Effect of Phenobarbitone on Plasma Lipids in Normal Subjects

1976 ◽  
Vol 50 (5) ◽  
pp. 349-353 ◽  
Author(s):  
P. N. Durrington ◽  
C. J. C. Roberts ◽  
Lyn Jackson ◽  
R. A. Branch ◽  
M. Hartog
Keyword(s):  
Ldl Cholesterol ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Normal Subjects ◽  
Low Density ◽  
Total Plasma Cholesterol ◽  
Total Plasma ◽  
Antipyrine Clearance

1. Phenobarbitone in a dose of 180 mg daily was administered to ten normal subjects for 3 weeks. There was a significant increase in total plasma cholesterol, plasma low-density-lipoprotein cholesterol, plasma low-density-lipoprotein (LDL) triglycerides and plasma LDL protein. The increase in plasma LDL cholesterol accounted for the increase in total plasma cholesterol. There was a significant reduction in the ratio of LDL cholesterol to LDL protein. 2. No significant changes were observed in total plasma triglycerides, plasma very-low-density-lipoprotein (VLDL) triglycerides, plasma VLDL cholesterol or plasma VLDL protein. 3. Evidence that drug-metabolizing enzymes were induced by phenobarbitone was provided by an increase in antipyrine clearance. No relationship was observed between changes in plasma cholesterol and changes in antipyrine clearance. Serum γ-glutamyl transpeptidase was also increased after phenobarbitone administration, the increase being unrelated to changes in antipyrine clearance or plasma cholesterol.

Plasma Lipid Variability in the Toronto Twin Register

1980 ◽  
Vol 29 (4) ◽  
pp. 299-302 ◽  
Author(s):  
Jean Milner ◽  
Joe C. Christian ◽  
David Hewitt
Keyword(s):  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Total Plasma Cholesterol ◽  
Total Plasma ◽  
Low Density Lipoprotein Cholesterol ◽  
Mz Twins

Plasma lipids were studied on 92 pairs of twins (66 MZ and 26 like-sexed DZ). The DZ twins had significantly greater total variance than the MZ twins for total plasma cholesterol but not for triglycerides or the high, low, and very low-density lipoprotein cholesterol fractions.

Abstract 20120: Protease-activated Receptor 4 Deficiency Reduces Atherosclerosis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
A. Phillip Owens ◽  
Deborah A Howatt ◽  
Alan Daugherty ◽  
Nigel Mackman
Keyword(s):  
Mouse Model ◽  
Aortic Root ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Total Plasma Cholesterol ◽  
Total Plasma ◽  
Density Lipoprotein Receptor

Objective: Platelet activation is emerging as a critical process in both the formation and propagation of atherosclerosis. The coagulation protease thrombin activates platelets by cleavage of protease-activated receptor 4 (PAR4) in mice. Recent studies have demonstrated direct thrombin inhibitors reduce atherosclerosis in hypercholesterolemic mice. However, PAR4 deficiency had no effect on atherosclerosis in the apolipoprotein E (Apoe-/-) mouse model. The objective of this study was to re-examine the role of PAR4 deficiency in atherosclerosis using the alternative low-density lipoprotein receptor deficient mouse model. Methods and Results: To examine the effects of PAR4 deficiency on early atherosclerotic formation, low-density lipoprotein receptor deficient (Ldlr-/-) mice that were either PAR4+/+ (n = 11) or PAR4-/- (n = 12) were fed a fat-enriched diet (21% milk fat) and infused with angiotensin II (AngII; 1,000 ng/kg/min) for 28 days. PAR4 deficiency reduced AngII-induced aortic root atherosclerosis (+/+: 107 ± 22.1; -/-: 28.3 ± 7.50 μm2; P = 0.007). Bone marrow transplantation experiments were performed to determine the cellular source of PAR4 in atherosclerosis. Preliminary results demonstrate this reduction is dependent upon hematopoietic-derived PAR4 (+/+ into +/+: 230 ± 41; +/+ into -/-: 194 ± 23; -/- into +/+: 78 ± 18; and -/- into -/-: 68 ± 13 μm2; n = 4 each group; P < 0.02 +/+ hematopoietic versus -/- hematopoietic). PAR4 deficiency had no effects on total plasma cholesterol concentrations, lipoprotein-cholesterol distributions, or AngII increased systolic blood pressure. To determine the effects of a longer interval of diet-induced atherosclerosis, Ldlr-/-/PAR4+/+ (n = 12) or Ldlr-/-/PAR4-/- (n = 12) were fed a fat-enriched diet for 12 weeks. PAR4 deficiency attenuated aortic root atherosclerosis (+/+: 299 ± 15; -/-: 188 ± 18 μm2; P = 0.001) with no effects on total plasma cholesterol concentrations or lipoprotein distributions. Conclusion: We demonstrated that PAR4 deficiency resulted in an early (AngII: 74%) and late (Diet-induced: 37%) reduction in aortic root atherosclerosis. These results suggest that thrombin activation of PAR4 on platelets contributes to atherosclerosis in the Ldlr-/- model, but not the Apoe-/- model.

scholarly journals (Pro)renin Receptor Inhibition Reduces Plasma Cholesterol and Triglycerides but Does Not Attenuate Atherosclerosis in Atherosclerotic Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Dien Ye ◽  
Xiaofei Yang ◽  
Liwei Ren ◽  
Hong S. Lu ◽  
Yuan Sun ◽  
...  
Keyword(s):  
Plasma Lipids ◽  
Inflammatory Responses ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Low Density ◽  
Beneficial Effects ◽  
Receptor Inhibition ◽  
Density Lipoprotein Receptor

Objective: Elevated plasma cholesterol concentrations contributes to ischemic cardiovascular diseases. Recently, we showed that inhibiting hepatic (pro)renin receptor [(P)RR] attenuated diet-induced hypercholesterolemia and hypertriglyceridemia in low-density lipoprotein receptor (LDLR) deficient mice. The purpose of this study was to determine whether inhibiting hepatic (P)RR could attenuate atherosclerosis.Approach and Results: Eight-week-old male LDLR−/− mice were injected with either saline or N-acetylgalactosamine-modified antisense oligonucleotides (G-ASOs) primarily targeting hepatic (P)RR and were fed a western-type diet (WTD) for 16 weeks. (P)RR G-ASOs markedly reduced plasma cholesterol concentrations from 2,211 ± 146 to 1,128 ± 121 mg/dL. Fast protein liquid chromatography (FPLC) analyses revealed that cholesterol in very low-density lipoprotein (VLDL) and intermediate density lipoprotein (IDL)/LDL fraction were potently reduced by (P)RR G-ASOs. Moreover, (P)RR G-ASOs reduced plasma triglyceride concentrations by more than 80%. Strikingly, despite marked reduction in plasma lipid concentrations, atherosclerosis was not reduced but rather increased in these mice. Further testing in ApoE−/− mice confirmed that (P)RR G-ASOs reduced plasma lipid concentrations but not atherosclerosis. Transcriptomic analysis of the aortas revealed that (P)RR G-ASOs induced the expression of the genes involved in immune responses and inflammation. Further investigation revealed that (P)RR G-ASOs also inhibited (P)RR in macrophages and in enhanced inflammatory responses to exogenous stimuli. Moreover, deleting the (P)RR in macrophages resulted in accelerated atherosclerosis in WTD fed ApoE−/− mice.Conclusion: (P)RR G-ASOs reduced the plasma lipids in atherosclerotic mice due to hepatic (P)RR deficiency. However, augmented pro-inflammatory responses in macrophages due to (P)RR downregulation counteracted the beneficial effects of lowered plasma lipid concentrations on atherosclerosis. Our study demonstrated that hepatic (P)RR and macrophage (P)RR played a counteracting role in atherosclerosis.

The carbohydrate composition of human apo low density lipoprotein from normal and type II hyperlipoproteinemic subjects

1976 ◽  
Vol 54 (1) ◽  
pp. 42-49 ◽  
Author(s):  
P. Lee ◽  
W. Carl Breckenridge
Keyword(s):  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Normal Subjects ◽  
Low Density ◽  
Type Ii ◽  
Carbohydrate Composition ◽  
Acetylneuraminic Acid ◽  
Liquid Chromatographic Analysis ◽  
Liquid Chromatographic

The carbohydrate composition of the apoprotein from low density lipoprotein (LDL) of normal (average LDL cholesterol, 122 mg/100 ml) and type II hyperlipoproteinemic (average LDL cholesterol, 236 mg/100 ml) males was studied using gas–liquid chromatographic analysis of the methyl glycoside derivatives. All samples containing detectable sinking pre-beta-lipoprotein were excluded from the study.The apo LDL from both groups of subjects contained mannose, galactose, N-acetylglucosamine, and N-acetylneuraminic acid. Glucose and fucose were not found while trace quantities of galactosamine were detected. Although the quantities of galactose and N-acetylglucosamine were the same in the two groups, lower quantities of mannose [Formula: see text] and N-acetylneuraminic acid [Formula: see text] were found in the type II patients as opposed to normal subjects.

Effect of changing dietary fat saturation on low-density lipoprotein metabolism in man

1981 ◽  
Vol 241 (1) ◽  
pp. E57-E63 ◽  
Author(s):  
J. D. Turner ◽  
N. A. Le ◽  
W. V. Brown
Keyword(s):  
Production Rate ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Saturated Fat ◽  
Density Lipoprotein ◽  
Normal Subjects ◽  
Low Density ◽  
Type Ii ◽  
Polyunsaturated Fat ◽  
Fat Saturation

The mechanism of change in low-density lipoprotein (LDL) levels by diets differing in fat saturation have been studied. Turnover of 125I-LDL was measured in eight subjects with type II hyperlipoproteinemia and in seven normal control subjects during two dietary periods containing 40% of calories as either safflower oil (polyunsaturated fat, PSF) or as lard (saturated fat, SF). Higher levels of LDL apoprotein and LDL-cholesterol were observed in both groups on saturated fat. Subjects with elevated LDL levels (type II) showed a more marked effect of polyunsaturated fat with 25% lower LDL production rate as compared to a reduction of only 10% for the control group. On the PSF diet, the production rate in type II (12.7 mg.kg-1.day-1) was not statistically different from normal subjects (10.5 mg.kg-1.day-1). On this diet, the higher levels of LDL cholesterol in the type II subjects (as compared to controls) were due to a lower fractional clearance rate, mean of 0.27/day compared to a mean of 0.39/day for the normal subjects. Although individuals with type II hyperlipoproteinemia may have a primary clearance defect, the major reduction in plasma cholesterol concentrations achieved with a diet high in polyunsaturated fat can be attributed to a significantly lower LDL production.

Plasma Lipid and Lipoprotein Abnormalities in Patients with Malabsorption

1973 ◽  
Vol 45 (5) ◽  
pp. 583-592 ◽  
Author(s):  
Gilbert R. Thompson ◽  
J. Paul Miller
Keyword(s):  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Plasma Lipoproteins ◽  
Low Density ◽  
Cholesterol Levels ◽  
Lipids And Lipoproteins

1. Plasma lipids and lipoproteins have been studied in control subjects and patients with various types of steatorrhoea. 2. Low plasma cholesterol levels were found in malabsorbers and were associated with decreased amounts of low-density lipoprotein (LDL) in males and high-density lipoprotein (HDL) in females. 3. Serum triglyceride levels were normal in males, but exceeded control values in some of the females, due to an increase in very-low-density lipoprotein. 4. LDL composition was abnormal in both male and female malabsorbers, with a decreased proportion of cholesterol ester and an increased proportion of triglyceride. There was also an increased proportion of triglyceride in HDL. 5. These findings show that malabsorption markedly influences not only the concentration but also the composition of plasma lipoproteins.

Tri-iodothyronine prevents the amiodarone-induced decrease in the expression of the liver low-density lipoprotein receptor gene

1997 ◽  
Vol 152 (3) ◽  
pp. 413-421 ◽  
Author(s):  
F Hudig ◽  
O Bakker ◽  
W M Wiersinga
Keyword(s):  
Ldl Cholesterol ◽  
Plasma Cholesterol ◽  
Receptor Gene ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Ldl Receptors ◽  
Receptor Mrna ◽  
Receptor Gene Expression

Treatment with amiodarone, a potent antiarrhythmic drug, is associated with a dose-dependent increase in plasma cholesterol resulting from a decreased number of liver low-density lipoprotein (LDL) receptors. Similar changes occur in hypothyroidism, and it has been suggested that amiodarone acts via induction of a local 'hypothyroid-like' state in extrathyroidal tissues. The present study was designed to evaluate whether exogenous tri-iodothyronine (T3) could prevent the effects of amiodarone on LDL cholesterol. Rats were treated for 14 days with water, amiodarone 10 mg/100 g body weight (BW), or amiodarone and 2·5, 5 or 10 μg T3/100 g BW respectively. Relative to controls, amiodarone increased plasma LDL cholesterol by 31% and decreased liver LDL receptor mRNA by 56% and protein by 45%; liver T3 content was reduced by 21%. Addition of T3 to the treatment with amiodarone dose-dependently reversed all these changes, with a return to control values of plasma cholesterol and the number of liver LDL receptors, although LDL receptor mRNA remained slightly lower. Treatment of rats for 14 days with T3 alone (5 μg/100 g BW) decreased plasma LDL cholesterol by 19% and increased liver LDL receptor mRNA by 41%. In conclusion, T3 prevents the amiodarone-induced changes in plasma LDL cholesterol and liver LDL receptor gene expression. These findings suggest that the inhibitory effect of amiodarone on LDL receptor gene expression is mediated by T3-dependent pathways. Journal of Endocrinology (1997) 152, 413–421

scholarly journals Lipid and Lipoprotein Concentrations in Pregnancies Complicated by Intrauterine Growth Restriction1

1999 ◽  
Vol 84 (1) ◽  
pp. 128-130 ◽  
Author(s):  
Naveed Sattar ◽  
Ian A. Greer ◽  
Peter J. Galloway ◽  
Chris J. Packard ◽  
James Shepherd ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Plasma Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Intermediate Density Lipoprotein ◽  
Third Trimester ◽  
Intrauterine Growth ◽  
The Third ◽  
Intermediate Density

Previous studies have shown that in preeclampsia, plasma lipids climb substantially above levels seen in normal pregnancies. Such lipid changes may play a role in the endothelial damage characteristic of preeclampsia. Pregnancies complicated by intrauterine growth restriction (IUGR), without preeclampsia, have similar placental pathology to preeclampsia despite the absence of the maternal systemic manifestations of hypertension and proteinuria. The aim of this study was to perform a cross-sectional study of lipid and lipoprotein concentrations in the third trimester, from normal pregnancies, and those complicated by IUGR without preeclampsia. Our hypothesis was that, in contrast to the exaggerated lipid changes seen in preeclampsia, lipid and lipoprotein concentrations in IUGR would be similar to those of matched healthy pregnant controls. Fasting blood samples for lipids and lipoprotein fractions were taken in the third trimester, from eight women with IUGR; and eight women with uncomplicated pregnancies, matched as a group for age, booking weight, parity, and gestational age at sampling. There were no significant differences (P &gt; 0.05) in the median concentrations of triglyceride, high-density lipoprotein, and very-low-density lipoprotein 1 (VLDL1), between cases and controls. However, women with IUGR pregnancies had significantly lower cholesterol [4.95 mmol/L (3.35–7.10) vs. 7.47 (5.75–8.45); median (range) for IUGR patients and controls, respectively; P &lt; 0.01], low-density lipoprotein (LDL)-cholesterol [2.45 mmol/L (0.95–3.60) vs. 4.25 (3.35–5.60); P &lt; 0.01], VLDL2 mass[ 59.0 mg/dL (37–87) vs. 103.0 (64–168); P &lt; 0.01], intermediate-density lipoprotein mass[ 56.0 mg/dL (31–110) vs. 125.6 (91–157); P &lt; 0.01], and total LDL mass [221.0 mg/dL (104–237) vs. 380.3 (267–534); P&lt; 0.01]. In addition, it was noteworthy that, with respect to LDL-cholesterol and total LDL mass, there was little or no overlap in the ranges of concentrations measured between cases and controls. Because VLDL2 and intermediate-density lipoprotein are the synthetic precursors to LDL in the circulation, their significantly lower median concentrations imply a failure of appropriate LDL synthesis in IUGR pregnancies. Whatever the mechanism, if our results are confirmed in larger studies and longitudinal investigations, then LDL-cholesterol measurements (when LDL-cholesterol fails to rise appropriately or is low in the third trimester) may be of use in identifying mothers with, or at risk of, a pregnancy complicated by IUGR.

Plasma lipids, lipoproteins, and triglyceride turnover in eu- and hypo-thyroid rats and rats on a hypocaloric diet

1981 ◽  
Vol 59 (8) ◽  
pp. 715-721 ◽  
Author(s):  
Ladislav Dory ◽  
Brian R. Krause ◽  
Paul S. Roheim
Keyword(s):  
Half Life ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Caloric Intake ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Plasma Triglyceride ◽  
Low Density ◽  
Control Groups

Lipid and lipoprotein concentration, and triglyceride turnover were studied in control, thyroidectomized, and pair-fed control rats (pair-fed to match the food intake of the thyroidectomized rats). Thyroidectomy induced a significant increase in plasma cholesterol (and low density lipoprotein) concentrations and a decrease in plasma triglyceride (and very low density lipoprotein) concentrations. Changes in similar direction but of smaller magnitude were observed in the plasma of the pair-fed control rats. To further investigate triglyceride metabolism in these three groups of animals, triglyceride turnover was studied in fasted, unrestrained, and unanesthetized rats, following injection of [2-3H]glycerol. Peak incorporation of [2-3H]glycerol into plasma triglyceride occurred in all three groups of animals at 25 min after precursor administration, although the maximal incorporation was substantially lower in the thyroidectomized group than in either of the control groups. Thereafter, plasma triglyceride radioactivity decayed monoexponentially with a half-life of 24 ± 1 min for both normal and pair-fed control rats, compared with the half-life of 41 ± 3 min observed in the thyroidectomized rats. The calculated apparent fractional catabolic rates were thus 0.029 min−1 for both control groups and only 0.017 min−1 for the thyroidectomized animals. The apparent total catabolic rates of plasma triglyceride were 299 ± 11, 138 ± 11, and 48 ± 4 μg triglyceride∙min−1 for the normal controls, pair-fed controls, and thyroidectomized rats, respectively. These data further emphasize the importance of thyroid hormones in regulating plasma lipid and lipoprotein metabolism and, specifically, indicate that hypothyroidism results in a reduction of triglyceride secretion into, and the removal from, circulation. Furthermore, evidence was presented that the decreased caloric intake of the hypothyroid animals cannot, in itself, account for this observation.

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