Effect of uremia on HDL composition, vascular inflammation, and atherosclerosis in wild-type mice

2007 ◽  
Vol 293 (4) ◽  
pp. F1325-F1331 ◽  
Author(s):  
Christian A. Bang ◽  
Susanne Bro ◽  
Emil D. Bartels ◽  
Tanja X. Pedersen ◽  
Lars B. Nielsen

Wild-type mice normally do not develop atherosclerosis, unless fed cholic acid. Uremia is proinflammatory and increases atherosclerosis 6- to 10-fold in apolipoprotein E-deficient mice. This study examined the effect of uremia on lipoproteins, vascular inflammation, and atherosclerosis in wild-type C57BL/6J mice. Uremia was induced by nephrectomy (NX) and increased plasma urea and creatinine concentrations 2.5- to 4.5-fold; control mice were sham operated. After NX, mice were fed a Western-type diet or the same diet with 0.5% cholic acid. Cholic acid-fed NX mice did not thrive and were killed. In NX mice fed the Western-type diet ( n = 7), the total plasma cholesterol concentration was similar to that in sham mice ( n = 11), but on gel filtration the LDL/HDL cholesterol ratio was increased. HDL from NX mice contained more serum amyloid A and triglycerides and less cholesterol than HDL from sham mice. Plasma concentrations of sICAM-1 and sVCAM-1 and aortic mRNA expression of ICAM-1 and VCAM-1 did not differ between NX and sham mice. Twenty-six weeks after NX, the average oil red O-stained area of the aortic root was similar in NX and sham mice fed the Western-type diet, while it was increased in cholic acid-fed sham mice. The results suggest that moderate uremia neither induces aortic inflammation nor atherosclerosis in C57BL/6J mice despite increased LDL/HDL cholesterol ratio and altered HDL composition.

2020 ◽  
Vol 150 (8) ◽  
pp. 2023-2030 ◽  
Author(s):  
Jaume Amengual ◽  
Johana Coronel ◽  
Courtney Marques ◽  
Celia Aradillas-García ◽  
Juan Manuel Vargas Morales ◽  
...  

ABSTRACT Background Plasma cholesterol is one of the strongest risk factors associated with the development of atherosclerotic cardiovascular disease (ASCVD) and myocardial infarction. Human studies suggest that elevated plasma β-carotene is associated with reductions in circulating cholesterol and the risk of myocardial infarction. The molecular mechanisms underlying these observations are unknown. Objective The objective of this study was to determine the impact of dietary β-carotene and the activity of β-carotene oxygenase 1 (BCO1), which is the enzyme responsible for the conversion of β-carotene to vitamin A, on circulating cholesterol concentration. Methods In our preclinical study, we compared the effects of a 10-d intervention with a diet containing 50 mg/kg of β-carotene on plasma cholesterol in 5-wk-old male and female C57 Black 6 wild-type and congenic BCO1-deficient mice. In our clinical study, we aimed to determine whether 5 common small nucleotide polymorphisms located in the BCO1 locus affected serum cholesterol concentrations in a population of young Mexican adults from the Universities of San Luis Potosí and Illinois: A Multidisciplinary Investigation on Genetics, Obesity, and Social-Environment (UP AMIGOS) cohort. Results Upon β-carotene feeding, Bco1−/− mice accumulated >20-fold greater plasma β-carotene and had ∼30 mg/dL increased circulating total cholesterol (P < 0.01) and non–HDL cholesterol (P < 0.01) than wild-type congenic mice. Our results in the UP AMIGOS cohort show that the rs6564851 allele of BCO1, which has been linked to BCO1 enzymatic activity, was associated with a reduction in 10 mg/dL total cholesterol concentrations (P = 0.009) when adjusted for vitamin A and carotenoid intakes. Non–HDL-cholesterol concentration was also reduced by 10 mg/dL when the data were adjusted for vitamin A and total carotenoid intakes (P = 0.002), or vitamin A and β-carotene intakes (P = 0.002). Conclusions Overall, our results in mice and young adults show that BCO1 activity impacts circulating cholesterol concentration, linking vitamin A formation with the risk of developing ASCVD.


2019 ◽  
Vol 51 (1) ◽  
pp. 24-33
Author(s):  
Jelena M Janac ◽  
Aleksandra Zeljkovic ◽  
Zorana D Jelic-Ivanovic ◽  
Vesna S Dimitrijevic-Sreckovic ◽  
Jelena Vekic ◽  
...  

AbstractBackgroundWe evaluated the qualitative characteristics of high-density lipoprotein (HDL) particles in metabolically healthy and unhealthy overweight and obese subjects.MethodsThe study involved 115 subject individuals classified as metabolically healthy and unhealthy, as in overweight and obese groups. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure oxidized HDL (OxHDL) and serum amyloid A (SAA) concentrations. Lipoprotein subfractions were separated using nondenaturing gradient gel electrophoresis.ResultsAn independent association was shown between increased OxHDL/HDL-cholesterol ratio and the occurrence of metabolically unhealthy phenotype in the overweight and obese groups. The OxHDL/HDL-cholesterol ratio showed excellent and acceptable diagnostic accuracy in determination of metabolic health phenotypes (overweight group, AUC = 0.881; obese group, AUC = 0.765). Accumulation of smaller HDL particles in metabolically unhealthy subjects was verified by lipoprotein subfraction analysis. SAA concentrations did not differ significantly between phenotypes.ConclusionsIncreased OxHDL/HDL-cholesterol ratio may be a potential indicator of disturbed metabolic health in overweight and obese individuals.


1989 ◽  
Vol 61 (2) ◽  
pp. 257-265 ◽  
Author(s):  
Susan M. Shutler ◽  
Gemma M. Bircher ◽  
Jacki A. Tredger ◽  
Linda M. Morgan ◽  
Ann F. Walker ◽  
...  

1. Thirteen normo-cholesterolaemic male students consumed one 450 g can of baked beans (Phaseolus vulgaris) in tomato sauce, daily, for 14 d as part of their normal diet. After a 14 d washout period, eleven of the students went on to consume one 440 g can of spaghetti in tomato sauce, daily, for 14 d.2. Fasting blood samples were taken frequently for measurement of plasma cholesterol, high-density lipoprotein (HDL)-cholesterol, triacylglycerols, glucose, insulin and C-peptide. Diet diaries (3 d) were completed by the subjects during each period.3. Consumption of beans and spaghetti led to a significant reduction in the amount of fat eaten daily (P< 0.05). Bean consumption also resulted in significant increases in protein, fibre and sugar intakes (P< 0.02,P< 0.001 andP< 0.05 respectively).4. During the bean-eating period the mean total plasma cholesterol level of the students fell significantly from 5.1 to 4.5 mmol/l (P< 0.02). No reduction in plasma cholesterol occurred during the spaghetti-eating period.5. HDL-cholesterol levels fell significantly during both periods (P< 0.001), but HDL:total cholesterol ratio was significantly reduced only during the spaghetti-eating period (P< 0.001). Neither beans nor spaghetti affected triacylglycerol, insulin or C-peptide levels.6. The benefits of a legume-rich diet are discussed.


2020 ◽  
Author(s):  
Valeria Sutti Nunes ◽  
Angela Oliveira Godoy Ilha ◽  
Guilherme Silva Ferreira ◽  
Renata Paula Assis Bombo ◽  
Milessa Silva Afonso ◽  
...  

Abstract Background Because the plasma campesterol/cholesterol ratio does not differ between groups that absorb different amounts of cholesterol measured by the gold standard isotopic procedure we investigated whether the intestinal absorption of phytosterols (PS) depends on the body's cholesterol synthesis rate. Methods 38 volunteers (58 ± 12 years; low-density lipoprotein cholesterol (LDL-C) ≥ 130 mg/dL) were randomly assigned to consume 400 mL/day of soy milk or soy milk + PS (1.6 g/day) for 4 weeks in a double-blind, placebo-controlled, cross-over study. Blood samples were collected and markers of phytosterol (PS) absorption and non-cholesterol sterol synthesis precursors measured. Results PS treatment reduced plasma total cholesterol concentration (-5,5%, p < 0.001), LDL-C (-7.6%, p < 0.001), triglycerides (-13.6%, p < 0.0085), and apolipoprotein B (apo B) (-6.3%, p < 0.008), without changing high density lipoprotein cholesterol (HDL-C concentration). The lathosterol-to-cholesterol ratio in serum predicted the serum cholesterol response to PS feeding where high basal cholesterol synthesis was associated with lack of response of plasma cholesterol to PS in the diet. Cholesterol synthesis being elevated in the placebo phase in non-responders to dietary PS indicated they were resistant to further synthesis rise, whereas responders, because they have lower synthesis rate than non-responders in the placebo phase, are capable expanding synthesis under the effect of alimentary PS. Conclusions responders absorbed more PS than non-responders likely resulting from responders delivering less endogenous cholesterol than non-responders into the intestinal lumen that facilitates greater absorption of PS by the intestine.


1995 ◽  
Vol 73 (5) ◽  
pp. 733-751 ◽  
Author(s):  
D. L. Frape ◽  
A. M. Jones

We questioned whether a dietary fibre supplement known to lower fasting plasma cholesterol concentrations can also lower the postprandial plasma cholesterol, glucose and insulin concentrations when it is administered just before a meal. Two studies were conducted in healthy middle-aged volunteers of both sexes in whom the fasting plasma total cholesterol concentrations were above normal. In the first study the dietary fibre treatments (2.2 g) were psyllium and a psyllium-citrus pectin mixture to which the subjects (four males, eight females) had no prior exposure. Controls received no supplement. The meals were high-fat breakfasts and lunches. In the second study the dietary fibre (6 g) was from sugar-beet root and the reference control was α-cellulose (2 g); the meal was of glucose. The volunteers (eight males, eight females) had prior exposure to the fibre supplements three times daily for 3 weeks. After adjustments for fasting values and changes in haemodilution, the psyllium and psyllium-citrus pectin mixture in the first experiment had no significant effects on the postprandial measurements of plasma glucose, insulin: glucose ratio, total-, LDL- and HDL-cholesterol, and triacylglycerol. By contrast, the sugar-beet fibre in the second study significantly decreased the area under the glucose response curve by 6·9%, the area under the insulin response curve was lower by 9·6%, although not significantly, and the post-glucose meal HDL-cholesterol concentration was significantly (12%) higher. Additionally, the 3-week treatment with sugar-beet fibre significantly lowered the fasting total- and LDL-cholesterol concentrations, by 8·5% and 9·6% respectively. We conclude that low doses of psyllium and citrus pectin at breakfast and lunch have no effects on the postprandial plasma measurements, but that sugar-beet fibre taken daily for 3 weeks affects both fasting and postprandial plasma metabolites favourably in these individuals with mildly increased risk of ischaemic heart disease. Further, we observed that small changes in haemodilution occur after meals, as indicated by plasma albumin concentration and packed cell volume. Underemphasis of the dietary fibre effects may occur when postprandial haemodilution is not taken into account.


1996 ◽  
Vol 76 (3) ◽  
pp. 387-397 ◽  
Author(s):  
A. Razdan ◽  
D. Pettersson

Broiler chickens (1-d-old) were fed ad libitum on a control diet based on maize and maize starch or diets containing low-, medium- or high-viscosity chitosans at an inclusion level of 15 g/kg. Body weights and feed intakes of chickens given chitosan-containing diets were generally depressed in comparison with those of control-fed animals on days 11 and 18 of the experiment. On days 12 and 19, feeding the low-viscosity-chitosan diet reduced plasma triacylglycerol and total plasma cholesterol concentrations in relation to chickens receiving the control diet, while the medium- and high-viscosity-chitosan-containing diets reduced total plasma cholesterol and elevated, although not significantly, plasma HDL-cholesterol concentrations compared with those of control-fed animals. Chitosan feeding generally improved plasma HDL-cholesterol: total cholesterol ratio in comparison with control feeding, which was attributed to the general reductions in plasma cholesterol concentrations rather than increases in plasma HDL-cholesterol concentrations. Feeding the high-viscosity-chitosan-containing diet significantly reduced the ileal digestibility of crude protein (N x 6·25) and crude fat compared with chickens given the control diet. The reduction in ileal crude fat digestibility was greatest among chickens receiving the high-viscosity-chitosan-containing diet and chitosan-containing diets reduced ileal fat digestibility by 8% on average compared with that of control-fed birds. However, increasing the viscosity of the chitosan fraction could not be correlated with increases in terminal ileal digesta viscosity and, therefore, it could not be established that increased ileal lumen viscosity alone contributed to reductions in body weight, feed intake and plasma cholesterol concentrations. However, the fact that ileal digestibility of fat was reduced by feeding chitosan to chickens suggests the action of other hypolipidaemic mechanisms


Animals ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 122 ◽  
Author(s):  
Jose Pesántez-Pacheco ◽  
Ana Heras-Molina ◽  
Laura Torres-Rovira ◽  
María Sanz-Fernández ◽  
Consolación García-Contreras ◽  
...  

Pregnancy and lactation are challenging states that affect maternal and lamb health. In Lacaune dairy sheep, we evaluated the impact of parity, pregnancy rank, and body condition on body weight and the condition of ewes and lambs in mid-pregnancy (75 ± 5 d), in late pregnancy (142 ± 4d), and postpartum (52 ± 5d pp). Maternal age was associated with initial decreases, followed by increases, in body weight and condition. After lambing, both mature and maiden ewes lost weight and body condition. Maternal indices of glucose, protein, and lipid metabolism were within physiological values during pregnancy, but postpartum values depended on maternal parity and pregnancy rank, with multiple-pregnant ewes showing a postpartum increase in glucose and maiden sheep a postpartum increase in plasma cholesterol concentration. Male lambs were heavier than female lambs at birth, and lambs born to mothers with higher body condition scores were heavier. Lambs born as singletons were heavier than those born in litters. Maternal age and pregnancy rank did not influence lamb metabolic indicators. Sex affected plasma concentrations of glucose, triglycerides, and cholesterol. Maternal metabolic indicators showed minimal effects on lamb phenotype. These results suggest that, when appropriately fed, dairy sheep can cover the metabolic demands of pregnancy and milk production, regardless of age and pregnancy rank.


1959 ◽  
Vol 197 (6) ◽  
pp. 1330-1332 ◽  
Author(s):  
Harry G. Light ◽  
C. Witmer ◽  
H. M. Vars

The effects of anesthesia, trauma and starvation upon the composition of bile collected immediately after operation were obviated by preparing an external enterohepatic circulatory system. After 4–7 days the cannulas were separated, bile collected in various fractions of the 1st day and analyzed for total cholic acid and cholesterol. Cholate concentration in the first 3-hour collection was high, approximately 47% of the first day's total output. Cholate concentration in hours 3–6 was about 15% of the initial period, then gradually increased to a plateau on day 3 or 4. There was little change in cholesterol concentration in the 1st day's samples, but it about doubled by day 3 or 4. Cholic acid/cholesterol ratio rapidly decreased during the first 6 hours and remained low throughout the 1st day. The initial changes occurred earlier than observed by Eriksson in samples collected immediately following operation. Changes of bile composition following interruption of the enterohepatic circulation must be considered in evaluating bile excretion studies.


2005 ◽  
Vol 289 (2) ◽  
pp. H652-H659 ◽  
Author(s):  
Karine Valeille ◽  
Jacqueline Férézou ◽  
Ghislaine Amsler ◽  
Annie Quignard-Boulangé ◽  
Michel Parquet ◽  
...  

Conjugated linoleic acid (CLA) mixtures demonstrated antiatherogenic properties in several animal models, including hamsters, but the mechanism of action of the main food-derived CLA isomer is unknown in this species. This study thus focused on cis-9, trans-11-CLA (rumenic acid), and its effect was compared with that of fish oil, which is known to influence several aspects of atherogenesis. Syrian hamsters were fed (for 12 wk) diets containing 20% (wt/wt) butter fat (B diet) or the same diet augmented with either 1% (wt/wt) of a cis-9, trans-11-CLA-rich oil (BR diet) or 1% (wt/wt) fish oil (BF diet). The BR diet induced the lowest aortic lipid deposition (from −30% to −45%) among the butter oil-fed hamsters. In this group, plasma also displayed a reduced non-HDL-to-HDL-cholesterol ratio (21% less than in the butter oil group) and inflammatory serum amyloid A levels (70–80%) and an improvement of anti-oxidized LDL paraoxonase activity (all P < 0.05). Compared with the B group, the beneficial effects of the BR diet could be further explained in part by preventing the high VCAM-1 expression rate, increasing (30%) ATP-binding cassette subfamily A1 expression in the aorta, and downregulating expression of inflammatory-related genes (TNF-α, IL-1β, and cyclooxygenase 2, 2- to 2.8-fold, P < 0.05). This effect was partly associated with an activation of peroxisome proliferator-activating receptor (PPAR)/liver X receptor (LXR)-α signaling cascade. Interestingly, activation of PPAR/LXR-α signaling was not observed in hamsters fed the BF diet, in which the early signs of atherogenesis were increased. In conclusion, this study demonstrated that milk fat-rich cis-9, trans-11-CLA reduces the atherogenic process in hyperlipidemic hamsters.


1999 ◽  
Vol 81 (3) ◽  
pp. 251-255 ◽  
Author(s):  
John S. Munday ◽  
Keith G. Thompson ◽  
Kerry A. C. James

Conjugated linoleic acids (CLA) are positional isomers of linoleic acid which have been suggested by some to possess antiatherosclerotic properties. To test this hypothesis, three groups of twenty C57BL/6 mice were fed on atherogenic diets containing: 5 g CLA/kg, 2·5 g CLA + 2·5 g linoleic acid/kg or 5 g linoleic acid/kg. All diets were fed for 15 weeks and contained (g/kg): triacylglycerol 145, free fatty acids 5, cholesterol 10 and cholic acid 5. At the completion of the experimental period, when data from both groups fed on CLA were combined, dietary CLA did not produce significant differences in body weight, serum total cholesterol concentration or serum HDL-cholesterol concentration. However, mice receiving CLA developed a significantly higher serum HDL-cholesterol: total cholesterol ratio and a significantly lower serum triacylglycerol concentration than controls. Despite causing a serum lipoprotein profile considered to be less atherogenic, the addition of CLA to the atherogenic diet increased the development of aortic fatty streaks. Considering the increased atherogenesis associated with dietary CLA in the present study, and the failure to demonstrate a significant beneficial effect of CLA in other animal studies, there is currently no conclusive evidence to support the hypothesis that CLA protect against atherogenesis.


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