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Biomedical subjects

B Föger

Publications and source records attributed to B Föger.

At least 19 recordsLinked to original sources
PubMed1997

High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithin-cholesteryl acyltransferase.

A subset of patients with high plasma HDL concentrations have enhanced rather than reduced atherosclerosis. We have developed a new transgenic mouse model overexpressing human lecithin-cholesteryl acyltransferase (LCAT) that has elevated HDL and increased diet-induced atherosclerosis. LCAT transgenic mouse HDLs are abnormal in both composition and function. Liver uptake of [3H]cholesteryl ether incorporated in transgenic mouse HDL was reduced by 41% compared with control HDL, indicating ineffective transport of HDL-cholesterol to the liver and impaired reverse cholesterol transport. Analysis of this LCAT-transgenic mouse model provides in vivo evidence for dysfunctional HDL as a potential mechanism leading to increased atherosclerosis in the presence of high plasma HDL levels.

Animals↗
PubMed1996

Effects of pancreas transplantation on distribution and composition of plasma lipoproteins.

In type I (insulin-dependent) diabetic patients, peripheral hyperinsulinemia due to subcutaneous insulin treatment is associated with increased high-density lipoprotein (HDL) cholesterol, and also with an altered surface composition of HDL. Pancreas grafts also release insulin into the systemic rather than into the portal venous system, giving rise to pronounced peripheral hyperinsulinemia. We hypothesized that if peripheral hyperinsulinemia is responsible for high HDL cholesterol and/or altered surface composition of HDL in diabetic subjects, similar changes in the lipid profile should be present in pancreas-kidney transplant recipients (PKT-R). Using zonal ultracentrifugation, we isolated HDL2, HDL3, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) from fasting plasma of 14 type I diabetic PKT-R, eight nondiabetic kidney transplant recipients (KT-R), and 14 healthy control subjects and determined the level and composition of the above lipoproteins. HDL2 cholesterol was increased in PKT-R as compared with KT-R and healthy controls (both P < .05), whereas HDL3 cholesterol was unchanged. However, an altered lipoprotein surface composition was evident in PKT-R: HDL2, HDL3, and LDL were enriched in unesterified cholesterol ([UC] PKT-R v KT-R, P=.13, P < .005, and P < .05, respectively; PKT-R v controls, all P < .005); HDL2 was enriched in phospholipids; and LDL was depleted of phospholipid. KT-R, in contrast, showed no changes in lipoprotein surface composition but a substantial triglyceride enrichment of HDL2 as compared with PKT-R and healthy controls (both P < .05). LDL size as determined by gradient gel electrophoresis was increased in PKT-R compared with controls (P < .005). The plasma concentration of cholesteryl ester (CE) transfer protein (CETP), involved also in phospholipid transfer, was increased in both transplant groups compared with healthy controls (both P < .05). Insulin concentrations in fasting plasma were directly related to CETP levels and to the weight-percentage of UC in HDL3, and inversely to the weight-percentage of phospholipids in LDL (all P < .05). We explain the increase in HDL2 cholesterol and LDL size in PKT-R by their high lipoprotein lipase (LPL) activity conferring an excellent capacity to clear chylomicron triglycerides. Effective handling of postprandial triglycerides, high HDL2 cholesterol, and predominance of LDL pattern A, respectively, are established indicators of a low risk of atherosclerosis. However, it is presently unclear what effects the compositional changes on the surface of HDL and LDL may have on cardiovascular risk in clinically stable PKT-R.

Adult↗
PubMed1996

Relationship of plasma cholesteryl ester transfer protein to HDL cholesterol. Studies in normotriglyceridemia and moderate hypertriglyceridemia.

To evaluate the independent effect of cholesteryl ester transfer protein (CETP) on HDL concentrations in humans, we measured lipids, lipoproteins, postprandial lipemia after an oral fat load, CETP mass, and the activities of CETP, lipoprotein lipase (LPL), and hepatic lipase in 16 healthy, normotriglyceridemic men and in 23 men with moderate, primary hypertriglyceridemia on an American Heart Association Step I diet. Fasting triglycerides and postprandial lipemia were increased and HDL cholesterol (HDL-C) was decreased in hypertriglyceridemic men compared with control subjects (P < .001). In the normotriglyceridemic group, CETP mass (P < .001) and activity (P < .005) were directly related to LPL activity After statistical adjustment for this close association, no significant relationship of CETP to HDL-C independent of LPL activity could be demonstrated in the normotriglyceridemic subjects. In contrast, CETP was unrelated to LPL activity in the hypertriglyceridemic subjects, but CETP concentrations showed a close inverse relationship to HDL-C (r = -.504, P = .014). Structural equation modeling of the association structures between HDL and fasting and postprandial triglycerides, endothelial lipases, and CETP in both groups indicated that the overall regression models for the two groups differed (P < .05). Specifically, the associations between CETP mass and activity and HDL-C differed between both groups (both P < .01). We conclude that high-normal CETP levels lower HDL-C in nonsmoking, nonobese men with moderate, primary hypertriglyceridemia on a hypolipidemic diet, but not in healthy, normotriglyceridemic men on an unrestricted diet. Thus, variation in CETP plasma concentrations may contribute to the high-triglyceride, low-HDL phenotype.

Adult↗
PubMed1995

[Effect of pancreas transplantation on triglyceride metabolism].

Transplantation of pancreatic gland with systemic venous drainage of the graft causes elevated plasma levels of insulin. To examine lipid metabolism triglyceride clearance capacity, lipolytic enzymes, plasma lipids and lipoproteins were quantified in pancreas-kidney transplant recipients and compared them to lipid parameters of healthy controls and those of patients who had received only kidney transplants. Eleven pancreas-kidney transplant recipients with type I diabetes, 9 non-diabetic kidney transplant recipients as controls for the effects of immunosuppressive medication, and 11 healthy controls were studied. In pancreas-kidney transplant recipients fasting cholesterol, non-HDL cholesterol, triglyceride levels were found 5.5 (+/- 1.0), 3.4 (+/- 0.78) and 1.06 (+/- 0.29) respectively and expressed in mmol/L (mean +/- SE). The results were statistically not different from those of healthy controls. In contrast, non-diabetic kidney transplant recipients cholesterol, non-HDL cholesterol and triglyceride levels were increased to 6.1 (+/- 0.81) (p < 0.05), 4.6 (+/- 1.1) (p < 0.05) and 2.34 (+/- 1.53) mmol/L (p < 0.05). HDL cholesterol averaged 2.08 (+/- 0.36) in pancreas-kidney transplant recipients, clearly higher than that of kidney transplant recipients 1.53 (+/- 0.39) mmol/L (p > 0.01), or of controls 1.61 (+/- 0.37) mmol/L (p < 0.05). In pancreas-kidney transplant recipients postprandial lipaemia was the lowest and lipase activity was the highest compared both to kidney transplant recipients (p < 0.001, p < 0.05) and controls (p < 0.01, p < 0.05). This excellent triglyceride clearing capacity appears to be the result of a high activity of lipoprotein lipase, which, can be explained by the peripheral hyperinsulinaemia.

Endopeptidases↗
PubMed1995

Relationship of high-density lipoprotein subfractions and cholesteryl ester transfer protein in plasma to carotid artery wall thickness.

High plasma concentrations of high-density lipoprotein (HDL) cholesterol are a powerful indicator of low vascular risk. By decreasing HDL cholesterol, cholesteryl ester transfer protein (CETP) could perhaps constitute an atherogenic protein. We measured HDL cholesterol and HDL subfractions and quantified CETP mass in fasting plasma in 21 asymptomatic probands, and related these variables to the mean intima media thickness of the extracranial carotid arteries. HDL2 cholesterol, the less dense HDL subfraction, was inversely related to carotid wall thickness (r = -0.378; P < 0.05), and CETP was directly related to carotid wall thickness (r = 0.436; P < 0.05). In plasma CETP is associated mostly with the HDL3 subfraction. We therefore calculated from our measurements the relative CETP content of HDL3, i.e., CETP/HDL3 cholesterol. This ratio was correlated with carotid wall thickness stronger than any other variable measured (r = 0.718, P < 0.001). We conclude that variation in HDL subfractions and CETP may be more closely associated with carotid intima media thickness than the accepted strong risk factor of HDL cholesterol.

Adult↗
PubMed1995

Treatment of primary mixed hyperlipidemia with etophylline clofibrate: effects on lipoprotein-modifying enzymes, postprandial lipoprotein metabolism, and lipoprotein distribution and composition.

In 17 patients with primary mixed hyperlipidemia we studied levels and composition of lipoproteins in fasting plasma, lipoprotein-modifying enzymes, and postprandial lipoprotein metabolism after an oral fat-tolerance test supplemented with vitamin A before, and 12 weeks after treatment with etophylline clofibrate. With treatment, fasting plasma cholesterol, triglycerides, and the levels of very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL) decreased significantly; high density lipoprotein (HDL) cholesterol increased significantly. Treatment caused also an increase in the protein content of IDL, a decrease in the triglyceride content of LDL, and an increase in the size of LDL as assessed by gradient gel electrophoresis. Concentrations of triglycerides, chylomicrons, and chylomicron remnants after an oral fat load supplemented with vitamin A decreased by 33%, 30% and 6%, respectively (P < 0.005; P < 0.01; and P < 0.05). The activity of lipoprotein lipase and hepatic lipase in postheparin plasma increased by 51% and 45%, respectively (P < 0.01; P < 0.05). We found a decrease in the mass concentration of cholesteryl ester transfer protein (P < 0.05). Stepwise multiple regression analysis showed that the triglyceride content of LDL is determined primarily by fasting triglycerides (r = + 0.53, P < 0.05;baseline) and cholesteryl ester transfer protein (r = + 0.49, P < 0.05; 12 weeks); in contrast, the triglyceride content of HDL3 is determined exclusively by accumulation of postprandial triglycerides (r = + 0.67; P < 0.05; baseline) and postprandial chylomicrons (r = +0.87; P < 0.005; 12 weeks). We conclude that hypolipidemic treatment with etophylline clofibrate favorably affects the cardiovascular risk factor profile in primary mixed hyperlipidemia.

Carrier Proteins↗
PubMed1995

Exercise and postprandial lipaemia.

Postprandial hyperlipidaemia is a risk factor for atherosclerosis in multiple vascular beds, independently of high-density lipoprotein (HDL) cholesterol. An increased level of HDL cholesterol is a strong indicator of a low risk of atherosclerosis. Exercise decreases postprandial lipaemia and, in turn, increases levels of HDL cholesterol. The favourable effects of exercise on lipoprotein metabolism, particularly evident in the postprandial state, may thus help to decrease susceptibility to atherosclerosis in exercise-trained people.

Arteriosclerosis↗
PubMed1994

Effect of pancreas transplantation on lipoprotein lipase, postprandial lipemia, and HDL cholesterol.

Pancreas transplantation with systemic venous drainage of the graft causes elevated plasma levels of insulin, known to be a potent regulator of plasma lipoprotein metabolism. We studied 11 post-type I diabetic pancreas-kidney transplant recipients, 9 type I diabetic kidney transplant recipients displaying peripheral hyperinsulinemia due to subcutaneous insulin treatment, 11 nondiabetic kidney transplant recipients as controls for the effects of immunosuppressive medication, and 11 healthy control subjects, all matched for age, sex, and body mass index. We determined fasting lipids, lipoproteins and lipolytic enzymes, as well as postprandial lipid metabolism after a standardized oral fat load. High-density lipoprotein (HDL) cholesterol averaged 1.98 (0.40) mmol/L in pancreas-kidney transplant patients, clearly higher than that of kidney transplant recipients (1.52 (0.36) mmol/L, P < 0.05) or of controls (1.50 (0.38) mmol/L, P < 0.05). In pancreas-kidney transplant patients postprandial lipemia was lowest and lipoprotein lipase activity was highest (average 32% and 154%, respectively, of the mean of the controls) compared with nondiabetic kidney transplant recipients (P < 0.005, P < 0.05) and healthy controls (P < 0.001, P < 0.01). In type I diabetic kidney transplant recipients the levels of HDL cholesterol (1.88 (0.63) mmol/L), postprandial lipemia, and lipoprotein lipase activity were intermediate between pancreas-kidney transplant patients and healthy controls. The distinctly elevated HDL cholesterol in pancreas-kidney transplant patients can be readily explained by the low postprandial triglyceride levels resulting from a high activity of lipoprotein lipase. The very favorable lipid profile in post-diabetic pancreas-kidney transplant recipients could be expected to counteract the severe atherosclerotic risk of long-standing diabetes.

Adult↗
PubMed1994

Fenofibrate improves postprandial chylomicron clearance in II B hyperlipoproteinemia.

In 11 patients with IIB hyperlipoproteinemia we studied fasting lipids, lipoproteins, lipoprotein-modifying enzymes, and postprandial lipid metabolism after a standardized oral fat load supplemented with vitamin A before and 12 weeks after treatment with fenofibrate, a third-generation fibric acid derivative. Fasting plasma cholesterol, triglycerides, low-density lipoprotein cholesterol decreased significantly (P < 0.05, P < 0.01, P < 0.01), high-density lipoprotein subfraction 3 cholesterol increased significantly (P < 0.05), and high-density lipoprotein subfraction 2 cholesterol remained unchanged. Postprandial lipemia, i.e., the integrated postprandial triglyceride concentrations corrected for the fasting triglyceride level, and postprandial chylomicron concentrations, as assessed by biosynthetic labeling of chylomicrons with retinyl palmitate, decreased by 40.6% and 60.1% (P < 0.05; P < 0.05), respectively. The activity of lipoprotein lipase (LPL) increased by 33.6% (P < 0.05); the increase in LPL during fenofibrate treatment was positively correlated with the increase in high-density lipoprotein cholesterol (r = 0.84; P < 0.005). Hepatic lipase and cholesteryl ester transfer protein mass and activity remained unchanged. We conclude that lipid-lowering therapy with fenofibrate ameliorates fasting and, more profoundly, postprandial lipoprotein transport in hypertriglyceridemia by curbing postprandial triglyceride and chylomicron accumulation, at least in part, through an increase in LPL activity.

Adult↗
PubMed1994

The immunosuppressive substance 2-chloro-2-deoxyadenosine modulates lipoprotein metabolism in a murine macrophage cell line (P388 cells).

A recently developed immunosuppressive substance, 2-chloro-2-deoxyadenosine (2-CdA), was reported to inhibit monocyte functions at low concentration. Because macrophages play a key role in the formation of atherosclerotic plaques, it was of interest to study the effect of 2-CdA on cellular lipid metabolism. For this purpose we have used a macrophage cell line (P388) to perform incubation studies in the presence of acetylated low density lipoprotein (Ac-LDL) and 2-CdA. The addition of 2-CdA, in concentrations ranging from 5-20 nM, induced a dose-dependent decrease in cellular cholesterol content and in the amount of extracellular [14C]oleic acid (OA) incorporated into the cholesteryl ester (CE) fraction. The effect was maximized at 20 nM 2-CdA with an 86% reduction in cholesterol esterification compared to controls (P < 0.008). To evaluate the mechanism of interaction of 2-CdA with cellular lipid metabolism, deoxycytidine (dCyt) and 3-methoxybenzamide (3-MOB), substances known to antagonize the effect of 2-CdA in different ways, were co-administered with 2-CdA. dCyt, a competitive inhibitor of dCyt kinase, which catalyzes phosphorylation to the active metabolite, antagonized the effects of 20 nM 2-CdA, producing significantly greater incorporation of extracellular [14C]OA into the CE fraction than in the presence of 2-CdA alone (P < 0.0086). Co-incubation with 2-CdA and the poly-ADP-ribose synthetase inhibitor 3-MOB, which is known to render cells resistant to 2-CdA toxicity by preventing cellular nicotinamide adenine dinucleotide (NAD)- and adenosine triphosphase-depletion, also reversed the effect of 2-CdA on lipid accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1994

Kinetics of lipids, apolipoproteins, and cholesteryl ester transfer protein in plasma after a bicycle marathon.

The short-term effects of prolonged intense exercise on plasma lipid transport parameters including cholesterol, triglycerides (TGs), low-density lipoprotein (LD) cholesterol, high-density lipoprotein (HDL) cholesterol, and its subfractions HDL2 cholesterol and HDL3 cholesterol, on apolipoproteins (apos) A-I, A-II, and B, and on mass and activity of cholesteryl ester transfer protein (CETP) were studied in eight male endurance-trained athletes over the first week after a bicycle marathon. CETP mass concentration in plasma was quantified by a newly developed immunoradiometric assay (IRMA). Plasma concentrations of cholesterol, TGs, LDL cholesterol, apo B, CETP, and cholesteryl ester transfer activity (CETA) were significantly reduced in the recovery period compared with pre-exercise values (cholesterol by 20%, P < .05; TGs by 63%, P < .05; LDL cholesterol by 32%, P < .05; apo B by 18%, P < .05; CETP mass by 29%, P < .05; and CETA by 14%, P < .05). HDL cholesterol and HDL2 cholesterol, in contrast, were significantly increased in the post-exercise period (HDL cholesterol by 12%, P < .05, and HDL2 cholesterol by 96%, P < .05), whereas HDL3 cholesterol showed a tendency to decrease in the late recovery period (by 8%, NS). Although changes in cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apo B, and CETP mass and activity were already evident in the early recovery period, HDL2 cholesterol showed a delayed response, reaching its maximum 72 hours after initiation of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Low-density lipoproteins of the postprandial state induce cellular cholesteryl ester accumulation in macrophages.

Chemically or biologically modified low-density lipoproteins (LDL) but not native unmodified LDL lead to foam cell formation in monocyte-derived macrophages. Since the magnitude of postprandial lipemia after a challenge test seems to be associated with coronary artery disease, we tested the hypothesis that in the course of postprandial lipemia, LDL appear in plasma that are capable of leading to foam cell formation even without prior modification. We incubated the macrophage-like cell line P388 with unmodified postabsorptive and postprandial LDL from 17 healthy donors and measured the cellular cholesterol and triglyceride contents and amounts of exogenous [14C]oleic acid incorporated into the cholesteryl ester fraction. Postprandial LDL induced a significantly more pronounced cholesteryl ester accumulation than did postabsorptive LDL (477 +/- 286% versus 212 +/- 173%, respectively; P < .003). The increase in cellular total cholesterol was significantly higher as a result of cell incubation with postprandial LDL (107 +/- 61%) than with postabsorptive LDL (54 +/- 40%, P < .003), whereas no increase in triglyceride content was observed (P < .589) in either case. After CuSO4 incubation and incubation with P388 cells, postprandial LDL revealed more thiobarbituric acid-reacting substances than did postabsorptive LDL (55 +/- 10 versus 28 +/- 9 nmol/mg protein, P < .018; 28 +/- 4 versus 20 +/- 3 nmol/mg protein). The increase in cellular cholesteryl ester synthesis caused by postprandial LDL was reduced by more than 50% when lipoproteins and cells were incubated in the presence of ascorbic acid (P < .007).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Hypertriglyceridemia and acute pancreatitis].

Data of 26 patients suffering from severe pancreatitis, who were treated at the anesthesiologic intensive care unit during the years 1991 and 1992, were evaluated with respect to etiologic factors, especially hypertriglyceridemia, stage of the disease and clinical outcome. Hypertriglyceridemia was found in 13 cases (11 men, 2 women, mean age 42 +/- 9 years) with values between 330 mg/dl and 4000 mg/dl. Lipid electrophoresis revealed a pattern typical for type IV hyperlipidemia. Insulin dependent diabetes was present in 4 patients and 5 reported about an unusual high alcohol intake preceding pancreatitis. Beside surgical approaches, including drainage and lavage, and basic intensive care treatment plasmapheresis was performed in 8 patients with hypertriglyceridemia. 5 patients with pancreatitis and hypertriglyceridemia died out of multiorganic failure, and so the mortality rate was 38%. The group of patients with pancreatitis caused by cholelithiasis or chronic alcohol consumption showed a mortality rate of 46%. The poor outcome of pancreatitis associated with hypertriglyceridemia demonstrates the importance of the treatment of hypertriglyceridemia in order to prevent the development of pancreatitis. The determination of plasma triglyceride values should belong to the routine diagnostic procedures in acute pancreatitis.

Acute Disease↗
PubMed1994

High density lipoproteins with differing apolipoproteins: relationships to postprandial lipemia, cholesteryl ester transfer protein, and activities of lipoprotein lipase, hepatic lipase, and lecithin: cholesterol acyltransferase.

To gain insight into metabolic determinants of high density lipoproteins (HDL) containing apolipoproteins A-I and A-II (LpA-I/A-II) and those containing A-I, but devoid of A-II (LpA-I), the plasma concentration of LpA-I and LpA-I/A-II within the HDL2 and HDL3 density spectrum was measured in 14 normolipidemic male subjects on a standardized diet. Apolipoprotein plasma concentrations of HDL subspecies were compared with the magnitude of postprandial lipemia, activities of lipoprotein lipase and hepatic lipase in postheparin plasma, plasma lecithin:cholesterol acyltransferase (LCAT) activity, and cholesteryl ester transfer protein (CETP) mass. Plasma levels of LpA-I/A-II were 2.5 times higher than levels of LpA-I (123 +/- 20 vs. 48.3 +/- 22.1 mg protein/dl) and the partition of LpA-I and LpA-I/A-II between HDL2 and HDL3 differed in that the proportion of LpA-I associated with HDL2 was greater than that of LpA-I/A-II (23 +/- 19 vs. 6 +/- 6%, P < 0.002). With increasing levels of HDL2, the proportion of LpA-I in HDL2 increased (P < 0.002). Furthermore, levels of LpA-I and LpA-I/A-II were strongly correlated within the HDL2 but not within the HDL3 density region. Plasma levels of LpA-I, but not LpA-I/A-II, were inversely correlated with the magnitude of postprandial lipemia. However, activities of lipoprotein lipase and hepatic lipase tended to show stronger associations with the partition of LpA-I/A-II between HDL2 and HDL3 than with that of LpA-I. Within the HDL3, but not the HDL2 density spectrum, LpA-I/A-II exhibited a positive association with plasma LCAT activity, while LpA-I displayed an inverse association with plasma CETP mass. These results are consistent with differences in substrate properties of LpA-I and LpA-I/A-II for lipoprotein modifying enzymes and imply different, but overlapping metabolic pathways of LpA-I and LpA-I/A-II.

Adult↗
PubMed1994

[Hypertriglyceridemia].

The hypertriglyceridemias comprise a heterogenous group of lipoprotein disorders varying with respect to etiology, lipoprotein pattern, and its major clinical sequelae, i.e. pancreatitis and atherosclerosis. Therefore goals and modalities of treatment should be individualized to a large extent. Behavioral measures like diet, weight control, exercise, reduced alcohol consumption and smoking cessation form the cornerstone of medical management. Lipid lowering drugs should be considered when triglyceride levels exceed 1000 mg/dl to reduce the risk of pancreatitis and in patients at high risk for atherosclerosis, often characterized by a high total cholesterol/HDL ratio, to reduce cardiovascular endpoints.

Combined Modality Therapy↗
PubMed1993

Heterozygous lipoprotein lipase deficiency due to a missense mutation as the cause of impaired triglyceride tolerance with multiple lipoprotein abnormalities.

In 16 members of two Austrian families affected by a missense mutation at codon 188 of the lipoprotein lipase (LPL) gene (8 heterozygous and 8 normal subjects), carrier status for the mutation as determined by DNA analysis was related to LPL activity in postheparin plasma, to the magnitude of postprandial lipemia, and to concentration, composition, and size of the major lipoprotein classes of postabsorptive plasma. Carriers exhibited clearly reduced LPL activity, normal fasting triglycerides, but pronounced postprandial lipemia. The carriers' impaired triglyceride tolerance, as evident in the postprandial state of challenge only, was associated with a fasting lipoprotein constellation characterized by (a) enrichment of HDL2 with triglycerides, (b) reduced HDL2-cholesterol, (c) enrichment of VLDL and intermediate density lipoprotein (IDL) with cholesteryl esters, (d) elevated IDL levels, and (e) small-sized LDL. Within any given individual, the degrees of expression of these characteristics were quantitatively and continuously related with each other as well as with the magnitude of lipemia and with LPL activity.

Adolescent↗