Biomedical subjects

V Atger

Publications and source records attributed to V Atger.

At least 37 records · Page 2Linked to original sources

PubMed1996

Role of HDL phospholipid in efflux of cell cholesterol to whole serum: studies with human apoA-I transgenic rats.

Sera of transgenic rats expressing human apoA-I were tested for their ability to stimulate efflux of radiolabeled cholesterol from Fu5AH rat hepatoma cells. Expression of human apoA-I resulted in a dose-dependent increase in HDL, as measured by both HDL-cholesterol and HDL-phospholipid, and produced a decrease in rat apoA-I. In rats expressing high concentrations of human apoA-I (TgR[hAI]high, human apoA-I > 250 mg/dl), the increase in HDL-phospholipid was not proportional to the increase in human apoA-I, as illustrated by a HDL-PL/total apoA-I ratio of 0.84 +/- 0.19 compared to a ratio of 1.28 +/- 0.29 for control rats and of 1.28 +/- 0.39 for rats expressing low levels of human apoA-I (TgR[hAI]low, human apoA-I < 250 mg/dl). Compared to sera from control animals, efflux of cell cholesterol was increased by 26% in the sera from TgR[hAI]low, and by 76% in the TgR[hAI]high. An examination of the relationships between efflux and HDL-related parameters demonstrated a hyperbolic relationship between efflux and either HDL-cholesterol or HDL-apoA-I. In contrast, there was a strong linear association (r2 = 0.84) between cholesterol efflux and HDL-phospholipid, indicating that this parameter is the component of HDL that best reflects the serum's efflux efficiency. The importance of phospholipids in modulating cholesterol efflux was further explored by measuring the effect of supplementation of serum with dimyristoylphosphatidylcholine (DMPC) vesicles, apoA-I, or both DMPC vesicles and apoA-I. Whereas addition of human apoA-I had no effect on efflux, supplementation with DMPC vesicles produced a substantial increase in efflux that was further stimulated by the combination of DMPC vesicles and apoA-I. These results demonstrate that a major component of HDL that modulates cell cholesterol efflux is phospholipid.

Animals↗

PubMed1995

Reactivity of lecithin-cholesterol acyl transferase (LCAT) towards glycated high-density lipoproteins (HDL).

Hyperglycaemia in diabetic patients results in non-enzymatic glycation of plasma proteins, including lipoproteins such as high-density lipoproteins (HDL). We studied the effects of in vitro HDL glycation on the activity of lecithin-cholesterol acyl transferase (LCAT), a key enzyme in HDL plasma metabolism. LCAT was prepared from non-diabetic subjects and HDL by sequential density ultracentrifugation (in the density range of 1.063-1.21 g/ml) from both diabetic and non-diabetic patients. HDL from non-diabetic patients were glycated in vitro by incubating lipoproteins with 100 mmol/l glucose for various times at 37 degrees C with sodium cyanoborohydride as reducing agent. Glycation of HDL protein was quantified by measuring the percentage of derived amino acid residues using the TNBS assay. Kinetic parameters of LCAT were first determined using native HDL from non-diabetic patients and in vitro glycated HDL. With native HDL, Km and Vmax were 51.1 +/- 4.2 mumol/l (n = 8) and 12.9 +/- 2.4 nmol/ml/h (n = 8), respectively. Enzyme reactivity, calculated as the Vmax/Km ratio, was 0.25 +/- 0.04 h-1 (n = 8). In the case of moderate glycation (derived residues < 30%; n = 19) a significant increase in both Km (18.2 +/- 3.4%; mean +/- S.D.) and Vmax (9.3 +/- 2.4%) was observed. In contrast, with a high level of glycation (derived residues > 30%; n = 8), both parameters fell (Km, 25 +/- 6.3%; Vmax, 34.1 +/- 3.3%). In addition, whatever the level of glycation, enzyme reactivity was lower in the presence of in vitro glycated HDL. This decrease in LCAT reactivity was not due to a peroxidative process nor to an alteration of the protein and lipid composition of in vitro glycated HDL. It could, however, be explained by glycation of lysine residues in apolipoprotein A-I, which is the most potent activator of LCAT. In a second series of experiments, native diabetic HDL preparations were used as LCAT substrate. No alteration in Km values was observed, but there was a significant decrease in both Vmax (28%) and enzyme reactivity (32%). This difference in Km and Vmax alterations between native diabetic HDL and in vitro glycated HDL with low levels of glycation might be explained by the impact of physiological modifications, other than glycation, which could differently affect the chemicophysical properties of HDL in diabetic patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes Mellitus↗

PubMed1995

High-density lipoprotein subfractions as markers of early atherosclerosis. PCVMETRA Group. Prévention Cardio-Vasculaire en Medecene du Travail.

Although the inverse relation between high-density lipoprotein (HDL) cholesterol concentration and the risk of ischemic heart disease is well established, little is known about the relation of HDL subfractions HDL2 and HDL3 or lipoprotein A-I and A-I-A-II to extracoronary disease, particularly at its silent phase before the appearance of clinical lesions. We investigated the potential influence of HDL subfractions as risk markers, among the other main lipid and nonlipid risk factors, by assessing early atherosclerotic plaques detected by 3 ultrasound imaging sites in 181 hypercholesterolemic symptom-free men. No plaques were found in 36% of the patients, but plaques were found at carotid, aortic, and femoral sites in 24%, 40%, and 46% of subjects, respectively. Data were analyzed using univariate comparisons and multiple logistic regression. According to the logistic analysis, plaques were associated (1) with blood pressure (p = 0.008) and low-density lipoprotein (LDL) cholesterol (p = 0.02) in the carotid arteries; (2) with age (p = 0.0005), triglycerides (p = 0.002), and cigarette smoking (p = 0.02) at the aortic site; and (3) inversely with HDL3 cholesterol (p = 0.0008) and positively with cigarette smoking (p = 0.004), and age (p = 0.04) in the femoral site. The number of arterial sites affected (0, 1, 2, and 3) by plaques was inversely associated with HDL3 cholesterol (p = 0.001), and positively associated with smoking (p = 0.002), blood pressure (p = 0.002), LDL cholesterol (p = 0.003), and age (p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Cholesterol efflux potential of sera from mice expressing human cholesteryl ester transfer protein and/or human apolipoprotein AI.

The ability of whole serum to promote cell cholesterol efflux and the relationships between apoprotein and lipoprotein components of human serum efflux have been investigated previously (de la Llera Moya, M., V. Atger, J.L. Paul, N. Fournier, N. Moatti, P. Giral, K.E. Friday, and G.H. Rothblat. 1994. Arterioscler. Thromb. 14:1056-1065). We have now used this experimental system to study the selective effects of two human lipoprotein-related proteins, apoprotein AI (apo AI) and cholesteryl ester transfer protein (CETP) on cell cholesterol efflux, when these proteins are expressed in transgenic mice. The percent efflux values for cholesterol released in 4 h from Fu5AH donor cells to 5% sera from the different groups of mice were in the order: background = human apo AI transgenic (HuAITg) > human CETP transgenic (HuCETPTg) > human apo AI and CETP transgenic (HuAICETPTg) >> apo AI knockout mice. In each group of mice a strong, positive correlation (r2 ranging from 0.64 to 0.76) was found between efflux and HDL cholesterol concentrations. The slopes of these regression lines differed between groups of mice, indicating that the cholesterol acceptor efficiencies of the sera differed among groups. These differences in relative efficiencies can explain why cholesterol efflux was not proportional to the different HDL levels in the various groups of mice. We can conclude that: (a) HDL particles from HuAITg mice are less efficient as cholesterol acceptors than HDL from the background mice; (b) despite a lower average efflux due to lower HDL cholesterol concentrations, HDL particles are more efficient in the HuCETPTg mice than in the background mice; and (c) the coexpression of both human apo AI and CETP improves the efficiency of HDL particles in the HuAICETPTg mice when compared with the HuAITg mice. We also demonstrated that the esterification of the free cholesterol released from the cells by lecithin cholesterol acyltransferase in the serum was reduced in the HuAITg and AI knockout mice, whereas it was not different from background values in the two groups of mice expressing human CETP.

Animals↗

PubMed1995

[Value of transgenic mouse as model for the study of human lipoprotein metabolism].

Lipoprotein transport genes have been used to make either transgenic or knockout mice with altered lipoprotein levels and metabolism. These models have provided information in at least three major issues. First, transgenic mice allow to study gene expression regulation. This approach has been helpful in identifying tissue specific expression of two clusters of apolipoprotein genes apo E/CI/CII and apo AI/CIII/AIV. Another example is the identification of a cis-acting region controlling transcription of the CETP gene in response to diet. Second, transgenic mice model provides relevant insights into lipoprotein metabolism: the structural role of human apo AII, the effect of apo AI on HDL subfractions distribution, the contribution of apo CIII to hypertriglyceridemia, and by contrast of apo E in the clearance of atherogenic TG rich lipoproteins, the role of CETP in the balance of LDL and HDL concentration and distribution. Finally, certain strains of mice under specific conditions of diet develop atherosclerotic lesions which have been shown to be reduced in human apo AI transgenic animals. However, the best mouse model for further investigation of human atherosclerosis seems to be apo E knockout mice.

Animals↗

PubMed1994

Structural changes of high-density-lipoprotein apolipoproteins following incubation with human polymorphonuclear cells.

Based on the analogy in mechanisms and events between the pathogenesis of atherosclerosis and the inflammatory reaction, we investigated the impact of human polymorphonuclear leukocyte (PMN) degranulation and oxidative process on high-density-lipoprotein (HDL) structure. HDL were incubated (37 degrees C) with PMN at a physiological ratio (370 nmol cholesterol-HDL/ml with 2 x 10(6) PMN/ml) for 15, 30 and 60 min with or without stimulating agent. PMN activation was assessed by measurement of superoxide anion generation and elastase production, which both reached peak concentration at 15 min. HDL apolipoproteins (apo) analysed by immunoblotting after SDS/PAGE and electrofocusing evidenced the following modifications: (a) a slow hydrolysis of apo AII and apo Cs; (b) a rapid hydrolysis of apo E; (c) a change in apo AI isoform distribution with an increase in the most acidic isoform (AI-2) at the expense of a less acidic form (AI-1); (d) a shift of the major apo AII isoform into two more basic forms. In contrast, no quantifiable lipid modification nor lipid oxidation, assessed by thiobarbituric-acid-reactive substances (TBARS) were noted. Despite a lack of variation of TBARS, a decrease in HDL vitamin E content by 80% was observed. Since this decrease was prevented by addition of superoxide dismutase in the medium, we concluded the occurrence of an oxidative process affecting HDL. Experiments with proteolytic inhibitors showed that elastase caused the proteolytic cleavage of apolipoprotein E, AII and Cs. In contrast, apo AI modification might involve both oxidative and proteolytic processes.

Amino Acid Sequence↗

PubMed1994

Influence of HDL subfractions on erythrocyte aggregation in hypercholesterolemic men. PCVMETRA Group.

Recent studies have suggested that rheological mechanisms may be involved in the pathogenesis of ischemic syndromes in hyperlipidemias. We investigated the association between erythrocyte aggregation and components of lipoproteins in the blood of 60 normotensive, hypercholesterolemic men aged 45 +/- 8 years. The rheological parameters assessed were aggregation index (AI) and disaggregation shear rate threshold (gamma t) as determined by laser reflectometry, plasma fibrinogen, total serum protein, and hematocrit. The lipoprotein variables included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol and its subfractions HDL2 cholesterol and HDL3 cholesterol, apolipoprotein (apo) B, apoA-I, HDL particles containing apoA-I without apoA-II (LpA-I), and HDL particles containing both apoA-I and apoA-II (LpA-I/A-II). Covariables considered for possible confounding effects were age, body mass index, and smoking behavior. Fibrinogen, total serum protein, and both aggregation parameters (AI and gamma t) were elevated in this hypercholesterolemic population. Univariate analysis showed that both AI and gamma t correlated positively with fibrinogen (P < .001) and total serum protein (P < .01) and negatively with HDL2 cholesterol (P < .01) and LpA-I (P < .01); gamma t also provided a positive correlation with LpA-I/A-II (P < .05). A multivariate model analysis demonstrated that HDL2 cholesterol, LpA-I, and LpA-I/A-II also emerged as significant factors influencing erythrocyte aggregation; 60% to 68% of the variance of AI and 47% to 64% of the variance of gamma t could be explained by these factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

A cell culture system for screening human serum for ability to promote cellular cholesterol efflux. Relations between serum components and efflux, esterification, and transfer.

A cell culture system was employed to test a large number of samples of human serum for the ability to stimulate the efflux of cell cholesterol. The extent of efflux obtained with each specimen was correlated with the serum concentrations of cholesterol, triglycerides, apoprotein (apo) B, apo A-I, apo A-II, and lipoprotein subfractions (ie, high-density lipoprotein2 [HDL2], HDL3, lipoprotein [Lp] A-I, and LpA-I:A-II). In addition, the subsequent esterification of the released cholesterol and the distribution of the synthesized exogenous cholesteryl esters between HDL and low-density lipoprotein/very-low-density lipoprotein provided estimates of the lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities of each serum. The values for these activities were analyzed for correlations with cell efflux and the various serum parameters. Cell cholesterol efflux best correlated with serum total HDL cholesterol values. HDL2 and HDL3 correlated about equally well with efflux, whereas LpA-I demonstrated a much greater association with efflux than did LpA-I:A-II. Analysis of the data by partial correlation analysis indicated that HDL3 and LpA-I were the HDL subfractions most closely associated with efflux. Esterification of the released radiolabeled cholesterol was strongly and positively correlated with serum triglyceride concentrations and negatively related to the serum concentrations of HDL2. There was no relation between esterification values, which reflect LCAT activity, and efflux. The transfer of the labeled cholesteryl esters between HDL and apoB-containing lipoproteins was used as a measure of CETP activity and demonstrated a pattern in which all apoB-related parameters were positively correlated to transfer of esterified cholesterol, and all HDL associated parameters, particularly HDL3, were negatively related to transfer. No relations were observed between efflux, esterification, and transfer.

Adult↗

PubMed1994

A relationship between aortic stiffness and serum HDL3 cholesterol concentrations in hypercholesterolaemic, symptom-free men. The PCVMETRA Group (Groupe de Prévention Cardiovasculaire en Médecine du Travail).

OBJECTIVE: We set out to evaluate the relationship between aortic stiffness and serum lipids and lipoprotein fractions, including high-density-lipoprotein (HDL) cholesterol subfractions. METHODS: One hundred and five asymptomatic, normotensive, untreated, hypercholesterolaemic men underwent measurement of aortic pulse-wave velocity (PWV) by mecanography and assay of total cholesterol, triglycerides, HDL cholesterol and its subfractions (HDL2 cholesterol and HDL3 cholesterol), determined by electrophoresis. RESULTS: PWV was related to HDL cholesterol (r = 0.21, p = 0.05) and more specifically to HDL3 cholesterol subfraction (r = 0.29, p < 0.01). The latter association remained significant after adjustment for systolic blood pressure and age. Multivariate analysis demonstrated an independent association of PWV (r2 = 0.27, P < 0.001) with age, systolic blood pressure and HDL3 cholesterol. CONCLUSION: Although hypercholesterolaemia was not accompanied by increased aortic rigidity, there was a positive relationship between PWV and HDL cholesterol and between PWV and HDL3 cholesterol independently of the influence of age and systolic blood pressure on PWV. These results suggest that, in hypercholesterolaemic men, HDL3 could, in addition to its anti-atherogenic property, have a prosclerotic stiffening effect. This duality could explain why, in clinical studies, although the level of the HDL2 subfraction is frequently associated with a lower incidence of coronary artery disease, results for the HDL3 subfraction are less convincing and remain equivocal.

Adult↗

PubMed1994

[Vitamin E: metabolism and role in atherosclerosis].

Vitamin E is the term used for eight naturally occurring fat-soluble nutrients. Alpha-tocopherol predominates in many species and has the highest biological activity. Vitamin E is absorbed via the lymphatic pathway and transported in association with CM. Vitamin E is carried in plasma by lipoproteins. It is secreted by the liver in nascent VLDL with a preferential incorporation of alpha-tocopherol. Most of the plasma vitamin E is in LDL and in HDL. Vitamin E is exchanged readily between lipoproteins: tocopherol in HDL readily transfers to apolipoprotein B-containing lipoproteins (VLDL, LDL), with little return of tocopherol from the apolipoprotein B-containing lipoproteins to HDL. The mechanisms of tissue uptake of vitamin E from the lipoproteins is poorly understood. This uptake may occur during catabolism of triacylglycerol-rich lipoproteins by the activity of lipoprotein lipase, via the LDL receptor or by nonreceptor-mediated uptake. Vitamin E may act to prevent the initiation/progression of spontaneous atherosclerosis. This concept is based on in-vitro data: vitamin E influences the responses of cells (vascular endothelial cells, leukocytes, vascular smooth muscle cells) and the modification of lipoproteins (especially LDL) which, at least in principle, could contribute to the initiation/progression of spontaneous atherosclerosis. In vivo studies are clearly required to establish the extent and mode of vitamin E's antiatherosclerotic impact and, hence, its therapeutic potential.

Arteriosclerosis↗

PubMed1994

Abnormalities of lipid metabolism and arterial rigidity in young subjects with borderline hypertension.

Plasma lipoprotein levels and carotid-femoral pulse wave velocity, used as a marker of aortic rigidity, were evaluated in 53 young subjects with borderline hypertension by comparison with normotensive controls of the same age and body surface area. Subjects with body weight excess, exaggerated alcohol intake, and/or tobacco consumption were excluded from the study. Borderline hypertensive patients were characterized by significantly higher values of pulse wave velocity and plasma levels of glucose, total cholesterol, high density lipoprotein subfraction HDL3, apolipoprotein B, and lipoprotein (a). There were no group/sex interactions. A significant dyslipidemia was observed in 13 males of the 53 borderline hypertensive subjects. Only in this subgroup did subjects exhibit a strong positive relationship between pulse wave velocity and either plasma total cholesterol or apolipoprotein B. The correlation was observed even after adjustment for blood pressure. The study provides evidence that, in young males with borderline hypertension, some abnormalities of plasma lipoproteins requiring treatment may be present and are associated with an increased stiffness of the arterial wall.

Adolescent↗

PubMed1993

Elevated high density lipoprotein concentrations in heart transplant recipients are related to impaired plasma cholesteryl ester transfer and hepatic lipase activity.

Accelerated atherosclerosis is a major complication of heart transplantation, and is frequently associated with a dyslipoproteinemia characterized by a paradoxical increase in HDL-cholesterol concentration. To define this abnormality, the lipoprotein profiles of 25 heart transplant recipients (HTR) were analyzed and compared with those of 26 control subjects. HDL, as separated on the basis of density in 3 subfractions, were increased in concentration: HDL2: +51%, HDL3a: +29%, HDL3b: +32%. HDL2 and HDL3a displayed an enrichment in surface components, phospholipids, unesterified cholesterol and apo E, leading to an increased size compared with subfractions of similar density in the controls. The major steps of plasma HDL metabolism were investigated: cholesterol esterification (LCAT activity), cholesteryl ester transfer to apo B-containing lipoproteins (CETP) and the hepatic hydrolysis of HDL components (HL activity). We demonstrated a partial deficiency in CETP (-28%) and hepatic lipase (-36%) activities with normal LCAT activity. Correlations in total study population (HTR plus controls) evidenced negative associations between CETP activity and HDL3a concentrations and between HL activity and HDL2-cholesterol as a percent of total HDL-cholesterol. Therapeutic agents used in post transplantation treatment such as glucocorticoids and/or cyclosporine may be speculated thus to affect both CETP and HL activities and, by arresting the HDL cycle in a CE-saturated state, do decrease the efficiency of reverse cholesterol extraction at the site of the graft.

Apolipoproteins↗

PubMed1992

Serum Lp(a) as a discriminant marker of early atherosclerotic plaque at three extracoronary sites in hypercholesterolemic men. The PCVMETRA Group.

To investigate the role of lipoprotein (a) (Lp[a]) as an atherogenic condition related to hypercholesterolemia, we studied the serum concentration of Lp(a) as measured by immunonephelometry in relation to the presence of asymptomatic echographic plaques in the peripheral arteries of 103 untreated hypercholesterolemic, normotensive, middle-aged men. Plaque was found at carotid, aortic, and femoral sites in 36%, 51%, and 53% of subjects, respectively. The Lp(a) level was higher in the group with carotid plaques than in the group without (0.29 +/- 0.20 versus 0.17 +/- 0.14 g/l, p < 0.01), not significantly higher in the group with aortics plaque than in the group without (0.24 +/- 0.19 versus 0.19 +/- 0.16 g/l), and not different between groups with and without femoral plaques (0.21 +/- 0.18 versus 0.22 +/- 0.17 g/l). A logistic regression analysis confirmed that Lp(a) was associated with carotid plaques (p = 0.004), independent of other risk factors. However, in patients with low density lipoprotein cholesterol values above the group median value (4.7 mmol/l), Lp(a) was associated not only with carotid plaques (p < 0.01) but also with aortic plaques (p < 0.05), as well as with the number of diseased sites (p = 0.02). In contrast, in patients with low density lipoprotein cholesterol levels below or equal to 4.7 mmol/l, Lp(a) only remained associated with carotid plaques (p < 0.05). Thus, in symptom-free, hypercholesterolemic men, early atherosclerosis was influenced by serum Lp(a), particularly in the carotid arteries, as well as by the presence of a higher level of low density lipoprotein cholesterol.

Adult↗

PubMed1992

Coronary calcification and its relation to extracoronary atherosclerosis in asymptomatic hypercholesterolemic men. The PCV METRA Group.

BACKGROUND: The prevalence of coronary calcifications and extracoronary plaques was studied in patients with asymptomatic hypercholesterolemia. METHODS AND RESULTS: Ultrafast computed tomography for coronary calcification (presence or absence: calcium score) and echographic assessment of carotid, aortic, and femoral plaques were performed in 111 hypercholesterolemic men: 65% had coronary calcification, 72% had extracoronary plaque. The two lesions were associated as: 1) compared with subjects without coronary calcification, those with calcification had a higher prevalence of aortic (p less than 0.05) and femoral (p less than 0.01) plaque and of two diseased sites (p less than 0.05); 2) the prevalence of coronary calcification was higher in the presence than in the absence of aortic (p less than 0.05) or femoral (p less than 0.01) plaque and higher in two (p less than 0.01) and three diseased (p less than 0.05) sites than in no diseased site; 3) the calcium score was higher in the presence than in the absence of carotid (p less than 0.05), aortic (p less than 0.05), or femoral (p less than 0.001) plaque, higher in two (p less than 0.001) and three diseased (p less than 0.05) sites than in no diseased sites, and higher in two (p less than 0.01) than in one diseased site; and 4) the calcium score correlated with femoral plaque (p less than 0.001). Overall, the presence of two or three diseased extracoronary sites versus no or one diseased site showed a power of 78% for predicting coronary calcification. Coronary calcium score correlated with age (p less than 0.01) and triglycerides (p less than 0.05). CONCLUSIONS: The close relation between coronary calcium and extracoronary plaques suggests that echography of extracoronary vessels could aid in the screening of coronary atherosclerosis in high-risk, asymptomatic individuals.

Adult↗

PubMed1992

[Hypertension has no effect on coronary calcifications in asymptomatic patients with hypercholesterolemia].

Since calcium in coronary artery walls is considered as an indicator for atherosclerosis, we used ultrafast computed tomography to quantify it non invasively in 111 hypercholesterolemic men. They were selected at worksite by a cholesterol screening program, had total cholesterol (TC) above 5.2 (6.88 +/- 0.82, SD) mmol/l, were aged from 30 to 63 (46 +/- 5 years), had never been treated with lipid lowering or antihypertensive drug, and had no clinical coronary heart disease. Body mass index, blood pressure, smoking and other serum lipids as HDL cholesterol, triglyceride (TG) were evaluated. Calcium score of proximal coronary arteries was calculated on 30 contiguous 3 mm slices from areas and peak density of calcium lesions. The mean score was 30 +/- 69 and ranged from 0 to 440. A zero score was found in 39 subjects who differed from the 72 others only by TG levels (1.44 +/- 0.60 vs 1.85 +/- 0.80; p < 0.05). A multiple regression analysis showed that elevated calcium score was associated independently to age (F = 6.6; p < 0.05) and TG (F = 6; p < 0.05) but not to blood. Thus 65% of these asymptomatic subjects had a non-zero calcium score in coronary arteries. Elevated calcium score was influenced independently by age and triglyceride level, but not by other risk factors, such as blood pressure. This potential adverse effect of moderate triglyceride elevation on large coronary arteries merits attention in the assessment of the risk of coronary heart disease.

Adult↗

PubMed1991

Cholesterol distribution between high-density-lipoprotein subfractions HDL2 and HDL3 determined in serum by discontinuous gradient gel electrophoresis.

We used discontinuous gradients of polyacrylamide gel to determine the high-density-lipoprotein (HDL) subfractions HDL2 and HDL3 of serum lipoproteins. Serum (40 microL) prestained with Sudan Black was electrophoresed in cylindrical tubes over successive layers of 3.5%, 6%, 13%, and 17.5% acrylamide gels in a Tris.glycine buffer (3-4 h, 300 V). Very-low- (VLDL) and low-density lipoprotein (LDL) were retained by the 3.5% and 6% gels. HDL2 was concentrated at the interface between the 13% and 17.5% gels, and HDL3 migrated into the 17.5% gel. The distribution between HDL2 and HDL3 was obtained by densitometric scanning. Application of the respective percentages to HDL cholesterol assayed after phosphotung-state-Mg2+ precipitation of VLDL and LDL gave calculated concentrations of HDL2 and HDL3 cholesterol. The calculated values for HDL2 cholesterol were in excellent agreement with those for HDL2 isolated by ultracentrifugation (r = 0.920 for n = 120 sera; differences nonsignificant by Student's paired t-test). Besides being highly discriminating, the method is rapid, easily performed, and economical.

Cholesterol↗

PubMed1990

Distribution of HDL2 and HDL3 in a random population of healthy French males and females--evaluation by a two-step precipitation procedure.

A rapid and reliable method for the determination of HDL2 and HDL3 cholesterol is described. The Apo B containing fractions (VLDL, IDL, LDL) were precipitated by addition of dextran sulfate (Mr 500,000) to 2 mmol/l final concentration followed by MgCl2 to a final concentration of 0.05 mol/l. The supernatant, was brought to 6 mmol/l dextran sulfate and 0.250 mol/l MgCl2 to precipitate HDL2. Cholesterol determination on total serum and both supernatants yielded the concentrations of Apo B-associated cholesterol, total HDL, HDL2 and HDL3 cholesterol. The application of this technique to a random population of healthy French people gave HDL-cholesterol values of 1.35 and 1.54 mmol.l-1, respectively, in 93 males and 95 females (p less than 0.001). All of the difference was attributable to HDL2 (0.43 vs 0.65 mmol.l-1, p less than 0.001) while HDL3 were almost identical at 0.92 and 0.91 nmol.l-1. These values are in good agreement with previously reported figures for French individuals, but markedly higher in males than values reported from North America.

Apolipoproteins A↗

PubMed1990

Serum lipid abnormalities in heart transplant recipients: predominance of HDL2-like particles in the HDL pattern.

Accelerated coronary atherosclerosis is a major risk limiting long-term survival after heart transplantation and is commonly associated with dyslipoproteinemia even in subjects who were not dyslipoproteinemic before intervention. The purpose of this study was to analyse the abnormalities in the lipid profiles of 2 different groups of heart-transplanted males: 18 subjects with underlying ischemic heart disease (IHD) and 19 subjects with non-obstructive cardiomyopathy of unknown aetiology (CM). Both groups were compared to 33 healthy males. All patients were under immunosuppressive therapy including prednisone, cyclosporin A and azathioprine. A moderate hyperlipidemia was found in all transplant recipients, associated with high HDL-cholesterol concentrations in the CM group (1.80 +/- 0.37 vs. 1.29 +/- 0.23 mmol/l) and normal HDL-cholesterol levels in the IHD group (1.40 +/- 0.23 mmol/l). HDL subfractionation showed a marked increase in HDL2-cholesterol (CM: 1.12 +/- 0.32; IHD: 0.69 +/- 0.28; control: 0.40 +/- 0.17 mmol/l) while HDL3-cholesterol was significantly lower than in the control group. Analysis of HDL particle sizes showed in all transplant subjects an increase of an intermediate size particle HDL2a (diameter 9.0 +/- 0.10 nm) which is a minor form in control subjects. In the CM group, both the common HDL2b (10.2 +/- 0.13 nm) and HDL2a were abundant in 13 of 17 patients. The pattern was more heterogeneous in the IHD group but witnessed to a high frequency of HDL2a particles either alone (5/14) or associated with larger HDL2b (4/14) or with small HDL3 (4/14).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathies↗