The influence of repeated administration of poloxamer 407 on serum lipoproteins and protease activity in mouse liver and heart

2012 ◽  
Vol 90 (11) ◽  
pp. 1456-1468 ◽  
Author(s):  
Tatyana A. Korolenko ◽  
Fedor V. Tuzikov ◽  
Thomas P. Johnston ◽  
Natalia A. Tuzikova ◽  
Yana A. Kisarova ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Repeated Administration ◽  
Poloxamer 407 ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Scattering Method ◽  
Low Density ◽  
Drastic Increase

The effects of repeated administration of poloxamer 407 (P-407) on lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions, as well as the effect on liver and heart proteases, were studied. Repeated administration of P-407 to male CBA mice resulted in a model of atherosclerosis with increased diastolic blood pressure; there was a drastic increase in total serum cholesterol and especially TG. A novel small-angle X-ray scattering method for the determination of the fractional and subfractional composition of LP-C and LP-TG was used. In chronically P-407-treated mice, P-407 significantly increased atherogenic low-density lipoprotein C (LDL-C) fractions, as well as intermediate-density lipoprotein C (IDL-C), and LDL1–3-C subfractions, and very-low-density lipoprotein-C (VLDL-C) fractions, as well as VLDL1–2-C and VLDL3–5-C subfractions), to a lesser extent, the total anti-atherogenic high-density lipoprotein C (HDL-C) fraction, as well as HDL2-C and HDL3-C subfractions. Additionally, we demonstrated an increase in the serum chitotriosidase activity, without significant changes in serum matrix metalloprotease (MMP) activity. Morphological changes observed in P-407-treated mice included atherosclerosis in the heart and storage syndrome in the liver macrophages. P-407 significantly increased the activity of cysteine, aspartate proteases, and MMPs in the heart, and only the activity of cathepsin B and MMPs in the liver of mice. Thus, repeated administration of P-407 to mice induced atherosclerosis secondary to sustained dyslipidemia and formation of foamy macrophages in liver, and also modulated the activity of heart and liver proteases.

Effect of serum lipoprotein(a) on estimation of low-density lipoprotein cholesterol by the Friedewald formula

1994 ◽  
Vol 40 (4) ◽  
pp. 571-573 ◽  
Author(s):  
K M Li ◽  
D E Wilcken ◽  
N P Dudman
Keyword(s):  
Serum Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipoprotein A ◽  
Friedewald Formula

Abstract The calculation of serum low-density lipoprotein cholesterol (LDL-C) by the Friedewald formula does not account for the cholesterol associated with lipoprotein(a) [Lp(a)]. To quantify the contribution of Lp(a) cholesterol to total serum cholesterol, we measured concentrations of serum Lp(a) by an ELISA and concentrations of other serum lipids and lipoproteins by standard assays in 23 normolipemic women, ages 50-60 years. In measuring serum high-density lipoprotein we found that polyethylene glycol 6000 precipitated > 99.8% of all Lp(a). When serum Lp(a) concentrations were < or = 300 mg/L, 301-600 mg/L, and > 600 mg/L, the uncorrected serum LDL-C was overestimated, respectively, by a mean of 4.1% (n = 7), 8.5% (n = 8), and 21.4% (n = 8). Serum Lp(a) concentrations were positively correlated with percentage overestimation (P < 0.001), but were not correlated with either corrected or uncorrected serum LDL-C. We conclude that the Friedewald formula should be modified to take into account the contribution of Lp(a) cholesterol to total serum cholesterol.

Enzyme Induction and Serum and Lipoprotein Lipids: A Study of Glutethimide in Normal Subjects

1980 ◽  
Vol 58 (5) ◽  
pp. 419-421 ◽  
Author(s):  
C. H. Bolton ◽  
LYN Jackson ◽  
C. J. C. Roberts ◽  
M. Hartog
Keyword(s):  
Enzyme Induction ◽  
Time Course ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Low Density ◽  
Acid Excretion ◽  
Glucaric Acid

1. Serum and lipoprotein cholesterol and triglycerides were measured before, during and after the administration of glutethimide (500 mg daily) for 21 days to six healthy volunteer subjects. 2. Evidence of enzyme induction was provided by significant rises in d-glucaric acid excretion and antipyrine clearance. 3. Concentrations of total serum cholesterol, very-low-density-lipoprotein-, low-density-lipoprotein-and high-density-lipoprotein-cholesterol rose significantly during treatment. 4. The time course of these changes was delayed in comparison with the rise and fall in d-glucaric acid excretion. 5. There was no change in the triglyceride content of either whole serum or lipoprotein fractions at any time during the trial. 6. The study provides further evidence that enzyme-inducing agents cause a rise in certain lipid concentrations.

Tracking of Serum Cholesterol and Lipoprotein Levels From the First Year of Life

PEDIATRICS ◽  
1993 ◽  
Vol 91 (5) ◽  
pp. 949-954
Author(s):  
Markku J. T. Kallio ◽  
Leena Salmenperä ◽  
Martti A. Siimes ◽  
Jaakko Perheentupa ◽  
Tatu A. Miettinen
Keyword(s):  
Serum Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Concentration ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
First Year ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
First Year Of Life

Objective. To examine the development of tracking of serum cholesterol concentration from birth to childhood. Design. In a longitudinal study of healthy children, concentrations of total serum cholesterol and triglyceride were determined at birth (n = 193); at 2 (n = 192), 4 (n = 192), 6 (n = 190), 7.5 (n = 118), 9 (n = 188), and 12 months (n = 196); and at 5 years of age (n = 162). Concentrations of cholesterol—very-low-density lipoprotein, low-density lipoprotein, high-density lipoprotein-2 (HDL2), and HDL3—were determined at 2, 6, 9, and 12 months (n = 36) and at 5 years (n = 162). Results. The correlation coefficients of total cholesterol levels during the first year of life with the level at 5 years of age were as follows: at birth .04, at 2 months .36 (P < .001), at 4 months .26 (P < .001), at 6 months .28 (P < .001), at 7.5 months .25 (P < .001), at 9 months .35 (P < .001), and at 12 months .48 (P < .001). The correlation for exclusively breast-fed children between 6 months and 5 years of age was r = .37, P < .001, while that for children receiving partially breast milk, formula, or solid foods was r = .12, P = not significant (NS), and between 9 months and 5 years r = .38, P < .01, and r = .28, P < .05, respectively. The correlation coefficients of the lipoprotein levels between ages 12 months and 5 years were as follows: low-density lipoprotein cholesterol .58 (P < .001), total HDL cholesterol .30 (P < .05), HDL2 cholesterol .34 (P < .05), HDL3 cholesterol .17 (P = NS), very-low-density lipoprotein cholesterol .24 (P = NS), total triglyceride .37 (P < .05), and triglyceride-very-low-density lipoprotein .37 (P < .05). Of the children whose total serum cholesterol level was above the 90th percentile at birth, or at 2, 4, 6, 7.5, 9, or 12 months, 6%, 35%, 29%, 30%, 31%, 33%, and 45%, respectively, were above the 90th percentile at 5 years of age. In retrospect, 45% of the children whose serum cholesterol level was above the 90th percentile at 5 years were above the 90th percentile at the age of 12 months and 80% were in the highest quartile. Conclusions. The results indicate that tracking of serum cholesterol concentration during the first year of life is stronger when examining children who are receiving a relatively homogenous diet, such as exclusive breast-feeding, and weaker as children are weaned to formula and solid foods. After the weaning process is completed, children's relative serum cholesterol levels have become established and the tracking of serum cholesterol is of the same magnitude as for older children and adolescents.

Activity of low-density lipoprotein receptors as estimated from concentrations of apolipoprotein B and C-II in serum.

1988 ◽  
Vol 34 (11) ◽  
pp. 2224-2227 ◽  
Author(s):  
H Ito ◽  
C Naito ◽  
H Hayashi ◽  
M Kawamura
Keyword(s):  
Serum Cholesterol ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Receptor Activity ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Low Density ◽  
Apo B ◽  
Apo E

Abstract The correlation between low-density lipoprotein (LDL) receptor activity and concentrations of lipids and apolipoproteins in serum was examined in 12 subjects with heterozygous familial hypercholesterolemia (FH) and in four with non-FH type II hyperlipoproteinemia. Concentrations of high-density lipoprotein cholesterol and of apolipoproteins (apo) A-I, C-II, and C-III were significantly positively correlated with LDL receptor activity, whereas LDL receptor activity was significantly inversely correlated with LDL cholesterol and apo B concentrations, and with apo ratios B/A-I and B/A-II. Neither total serum cholesterol, triglyceride, phospholipid, apo A-I, nor apo E concentrations correlated significantly with LDL receptor activity. Multiple regression analysis, with LDL receptor activity as the dependent variable, revealed concentrations of apo B and apo C-II to be the principal determinant factors. To confirm this, we subsequently calculated the LDL receptor activities before and after administration of CS-514, an inhibitor of hydroxymethylglutaryl-CoA reductase (EC 1.1.1.88), which increases the hepatic LDL receptor activity and decreases the concentration of cholesterol in serum. This drug increased calculated LDL receptor activities significantly, with a significant decrease in serum cholesterol.

scholarly journals Changes in fatty acid compositions of total serum and lipoprotein particles, in growing rats given protein-deficient diets with either hydrogenated coconut or salmon oils as fat sources

1994 ◽  
Vol 71 (3) ◽  
pp. 375-387 ◽  
Author(s):  
Mahmoud Bouziane ◽  
Josiane Prost ◽  
Jacques Belleville
Keyword(s):  
Fatty Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coconut Oil ◽  
Protein Malnutrition ◽  
Total Serum ◽  
Low Density ◽  
Apo B ◽  
Growing Rats ◽  
Arachidonic Acids

The present study examines the effects of dietary saturated (hydrogenated coconut oil) and polyunsaturated (salmon oil) fats on the composition and metabolism of lipoproteins in growing rats fed on protein-deficient diets. Four groups of rats were fed on the following diets for 28 d: 200 g casein+50 g coconut oil (COC)/kg, 20 g casein+50 g coconut oil (COd)/kg, 200 g casein + 50 g salmon oil (SAC)/kg, 20 g casein+50 g salmon oil (SAd)/kg. Both protein-deficient groups exhibited low concentrations of protein and triacylglycerol (in serum, very-low-density lipoprotein (VLDL), low-density lipoprotein-high-density lipoprotein, (LDL-HDL1) and HDL2-3), of cholesterol (in LDL-HDL1) and of phospholipids (in VLDL). Furthermore, serum and VLDL cholesterol concentrations were also reduced in the SAd group. Compared with rats given 200 g casein/kg diets, those fed on low-protein diets presented lower linoleic and arachidonic acid levels, in serum phospholipids and a dramatic decrease in the polyunsaturated: saturated fatty acid value. Relative amounts of linoleic and arachidonic acids in phospholipids of VLDL and HDL2-3 were also lowered in the Cod group but not in the SAd group. However, proportions of 22:5n-6 and 22:6n-3 in VLDL and HDL2-3 phospholipid fractions were enhanced in the Cod and SAd groups respectively. The most affected apolipoproteins (apo) were apo B100 and apo B48 in rats fed on protein-deficient diets, apo A1 and apo E in the Cod group, and apo AIV, in the SAd group. Compared with rats fed hydrogenated coconut oil diets, those fed salmon oil diets had enhanced LDL-HDL1 and HDL2-3 but lower VLDL total apolipoproteins (mainly due to a fall in apo B100, and apo B48). Arachidonic and eicosapentaenoic acids, which are impaired by protein deficiency, are the precursors of prostaglandins, thromboxanes and leukotrienes which are implicated in a number of regulatory processes. Our results demonstrate that protein malnutrition is associated with impaired metabolism of arachidonic and eicosapentaenoic acids. Protein malnutrition and essential fatty acid (EFA) deficiency are characterized by many common clinical features and the Link between the two may be an impaired production of eicosanoids, since arachidonic and eicosapentaenoic acids are the precursors of these important metabolic regulators. Because of the apparent involvement of EFA deficiency in the aetiology of protein malnutrition, it may he prudent to include adequate amounts of EFA in diets of infants suffering from kwashiorkor.

scholarly journals SUN-571 The Associations Between p,p’-DDE Levels and Serum Levels of Lipoproteins and Their Subclasses in an Elderly Population Determined by Lipidomics Analysis

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Juliann Amela Jugan ◽  
P Monica Lind ◽  
Samira Salihovic ◽  
Jordan Stubleski ◽  
Anna Kärrman ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Resolution Mass Spectrometry ◽  
Solid Phase ◽  
Total Concentration ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Total Serum ◽  
Resonance Spectroscopy ◽  
Low Density

Abstract Low biodegradability and high lipophilicity of p,p’-dichlorodiphenyldichloroethylene (DDE), a metabolite of the insecticide DDT, leads to transport with lipids and accumulation in adipose tissue. This persistence allows for DDE to effect adipose tissue and lipid metabolism. A few small human studies have shown an association between DDE and blood lipids, although with some inconsistent conclusions. The aim of this study was to investigate the association between DDE exposure and altered levels of circulating lipids in a large human cohort. To evaluate the associations between DDE and human lipid profiles, plasma was collected from a subset of elderly Swedes in the Prospective Investigation of the Vasculature of Uppsala Seniors (PIVUS) cohort who were free from lipid lowering medication (n = 571). DDE concentrations in plasma were measured using high-throughput solid phase extraction and gas chromatography-high resolution mass spectrometry. Lipidomic analysis of plasma was performed with nuclear magnetic resonance spectroscopy. Linear models of lipids and DDE were statistically adjusted for sex and body mass index. Detectable levels of DDE were found in the plasma samples of all subjects. With elevated DDE levels, the comprehensive lipoprotein profile showed an elevation in total concentration of all diameters of very low density lipoprotein (VLDL) (p<0.001), low density lipoprotein (LDL) (p<0.008), intermediate density lipoprotein (IDL) (p<0.02), and in small high density lipoprotein (HDL) (p<0.05). Triglycerides and DDE were associated to varying degrees in lipoproteins (IDL > VLDL > LDL > HDL) and within total serum (p<0.005). DDE levels were positively associated with cholesterol and cholesterol ester levels only in VLDL and LDL (p<0.05) and with apolipoprotein B (p<0.0009). The positive associations observed between each lipoprotein class and elevated DDE support previous data suggesting that DDE interacts with lipoproteins within plasma. We speculate that both physio-chemical and biological mechanisms may explain why DDE does not uniformly associate with lipids across lipoproteins.

scholarly journals The Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 and Cardiovascular Disease

1970 ◽  
Vol 3 (2) ◽  
pp. 169-177
Author(s):  
MSA Sheikh ◽  
T Yang ◽  
U Salma ◽  
M Ali
Keyword(s):  
Signal Transduction ◽  
Endothelial Dysfunction ◽  
Morphological Changes ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Soluble Form ◽  
Low Density ◽  
Coronary Syndrome

Lectin-like oxidized LDL receptor-1 (LOX-1), a lectin-like 50-kD receptor for oxidized low-density lipoproteins (ox-LDL), is present primarily on endothelial cells. Oxidatively modified low-density lipoprotein (oxLDL) is implicated in the pathogenesis of atherosclerosis. Endothelial dysfunction is the initial change in the vascular wall that induces morphological changes for atheroma-formation. LOX-1 was identified as the receptor for oxLDL that was thought to be a major cause of endothelial dysfunction. LOX-1 has been demonstrated to contribute not only to endothelial dysfunction, but also to atherosclerotic-plaque formation, hypertension, myocardial infarction and intimal thickening after balloon injury. Studies with transgenic and knockout mouse models have elucidated in part the role of LOX-1 in the pathogenesis of atherosclerosis and cardiac remodeling. Recently, a circulating soluble form of LOX-1(sLOx-1), corresponding solely to its extracellular domain, has been identified in human serum. Circulating levels of sLOX-1 are increased in inflammatory and atherosclerotic conditions and are associated with acute coronary syndrome, with the severity of coronary artery disease, and with serum biomarkers for oxidative stress and inflammation, suggesting that they could be useful marker for vascular injury. Identification and regulation of this receptor and understanding of signal transduction pathways might open new gateways from diagnosis to therapeutics for cardiovascular diseases. Keywords: Atherosclerosis; Endothelial dysfunction; LOX-1; ox-LDL; Signal transduction. DOI: http://dx.doi.org/10.3329/cardio.v3i2.9187 Cardiovasc. J. 2011; 3(2): 169-177

Niacin Treatment of Hypercholesterolemia in Children

PEDIATRICS ◽  
1993 ◽  
Vol 92 (1) ◽  
pp. 78-82
Author(s):  
Richard B. Colletti ◽  
Nancy K. Roff ◽  
Ellis J. Neufeld ◽  
Annette L. Baker ◽  
Jane W. Newburger ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Total Serum ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Serum Aminotransferase ◽  
Hospital Referral

Objective. To determine the efficacy and adverse effects of niacin treatment of hypercholesterolemia in children. Design. Retrospective review. Setting. Two university hospital referral clinics. Patients. All children who received single-drug niacin treatment for severe hypercholesterolemia between 1980 and 1991. Results. Twenty-one children, aged 4 to 14 years, were treated with niacin, 500 to 2250 mg daily. Pretreatment total serum cholesterol value (mean ± SD) was 7.84 ± 1.14 mmol/L (303 ± 44 mg/dL), and low-density lipoprotein cholesterol value was 6.28 ± 1.16 mmol/L (243 ± 45 mg/dL). Niacin treatment in daily doses >1000 mg reduced total cholesterol by 23% and low-density lipoprotein cholesterol by 30% (P < .001) but had no effect on highdensity lipoprotein cholesterol and triglycerides. As in adults, reversible adverse effects were common, occurring in 16 (76%) of the 21 children. Six children (29%) had reversible dose-related elevations of serum aminotransferase levels. Niacin therapy was discontinued in 8 children (38%) because of flushing, abdominal pain, vomiting, headache, or elevated serum aminotransferase levels. Conclusions. This study suggests that although niacin treatment in children is efficacious, adverse effects are common. Until further study demonstrates long-term safety, niacin treatment should be reserved for the closely-supervised treatment of severe hypercholesterolemia by a lipid specialist.

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