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1-29 of 29
Keywords: lipoproteins
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Articles
Circulating miR-33a and miR-33b are up-regulated in familial hypercholesterolaemia in paediatric age
Francesco Martino, Fabrizio Carlomosti, Daniele Avitabile, Luca Persico, Mario Picozza, Francesco Barillà, Marcello Arca, Anna Montali, Eliana Martino, Cristina Zanoni, Sandro Parrotto, Alessandra Magenta
Journal:
Clinical Science
Clin Sci (Lond) (2015) 129 (11): 963–972.
Published: 10 September 2015
... control, therefore, together with atherogenic factors, they can stimulate atherosclerotic degeneration of the vessel walls of arteries. miR-33a and miR-33b play a pivotal role in a variety of biological processes including cholesterol homoeostasis, HDL (high-density lipoprotein)-cholesterol formation...
Abstract
Hypercholesterolaemia is one of the major causes of CVD (cardiovascular disease). It is associated with enhanced oxidative stress, leading to increased lipid peroxidation which in turn determines endothelial dysfunction and susceptibility to coronary vasoconstriction and atherosclerosis. Different miRNAs are involved in the pathogenesis of CVD and play an important role in inflammatory process control, therefore, together with atherogenic factors, they can stimulate atherosclerotic degeneration of the vessel walls of arteries. miR-33a and miR-33b play a pivotal role in a variety of biological processes including cholesterol homoeostasis, HDL (high-density lipoprotein)-cholesterol formation, fatty acid oxidation and insulin signalling. Our study aimed to determine whether circulating miR-33a and miR-33b expression was altered in familial hypercholesterolaemic children. Total RNA was extracted from plasma, and miR-33a and miR-33b were measured by quantitative real-time PCR. We found that miR-33a and miR-33b were significantly up-regulated in the plasma of 28 hypercholesterolaemic children compared with 25 healthy subjects (4.49±0.27-fold increase, P <0.001, and 3.21±0.39-fold increase, P <0.05 respectively), and for both miRNAs, a positive correlation with total cholesterol, LDL (low-density lipoprotein)-cholesterol, LDL-cholesterol/HDL-cholesterol ratio, apolipoprotein B, CRP (C-reactive protein) and glycaemia was found. OLS (ordinary least squares) regression analysis revealed that miR-33a was significantly affected by the presence of FH (familial hypercholesterolaemia), glycaemia and CRP ( P <0.001, P <0.05 and P <0.05 respectively). The same analysis showed that miR-33b was significantly related to FH and CRP ( P <0.05 and P <0.05 respectively). Although it is only explorative, the present study could be the first to point to the use of miR-33a and miR-33b as early biomarkers for cholesterol levels in childhood, once validated in independent larger cohorts.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (2002) 103 (5): 451–460.
Published: 03 October 2002
... 2002 The Biochemical Society and the Medical Research Society ©2002 2002 atherosclerosis endothelial function lipoproteins nitric oxide vasoconstriction/dilation 451Clinical Science (2002) 103, 451 460 (Printed in Great Britain) Chylomicron-remnant-like particles inhibit receptor...
Abstract
The influence of native and oxidized chylomicron-remnant-like particles (CMR-LPs) on endothelium-dependent relaxation in pig coronary arteries was studied. Artificial lipid particles of a size and lipid composition resembling chylomicron remnants and containing pig apolipoprotein E were used to investigate the effects of chylomicron remnants on the relaxation of isolated segments of pig coronary arteries in response to three endothelium dilators: 5-hydroxytryptamine (5-HT), bradykinin and the calcium ionophore A23187. CMR-LPs caused significant inhibition of the maximum relaxation response of the vessels to 5-HT, but not that to bradykinin or A23187 ( P <0.05). In contrast, CMR-LPs that had been oxidized by incubation with 10 μ M CuSO 4 (oxidized CMR-LPs) were found to significantly reduce maximal relaxation to bradykinin by 13% ( P <0.05) and to reduce the sensitivity of the tissue to A23187 by 1.7-fold ( P <0.05). In experiments in which either the L -arginine/nitric oxide (NO) pathway or the endothelium-derived hyperpolarizing factor (EDHF) pathway was selectively inhibited, leaving the other intact, the inhibitory effect of oxidized CMR-LPs was observed only in vessels in which the L -arginine/NO-mediated pathway was operative. Furthermore, the oxidized particles had no inhibitory effect on the relaxation of the vessel segments to the non-endothelium-dependent agonists S -nitro- N -acetylpenicillamine, 5'-( N -ethylcarboxamido)adenosine or pinacidil. These results demonstrate that CMR-LPs inhibit vascular relaxation in pig coronary arteries by an endothelium-dependent mechanism involving the L -arginine/NO pathway, but not the EDHF pathway, and provide evidence in support of a role for chylomicron remnants in the endothelial dysfunction associated with hypercholesterolaemia and atherogenesis.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1999) 97 (6): 697–706.
Published: 15 November 1999
...A. BARDEN; L. J. BEILIN; K. BOTH; J. RITCHIE; P. LEEDMAN; B. N. WALTERS; C. A. MICHAEL In order to evaluate whether lipid abnormalities may contribute to endothelial dysfunction in pre-eclampsia, the present study examined the in vitro effects of very-low-density lipoprotein (VLDL), low-density...
Abstract
In order to evaluate whether lipid abnormalities may contribute to endothelial dysfunction in pre-eclampsia, the present study examined the in vitro effects of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), isolated from women with pre-eclampsia and matched controls, on the endothelial synthesis of 6-oxo-prostaglandin F 1α (6-oxo-PGF 1α ; a metabolite of prostacyclin) and endothelin 1, and on the expression of nitric oxide synthase 3 (NOS3) mRNA. VLDL, LDL and HDL cholesterol were isolated from 20 pre-eclamptic and 20 age- and gestation-matched normal pregnant women. The lipoproteins (50 μ g/ml) and lipoprotein-free control plasma were incubated for 1, 3 and 6 h at 37 °C with a human umbilical endothelial cell line. The synthesis of 6-oxo-PGF 1α and endothelin 1, and NOS3 mRNA expression, were measured at each time point. VLDL from pre-eclamptic women stimulated endothelial cell 6-oxo-PGF 1α synthesis to a lesser extent than that from normal pregnant women ( P < 0.05). LDL from women with pre-eclampsia also stimulated 6-oxo-PGF 1α synthesis to a lesser extent than LDL from normal pregnant women, but the effect was less sustained. The effect of HDL from women with pre-eclampsia on 6-oxo-PGF 1α synthesis was similar to that of HDL from normal pregnant women. The pre-incubation levels of lipid peroxides in VLDL and LDL were not different between the normal pregnant and pre-eclamptic women, and cannot account for the decrease in 6-oxo-PGF 1α synthesis. VLDL, LDL and HDL from women with pre-eclampsia did not affect endothelial cell synthesis of endothelin 1 or expression of NOS3 mRNA differently from lipoproteins from normal pregnant women. This study suggests that VLDL, and to a lesser extent LDL, from women with pre-eclampsia could potentially contribute to the reduced systemic 6-oxo-PGF 1α synthesis observed in the pre-eclamptic syndrome.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1999) 97 (2): 175–181.
Published: 18 June 1999
...Duo LI; Madeleine BALL; Melinda BARTLETT; Andrew SINCLAIR In the present study we investigated serum lipoprotein(a) [Lp(a)] levels, plasma lipids, the serum phospholipid polyunsaturated fatty acid profile and correlates of serum Lp(a) in healthy free-living female vegetarians ( n = 50) and...
Abstract
In the present study we investigated serum lipoprotein(a) [Lp(a)] levels, plasma lipids, the serum phospholipid polyunsaturated fatty acid profile and correlates of serum Lp(a) in healthy free-living female vegetarians ( n = 50) and omnivores ( n = 24) to assess differences which may have implications for cardiovascular risk. Dietary saturated fat and total plasma cholesterol were significantly lower in the vegetarians compared with omnivores. The mean serum Lp(a) concentration was lower in the vegetarians (171 mg/l) than in the omnivores (247 mg/l). The serum Lp(a) concentration was significantly negatively correlated with carbohydrate intake (as % of energy), and positively correlated with plasma total cholesterol. Compared with the omnivores, the vegetarians had significantly lower concentrations of 20:3, n -6, 20:4, n -6, 22:5, n -6, 20:5, n -3, 22:6, n -3 and total n -6 and n -3 polyunsaturated fatty acids, and a lower n -3/ n -6 polyunsaturated fatty acid ratio, in serum phospholipids. Lower concentrations of plasma total cholesterol, serum phospholipid total fatty acids, total saturated fatty acids and arachidonic acid, and a tendency towards a lower serum Lp(a) concentration, in vegetarians may have beneficial effects on cardiovascular disease risk. However, the decreased concentration of serum phospholipid n -3 polyunsaturated fatty acids may potentially promote thrombotic risk. Based on the present data, it would seem appropriate for omnivores to reduce their dietary intake of total fat and saturated fat in order to decrease their plasma cholesterol, and vegetarians should perhaps increase their dietary intake of n -3 polyunsaturated fatty acids, and thus improve the balance of n -3/ n -6, in order to reduce any thrombotic tendency that might increase their generally low risk of cardiovascular disease.
Articles
Pascale Richard, Isabelle Beucler, Maria Pascual De Zulueta, Nicolas Biteau, Jean-Luc De Gennes, Albert Iron
Journal:
Clinical Science
Clin Sci (Lond) (1997) 93 (1): 89–95.
Published: 01 July 1997
... at the age of 10. 3. The exploration of apoE status associated with plasma lipid levels and lipoprotein profiles in this three-generation pedigree made it possible to describe a compound heterozygote for two mutated alleles, one mutation being located in the N-terminal domain of the apoE protein and...
Abstract
1. A French multigeneration pedigree with hyperlipoproteinaemia was investigated for the transmission of the rare apolipoprotein E1(Gly 127 → Asp, Arg 158 → Cys) variant. The proband, a 46-year-old male carrying the rare apoE1 variant, presented a severe type III hyperlipoproteinaemia like his three brothers and his sister. 2. ApoE phenotyping and genotyping showed a discrepancy in the second allele carried by the proband's wife and two of her children, thus suggesting another apoE gene mutation. Cloning and sequencing of the entire exon 4 demonstrated a point mutation at codon 251, leading to an apoE3(Cys 112 → Arg, Arg 251 → Gly) allele. The proband's wife was normolipaemic and heterozygous for this rare isoform and the common apoE3 protein. The rare apoE3(Cys 112 → Arg, Arg 251 → Gly) allele has been transmitted to her two daughters. The first, aged 19, was normolipaemic and heterozygous for this allele and the common apoE2 allele. The second, carrying both the rare isoforms apoE1(Gly 127 → Asp, Arg 158 → Cys) and apoE3(Cys 112 → Arg, Arg 251 → Gly), presented a hypertriglyceridaemia at the age of 10. 3. The exploration of apoE status associated with plasma lipid levels and lipoprotein profiles in this three-generation pedigree made it possible to describe a compound heterozygote for two mutated alleles, one mutation being located in the N-terminal domain of the apoE protein and the other arising in the C-terminal domain.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1997) 92 (5): 473–479.
Published: 01 May 1997
...-density lipoprotein and high-density lipoprotein on blood viscosity correlate with their association with risk of atherosclerosis. 2. Blood viscometry was performed on samples from 28 healthy, non-fasting adult volunteers using a capillary viscometer. Data were correlated with haematocrit, fibrinogen...
Abstract
1. Increased blood or plasma viscosity has been observed in almost all conditions associated with accelerated atherosclerosis. Cognizant of the enlarging body of evidence implicating increased viscosity in atherogenesis, we hypothesize that the effects of low-density lipoprotein and high-density lipoprotein on blood viscosity correlate with their association with risk of atherosclerosis. 2. Blood viscometry was performed on samples from 28 healthy, non-fasting adult volunteers using a capillary viscometer. Data were correlated with haematocrit, fibrinogen, serum viscosity, total cholesterol, high-density lipoprotein-cholesterol, triglycerides and calculated low-density lipoprotein-cholesterol. 3. Low-density lipoprotein-cholesterol was more strongly correlated with blood viscosity than was total cholesterol ( r = 0.4149, P = 0.0281, compared with r = 0.2790, P = 0.1505). High-density lipoprotein-cholesterol levels were inversely associated with blood viscosity ( r = −0.4018, P = 0.0341). 4. To confirm these effects, viscometry was performed on erythrocytes, suspended in saline, which had been incubated in plasma of various low-density lipoprotein/high-density lipoprotein ratios. Viscosity correlated directly with low-density lipoprotein/high-density lipoprotein ratio ( n = 23, r = 0.8561, P < 0.01). 5. Low-density lipoprotein receptor occupancy data suggests that these effects on viscosity are mediated by erythrocyte aggregation. 6. These results demonstrate that the effects of low-density lipoprotein and high-density lipoprotein on blood viscosity in healthy subjects correlate with their association with risk of atherosclerosis. These effects on viscosity may play a role in atherogenesis by modulating the dwell or residence time of atherogenic particles in the vicinity of the endothelium.
Articles
Richard H. Neary, Mark D. Kilby, Padma Kumpatula, Francis L. Game, Deepak Bhatnagar, Paul N. Durrington, P. M. Shaughn O'Brien
Journal:
Clinical Science
Clin Sci (Lond) (1995) 88 (3): 311–318.
Published: 01 March 1995
... to establish whether the placenta has a role in feto-maternal cholesterol metabolism through either synthesis or transplacental cholesterol flux. The potential for free cholesterol diffusion between mother and fetus and rates of cholesterol esterification and transfer between lipoproteins were...
Abstract
1. Lipid, apolipoprotein concentration and composition were determined in maternal venous and umbilical arterial and venous blood at delivery by elective Caesarean section in 13 full-term pregnancies and in 25 healthy non-pregnant females. The indications of Caesarean section were a previous Caesarean section or breech presentation. None of the women was in labour and there were no other complications of pregnancy or fetal distress. 2. The objectives of the study were to establish whether the placenta has a role in feto-maternal cholesterol metabolism through either synthesis or transplacental cholesterol flux. The potential for free cholesterol diffusion between mother and fetus and rates of cholesterol esterification and transfer between lipoproteins were determined and related to the differences in composition between fetal and maternal lipoproteins. 3. Pregnant women had raised levels of all lipid and lipoprotein fractions compared with control subjects. The greatest increases were in free cholesterol and triacylglycerol ( P < 0.0001). Lipoprotein (a) levels were significantly greater in the pregnant women [112(12.2) mg/l] than in the control women [50 (10.0) mg/l]. 4. The only significant correlation between maternal and fetal lipoprotein concentrations was in lipoprotein (a) levels ( r = 0.791, P = 0.002). In both umbilical venous and arterial blood, concentrations of very-low- and low-density lipoproteins, particularly apolipoprotein B, cholesteryl ester and triacylglycerol, were lower than in maternal blood ( P < 0.0001), but high-density lipoprotein levels were similar. 5. There was no umbilical arteriovenous differences in lipoprotein concentration or composition. This suggests that cholesterol synthesis or free cholesterol diffusion does not occur in the placenta. The relative concentrations of free cholesterol to phospholipid in maternal and fetal lipoproteins do not indicate the existence of a concentration gradient favouring free cholesterol diffusion across the placenta. 6. The esterification of free cholesterol was significantly reduced in maternal [17.7 (2.4) μmol h −1 l −1 , P < 0.001] and fetal [6.7 (3.5) μmol h −1 l −1 , P < 0.0001] compared with control [40.9 (13.2) μmol h −1 l −1 ] blood. 7. In fetal compared with maternal high-density lipoproteins the ratios cholesteryl ester/apoliproprotein A-I [0.84 (0.35) versus 0.40 (0.05), P < 0.01] and phospholipid/apolipoprotein A-I [1.66 (0.14) versus 0.58 (0.10), P < 0.0001] indicated lipid enrichment of these particles in the fetus. 8. Lipid enrichment of high-density lipoprotein is due in part to a marked reduction in transfer of cholesteryl ester in the fetus [1.0 (0.6) μmol h −1 l −1 ] compared with maternal [6.15 (1.3) μmol h −1 l −1 , P = 0.004] and control [17.3 (7.2) μmol h −1 l −1 , P < 0.0001] blood. 9. In conclusion, there was no evidence for involvement of the placenta in cholesterol metabolism during pregnancy. In fetal life high-density lipoproteins are lipid rich, partly because of a reduction in transfer of esterified cholesterol to other particles. Maternal and fetal lipoprotein levels are not correlated, although the results suggested that lipoprotein (a) levels may be related.
Articles
Shui-Ping Zhao, Arn M. J. M. Van den Maagdenberg, Ton F. F. P. Vroom, Ferdinand M. Van't Hooft, Jan A. Gevers Leuven, Louis M. Havekes, Rune R. Frants, Arnoud Van Der Laarse, Augustinus H. M. Smelt
Journal:
Clinical Science
Clin Sci (Lond) (1994) 86 (3): 323–329.
Published: 01 March 1994
...Shui-Ping Zhao; Arn M. J. M. Van den Maagdenberg; Ton F. F. P. Vroom; Ferdinand M. Van't Hooft; Jan A. Gevers Leuven; Louis M. Havekes; Rune R. Frants; Arnoud Van Der Laarse; Augustinus H. M. Smelt 1. The plasma lipoprotein profiles of eight members of a Dutch pedigree spanning three generations...
Abstract
1. The plasma lipoprotein profiles of eight members of a Dutch pedigree spanning three generations where two rare apolipoprotein E mutants, APOE*3(Cys-112→Arg; Arg-251→Gly) and APOE*2(Val-236 →Glu), segregate were analysed to determine whether the APOE mutants were associated with dyslipidaemia. 2. The proband, a 51-year-old Caucasian male, was a carrier of APOE*3(Cys-112→Arg; Arg-251→Gly) and his spouse was a carrier of APOE*2(Val-236→Glu). Four other family members were carriers of one or both of the mutant APOE genes. 3. The plasma cholesterol and triacylglycerol concentrations were markedly elevated in the proband and were classified as type IV hyperlipoproteinaemia. The plasma triacylglycerol concentration was moderately increased in a sister, who was a carrier of APOE*3(Cys-112→Arg; Arg-251→Gly), and in the son, who was a compound heterozygote for both mutant APOE alleles. Normal plasma lipid levels were observed in all other family members. In the plasma samples of the proband and his family members β-very-low-density lipoprotein was not detectable and the molar ratio of very-low-density lipoprotein-cholesterol to very-low-density lipoprotein-triacylglycerol was less than 0.9. The concentration of intermediate-density lipoprotein was within normal limits. 4. None of the family members carrying APOE*3-(Cys-112→Arg; Arg-251→Gly) and/or APOE*2(Val-236→Glu) exhibited lipoprotein abnormalities characteristic of familial dysbetalipoproteinaemia, although three family members carrying APOE*3-(Cys-112→Arg; Arg-251→Gly) showed hypertriglyceridaemia.
Articles
D. J. Stensel, A. E. Hardman, K. Brooke-Wavell, D. Vallance, P. R. M. Jones, N. G. Norgan, A. F. Winder
Journal:
Clinical Science
Clin Sci (Lond) (1993) 85 (6): 701–708.
Published: 01 December 1993
...D. J. Stensel; A. E. Hardman; K. Brooke-Wavell; D. Vallance; P. R. M. Jones; N. G. Norgan; A. F. Winder 1. The purpose of this study was to examine the influence of brisk walking on serum lipoprotein variables. 2. Seventy-two apparently healthy but physically inactive men (aged 42–59 years) were...
Abstract
1. The purpose of this study was to examine the influence of brisk walking on serum lipoprotein variables. 2. Seventy-two apparently healthy but physically inactive men (aged 42–59 years) were recruited. These men were normotensive non-smokers without a history of dyslipidaemia. Subjects were randomly allocated on a 2 to 1 basis into either a walking group ( n = 48) or a control group ( n = 24). Walkers followed a self-monitored programme of brisk walking for 1 year, whereas control subjects maintained their habitual lifestyle. 3. Treadmill walking tests were conducted to examine changes in fitness. Concentrations of serum lipids and lipoproteins were determined in fasting subjects. The amount of body fat was measured by body density. Circumferences at the waist and hip and skinfold thicknesses were used to determine the distribution of body fat. Dietary intakes were assessed by weighed food inventories. 4. Seven subjects (six walkers and one control subject) dropped out during the study. Walkers did an average of 28 (SEM 1.4; n = 42) min of brisk walking/day. This improved endurance fitness but did not influence serum concentrations of total cholesterol, high-density lipoprotein cholesterol, triacylglycerol, apolipoprotein A-1, apolipoprotein B or lipoprotein (a). Neither body mass nor the amount of body fat changed, relative to control subjects. 5. These data suggest that brisk walking does not modify lipoprotein metabolism in normolipidaemic middle-aged men.
Articles
Robert A. Hegele, George Zahariadis, Alexandra L. Jenkins, Philip W. Connelly, Hanoch Kashtan, Hartley Stern, Robert Bruce, David J. A. Jenkins
Journal:
Clinical Science
Clin Sci (Lond) (1993) 85 (3): 269–275.
Published: 01 September 1993
... apolipoprotein B-containing lipoprotein concentrations to increases in dietary fibre. 2. We studied 67 subjects (43 men and 24 women) who had taken part in parallel 2 week metabolic dietary studies involving either wheat bran or oat bran supplementation. Fasting blood lipid, lipoprotein and apolipoprotein...
Abstract
1. We hypothesized that differences within genes whose protein products are involved in apolipoprotein B metabolism could influence the response of plasma apolipoprotein B-containing lipoprotein concentrations to increases in dietary fibre. 2. We studied 67 subjects (43 men and 24 women) who had taken part in parallel 2 week metabolic dietary studies involving either wheat bran or oat bran supplementation. Fasting blood lipid, lipoprotein and apolipoprotein concentrations were measured at the start and end of the 2 week metabolic period. Genotypes were determined using DNA markers for the low-density lipoprotein receptor, apolipoprotein B, apolipoprotein CIII and hepatic lipase gene loci. 3. Reductions in plasma concentrations of apolipoprotein B were significantly different depending on genotype determined with a low-density lipoprotein receptor DNA marker ( P = 0.03). There was no significant variation in the reduction of plasma total cholesterol, low-density lipoprotein cholesterol or apolipoprotein B concentrations for alleles of other genes tested. 4. Thus, genetic variability is associated with inter-individual differences in the fibre-related reduction in plasma apolipoprotein B and apolipoprotein B-containing lipoprotein concentrations. Implementation of current dietary recommendations to reduce plasma lipoprotein levels with fibre may have variable effects in different individuals in part because of structural differences in candidate genes whose products are involved in lipoprotein metabolism.
Articles
C. A. Abbott, M. I. MacKness, S. Kumar, A. O. Olukoga, C. Gordon, S. Arrol, D. Bhatnagar, A. J. M. Boulton, P. N. Durrington
Journal:
Clinical Science
Clin Sci (Lond) (1993) 85 (1): 77–81.
Published: 01 July 1993
... the normal range. 6. These results are consistent with the view that butyrylcholinesterase may have a role in the altered lipoprotein metabolism in hypertriglyceridaemia associated with insulin insensitivity or insulin deficiency in diabetes mellitus. 24 3 1993 6 4 1993 © 1993 The...
Abstract
1. The activity of serum butyrylcholinesterase (‘pseudocholinesterase’, EC3.1.1.8) was investigated in 56 patients with type 1 diabetes mellitus, 51 patients with type 2 diabetes mellitus and 101 healthy control subjects. 2. Butyrylcholinesterase activity was significantly elevated in both type 1 (8.10 ± 3.35 units/ml) and type 2 (7.22 ± 1.95 units/ml) diabetes compared with the control subjects (4.23 ± 1.89 units/ml) ( P <0.001). 3. In the patients with type 1 and type 2 diabetes, serum butyrylcholinesterase activity was correlated with log serum fasting triacylglycerol concentration ( r = 0.41 and r = 0.43, respectively, P <0.001). In the type 2 population serum butyrylcholinesterase activity was also correlated with insulin sensitivity ( r = −0.51, P <0.001). 4. Serum butyrylcholinesterase activity was unrelated to age, gender, serum γ-glutamyltranspeptidase activity, body mass index, or treatment for diabetes in both the diabetic populations. 5. In 37 non-diabetic patients with butyrylcholinesterase deficiency serum triacylglycerol levels were in the normal range. 6. These results are consistent with the view that butyrylcholinesterase may have a role in the altered lipoprotein metabolism in hypertriglyceridaemia associated with insulin insensitivity or insulin deficiency in diabetes mellitus.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1992) 83 (3): 353–356.
Published: 01 September 1992
.... The plasma and erythrocyte cholesterol-to-phospholipid molar ratios remained closely correlated ( r = 0.77, P <0.01) before and after treatment, suggesting that S -adenosyl- l -methionine had not acted directly on the cells but rather had improved their lipoprotein milieu. Further support for this...
Abstract
1. S -Adenosyl- l -methionine is reported to improve serum liver function tests in chronic liver disease. Because liver disease is complicated by cholesterol deposition in hepatic and extrahepatic membranes, we have assessed whether oral administration of S -adenosyl- l -methionine to patients with hepatic disease can reverse the cholesterol enrichment of their erythrocytes. 2. The mean erythrocyte cholesterol-to-phospholipid molar ratio in 13 jaundiced patients was reduced 2 weeks after oral administration of S -adenosyl- l -methionine (from 0.874 ± 0.112 to 0.844 ± 0.102, P <0.05) with 10 of the patients (77%) showing a decrease. By contrast, only four of 11 untreated patients (36%) had a reduced erythrocyte cholesterol-to-phospholipid molar ratio after 2 weeks and the mean values did not differ. 3. The plasma and erythrocyte cholesterol-to-phospholipid molar ratios remained closely correlated ( r = 0.77, P <0.01) before and after treatment, suggesting that S -adenosyl- l -methionine had not acted directly on the cells but rather had improved their lipoprotein milieu. Further support for this concept was provided by following one patient, who initially failed to respond, during an additional 3 weeks of S -adenosyl- l -methionine administration. The plasma cholesterol-to-phospholipid molar ratio fell steadily from week 1 to week 5 and was accompanied by a progressive decrease in the erythrocyte cholesterol-to-phospholipid molar ratio. Moreover, the initially suppressed acetylcholinesterase activity of the erythrocyte membranes returned towards normal during this period. 4. This preliminary study is the first evidence in jaundiced patients that a drug can help to reverse the deposition of cholesterol in an extrahepatic membrane. It merits, therefore, placebo-controlled, crossover investigations into the therapeutic potential of S -adenosyl- l -methionine in chronic liver disease.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1992) 82 (5): 535–541.
Published: 01 May 1992
... acetylhydrolase activity and serum total cholesterol and low-density-lipoprotein-cholesterol concentrations in both subject groups. Although acetylhydrolase activity was most closely associated with the low-density-lipoprotein-cholesterol fraction, the activity for a given serum level of low-density-lipoprotein...
Abstract
1. Platelet-activating factor is inactivated in plasma by the action of a specific acetylhydrolase that cleaves the acetate moiety from the sn -2 position. Degradation was determined under optimized conditions and under conditions closer to those which may occur in vivo. The latter, or platelet-activating factor half-life, was measured by a modified method that is simple, inexpensive and reliable. 2. A hyperbolic relationship was found to exist between the two measures of degradation, the values in both normal subjects and patients with coronary artery disease falling on the tail of the hyperbola. Thus, there is an increase in platelet-activating factor half-life associated with a lowering of acetylhydrolase activity, but this increase is relatively small. 3. There were significant direct linear relationships between acetylhydrolase activity and serum total cholesterol and low-density-lipoprotein-cholesterol concentrations in both subject groups. Although acetylhydrolase activity was most closely associated with the low-density-lipoprotein-cholesterol fraction, the activity for a given serum level of low-density-lipoprotein-cholesterol was higher in patients with coronary artery disease.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1992) 82 (1): 1–8.
Published: 01 January 1992
...Keith N. Frayn; Simon W. Coppack © 1992 The Biochemical Society and the Medical Research Society 1992 adipose tissue coronary heart disease insulin insulin resistance lipoproteins non-esterified fatty acids triacylglycerol Clinical Science (1992) 82, 1-8 (Printed in Great Britain...
Articles
Peter H. Winocour, Paul N. Durrington, Monica Ishola, Chris Gordon, Julie Jeacock, David C. Anderson
Journal:
Clinical Science
Clin Sci (Lond) (1989) 77 (4): 369–374.
Published: 01 October 1989
...). Its role in lipid metabolism in IDDM is not clearly defined. We examined the relationships between serum lipid and lipoprotein concentrations and the response of circulating C-peptide to a test meal in 205 subjects with IDDM. 2. Lipid and lipoprotein levels and glycaemic control did not differ...
Abstract
1. Residual endogenous insulin secretion can be assessed by the circulating C-peptide concentration and is present in up to 15% of subjects with established insulin-dependent diabetes mellitus (IDDM). Its role in lipid metabolism in IDDM is not clearly defined. We examined the relationships between serum lipid and lipoprotein concentrations and the response of circulating C-peptide to a test meal in 205 subjects with IDDM. 2. Lipid and lipoprotein levels and glycaemic control did not differ significantly between patients with undetectable, low or high C-peptide responses. 3. High density lipoprotein (HDL) cholesterol and its subfractions were inversely related to concentrations of serum triacylglycerols ( P < 0.01–0.001), but not to C-peptide or glycated haemoglobin (HbA,) levels. Levels of HbA, and triacylglycerols were correlated with one another ( P < 0.01). Analysis of variance revealed that differences in gender and triacylglycerol concentrations were the most important determinants of HDL and HDL 2 cholesterol levels. C-peptide only exerted a weak effect on HDL 2 cholesterol levels and no significant predictors of HDL 3 cholesterol were found. 4. It is concluded that endogenous insulin secretion (assessed by C-peptide concentration) is relatively unimportant in modifying HDL metabolism in IDDM and that associated clinical features, in particular ambient hypertriglyceridaemia, are of greater importance.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1987) 72 (5): 549–556.
Published: 01 May 1987
...Robin J. Northcote; David Ballantyne 1. β-Adrenoceptor blocker therapy is known to cause disturbances of the lipoprotein profile. The long-term effects of β-adrenoceptor blockers and the influence of intrinsic sympathomimetic activity (ISA) has not been clearly defined. We measured serum...
Abstract
1. β-Adrenoceptor blocker therapy is known to cause disturbances of the lipoprotein profile. The long-term effects of β-adrenoceptor blockers and the influence of intrinsic sympathomimetic activity (ISA) has not been clearly defined. We measured serum lipoproteins during chronic β-adrenoceptor blockade in patients with stable angina pectoris treated with propranolol (without ISA) (n = 21) or pindolol (with ISA) ( n = 19). 2. No significant changes occurred in the lipoprotein profile of the patients taking pindolol. In those taking propranolol, very low density lipoprotein (VLDL) increased at 52 weeks ( P < 0.05) and total high density lipoprotein (HDL) decreased at 26 weeks ( P < 0.01) and at 52 weeks ( P < 0.05). However, HDL 2 rose significantly at 52 weeks ( P < 0.05). There was a corresponding increase in HDL 2/ HDL 3 ratio. 3. We conclude that pindolol is less likely to exert a harmful effect on plasma lipoproteins than β-adrenoceptor blockers without ISA.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1985) 68 (5): 581–587.
Published: 01 May 1985
...M. Boberg; L. B. Croon; I.-B. Gustafsson; B. Vessby 1. The fatty acid composition in platelet phospholipids and in the plasma lipid esters as well as the serum lipoprotein lipid concentrations were determined in 67 healthy male subjects in order to establish the relationships between blood lipids...
Abstract
1. The fatty acid composition in platelet phospholipids and in the plasma lipid esters as well as the serum lipoprotein lipid concentrations were determined in 67 healthy male subjects in order to establish the relationships between blood lipids and platelets. 2. A positive correlation was found between the concentrations of the triglyceride rich serum lipoprotein lipids and the relative percentage of saturated and monounsaturated fatty acids in plasma. The correlations were also positive between the serum high density lipoprotein-cholesterol concentration and the relative content of linoleic acid in the plasma cholesterol esters and phospholipids. 3. Negative correlations were found between the relative percentage of saturated and monounsaturated fatty acids in the plasma lipid esters versus linoleic acid in plasma and in the platelets. On the other hand there were positive correlations between linoleic acid in the plasma lipid esters and in the platelet phospholipids. These results indicate a direct dietary influence on the platelet phospholipid fatty acid composition. 4. The correlations between the fatty acids of the n −6 series within plasma and platelets as well as between plasma and platelets indicate that a high linoleic acid content is not associated with an increased arachidonic acid concentration. The results also indicate that the limiting metabolic step in the conversion of linoleic acid into arachidonic acid may be located at different levels in plasma and in the platelets.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1983) 64 (6): 637–642.
Published: 01 June 1983
... lipoprotein-cholesterol levels decreased markedly, but pre-exchange levels were not achieved within 2 weeks. High density lipoprotein-cholesterol and apolipoprotein A-I levels also fell but returned to the original concentration after only 5 days. 2. Platelet aggregation and [ 14 C]serotonin release were...
Abstract
1. Repeated plasma exchange was carried out on three young patients with severe familial hypercholesterolaemia. There was a 3 week interval between each exchange. After a single exchange, plasma cholesterol, apolipoprotein B and low density lipoprotein-cholesterol levels decreased markedly, but pre-exchange levels were not achieved within 2 weeks. High density lipoprotein-cholesterol and apolipoprotein A-I levels also fell but returned to the original concentration after only 5 days. 2. Platelet aggregation and [ 14 C]serotonin release were increased in all three patients and dropped by 20% and 13% respectively after a single plasma exchange. Platelet function in vitro returned to pre-exchange levels with similar kinetics to that observed with the low density lipoprotein concentration. On removal of 100 g of plasma cholesterol, after repeated exchanges, low density lipoprotein concentration and platelet function were significantly decreased in comparison with values before initiation of plasma exchange. in addition there was a marked regression of xanthoma in all three patients. 3. Since this procedure is instrumental in achieving a negative cholesterol balance as well as inhibiting hypersensitive platelets, it may well result in a downgrading of the atherosclerotic risk.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1982) 62 (2): 125–129.
Published: 01 February 1982
...J. P. D. Reckless; J. Stocks; G. Holdsworth © 1982 The Biochemical Society and the Medical Research Society 1982 apolipoproteins C-apoproteins. high-density lipoproteins hypertriglyceridaemia lipoproteins triglyceride-rich lipoproteins. very-low-density lipoproteins Clinical Science...
Articles
Studies of a Variant Very-Low-Density Lipoprotein with an Acquired Deficiency of Apolipoprotein C-II
Journal:
Clinical Science
Clin Sci (Lond) (1982) 62 (1): 93–100.
Published: 01 January 1982
...J. P. D. Reckless; J. Stocks; G. Holdsworth; D. J. Galton; A. J. Suggett; K. W. Walton 1. A variant very-low-density lipoprotein was associated with severe hypertriglyceridaemia. Urea—polyacrylamide gel electrophoresis of the tetramethylurea-soluble apolipoproteins of these very-low-density...
Abstract
1. A variant very-low-density lipoprotein was associated with severe hypertriglyceridaemia. Urea—polyacrylamide gel electrophoresis of the tetramethylurea-soluble apolipoproteins of these very-low-density lipoproteins (VLDL) showed that the apolipoprotein C-II content was less than 10% of that in VLDL from hypertriglyceridaemic (3–120 mmol/l) controls. 2. VLDL were incubated with bovine milk lipoprotein lipase (LPL) and a 9,10- 3 H-labelled triglyceride emulsion. The VLDL deficient in apolipoprotein C-II were a poor activator of LPL, compared with the effect of VLDL with normal content of apolipoprotein C-II obtained from either normal or hypertriglyceridaemic sera. 3. The efficacies of various VLDL as substrates for activated LPL were examined. Apolipoprotein C-II-deficient VLDL were a poor substrate for the activated enzyme compared with normal or hypertriglyceridaemic VLDL, and compared with an artificial triglyceride emulsion. 4. The abnormal VLDL were obtained from a subject with an IgG3 lambda myeloma protein. Intravenous infusion of normal plasma containing apolipoprotein C-II was followed by rapid, complete, but short-lived (5–10 days) clearance of serum triglyceride. The effect was observed on three occasions until treatment of the myeloma was effective. 5. The monoclonal protein behaved as a cryoglobulin, and formed large particle complexes with triglyceride-rich lipoproteins, especially at temperatures below 37°C. The apolipoprotein C-II deficiency, and consequent hypertriglyceridaemia, may be secondary to an autoantibody directed against apolipoprotein C-II. VLDL from relatives with hypertriglyceridaemia, but without myeloma, had normal apolipoprotein content, activated LPL, and were efficient substrates for the enzyme.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1981) 61 (s7): 437s–439s.
Published: 01 December 1981
...A. Meier; H. Schiffl; P. Weidmann; R. Mordasini; W. Riesen; C. Bachmann 1. The effect of treatment with a thiazide-like diuretic alone or combined with a β-adrenoceptor blocker on serum lipoproteins was investigated in 35 patients with essential hypertension. 2. In group I (18 patients), serum low...
Abstract
1. The effect of treatment with a thiazide-like diuretic alone or combined with a β-adrenoceptor blocker on serum lipoproteins was investigated in 35 patients with essential hypertension. 2. In group I (18 patients), serum low-density lipoprotein cholesterol was increased ( P < 0.001) during monotherapy with chlorthalidone (100 mg/day) but not during combined chlorthalidone-β-blocker therapy. 3. This tendency was similar in subgroups studied with an inverse sequence of drug administration. In subgroup I A (11 men), a 22% increase ( P < 0.01) in low-density lipoprotein cholesterol after 6 weeks of chlorthalidone was reversed after use of a β-blocker as well as chlorthalidone; in subgroup I B (five men, two post-menopausal women), low-density lipoprotein cholesterol was increased by 41% ( P < 0.05) above placebo values 6 weeks after withdrawal of the β-blocker from combination therapy. 4. In group II (18 men), low-density lipoprotein cholesterol was increased by 13% ( P < 0.025) after 4 weeks of monotherapy with clopamide (5 mg/day) but restored to control levels 4 weeks after addition of pindolol (10 mg/day). 5. No significant changes occurred during any treatment phase in high-density lipoprotein cholesterol. 6. Certain β-receptor blocking agents may prevent or reverse diuretic-induced increases in serum low-density lipoprotein cholesterol.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1981) 61 (5): 649–651.
Published: 01 November 1981
...R. F. Heller; N. E. Miller; B. Lewis; A. Vermeulen; Angela Fairney; V. H. T. James; A. V. Swan 1. A study of 150 middle-aged male industrial employees has shown significant positive correlations between plasma levels of high-density-lipoprotein (HDL) cholesterol and both serum testosterone and...
Abstract
1. A study of 150 middle-aged male industrial employees has shown significant positive correlations between plasma levels of high-density-lipoprotein (HDL) cholesterol and both serum testosterone and alcohol intake, and significant negative correlations between HDL cholesterol and both serum thyroxine and obesity. These associations persist when examined by multiple linear regression, indicating their independence. 2. Significant positive correlations are also shown between plasma triglyceride levels and both obesity and serum thyrotropic hormone (TSH) levels. 3. There are no evident relationships between serum oestrone or oestradiol and either HDL cholesterol or triglyceride levels, nor between any of the hormones and either total or low-density-lipoprotein (LDL) cholesterol. 4. Because of the potential importance in relation to coronary heart disease prevention, further studies are needed to try and understand the mechanisms of the associations between HDL cholesterol and obesity, alcohol intake and thyroid and sex hormone levels.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1981) 61 (2): 129–133.
Published: 01 August 1981
...D. N. Brindley © 1981 The Biochemical Society and the Medical Research Society 1981 atherosclerosis diabetes diet ethanol fatty liver fructose glucocorticoids insulin lipid metabolism lipoprotein lipase lipoproteins obesity l-α-phosphatidate phosphohydrolase sorbitol stress...
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1980) 58 (5): 419–421.
Published: 01 May 1980
...C. H. Bolton; LYN Jackson; C. J. C. Roberts; M. Hartog 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...
Abstract
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.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1979) 57 (s5): 109s–110s.
Published: 01 December 1979
..., after a change in the tertiary structure, to the plasma protease inhibitors α 2 -macroglobulin, inter-α-trypsin inhibitor and α 2 -antithrombin. It binds also to lipoprotein and an unidentified plasma protein. No binding was seen to more than 50 other studied plasma proteins. 6. The high-molecular...
Abstract
1. The precursor synthesis of renin, the storage form in the kidney and the submaxillary gland, and the molecular nature of the forms in plasma were studied in the mouse. 2. Renin is synthesized as a precursor (pre-prorenin) with a molecular weight of 50 000. 3. Renin is stored in the submaxillary gland and the kidneys as fully active renin with a molecular weight of 40 000. 4. The predominant form of renin in plasma is the active mol. wt. 40 000 form. High-molecular-weight forms of renin (800 000 and 70 000) are also present in plasma. 5. Pure 125 I-labelled mol. wt. 40 000 renin binds, after a change in the tertiary structure, to the plasma protease inhibitors α 2 -macroglobulin, inter-α-trypsin inhibitor and α 2 -antithrombin. It binds also to lipoprotein and an unidentified plasma protein. No binding was seen to more than 50 other studied plasma proteins. 6. The high-molecular-weight forms of renin in plasma may be complexes of renin with plasma protease inhibitors and lipoprotein.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1979) 56 (1): 71–76.
Published: 01 January 1979
...G. D. Calvert; H. M. James 1. We studied the turnover of low-density lipoprotein, density 1·031–1·056 kg/l, in five normal subjects and in four subjects with hyperlipoproteinaemia, using as tracer low-density lipoprotein labelled in the protein moiety with 131 I. We analysed data derived with and...
Abstract
1. We studied the turnover of low-density lipoprotein, density 1·031–1·056 kg/l, in five normal subjects and in four subjects with hyperlipoproteinaemia, using as tracer low-density lipoprotein labelled in the protein moiety with 131 I. We analysed data derived with and without a whole-body radioactivity counter. Four models were used, including the integrated rate equations of Nosslin. 2. In most patients all methods gave similar results for the fractional catabolic rate. Use of the integrated rate equations allowed us to calculate the fractional catabolic rate in 3–5 days compared with 12 days for a multicompartmental method using plasma activity alone. The integrated rate equations method was valid only in a steady metabolic state, and could apparently be used when there was minor tracer denaturation. It was probably invalid when there was major partial tracer denaturation. The degree of partial denaturation could be estimated from the whole-body radioactivity graph. The whole-body counter was quick to use, required low levels of radioactivity and avoided error-prone urine collection. 3. Estimates of the relative size of the intravascular and extravascular compartments derived by five different methods were similar in studies in which there was insignificant denaturation of tracer.
Articles
Journal:
Clinical Science
Clin Sci Mol Med (1977) 52 (1): 75–82.
Published: 01 January 1977
...J. Green; S. Carney 1. Electrophoresis of pre-stained lipoproteins on acrylamide-gel gradients has been carried out on serum from populations of control subjects and patients with ischaemic heart disease. The technique resolves components intermediate in position and, by inference, in size, between...
Abstract
1. Electrophoresis of pre-stained lipoproteins on acrylamide-gel gradients has been carried out on serum from populations of control subjects and patients with ischaemic heart disease. The technique resolves components intermediate in position and, by inference, in size, between very-low-density and low-density lipoproteins. 2. These central band components were found in 37% of a control population but the incidence varied with age and sex, being lowest in young males and highest in elderly males. 3. The incidence of central band components in patients with ischaemic heart disease was 64% (males) and 71% (females), and the difference between these figures and those for matched control subjects was highly significant. The intensity of central band components in the group with ischaemic heart disease was significantly greater than in the control group. 4. The presence and intensity of central bands show positive correlation with serum cholesterol and triglyceride values, but many patients showing the phenomenon have normal lipid values. Of patients with ischaemic heart disease 31% showed central band components and had normal lipid values.
Articles
Journal:
Clinical Science
Clin Sci Mol Med (1975) 49 (6): 617–620.
Published: 01 December 1975
... there was a reduction of plasma lecithin—cholesterol acyltransferase activity as well as decreased ability of the lipoprotein substrates of the enzyme to support esterification. 3. On this diet, there was no change in the proportion of the plasma cholesterol esterified but the plasma cholesterol and...
Abstract
1. Cholesterol esterification has been studied in the plasma of subjects on diets rich in saturated or polyunsaturated fat. 2. The diet rich in polyunsaturated fat was associated with lower rates of plasma cholesterol esterification in vitro. The data suggest that there was a reduction of plasma lecithin—cholesterol acyltransferase activity as well as decreased ability of the lipoprotein substrates of the enzyme to support esterification. 3. On this diet, there was no change in the proportion of the plasma cholesterol esterified but the plasma cholesterol and triglyceride concentrations were reduced.
Articles
Observations on the Passage of Apoproteins from Plasma Lipoproteins into Peripheral Lymph in Two Men
Journal:
Clinical Science
Clin Sci Mol Med (1975) 49 (5): 419–426.
Published: 01 November 1975
...D. Reichl; A. Postiglione; N. B. Myant; J. J. Pflug; M. Press 1. The passage of radioactive apolipoproteins into lymph draining the foot was investigated in two men, each given a single intravenous injection of low-density lipoprotein containing 131 I-labelled apoprotein B and of very-low-density...
Abstract
1. The passage of radioactive apolipoproteins into lymph draining the foot was investigated in two men, each given a single intravenous injection of low-density lipoprotein containing 131 I-labelled apoprotein B and of very-low-density lipoprotein containing 125 I-labelled apoprotein A and apoprotein C. 2. Protein-bound 125 I and 131 I appeared in the lymph of both subjects. Immunoelectrophoresis of lymph lipoproteins against anti-(high-density lipoprotein) and anti-(low-density lipoprotein) showed the presence of apo-high-density lipoprotein and apo-low-density lipoprotein with faster mobilities than plasma high-density and low-density lipoprotein respectively. Most of the protein-bound 131 I in lymph was recovered in the precipitin line formed by the apoprotein B-containing lipoprotein after immunoelectrophoresis. Polyacrylamide gel electrophoresis of the lymph lipoprotein fraction showed the presence of 125 I-containing bands with mobilities similar to those of the apoprotein A of high-density lipoprotein and of three of the fast-moving C apoproteins. 3. These results suggest that most, if not all, of the apoproteins of plasma lipoproteins reach the interstitial fluids and that some lipoproteins undergo modification during their passage into peripheral lymph.