moreover, the Lo phase is commonly associated with cholesterol-enriched lipid rafts, which are thought to serve as platforms for signaling proteins in the plasma membrane. Cholesterol's location in lipid bilayers has been studied extensively, and it has been shown – at least in some bilayers – to align differently from its canonical upright orientation, where its hydroxyl group is in themore » vicinity of the lipid–water interface. In this study we review recent works describing cholesterol's location in different model membrane systems with emphasis on results obtained from scattering, spectroscopic and molecular dynamics studies.« less

  17. Mediation of Endogenous β-endorphin by Tetrandrine to Lower Plasma Glucose in Streptozotocin-induced Diabetic Rats

    PubMed Central

    2004-01-01

    The role of β-endorphin in the plasma glucose-lowering action of tetrandrine in streptozotocin-induced diabetic rats (STZ-diabetic rats) was investigated. The plasma glucose concentration was assessed by the glucose oxidase method. The enzyme-linked immunosorbent assay was used to determine the plasma level of β-endorphin-like immunoreactivity (BER). The mRNA levels of glucose transporter subtype 4 (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of STZ-diabetic rats were detected by Northern blotting analysis. The expressed protein of GLUT4 or PEPCK was characterized by Western blotting analysis. Tetrandrine dose-dependently increased plasma BER in a manner parallel to the decrease of plasma glucose in STZ-diabetic rats. Moreover, the plasma glucose-lowering effect of tetrandrine was inhibited by naloxone and naloxonazine at doses sufficient to block opioid μ-receptors. Further, tetrandrine failed to produce plasma glucose-lowering action in opioid μ-receptor knockout diabetic mice. Bilateral adrenalectomy eliminated the plasma glucose-lowering effect and plasma BER-elevating effect of tetrandrine in STZ-diabetic rats. Both effects were abolished by treatment with hexamethonium or pentolinium at doses sufficient to block nicotinic receptors. Tetrandrine enhanced BER release directly from the isolated adrenal medulla of STZ-diabetic rats and this action was abolished by the blockade of nicotinic receptors. Repeated intravenous administration of tetrandrine (1.0 mg/kg) to STZ-diabetic rats for 3 days resulted in an increase in the mRNA and protein levels of the GLUT4 in soleus muscle, in addition to the lowering of plasma glucose. Similar treatment with tetrandrine reversed the elevated mRNA and protein levels of PEPCK in the liver of STZ-diabetic rats. The obtained results suggest that tetrandrine may induce the activation of nicotinic receptors in adrenal medulla to enhance the secretion of β-endorphin, which could

  18. Low Plasma Hdl Cholesterol and Elevated C Reactive Protein further Increase Cardiovascular Disease Risk in Latinos with Type 2 Diabetes

    PubMed Central

    Calle, Mariana C; Vega-López, Sonia; Segura-Pérez, Sofia; Volek, Jeff S; Pérez-Escamilla, Rafael; Fernandez, Maria Luz

    2011-01-01

    The purpose of this study was to determine whether low plasma HDL and high C reactive protein (CRP) concentrations would further increase cardiovascular disease (CVD) risk in Latinos with poorly controlled type-2 diabetes, already at high risk for CVD. Subjects (n = 68) were grouped into High-HDL (≥ or 1.03 or 1.3 mmol/L) or Low-HDL (<1.03 or 1.3 mmol/L) for men and women, respectively. Following classification, risk factors for CVD including apolipoproteins, lipoprotein size and subfraction distribution were assesed. Similarly, participants were divided according to their CRP levels (≥ or < 3mg/L) and key inflammatory markers as well as leptin and adiponectin were analyzed. The Low-HDL group had higher concentrations of the atherogenic particles, large and medium VLDL and the smaller LDL subfractions compared to the High-HDL group (p<0.001). Consistently, VLDL diameter was larger and LDL diameter smaller in the Low HDL group (p<0.001). The High-CRP group had larger waist circumference (p<0.001) and body mass index (p<0.001) than the Low-CRP group. Leptin was also higher in the High- CRP group (p< 0.01). These data suggest that Latinos with type-2 diabetes having either Low-HDL or High-CRP concentrations are at a higher risk for atherosclerosis and CVD than their counterparts who have High-HDL or Low-CRP. PMID:22407331

  19. Neonatal dietary cholesterol and alleles of cholesterol 7-alpha hydroxylase affect piglet cerebrum weight, cholesterol concentration, and behavior

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This experiment was designed to test the effect of polymorphism in the cholesterol 7-alpha hydroxylase (CYP7) gene locus, and dietary cholesterol (C) on cerebrum C in neonatal pigs fed sow's milk formulas. Thirty-six pigs (18 male and 18 female) genetically selected for high (HG), or low (LG) plasma...

  20. Deleting myeloid IL-10 receptor signalling attenuates atherosclerosis in LDLR-/- mice by altering intestinal cholesterol fluxes.

    PubMed

    Stöger, J Lauran; Boshuizen, Marieke C S; Brufau, Gemma; Gijbels, Marion J J; Wolfs, Ine M J; van der Velden, Saskia; Pöttgens, Chantal C H; Vergouwe, Monique N; Wijnands, Erwin; Beckers, Linda; Goossens, Pieter; Kerksiek, Anja; Havinga, Rick; Müller, Werner; Lütjohann, Dieter; Groen, Albert K; de Winther, Menno P J

    2016-08-30

    Inflammatory responses and cholesterol homeostasis are interconnected in atherogenesis. Interleukin (IL)-10 is an important anti-inflammatory cytokine, known to suppress atherosclerosis development. However, the specific cell types responsible for the atheroprotective effects of IL-10 remain to be defined and knowledge on the actions of IL-10 in cholesterol homeostasis is scarce. Here we investigated the functional involvement of myeloid IL-10-mediated atheroprotection. To do so, bone marrow from IL-10 receptor 1 (IL-10R1) wild-type and myeloid IL-10R1-deficient mice was transplanted to lethally irradiated female LDLR-/- mice. Hereafter, mice were given a high cholesterol diet for 10 weeks after which atherosclerosis development and cholesterol metabolism were investigated. In vitro, myeloid IL-10R1 deficiency resulted in a pro-inflammatory macrophage phenotype. However, in vivo significantly reduced lesion size and severity was observed. This phenotype was associated with lower myeloid cell accumulation and more apoptosis in the lesions. Additionally, a profound reduction in plasma and liver cholesterol was observed upon myeloid IL-10R1 deficiency, which was reflected in plaque lipid content. This decreased hypercholesterolaemia was associated with lowered very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels, likely as a response to decreased intestinal cholesterol absorption. In addition, IL-10R1 deficient mice demonstrated substantially higher faecal sterol loss caused by increased non-biliary cholesterol efflux. The induction of this process was linked to impaired ACAT2-mediated esterification of liver and plasma cholesterol. Overall, myeloid cells do not contribute to IL-10-mediated atheroprotection. In addition, this study demonstrates a novel connection between IL-10-mediated inflammation and cholesterol homeostasis in atherosclerosis. These findings make us reconsider IL-10 as a beneficial influence on atherosclerosis. PMID:27358035

  1. Microbiota prevents cholesterol loss from the body by regulating host gene expression in mice.

    PubMed

    Zhong, Chun-Yan; Sun, Wei-Wei; Ma, Yinyan; Zhu, Hongling; Yang, Pan; Wei, Hong; Zeng, Ben-Hua; Zhang, Qian; Liu, Yu; Li, Wen-Xia; Chen, Yixin; Yu, Liqing; Song, Zhi-Yuan

    2015-05-27

    We have previously observed that knockout of Niemann-Pick C1-Like 1 (NPC1L1), a cholesterol transporter essential for intestinal cholesterol absorption, reduces the output of dry stool in mice. As the food intake remains unaltered in NPC1L1-knockout (L1-KO) mice, we hypothesized that NPC1L1 deficiency may alter the gut microbiome to reduce stool output. Consistently, here we demonstrate that the phyla of fecal microbiota differ substantially between L1-KO mice and their wild-type controls. Germ-free (GF) mice have reduced stool output. Inhibition of NPC1L1 by its inhibitor ezetimibe reduces stool output in specific pathogen-free (SPF), but not GF mice. In addition, we show that GF versus SPF mice have reduced intestinal absorption and increased fecal excretion of cholesterol, particularly after treatment with ezetimibe. This negative balance of cholesterol in GF mice is associated with reduced plasma and hepatic cholesterol, and likely caused by reduced expression of NPC1L1 and increased expression of ABCG5 and ABCG8 in small intestine. Expression levels of other genes in intestine and liver largely reflect a state of cholesterol depletion and a decrease in intestinal sensing of bile acids. Altogether, our findings reveal a broad role of microbiota in regulating whole-body cholesterol homeostasis and its response to a cholesterol-lowering drug, ezetimibe.

  2. Walnuts lower TRAMP prostate tumor growth by altering IGF-1, energy and cholesterol metabolism and is not due to their fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary changes could potentially reduce prostate cancer morbidity and mortality. Prostate tumor size, gene expression, metabolite and plasma responses to a 100 g of fat/kg diet (whole walnuts, walnut oil and other oils; balanced for macronutrients, tocopherols (a-and ' ) for 18 weeks were assessed ...

  3. Isoflavone and protein constituents of lactic acid-fermented soy milk combine to prevent dyslipidemia in rats fed a high cholesterol diet.

    PubMed

    Kobayashi, Maki; Egusa, Shintaro; Fukuda, Mitsuru

    2014-12-10

    A high cholesterol diet induces dyslipidemia. This study investigated whether isoflavone aglycones in lactic acid-fermented soy milk (LFS) improve lipid metabolism in rats fed a high cholesterol diet. Male Sprague-Dawley rats aged seven weeks were fed an AIN-93G diet, a 1% cholesterol diet (a high cholesterol diet), a high-cholesterol diet containing 4% isoflavone extract of LFS (LFS extract diet), a high-cholesterol diet containing 19.4% ethanol-washed LFS (ethanol-washed LFS diet, isoflavone-poor diet), or a high cholesterol diet containing 23.2% intact LFS (intact LFS diet) for five weeks. The plasma total cholesterol (TC) level was increased in the rats fed the LFS extract diet compared with those fed the high cholesterol diet. The TC level was decreased by the intact LFS and ethanol-washed LFS diets. The cholesterol-lowering effect was stronger in the rats fed the intact LFS diet than those fed the ethanol-washed LFS diet. The plasma triglyceride (TG) level was unchanged in the rats fed the LFS extract diet, but it decreased in rats fed the intact LFS and ethanol-washed LFS diets. Although, compared with the high cholesterol diet, the LFS extract and ethanol-washed LFS diets did not reduce hepatic cholesterol and TG, both levels were remarkably lowered by the intact LFS diet. These results suggest that the improvement in lipid metabolism of rats fed a high-cholesterol diet containing LFS isoflavone aglycones is not due to an independent effect but due to a cooperative effect with soy protein.

  4. Isoflavone and Protein Constituents of Lactic Acid-Fermented Soy Milk Combine to Prevent Dyslipidemia in Rats Fed a High Cholesterol Diet

    PubMed Central

    Kobayashi, Maki; Egusa, Shintaro; Fukuda, Mitsuru

    2014-01-01

    A high cholesterol diet induces dyslipidemia. This study investigated whether isoflavone aglycones in lactic acid-fermented soy milk (LFS) improve lipid metabolism in rats fed a high cholesterol diet. Male Sprague-Dawley rats aged seven weeks were fed an AIN-93G diet, a 1% cholesterol diet (a high cholesterol diet), a high-cholesterol diet containing 4% isoflavone extract of LFS (LFS extract diet), a high-cholesterol diet containing 19.4% ethanol-washed LFS (ethanol-washed LFS diet, isoflavone-poor diet), or a high cholesterol diet containing 23.2% intact LFS (intact LFS diet) for five weeks. The plasma total cholesterol (TC) level was increased in the rats fed the LFS extract diet compared with those fed the high cholesterol diet. The TC level was decreased by the intact LFS and ethanol-washed LFS diets. The cholesterol-lowering effect was stronger in the rats fed the intact LFS diet than those fed the ethanol-washed LFS diet. The plasma triglyceride (TG) level was unchanged in the rats fed the LFS extract diet, but it decreased in rats fed the intact LFS and ethanol-washed LFS diets. Although, compared with the high cholesterol diet, the LFS extract and ethanol-washed LFS diets did not reduce hepatic cholesterol and TG, both levels were remarkably lowered by the intact LFS diet. These results suggest that the improvement in lipid metabolism of rats fed a high-cholesterol diet containing LFS isoflavone aglycones is not due to an independent effect but due to a cooperative effect with soy protein. PMID:25514389

  5. Common polymorphisms of ATP binding cassette transporter A1, including a functional promoter polymorphism, associated with plasma high density lipoprotein cholesterol levels in Turks.

    PubMed

    Hodoğlugil, Uğur; Williamson, David W; Huang, Yadong; Mahley, Robert W

    2005-12-01

    The role of high levels of high density lipoprotein cholesterol (HDL-C) in protection against development of atherosclerosis is generally attributed to its role in reverse cholesterol transport, and the ATP binding cassette transporter A1 (ABCA1) is a key element of this process. We examined polymorphisms in ABCA1 in Turks, a population characterized by very low HDL-C levels. We discovered 36 variations in ABCA1 and genotyped informative polymorphisms in over 2,300 subjects. The rare alleles of C-14T and V771M polymorphisms were associated with higher HDL-C levels in men and, in combination with the rare alleles of R219K and I883M, respectively, with higher HDL-C in both sexes. Rare alleles of the C-14T and V771M polymorphisms were more frequent in the high HDL-C (>OR=40mg/dl) than in the low HDL-C group (plasma HDL-C levels in Turks.

  6. Plasma Current Start-up Experiment using Waves in the Lower Hybrid Frequency Range in TST-2

    SciTech Connect

    Takase, Y.; Wakatsuki, T.; Ejiri, A.; Kakuda, H.; Ambo, T.; Hanashima, K.; Hiratsuka, J.; Nagashima, Y.; Sakamoto, T.; Shino, R.; Sonehara, M.; Watanabe, O.; Yamaguchi, T.; Moeller, C. P.; Kasahara, H.; Kumazawa, R.; Saito, K.; Seki, T.; Shimpo, F.

    2011-12-23

    Noninductive plasma current (I{sub p}) start-up experiments using RF power in the lower hybrid frequency range are being conducted on the TST-2 spherical tokamak. The lower hybrid wave (LHW) has demonstrated efficient current drive in conventional tokamaks. However, in spherical tokamak (ST) plasmas with very high dielectric constants (;{epsilon}{approx}{omega}{sub pe}{sup 2}/{Omega}{sub e}{sup 2}>>1), accessibility of the LHW to the plasma core is severely limited. Our approach is to keep the plasma density low (such that {epsilon}{approx}1) during I{sub p} ramp-up. Once I{sub p} reaches a level sufficiently high for neutral beam current drive, plasma can be densified and transformed into an advanced tokamak plasma dominated by the self-driven bootstrap current. Initial plasma start-up experiments were performed on TST-2 using a combline antenna which excites a traveling fast wave. After formation of toroidal flux surfaces, RF power and vertical field were ramped up to increase I{sub p}. Up to 12 kA of Ip has been obtained by this method. Soft X-ray measurements indicate that the electron temperature increases as I{sub p} increases, and hard X-ray spectroscopy indicates that energetic electrons build up as I{sub p} is ramped up.

  7. Exercise Lowers Plasma Angiopoietin-Like 2 in Men with Post-Acute Coronary Syndrome

    PubMed Central

    Thorin-Trescases, Nathalie; Hayami, Doug; Yu, Carol; Luo, Xiaoyan; Nguyen, Albert; Larouche, Jean-François; Lalongé, Julie; Henri, Christine; Arsenault, André; Gayda, Mathieu; Juneau, Martin; Lambert, Jean

    2016-01-01

    Pro-inflammatory angiopoietin-like 2 (angptl2) promotes endothelial dysfunction in mice and circulating angptl2 is higher in patients with cardiovascular diseases. We previously reported that a single bout of physical exercise was able to reduce angptl2 levels in coronary patients. We hypothesized that chronic exercise would reduce angptl2 in patients with post-acute coronary syndrome (ACS) and endothelial dysfunction. Post-ACS patients (n = 40, 10 women) were enrolled in a 3-month exercise-based prevention program. Plasma angptl2, hs-CRP, and endothelial function assessed by scintigraphic forearm blood flow, were measured before and at the end of the study. Exercise increased VO2peak by 10% (p<0.05), but did not significantly affect endothelial function, in both men and women. In contrast, exercise reduced angptl2 levels only in men (-26±7%, p<0.05), but unexpectedly not in women (+30±16%), despite similar initial levels in both groups. Exercise reduced hs-CRP levels in men but not in women. In men, levels of angptl2, but not of hs-CRP, reached at the end of the training program were negatively correlated with VO2peak (r = -0.462, p = 0.012) and with endothelial function (r = -0.419, p = 0.033) measured at baseline: better initial cardiopulmonary fitness and endothelial function correlated with lower angptl2 levels after exercise. Pre-exercise angptl2 levels were lower if left ventricular ejection time was long (p<0.05) and the drop in angptl2 induced by exercise was greater if the cardiac output was high (p<0.05). In conclusion, in post-ACS men, angptl2 levels are sensitive to chronic exercise training. Low circulating angptl2 reached after training may reflect good endothelial and cardiopulmonary functions. PMID:27736966

  8. The Effects of the Scattering by Edge Plasma Density Fluctuations on Lower Hyybrid Wave Propagation

    SciTech Connect

    Bertelli, N; Bonoli, P T; Harvey, R W; Smirnov, A P; Baek, S G; Parker, R R; Phillips, C K; Valeo, E J; Wilson, J R; Wright, J C

    2012-08-27

    Scattering effects induced by edge density fluctuations on lower hybrid (LH) wave propagation are investigated. The scattering model used here is based on the work of Bonoli and Ott [Phys. Fluids 25 (1982) 361]. It utilizes an electromagnetic wave kinetic equation solved by a Monte Carlo technique. This scattering model has been implemented in GENRAY , a ray tracing code which explicitly simulates wave propagation, as well as collisionless and collisional damping processes, over the entire plasma discharge, including the scrape-off layer (SOL) that extends from the separatrix to the vessel wall. A numerical analysis of the LH wave trajectories and the power deposition profile with and without scattering is presented for Alcator CMod discharges. Comparisons between the measured hard x-ray emission on Alcator C-Mod and simulations of the data obtained from the synthetic diagnostic included in the GENRAY/CQL3D package are shown, with and without the combination of scattering and collisional damping. Implications of these results on LH current drive are discussed.

  9. On the Dirichlet Problem of Mixed Type for Lower Hybrid Waves in Axisymmetric Cold Plasmas

    NASA Astrophysics Data System (ADS)

    Lupo, Daniela; Monticelli, Dario D.; Payne, Kevin R.

    2015-07-01

    For a class of linear second order partial differential equations of mixed elliptic-hyperbolic type, which includes a well known model for analyzing possible heating in axisymmetric cold plasmas, we give results on the weak well-posedness of the Dirichlet problem and show that such solutions are characterized by a variational principle. The weak solutions are shown to be saddle points of natural functionals suggested by the divergence form of the PDEs. Moreover, the natural domains of the functionals are the weighted Sobolev spaces to which the solutions belong. In addition, all critical levels will be characterized in terms of global extrema of the functionals restricted to suitable infinite dimensional linear subspaces. These subspaces are defined in terms of a robust spectral theory with weights which is associated to the linear operator and is developed herein. Similar characterizations for the weighted eigenvalue problem and nonlinear variants will also be given. Finally, topological methods are employed to obtain existence results for nonlinear problems including perturbations in the gradient which are then applied to the well-posedness of the linear problem with lower order terms.

  10. [Role of HDL in Cholesterol Efflux and Reverse Cholesterol Transport].

    PubMed

    Ayaori, Makoto

    2016-01-01

    Low plasma levels of HDL-cholesterol (HDL-C) have been consistently associated with an increased risk of atherosclerotic cardiovascular diseases (CVD), and it is thus considered to be an anti-atherogenic lipoprotein. The development of novel therapies to enhance the atheroprotective properties of HDL may have the potential to further reduce the residual risk. Reverse cholesterol transport (RCT) is believed to be a primary atheroprotective property of HDL and its major protein, apolipoprotein A-I(apoA-I). HDL and apoA-I have been shown to promote the efflux of excess cholesterol from macrophage-derived foam cells via the cholesterol transporters, ATP-binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor class B, type I (SR-BI), and then transport it back to the liver for excretion into bile and eventually into the feces. In this regard, a validated murine assay that quantifies macrophage RCT may be a better predictor of atherosclerosis than the steady-state plasma concentration of HDL-C. Indeed, a recent clinical study demonstrated that the ability of serum HDL to mediate cholesterol efflux from macrophages was independently and negatively associated with the CVD risk even after adjustment for HDL-C levels, suggesting that HDL functionality is more important than its quantity. Therefore, the future development of HDL-targeted therapy should take both aspects into consideration to further reduce the residual risk.

  11. [Role of HDL in Cholesterol Efflux and Reverse Cholesterol Transport].

    PubMed

    Ayaori, Makoto

    2016-01-01

    Low plasma levels of HDL-cholesterol (HDL-C) have been consistently associated with an increased risk of atherosclerotic cardiovascular diseases (CVD), and it is thus considered to be an anti-atherogenic lipoprotein. The development of novel therapies to enhance the atheroprotective properties of HDL may have the potential to further reduce the residual risk. Reverse cholesterol transport (RCT) is believed to be a primary atheroprotective property of HDL and its major protein, apolipoprotein A-I(apoA-I). HDL and apoA-I have been shown to promote the efflux of excess cholesterol from macrophage-derived foam cells via the cholesterol transporters, ATP-binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor class B, type I (SR-BI), and then transport it back to the liver for excretion into bile and eventually into the feces. In this regard, a validated murine assay that quantifies macrophage RCT may be a better predictor of atherosclerosis than the steady-state plasma concentration of HDL-C. Indeed, a recent clinical study demonstrated that the ability of serum HDL to mediate cholesterol efflux from macrophages was independently and negatively associated with the CVD risk even after adjustment for HDL-C levels, suggesting that HDL functionality is more important than its quantity. Therefore, the future development of HDL-targeted therapy should take both aspects into consideration to further reduce the residual risk. PMID:27192798

  12. Relationship between bioavailability and hypocholesterolemic activity of YM17E, an inhibitor of ACAT, in cholesterol-fed rats.

    PubMed

    Uchida, T; Aoyama, K; Watanabe, T; Higuchi, S

    1998-03-01

    The relationship between bioavailability and the serum cholesterol-lowering effect of YM17E, an ACAT inhibitor was investigated. Serum cholesterol levels in cholesterol-fed rats decreased after both oral and intravenous administration of YM17E. Marked inhibition of cholesterol absorption was observed after oral administration, but not after intravenous administration. YM17E and its five active metabolites were primarily distributed in the liver after intravenous administration, but in small intestine and liver after oral administration. Hepatic ACAT activity in cholesterol-fed rats was inhibited by intravenous administration. Cholesteryl ester input into plasma by Triton WR-1339 treatment to the rats was inhibited by intravenous administration of YM17E. Plasma clearance of 125I-LDL in cholesterol-fed rats increased after YM17E treatment suggesting a decrease in LDL production. These results indicate that the hypocholesterolemic effect of intravenous YM17E was due to hepatic ACAT inhibition, not an inhibition of intestinal cholesterol absorption. The contribution of ACAT inhibition in small intestine and liver on the pharmacological effect could be explained by plasma inhibitor concentration after oral or intravenous administration of YM17E. From these results, it is concluded that the change in bioavailability of ACAT inhibitors change the mechanism of hypocholesterolemic effects, shifting the relative contributions of small intestinal and hepatic ACAT inhibition. PMID:9568741

  13. Prenatal detection of the cholesterol biosynthetic defect in the Smith-Lemli-Opitz syndrome by the analysis of amniotic fluid sterols.

    PubMed

    Abuelo, D N; Tint, G S; Kelley, R; Batta, A K; Shefer, S; Salen, G

    1995-04-10

    The Smith-Lemli-Opitz (SLO or RSH) syndrome is an autosomal recessive disorder characterized by a recognizable pattern of minor facial anomalies, congenital anomalies of many organs, failure to thrive, and mental retardation. Its cause is a defect in cholesterol biosynthesis characterized by abnormally low plasma cholesterol levels and concentrations of the cholesterol precursor 7-dehydrocholesterol (7DHC) elevated up to several thousand-fold above normal. We used capillary column gas-chromatography to quantify sterols in amniotic fluid, amniotic cells, plasma, placenta, and breast milk from a heterozygous mother who had previously given birth to an affected son and in cord blood and plasma from her affected newborn daughter. The cholesterol concentration in amniotic fluid at 16 weeks gestation was normal, but 7DHC, normally undetectable, was greatly elevated. In cultured amniocytes, the level of 7DHC was 11% of total cholesterol, similar to cultured fibroblasts from patients with SLO syndrome. At 38 weeks, a girl with phenotype consistent with the syndrome was born. Cholesterol concentrations were abnormally low in cord blood and in the baby's plasma at 12 weeks, while levels of 7DHC were grossly elevated, confirming the prenatal diagnosis. The mother's plasma cholesterol increased steadily during gestation but remained below the lower 95% limit reported for normal control women. We conclude that it is now possible to detect the SLO syndrome at 16 weeks gestation by analyzing amniotic fluid sterols.

  14. The N-terminal Domain of NPC1L1 Protein Binds Cholesterol and Plays Essential Roles in Cholesterol Uptake*

    PubMed Central

    Zhang, Jin-Hui; Ge, Liang; Qi, Wei; Zhang, Liqing; Miao, Hong-Hua; Li, Bo-Liang; Yang, Maojun; Song, Bao-Liang

    2011-01-01

    Niemann-Pick C1-like 1 (NPC1L1) is a multitransmembrane protein playing a crucial role in dietary and biliary cholesterol absorption. Cholesterol promotes the formation and endocytosis of NPC1L1-flotillin-cholesterol membrane microdomains, which is an early step in cholesterol uptake. How cholesterol is sensed in this step is unknown. Here, we find that the N-terminal domain (NTD) of NPC1L1 binds cholesterol. Mutation of residue Leu-216 in NPC1L1-NTD eliminates cholesterol binding, decreases the formation of NPC1L1-flotillin-cholesterol membrane microdomains, and prevents NPC1L1-mediated cholesterol uptake in culture cells and mice livers. NPC1L1-NTD specifically binds cholesterol but not plant sterols, which may account for the selective cholesterol absorption in intestine. Furthermore, 25- or 27-hydroxycholesterol competes with cholesterol to bind NPC1L1-NTD and inhibits the cholesterol induced endocytosis of NPC1L1. Together, these results demonstrate that plasma membrane-localized NPC1L1 binds exogenous cholesterol via its NTD, and facilitates the formation of NPC1L1-flotillin-cholesterol membrane microdomains that are then internalized into cells through the clathrin-AP2 pathway. Our study uncovers the mechanism of cholesterol sensing by NPC1L1 and proposes a mechanism for selective cholesterol absorption. PMID:21602275

  15. [Role of the ABC transporters A1 and G1, key reverse cholesterol transport proteins, in atherosclerosis].

    PubMed

    Demina, E P; Miroshnikova, V V; Schwarzman, A L

    2016-01-01

    Atherosclerosis is one of the most common causes of death worldwide. Epidemiology studies firmly established an inverse relationship between atherogenesis and distorted lipid metabolism, in particular, higher levels of total cholesterol, an accumulation of CH-laden macrophages (foam cells), and lower plasma levels of antiatherogenic high density lipoprotein (HDL). It is believed that the reverse cholesterol transport, a process that removes excess cholesterol from peripheral tissues/cells including macrophages to circulating HDL, is one of the main mechanisms responsible for anti-atherogenic properties of HDL. The key proteins of reverse cholesterol transport-ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1)-mediate the cholesterol efflux from macrophages and prevent their transformation into foam cells. This review focuses on the role of ABC transporters A1 and G1 in the pathogenesis of atherosclerosis.

  16. Detection of lower hybrid waves in the scrape-off layer of tokamak plasmas with microwave backscattering

    NASA Astrophysics Data System (ADS)

    Baek, S. G.; Shiraiwa, S.; Parker, R. R.; Bonoli, P. T.; Marmar, E. S.; Wallace, G. M.; Dominguez, A.; Kramer, G. J.; Lau, C.

    2014-01-01

    Microwave backscattering experiments have been performed on the Alcator C-Mod tokamak in order to investigate the propagation of lower hybrid (LH) waves in reactor-relevant, high-density plasmas. When the line-averaged density is raised above 1 × 1020 m-3, lower hybrid current drive efficiency is found to be lower than expected [Wallace et al., Phys. Plasmas 19, 062505 (2012)] and LH power is thought to be dissipated at the plasma edge. Using a single channel (60 GHz) ordinary-mode (O-mode) reflectometer system, we demonstrate radially localized LH wave measurements in the scrape-off layer of high density plasmas (n¯e ≳ 0.9×1020 m-3). Measured backscattered O-mode power varies depending on the magnetic field line mapping, suggesting the resonance cone propagation of LH waves. Backscattered power is also sensitive to variations in plasma density and the launched parallel refractive index of the LH waves. LH ray-tracing simulations have been carried out to interpret the observed variations. To understand the measured LH waves in regions not magnetically connected to the launcher, two hypotheses are examined. One is the weak single pass absorption and the other is scattering of LH waves by non-linear effects.

  17. Detection of lower hybrid waves in the scrape-off layer of tokamak plasmas with microwave backscattering

    SciTech Connect

    Baek, S. G. Shiraiwa, S.; Parker, R. R.; Bonoli, P. T.; Marmar, E. S.; Wallace, G. M.; Lau, C.; Dominguez, A.; Kramer, G. J.

    2014-01-15

    Microwave backscattering experiments have been performed on the Alcator C-Mod tokamak in order to investigate the propagation of lower hybrid (LH) waves in reactor-relevant, high-density plasmas. When the line-averaged density is raised above 1 × 10{sup 20} m{sup –3}, lower hybrid current drive efficiency is found to be lower than expected [Wallace et al., Phys. Plasmas 19, 062505 (2012)] and LH power is thought to be dissipated at the plasma edge. Using a single channel (60 GHz) ordinary-mode (O-mode) reflectometer system, we demonstrate radially localized LH wave measurements in the scrape-off layer of high density plasmas (n{sup ¯}{sub e} ≳ 0.9×10{sup 20} m{sup −3}). Measured backscattered O-mode power varies depending on the magnetic field line mapping, suggesting the resonance cone propagation of LH waves. Backscattered power is also sensitive to variations in plasma density and the launched parallel refractive index of the LH waves. LH ray-tracing simulations have been carried out to interpret the observed variations. To understand the measured LH waves in regions not magnetically connected to the launcher, two hypotheses are examined. One is the weak single pass absorption and the other is scattering of LH waves by non-linear effects.

  18. Effect of gas puffing from different side on lower hybrid wave-plasma coupling in experimental advanced superconductive tokamak

    NASA Astrophysics Data System (ADS)

    Ding, B. J.; Kong, E. H.; Zhang, T.; Ekedahl, A.; Li, M. H.; Zhang, L.; Wei, W.; Li, Y. C.; Wu, J. H.; Xu, G. S.; Zhao, H. L.; Wang, M.; Gong, X. Z.; Shan, J. F.; Liu, F. K.; EAST Team

    2013-10-01

    Effect of gas puffing from electron-side and ion-side on lower hybrid wave (LHW)-plasma is investigated in experimental advanced superconductive tokamak for the first time. Experimental results with different gas flow rates show that electron density at the grill is higher in the case of gas puffing from electron-side; consequently, a lower reflection coefficient is observed, suggesting better effect of puffing from electron-side on LHW-plasma. The difference in edge density between electron- and ion-side cases suggests that local ionization of puffed gas plays a dominant role in affecting the density at the grill due to different movement direction of ionized electrons and that part of gas has been locally ionized near the gas pipe before diffusing into the grill region. Such difference could be enlarged and important in ITER due to the improvement of plasma parameters and LHW power.

  19. Three-Dimensional Kinetic Simulation of the Nonlinear Evolution of Lower-Hybrid Waves in the Auroral Plasma

    NASA Technical Reports Server (NTRS)

    Singh, Nagendra

    2000-01-01

    Under this grant we have done research on the following topics. 1) Development of Parallel PIC Codes (PPIC); 2) Evolution of Lower-Hybrid Pump Waves; 3) Electron-beam Driven Plasma Electrodynamics; and 4) Studies on Inertial and Kinetic Alfven Waves. A brief summary of our findings and resulting publications are given.

  20. Posttraumatic Stress Disorder, Exposure to Combat, and Lower Plasma Cortisol among Vietnam Veterans: Findings and Clinical Implications.

    ERIC Educational Resources Information Center

    Boscarino, Joseph A.

    1996-01-01

    Clinical studies suggest individuals with posttraumatic stress disorder (PSD) experience neuroendocrine systems alterations, resulting in significantly lower plasma cortisol. To test this hypothesis, morning serum cortisol was compared among a national sample of Vietnam "theater" veterans (n=2,490) and a sample of Vietnam "era" veterans (n=1,972)…

  1. Dietary green tea extract lowers plasma and hepatic triglycerides and decreases the expression of sterol regulatory element-binding protein-1c mRNA and its responsive genes in fructose-fed, ovariectomized rats.

    PubMed

    Shrestha, Sudeep; Ehlers, Sarah J; Lee, Ji-Young; Fernandez, Maria-Luz; Koo, Sung I

    2009-04-01

    The objective of this study was to determine whether green tea (GT) inhibits the expression of genes regulating hepatic lipogenesis and intestinal lipid transport in fructose-fed ovariectomized (OX) rats. OX rats were assigned to: 1) a control group (S) fed the AIN-93G diet with corn starch as the major carbohydrate source; 2) another control group (F) fed the same diet but containing fructose at 60% as the major carbohydrate source; 3) a group fed the F diet but containing 0.5% GT; and 4) a group fed the F diet containing 1% GT. At 6 wk, plasma and liver triglyceride (TG) and cholesterol and expression of liver sterol regulatory element-binding protein-1c (SREBP-1c) and selected genes involved in lipogenesis and lipid transport were measured. Fructose elevated plasma TG and cholesterol compared with the S group. GT at 0.5 and 1.0% markedly lowered plasma and liver TG. Fructose increased the expression of SREBP-1c, fatty acid synthase, and stearoyl-CoA desaturase 1 mRNA in the liver, whereas GT decreased the expression of these lipogenic genes. Similarly, fructose increased the abundance of hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase mRNA, whereas GT significantly decreased its expression. GT did not alter the expression of scavenger receptor class B, type 1, microsomal TG transfer protein, and apobec 1 in the liver and intestine. The results suggest that the lipid-lowering effect of GT is mediated partly by its inhibition of hepatic lipogenesis involving SREBP-1c and its responsive genes without affecting lipoprotein assembly.

  2. Where does the interplay between cholesterol absorption and synthesis in the context of statin and/or ezetimibe treatment stand today?

    PubMed

    Descamps, Olivier S; De Sutter, Johan; Guillaume, Michel; Missault, Luc

    2011-08-01

    The evidence of the different concepts underlying the interplay between cholesterol absorption and synthesis in the context of statin and ezetimibe treatment were reviewed in the light of the eight major trials where cholesterol absorption and synthesis were analyzed on a large scale using the plasma levels of precursors of cholesterol and plant sterols. The only concept supported in all studies is a significant and consistent increase of cholesterol absorption with statin (correlated with the inhibition of synthesis) and of cholesterol synthesis with ezetimibe, whereas in combination, statin and ezetimibe reduce both cholesterol synthesis and absorption. In contrast, most of the other concepts failed to be clearly proven. At baseline, the inverse relationship between cholesterol absorption and synthesis (only examined in two studies) was found to be weak. On statin treatment, four studies showed that the changes in cholesterol synthesis and absorption, contributed less than 9% to the variability in cholesterol response to statin therapy. It has not been consistently demonstrated that good absorbers/bad synthesizers are bad responders to statin (6 studies) and good responders for ezetimibe (3 studies). There is also no clear inverse correlation between LDL reduction on statin treatment and that on ezetimibe treatment. Finally, the original idea from the first pioneer study of Miettinen et al. that, the higher the baseline intestinal ability to absorb cholesterol, the lower the benefit on the clinical cardiovascular outcomes was not reproduced in the PROSPER study. In conclusion, with the exception of a reverse effect of statin and ezetimibe on absorption and synthesis, most ideas supporting the interplay between cholesterol absorption and synthesis lacked consistency between studies. At present, the use of the plasma levels of plant sterols and cholesterol precursors as markers of cholesterol absorption and synthesis is far too limited to definitively solve these

  3. The Expression of Hepatic Carboxypeptidase E is Decreased in Patients with Cholesterol Gallstone

    PubMed Central

    Dai, Shu-Long; Zhou, Jin; Yang, Kun-Xing; Yang, Shi-Yong

    2015-01-01

    Background/Aims: Decreased carboxypeptidase E (CPE) expression is associated with numerous pathophysiological conditions. This study aimed to investigate the potential function of hepatic CPE in cholesterol gallstone formation. Patients and Methods: Patients with cholesterol gallstone (CGS group) and patients without cholesterol gallstones (non-CGS group) were enrolled. The serum total cholesterol, triglyceride, and biliary composition were analyzed. Eight liver samples from two patients without CGS and six patients with CGS were subjected to cDNA microarray analysis. Hepatic CPE expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical analysis. Plasma CCK level was measured by ELISA. Results: cDNA microarray identified CPE as a gene downregulated in the CGS group. RT-PCR showed that CPE mRNA level was lower in CGS group than in control (P < 0.05, t-test). Moreover, Western blot and immunohistochemistry analysis showed that CPE protein level was significantly lower in CGS group than in the control group. In addition, plasma CCK level was lower in CGS group than in the control group. A positive correlation was found between serum CCK level and hepatic CPE mRNA level (r2 = 0.713, P = 0.003). Conclusions: Down-expression of liver CPE may reduce the secretion of serum CCK and contribute to the formation of cholesterol gallstone. PMID:26228366

  4. Fish protein hydrolysates affect cholesterol metabolism in rats fed non-cholesterol and high-cholesterol diets.

    PubMed

    Hosomi, Ryota; Fukunaga, Kenji; Arai, Hirofumi; Kanda, Seiji; Nishiyama, Toshimasa; Yoshida, Munehiro

    2012-03-01

    Fish consumption is well known to provide health benefits in both experimental animals and human subjects. Numerous studies have demonstrated the beneficial effects of various protein hydrolysates on lipid metabolism. In this context, this study examined the effect of fish protein hydrolysates (FPH) on cholesterol metabolism compared with the effect of casein. FPHs were prepared from Alaska pollock meat using papain as a protease. Male Wistar rats were divided into the following four dietary groups of seven rats each: either casein (20%) or FPH (10%) + casein (10%), with or without 0.5% cholesterol and 0.1% sodium cholate. Serum and liver lipid levels, fecal cholesterol and bile acid excretions, and the hepatic expression of genes encoding proteins involved in cholesterol homeostasis were examined. In rats fed the FPH diets compared with casein diets with or without cholesterol and sodium cholate, the indexes of cholesterol metabolism-namely, serum cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels-were significantly lower, whereas fecal cholesterol and bile acid excretions were higher. Rats fed the FPH diets compared with casein with cholesterol exhibited a lower liver cholesterol level via an increased liver cholesterol 7α-hydroxylase (CYP7A1) expression level. This study demonstrates that the intake of FPH has hypocholesterolemic effects through the enhancement of fecal cholesterol and bile acid excretions and CYP7A1 expression levels. Therefore, fish peptides prepared by papain digestion might provide health benefits by decreasing the cholesterol content in the blood, which would contribute to the prevention of circulatory system diseases such as arteriosclerosis. PMID:22181072

  5. Cholesterol confusion and statin controversy

    PubMed Central

    DuBroff, Robert; de Lorgeril, Michel

    2015-01-01

    The role of blood cholesterol levels in coronary heart disease (CHD) and the true effect of cholesterol-lowering statin drugs are debatable. In particular, whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently, the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes, cancer, and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary, we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD. PMID:26225201

  6. The absorption of cholesterol and the sterol balance in the Tarahumara Indians of Mexico fed cholesterol-free and high cholesterol diets.

    PubMed

    McMurry, M P; Connor, W E; Lin, D S; Cerqueira, M T; Connor, S L

    1985-06-01

    The Tarahumara Indians of Mexico are habituated to a very low cholesterol, low fat diet and have lifelong low plasma cholesterol concentrations. To study cholesterol metabolism in these unusual people, 8 Tarahumara men were fed sequentially a cholesterol-free diet and then a diet containing 900 mg cholesterol under controlled conditions. The intestinal absorption of cholesterol, fecal steroid excretion and sterol balance were determined. During the high cholesterol diet period, the plasma cholesterol level increased from 113 +/- 8 mg/dl to 147 +/- 11 mg/dl (means +/- SD). Cholesterol biosynthesis decreased from 14.0 +/- 0.7 to 7.1 +/- 1.0 mg/kg/day (means +/- SE). The intestinal absorption of cholesterol was 27.7 +/- 6.7% (means +/- SE) during both dietary periods. Compared to other cultures, Tarahumaras had a reduced ability to absorb dietary cholesterol and higher total sterol turnover primarily because of an increased bile acid output. The total sterol disposition over three weeks of the high cholesterol diet accounted for all the absorbed dietary cholesterol.

  7. Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins.

    PubMed

    Duangjai, Acharaporn; Ingkaninan, Kornkanok; Praputbut, Sakonwun; Limpeanchob, Nanteetip

    2013-04-01

    Black pepper (Piper nigrum L.) lowers blood lipids in vivo and inhibits cholesterol uptake in vitro, and piperine may mediate these effects. To test this, the present study aimed to compare actions of black pepper extract and piperine on (1) cholesterol uptake and efflux in Caco-2 cells, (2) the membrane/cytosol distribution of cholesterol transport proteins in these cells, and (3) the physicochemical properties of cholesterol micelles. Piperine or black pepper extract (containing the same amount of piperine) dose-dependently reduced cholesterol uptake into Caco-2 cells in a similar manner. Both preparations reduced the membrane levels of NPC1L1 and SR-BI proteins but not their overall cellular expression. Micellar cholesterol solubility of lipid micelles was unaffected except by 1 mg/mL concentration of black pepper extract. These data suggest that piperine is the active compound in black pepper and reduces cholesterol uptake by internalizing the cholesterol transporter proteins.

  8. Characterization of the CW starter plasma RF matching network for operating the SNS H⁻ ion source with lower H₂ flows.

    PubMed

    Han, B X; Stockli, M P; Kang, Y; Piller, C; Murray, S N; Pennisi, T R; Santana, M; Welton, R F

    2016-02-01

    The Spallation Neutron Source H(-) ion source is operated with a pulsed 2-MHz RF (50-60 kW) to produce the 1-ms long, ∼50 mA H(-) beams at 60 Hz. A continuous low power (∼300 W) 13.56-MHz RF plasma, which is initially ignited with a H2 pressure bump, serves as starter plasma for the pulsed high power 2-MHz RF discharges. To reduce the risk of plasma outages at lower H2 flow rates which is desired for improved performance of the following radio frequency quadrupole, the 13.56-MHz RF matching network was characterized over a broad range of its two tuning capacitors. The H-α line intensity of the 13.56-MHz RF plasma and the reflected power of the 13.56-MHz RF were mapped against the capacitor settings. Optimal tunes for the maximum H-α intensity are consistent with the optimal tunes for minimum reflected power. Low limits of the H2 flow rate not causing plasma outages were explored within the range of the map. A tune region that allows lower H2 flow rate has been identified, which differs from the optimal tune for global minimum reflected power that was mostly used in the past. PMID:26932025

  9. Efficacy of platelet-rich plasma applied to post-extraction retained lower third molar alveoli. A systematic review

    PubMed Central

    Barona-Dorado, Cristina; González-Regueiro, Iria; Martín-Ares, María; Arias-Irimia, Oscar; Martínez-González, José M.

    2014-01-01

    Dental retentions have a high prevalence among the general population and their removal can involve multiple complications. The use of platelet rich plasma has been proposed in an attempt to avoid these complications, as it contains high growth factors and stimulates diverse biological functions that facilitate the healing of soft and hard tissues. Objectives: To evaluate the available scientific evidence related to the application of platelet-rich plasma in the post-extraction alveoli of a retained lower third molars. Material and Methods: A systematic review of published literature registered in the Medline, EMBASE, Cochrane and NIH databases. The following categories were included: human randomized clinical studies. Key search words were: platelet rich plasma; platelet rich plasma and oral surgery; platelet rich in growth factors and third molar. Results: Of 101 potentially valid articles, seven were selected, of which four were rejected as they failed to meet quality criteria. Three studies fulfilled all selection and quality criteria: Ogundipe et al.; Rutkowski et al.; Haraji et al. The studies all measured osteoblast activity by means of sintigraphy, and also registered pain, bleeding, inflammation, temperature, numbness as perceived by the patients, radiological bone density and the incidence of alveolar osteitis. Conclusions: Scientific evidence for the use of PRP in retained third molar surgery is poor. For this reason randomized clinical trials are needed before recommendations for the clinical application of PRP can be made. Key words:Platelet rich plasma, lower third molar surgery, postoperative. PMID:24316707

  10. Predominance of large LDL and reduced HDL2 cholesterol in normolipidemic men with coronary artery disease.

    PubMed

    Campos, H; Roederer, G O; Lussier-Cacan, S; Davignon, J; Krauss, R M

    1995-08-01

    Previous studies have indicated that a predominance of small, dense LDL particles is associated with coronary artery disease (CAD) risk. In the present study we examined the LDL peak particle diameter (determined by lipid-stained 2% to 16% gradient gel electrophoresis) in 92 normolipidemic men with CAD (total cholesterol < 200 mg/dL and triglyceride < 250 mg/dL) and 92 matched healthy controls. Plasma triglyceride, LDL cholesterol, and apo B levels were similar in subjects with CAD and in control subjects, whereas subjects with CAD had decreased HDL2 cholesterol levels (mean +/- SEM, 10 +/- 0.7 compared with 15 +/- 0.7 mg/dL in control subjects; P < .0002). Mean LDL particle diameter (+/- SEM) was increased in the subjects with CAD compared with control subjects (26.8 +/- 0.08 and 26.4 +/- 0.08 nm, respectively; P < .001). The association between large LDL size and CAD was significant (P < .0001) after adjustments were made for age, body mass index, HDL cholesterol levels, and VLDL cholesterol levels. An LDL particle size distribution characterized by a predominance of the largest of three classes of LDL particles (> 26.8 nm) was more prevalent among subjects with CAD (43%) than among control subjects (25%) (P < .002). Among subjects with this LDL size profile, subjects with CAD had significantly higher (P < .05) VLDL triglyceride, VLDL cholesterol, and VLDL apo B levels and significantly lower (P < .0001) HDL2 cholesterol levels than controls.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Systematic study of the effects of lowering low-density lipoprotein-cholesterol on regression of coronary atherosclerotic plaques using intravascular ultrasound

    PubMed Central

    2014-01-01

    Background Conflicting results currently exist on the effects of LDL-C levels and statins therapy on coronary atherosclerotic plaque, and the target level of LDL-C resulting in the regression of the coronary atherosclerotic plaques has not been settled. Methods PubMed, EMBASE, and Cochrane databases were searched from Jan. 2000 to Jan. 2014 for randomized controlled or blinded end-points trials assessing the effects of LDL-C lowering therapy on regression of coronary atherosclerotic plaque (CAP) in patients with coronary heart disease by intravascular ultrasound. Data concerning the study design, patient characteristics, and outcomes were extracted. The significance of plaques regression was assessed by computing standardized mean difference (SMD) of the volume of CAP between the baseline and follow-up. SMD were calculated using fixed or random effects models. Results Twenty trials including 5910 patients with coronary heart disease were identified. Mean lowering LDL-C by 45.4% and to level 66.8 mg/dL in the group of patients with baseline mean LDL-C 123.7 mg/dL, mean lowering LDL-C by 48.8% and to level 60.6 mg/dL in the group of patients with baseline mean LDL-C 120 mg/dL, and mean lowering LDL-C by 40.4% and to level 77.8 mg/dL in the group of patients with baseline mean LDL-C 132.4 mg/dL could significantly reduce the volume of CAP at follow up (SMD −0.108 mm3, 95% CI −0.176 ~ −0.040, p = 0.002; SMD −0.156 mm3, 95% CI −0.235 ~ −0.078, p = 0.000; SMD −0.123 mm3, 95% CI −0.199 ~ −0.048, p = 0.001; respectively). LDL-C lowering by rosuvastatin (mean 33 mg daily) and atorvastatin (mean 60 mg daily) could significantly decrease the volumes of CAP at follow up (SMD −0.162 mm3, 95% CI: −0.234 ~ −0.081, p = 0.000; SMD −0.101, 95% CI: −0.184 ~ −0.019, p = 0.016; respectively). The mean duration of follow up was from 17 ~ 21 months. Conclusions Intensive lowering LDL-C (rosuvastatin

  12. Cholesterol, oxysterol, triglyceride, and coenzyme Q homeostasis in ALS. Evidence against the hypothesis that elevated 27-hydroxycholesterol is a pathogenic factor.

    PubMed

    Wuolikainen, Anna; Acimovic, Jure; Lövgren-Sandblom, Anita; Parini, Paolo; Andersen, Peter M; Björkhem, Ingemar

    2014-01-01

    High plasma levels of cholesterol have been suggested to be neuroprotective for the degenerative disease amyotrophic lateral sclerosis (ALS) and to be associated with increased survival time. The gene encoding cholesterol 27-hydroxylase, CYP27A1, was recently identified as a susceptibility gene for sporadic ALS. A product of this enzyme is 27-hydroxycholesterol. We investigated plasma samples from 52 ALS patients and 40 control subjects (spouses) regarding cholesterol homeostasis, lipid profiles, and coenzyme Q. Eleven of the patients carried mutations in C9orf72 and seven in SOD1. Plasma levels of 27-hydroxycholesterol were significantly lower in male patients with ALS than in controls. It was not possible to link the reduced levels to any specific mutation, and there was no significant correlation between 27-hydroxycholesterol and survival. With normalization for diet using the spouses, a correlation was found between survival and total cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, and coenzyme Q. We conclude that cholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol and lipid profiles in plasma are of limited prognostic value in individual ALS patients. PMID:25415378

  13. Quantum-Mechanical Calculation of Ionization-Potential Lowering in Dense Plasmas

    NASA Astrophysics Data System (ADS)

    Son, Sang-Kil; Thiele, Robert; Jurek, Zoltan; Ziaja, Beata; Santra, Robin

    2014-07-01

    The charged environment within a dense plasma leads to the phenomenon of ionization-potential depression (IPD) for ions embedded in the plasma. Accurate predictions of the IPD effect are of crucial importance for modeling atomic processes occurring within dense plasmas. Several theoretical models have been developed to describe the IPD effect, with frequently discrepant predictions. Only recently, first experiments on IPD in Al plasma have been performed with an x-ray free-electron laser, where their results were found to be in disagreement with the widely used IPD model by Stewart and Pyatt. Another experiment on Al, at the Orion laser, showed disagreement with the model by Ecker and Kröll. This controversy shows a strong need for a rigorous and consistent theoretical approach to calculate the IPD effect. Here, we propose such an approach: a two-step Hartree-Fock-Slater model. With this parameter-free model, we can accurately and efficiently describe the experimental Al data and validate the accuracy of standard IPD models. Our model can be a useful tool for calculating atomic properties within dense plasmas with wide-ranging applications to studies on warm dense matter, shock experiments, planetary science, inertial confinement fusion, and nonequilibrium plasmas created with x-ray free-electron lasers.

  14. Electrostatic lower hybrid waves excited by electromagnetic whistler mode waves scattering from planar magnetic-field-aligned plasma density irregularities

    NASA Technical Reports Server (NTRS)

    Bell, T. F.; Ngo, H. D.

    1990-01-01

    This paper presents a theoretical model for electrostatic lower hybrid waves excited by electromagnetic whistler mode waves propagating in regions of the magnetosphere and the topside ionosphere, where small-scale magnetic-field-aligned plasma density irregularities are thought to exist. In this model, the electrostatic waves are excited by linear mode coupling as the incident electromagnetic whistler mode waves scatter from the magnetic-field-aligned plasma density irregularities. Results indicate that high-amplitude short-wavelength (5 to 100 m) quasi-electrostatic whistler mode waves can be excited when electromagnetic whistler mode waves scatter from small-scale planar magnetic-field-aligned plasma density irregularities in the topside ionosphere and magnetosphere.

  15. Anticholesterolemic effect of 3,4-di(OH)-phenylpropionic amides in high-cholesterol fed rats

    SciTech Connect

    Kim, Soon-Ja; Bok, Song-Hae; Lee, Sangku; Kim, Hye-Jin; Lee, Mi-Kyung; Park, Yong Bok; Choi, Myung-Sook . E-mail: mschoi@knu.ac.kr

    2005-10-01

    Two amide synthetic derivatives of 3,4-di(OH)-hydrocinnamate (HC), 3,4-dihydroxyphenylpropionic (L-serine methyl ester) amide (E030) and 3,4-dihydroxyphenylpropionic (L-aspartic acid) amide (E076), were investigated to compare their lipid-lowering efficacy with HC. Male rats were fed a 1 g/100 g high-cholesterol diet for 6 weeks with supplements of either clofibrate (0.02%, w/w), HC (0.025%, w/w), E030 (0.039%, w/w) or E076 (0.041%, w/w). The clofibrate supplement was used as a positive control for the lipid-lowering efficacy. The food intakes and body weight gains were not significantly different among the groups. The plasma and hepatic cholesterol and triglyceride levels were lower in clofibrate, HC, E030, and E076-supplemented groups compared to the control group. The supplementation of HC and its amide derivatives was as effective as clofibrate in increasing the ratio of HDL-cholesterol to total plasma cholesterol and reducing the atherogenic index (AI). The hepatic cholesterol level in the HC and E076 groups was significantly lower than that in the clofibrate group. The hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA reductase) and acyl-CoA:cholesterol acyltransferase (ACAT) activities were significantly lower in the all test groups than in the control group. The excretion of neutral sterol was significantly higher in the HC, E030, and E076-supplemented groups compared to the control group. The plasma AST and ALT activities, indirect indexes of hepatic toxicity, were significantly lower in the HC, E030, and E076-supplemented groups than in the control group. Accordingly, the current results suggest that E030 and E076, two amide synthetic derivatives of HC, are effective in lowering lipid activity.

  16. Talk with Your Health Care Provider about High Cholesterol

    MedlinePlus

    ... you do? Always ask your provider what your cholesterol numbers are and write them down. Discuss these ... provider may prescribe medicine to help lower your cholesterol. y y Take your medicine every day, or ...

  17. HIV/antiretroviral therapy-related lipodystrophy syndrome (HALS) is associated with higher RBP4 and lower omentin in plasma.

    PubMed

    Peraire, J; López-Dupla, M; Alba, V; Beltrán-Debón, R; Martinez, E; Domingo, P; Asensi, V; Leal, M; Viladés, C; Inza, M-I; Escoté, X; Arnedo, M; Mateo, G; Valle-Garay, E; Ferrando-Martinez, S; Veloso, S; Vendrell, J; Gatell, J Ma; Vidal, F

    2015-07-01

    Very little information is available on the involvement of newly characterized adipokines in human immunodeficiency virus (HIV)/antiretroviral therapy (ART)-associated lipodystrophy syndrome (HALS). Our aim was to determine whether apelin, apelin receptor, omentin, RBP4, vaspin and visfatin genetic variants and plasma levels are associated with HALS. We performed a cross-sectional multicentre study that involved 558 HIV type 1-infected patients treated with a stable highly active ART regimen, 240 of which had overt HALS and 318 who did not have HALS. Epidemiologic and clinical variables were determined. Polymorphisms in the apelin, omentin, RBP4, vaspin and visfatin genes were assessed by genotyping. Plasma apelin, apelin receptor, omentin, RBP4, vaspin and visfatin levels were determined by enzyme-linked immunosorbent assay in 163 patients (81 with HALS and 82 without HALS) from whom stored plasma samples were available. Student's t test, one-way ANOVA, chi-square test, Pearson and Spearman correlations and linear regression analysis were used for statistical analyses. There were no associations between the different polymorphisms assessed and the HALS phenotype. Circulating RBP4 was significantly higher (p < 0.001) and plasma omentin was significantly lower (p 0.001) in patients with HALS compared to those without HALS; differences in plasma levels of the remaining adipokines were nonsignificant between groups. Circulating RBP4 concentration was predicted independently by the presence of HALS. Apelin and apelin receptor levels were independently predicted by body mass index. Visfatin concentration was predicted independently by the presence of acquired immunodeficiency syndrome. HALS is associated with higher RBP4 and lower omentin in plasma. These two adipokines, particularly RBP4, may be a link between HIV/ART and fat redistribution syndromes.

  18. South Asian individuals at high risk of type 2 diabetes have lower plasma vitamin C levels than white Europeans.

    PubMed

    Carter, Patrice; Gray, Laura J; Morris, Danielle H; Davies, Melanie J; Khunti, Kamlesh

    2013-01-01

    Individuals of South Asian origin are at high risk of developing type 2 diabetes; the relationship between this risk and diet remains to be investigated fully. Furthermore, fruit and vegetable intake remains low throughout the world and previous data suggest that intake is associated with risk of diabetes. The aim of this research study was to compare plasma vitamin C concentrations, measured as a biomarker for fruit and vegetable intake, in South Asian and white European individuals. Participants recruited as part of the Let's Prevent Diabetes Study provided samples for the quantification of plasma vitamin C. We compared vitamin C levels by ethnicity using multiple regression, both unadjusted and adjusted for confounders, including glycaemic status. Mean plasma vitamin C was significantly lower in the South Asian participants compared with white European participants (34.5 (sd 19·8) v. 39·9 (sd 22·1) µmol/l, respectively; P ≤ 0·0001). Significantly fewer South Asian individuals consumed five portions of fruit and vegetables per d, as determined by a plasma vitamin C concentration of ≥ 50 µmol/l (23·2 % (n 58) v. 31·4 % (n 558); P = 0·01). Vitamin C reflects habitual fruit and vegetable consumption; thus results suggest that South Asians have lower fruit and vegetable intake. However, it cannot be excluded that vitamin C is utilised differently. Dietary advice specifically targeting the South Asian population should be developed.

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

    PubMed

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

    2014-02-01

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

  20. Structure of Cholesterol in Lipid Rafts

    NASA Astrophysics Data System (ADS)

    Toppozini, Laura; Meinhardt, Sebastian; Armstrong, Clare L.; Yamani, Zahra; Kučerka, Norbert; Schmid, Friederike; Rheinstädter, Maikel C.

    2014-11-01

    Rafts, or functional domains, are transient nano-or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking, and lipid or protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules, we observe raftlike structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to ordering of the cholesterol molecules in the raftlike structures were observed and indexed by two different structures: a monoclinic structure of ordered cholesterol pairs of alternating direction in equilibrium with cholesterol plaques, i.e., triclinic cholesterol bilayers.

  1. On the lower bound of the internal energy of the one-component-plasma

    SciTech Connect

    Khrapak, S. A.; Khrapak, A. G.

    2015-04-15

    A new simple yet accurate analytical estimate for the internal energy of the classical one-component-plasma is proposed. In the limit of weak coupling, it reduces to the Debye-Hückel result. In the opposite limit of strong coupling, the ion sphere approximation is recovered. The agreement with the accurate numerical results in the intermediate coupling regime is fairly good.

  2. A whole-grain cereal-rich diet increases plasma betaine, and tends to decrease total and LDL-cholesterol compared with a refined-grain diet in healthy subjects.

    PubMed

    Ross, Alastair B; Bruce, Stephen J; Blondel-Lubrano, Anny; Oguey-Araymon, Sylviane; Beaumont, Maurice; Bourgeois, Alexandre; Nielsen-Moennoz, Corine; Vigo, Mario; Fay, Laurent-Bernard; Kochhar, Sunil; Bibiloni, Rodrigo; Pittet, Anne-Cécile; Emady-Azar, Shahram; Grathwohl, Dominik; Rezzi, Serge

    2011-05-01

    Epidemiological studies have repeatedly found that whole-grain (WG) cereal foods reduce the risk of several lifestyle-related diseases, though consistent clinical outcomes and mechanisms are elusive. To compare the effects of a WG-rich diet with a matched refined-grain (RG) diet on plasma biomarkers and bowel health parameters, seventeen healthy subjects (eleven females and six males) completed an exploratory cross-over study with a 2-week intervention diet based on either WG- or RG-based foods, separated by a washout of at least 5 weeks. Both diets were the same except for the use of WG (150 g/d) or RG foods. Subjects undertook a 4 h postprandial challenge on day 8 of each intervention diet. After 2 weeks, the WG diet tended to decrease plasma total and LDL-cholesterol (both P = 0·09), but did not change plasma HDL-cholesterol, fasting glucose, C-reactive protein or homocysteine compared with the RG diet. Plasma betaine and alkylresorcinol concentrations were elevated after 1 week of the WG diet (P = 0·01 and P < 0·0001, respectively). Clostridium leptum populations in faeces were increased after the WG diet, along with a trend for decreased faecal water pH (P = 0·096) and increased stool frequency (P < 0·0001) compared with the RG diet. A short controlled intervention trial with a variety of commercially available WG-based products tended to improve biomarkers of CVD compared with a RG diet. Changes in faecal microbiota related to increased fibre fermentation and increased plasma betaine concentrations point to both fibre and phytochemical components of WG being important in mediating any potential health effects.

  3. A whole-grain cereal-rich diet increases plasma betaine, and tends to decrease total and LDL-cholesterol compared with a refined-grain diet in healthy subjects.

    PubMed

    Ross, Alastair B; Bruce, Stephen J; Blondel-Lubrano, Anny; Oguey-Araymon, Sylviane; Beaumont, Maurice; Bourgeois, Alexandre; Nielsen-Moennoz, Corine; Vigo, Mario; Fay, Laurent-Bernard; Kochhar, Sunil; Bibiloni, Rodrigo; Pittet, Anne-Cécile; Emady-Azar, Shahram; Grathwohl, Dominik; Rezzi, Serge

    2011-05-01

    Epidemiological studies have repeatedly found that whole-grain (WG) cereal foods reduce the risk of several lifestyle-related diseases, though consistent clinical outcomes and mechanisms are elusive. To compare the effects of a WG-rich diet with a matched refined-grain (RG) diet on plasma biomarkers and bowel health parameters, seventeen healthy subjects (eleven females and six males) completed an exploratory cross-over study with a 2-week intervention diet based on either WG- or RG-based foods, separated by a washout of at least 5 weeks. Both diets were the same except for the use of WG (150 g/d) or RG foods. Subjects undertook a 4 h postprandial challenge on day 8 of each intervention diet. After 2 weeks, the WG diet tended to decrease plasma total and LDL-cholesterol (both P = 0·09), but did not change plasma HDL-cholesterol, fasting glucose, C-reactive protein or homocysteine compared with the RG diet. Plasma betaine and alkylresorcinol concentrations were elevated after 1 week of the WG diet (P = 0·01 and P < 0·0001, respectively). Clostridium leptum populations in faeces were increased after the WG diet, along with a trend for decreased faecal water pH (P = 0·096) and increased stool frequency (P < 0·0001) compared with the RG diet. A short controlled intervention trial with a variety of commercially available WG-based products tended to improve biomarkers of CVD compared with a RG diet. Changes in faecal microbiota related to increased fibre fermentation and increased plasma betaine concentrations point to both fibre and phytochemical components of WG being important in mediating any potential health effects. PMID:21272402

  4. Lipid-lowering Activity of Natural and Semi-Synthetic Sterols and Stanols.

    PubMed

    Taha, Dhiaa A; Wasan, Ellen K; Wasan, Kishor M; Gershkovich, Pavel

    2015-01-01

    Consumption of plant sterols/ stanols has long been demonstrated to reduce plasma cholesterol levels. The objective of this review is to demonstrate the lipid-lowering activity and anti-atherogenic effects of natural and semi-synthetic plant sterols/ stanols based on evidence from cell-culture studies, animal studies and clinical trials. Additionally, this review highlights certain molecular mechanisms by which plant sterols/ stanols lower plasma cholesterol levels with a special emphasis on factors that affect the cholesterol-lowering activity of plant sterols/stanols. The crystalline nature and the poor oil solubility of these natural products could be important factors that limit their cholesterol-lowering efficiency. Several attempts have been made to improve the cholesterol-lowering activity by enhancing the bioavailability of crystalline sterols and stanols. Approaches involved reduction of the crystal size and/or esterification with fatty acids from vegetable or fish oils. However, the most promising approach in this context is the chemical modification of plant sterols /stanols into water soluble disodium ascorbyl phytostanyl phosphates analogue by esterification with ascorbic acid. This novel semi-synthetic stanol derivative has improved efficacy over natural plant sterols/ stanols and can provide additional benefits by combining the cholesterol-lowering properties of plant stanols with the antioxidant potential of ascorbic acid. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID:26626241

  5. Impact of ornithine phenylacetate (OCR-002) in lowering plasma ammonia after upper gastrointestinal bleeding in cirrhotic patients

    PubMed Central

    Ventura-Cots, Meritxell; Concepción, Mar; Arranz, José Antonio; Simón-Talero, Macarena; Torrens, Maria; Blanco-Grau, Albert; Fuentes, Inma; Suñé, Pilar; Alvarado-Tapias, Edilmar; Gely, Cristina; Roman, Eva; Mínguez, Beatriz; Soriano, German; Genescà, Joan; Córdoba, Juan

    2016-01-01

    Background: Ornithine phenylacetate (OP) has been proven effective in lowering ammonia plasma levels in animals, and to be well tolerated in cirrhotic patients. A trial to assess OP efficacy in lowering plasma ammonia levels versus placebo in cirrhotic patients after an upper gastrointestinal bleeding was performed. The primary outcome was a decrease in venous plasma ammonia at 24 hours. Methods: A total of 38 consecutive cirrhotic patients were enrolled within 24 hours of an upper gastrointestinal bleed. Patients were randomized (1:1) to receive OP (10 g/day) or glucosaline for 5 days. Results: The primary outcome was not achieved. A progressive decrease in ammonia was observed in both groups, being slightly greater in the OP group, with significant differences only at 120 hours. The subanalysis according to Child–Pugh score showed a statistically significant ammonia decrease in Child–Pugh C-treated patients at 36 hours, as well as in the time-normalized area under the curve (TN-AUC) 0–120 hours in the OP group [40.16 μmol/l (37.7–42.6); median (interquartile range) (IQR)] versus placebo group [65.5 μmol/l (54–126);p = 0.036]. A decrease in plasma glutamine levels was observed in the treated group compared with the placebo group, and was associated with the appearance of phenylacetylglutamine in urine. Adverse-event frequency was similar in both groups. No differences in hepatic encephalopathy incidence were observed. Conclusions: OP failed to significantly decrease plasma ammonia at the given doses (10 g/day). Higher doses of OP might be required in Child–Pugh A and B patients. OP appeared well tolerated. PMID:27803737

  6. The effects of ABCG5/G8 polymorphisms on plasma HDL cholesterol concentrations depend on smoking habit in the Boston Puerto Rican Health Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  7. Cholesterol granulomas in three meerkats (Suricata suricatta).

    PubMed

    Sladky, K K; Dalldorf, F G; Steinberg, H; Wright, J F; Loomis, M R

    2000-11-01

    Cholesterol granulomas are uncommon pathologic lesions in animals, although they are important intracranial tumors in humans. This report describes cholesterol granulomas associated with multiple organ systems of three captive meerkats. In the most severe case, meerkat No. 1, the pathologic behavior of the cholesterol granuloma was unique in that it appeared to locally invade the cerebrum and calvarium, possibly contributing to neurological deficits observed antemortem. A review of other meerkat necropsies revealed incidental, asymptomatic cholesterol granulomas in organs of two other individuals, meerkat Nos. 2 and 3. Histologically, all lesions were composed of cholesterol clefts admixed with large, foamy macrophages containing hemosiderin, multinucleated giant cells, lymphocytes, plasma cells, and foci of mineralization. Hypercholesterolemia was documented in two of the three meerkats.

  8. Cholesterol granulomas in three meerkats (Suricata suricatta).

    PubMed

    Sladky, K K; Dalldorf, F G; Steinberg, H; Wright, J F; Loomis, M R

    2000-11-01

    Cholesterol granulomas are uncommon pathologic lesions in animals, although they are important intracranial tumors in humans. This report describes cholesterol granulomas associated with multiple organ systems of three captive meerkats. In the most severe case, meerkat No. 1, the pathologic behavior of the cholesterol granuloma was unique in that it appeared to locally invade the cerebrum and calvarium, possibly contributing to neurological deficits observed antemortem. A review of other meerkat necropsies revealed incidental, asymptomatic cholesterol granulomas in organs of two other individuals, meerkat Nos. 2 and 3. Histologically, all lesions were composed of cholesterol clefts admixed with large, foamy macrophages containing hemosiderin, multinucleated giant cells, lymphocytes, plasma cells, and foci of mineralization. Hypercholesterolemia was documented in two of the three meerkats. PMID:11105964

  9. Ponderomotive Force and Lower Hybrid Turbulence Effects in Space Plasmas Subjected to Large-Amplitude Low-Frequency Waves

    NASA Technical Reports Server (NTRS)

    Khazanov, G. V.; Khazanov, George; Liemohn, M. W.; Stone, N. H.; Coffey, V. N.

    1997-01-01

    In the auroral region, simultaneous occurrences of upward-flowing ions and field-aligned electrons have been observed by the Viking satellite. The occurrence is strongly correlated with large amplitude low frequency fluctuations of the electric field. Large-amplitude shear Alfven waves have also been observed by sounding rockets in the auroral ionosphere. When such LF waves are propagating in a plasma, a ponderomotive force and other types of waves are produced which may lead to significant effects on the plasma. This force is directed toward decreasing density, providing the electromagnetic lift of the background plasma and an increase of collisionless plasma expansion. We find that even for modest wave strengths, the influence on the outflowing oxygen ions can be dramatic, increasing the high-altitude density by orders of magnitude. It is also demonstrated that large-amplitude low-frequency waves (LFW) may generate lower hybrid waves (LHW) in the auroral zone. The excitation of LHW by a LF wave may lead to the appearance of an additional channel of energy transfer from, for example, Alfven or fast magnetosonic waves, to particles. This process then influences the formation of the plasma distribution function at the expense of acceleration in the tail of the distribution during the collapse of the LHW. The ion energization due to the LHW can be comparable with that produced by the ponderomotive force of the LFW. It is shown that the LH turbulence leads to equalization of the ponderomotive acceleration of the different ion species. The mechanism of LHW excitation due to the oxygen ion relative drift in a plasma subjected to low-frequency waves is used for analysis of Viking satellite data for events in the cusp/cleft region. It is found that, in some cases, such a mechanism leads to LHW energy densities and ion distribution functions close to those observed.

  10. Impact of the loss of caveolin-1 on lung mass and cholesterol metabolism in mice with and without the lysosomal cholesterol transporter, Niemann-Pick type C1.

    PubMed

    Mundy, Dorothy I; Lopez, Adam M; Posey, Kenneth S; Chuang, Jen-Chieh; Ramirez, Charina M; Scherer, Philipp E; Turley, Stephen D

    2014-07-01

    Caveolin-1 (Cav-1) is a major structural protein in caveolae in the plasma membranes of many cell types, particularly endothelial cells and adipocytes. Loss of Cav-1 function has been implicated in multiple diseases affecting the cardiopulmonary and central nervous systems, as well as in specific aspects of sterol and lipid metabolism in the liver and intestine. Lungs contain an exceptionally high level of Cav-1. Parameters of cholesterol metabolism in the lung were measured, initially in Cav-1-deficient mice (Cav-1(-/-)), and subsequently in Cav-1(-/-) mice that also lacked the lysosomal cholesterol transporter Niemann-Pick C1 (Npc1) (Cav-1(-/-):Npc1(-/-)). In 50-day-old Cav-1(-/-) mice fed a low- or high-cholesterol chow diet, the total cholesterol concentration (mg/g) in the lungs was marginally lower than in the Cav-1(+/+) controls, but due to an expansion in their lung mass exceeding 30%, whole-lung cholesterol content (mg/organ) was moderately elevated. Lung mass (g) in the Cav-1(-/-):Npc1(-/-) mice (0.356±0.022) markedly exceeded that in their Cav-1(+/+):Npc1(+/+) controls (0.137±0.009), as well as in their Cav-1(-/-):Npc1(+/+) (0.191±0.013) and Cav-1(+/+):Npc1(-/-) (0.213±0.022) littermates. The corresponding lung total cholesterol contents (mg/organ) in mice of these genotypes were 6.74±0.17, 0.71±0.05, 0.96±0.05 and 3.12±0.43, respectively, with the extra cholesterol in the Cav-1(-/-):Npc1(-/-) and Cav-1(+/+):Npc1(-/-) mice being nearly all unesterified (UC). The exacerbation of the Npc1 lung phenotype and increase in the UC level in the Cav-1(-/-):Npc1(-/-) mice imply a regulatory role of Cav-1 in pulmonary cholesterol metabolism when lysosomal sterol transport is disrupted.

  11. Plasma diffusion at the magnetopause - The case of lower hybrid drift waves

    NASA Technical Reports Server (NTRS)

    Treumann, R. A.; Labelle, J.; Pottelette, R.

    1991-01-01

    The diffusion expected from the quasi-linear theory of the lower hybrid drift instability at the earth's magnetopause is recalculated. The resulting diffusion coefficient is marginally large enough to explain the thickness of the boundary layer under quiet conditions, based on observational upper limits for the wave intensities. Thus, one possible model for the boundary layer could involve equilibrium between the diffusion arising from lower hybrid waves and various loss processes.<