The role of lecithin:cholesterol acyltransferase for the low density lipoprotein composition and specific binding to the B receptor.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to F Krempler.
Explore the source record for details and available documents.
An elevated concentration of lipoprotein (a) [Lp(a)] in the serum has been considered a risk factor for coronary heart disease by various investigators. In the present study, the turnover of Lp(a) was investigated in nine individuals with serum Lp(a) levels ranging from 1 to 68 mg/100 ml. After intravenous injection of radioiodinated Lp(a), the radioactivity time-curve of the serum and the specific activitity time-curves of the isolated Lp(a) and Lp(a) apolipoproteins were measured for 14 d. More than 97% of the label was found in the protein moiety of Lp(a). During the entire study period, the serum radioactivity remained with Lp(a), only insignificant amounts of radioactivity were detectable in other lipoprotein fractions. The serum radioactivity time-curves and the specific activity time-curves of the isolated Lp(a) and Lp(a) apolipoproteins were identical. The kinetic parameters of Lp(a) turnover were calculated in terms of a two-compartment model. 76.5+/-5.1% (mean+/-1 SD) of total Lp(a) was contained in the intravascular space. The biological half-life of Lp(a) was 3.32+/-0.52 d, the fractional catabolic rate (FCR) was 0.306+/-0.054/d, and the rate of synthesis was 5.00+/-3.37 mg/kg/d. A positive correlation was found between serum concentration and synthetic rate of Lp(a) apoprotein. No relationship could be demonstrated between serum level and FCR of Lp(a). The results of this study indicate that Lp(a) is not converted to other serum lipoproteins. From the correlations between serum concentration and kinetic parameters of Lp(a) it is concluded that an elevated Lp(a) level is the consequence of an increased Lp(a) apoprotein synthesis.
With sensitive methods, the lipoprotein Lp(a) can be demonstrated in the serum of all human subjects, except patients with abetalipoproteinaemia. A high serum level of Lp(a) is considered as a risk factor for atherosclerotic vascular disease (coronary heart disease). The chemical and physical properties of Lp(a) are very similar to those of low density lipoproteins (LDL, Lp-B). In contrast to LDL, Lp(a) has an additional apolipoprotein, the specific Lp(a) antigen. From in vivo studies with 125I-labeled lipoproteins, the following conclusions can be drawn: 1. Lp(a) is not a metabolic product of other apolipoprotein B-containing lipoproteins. Apparently, Lp(a) is synthesized as a separate lipoprotein. 2. Lp(a) is not catabolized to other lipoproteins. Lp(a) leaves the plasma as an intact particle. 3. The fractional catabolic rate and the distribution between the intra- and extravascular compartment are similar for Lp(a) and LDL. 4. The serum level of Lp(a) is primarily determined by the synthetic rate and not by the catabolic rate.
Explore the source record for details and available documents.
125I-Labeled autologous very low density lipoprotein (VLDL) was injected intravenously into three lipoprotein (a) positive individuals. One other lipoprotein (a) positive subject received 125I-labeled VLDL from a a lipoprotein (a) negative donor. Specific activity of apolipoprotein B in VLDL, low density lipoprotein (LDL) and lipoprotein (a) was measured for 5 days. In the lipoprotein (a) fraction only traces of radioactivity could be detected, which were caused by contamination with labeled LDL. No precursor-product relationship existed between apolipoprotein B in VLDL or LDL and apolipoprotein B in lipoprotein (a). One lipoprotein (a)-positive individual was kept on a fat-free diet for 4 days to prevent chylomicron formation; no change in the serum level of lipoprotein (a) could be detected under these conditions. The data of this study indicate that lipoprotein (a) is not a metabolic product of VLDL or LDL. Also chylomicrons are not likely to play role as a precursor for lipoprotein (a). It is concluded that lipoprotein (a) is synthesized as a separate lipoprotein.
Explore the source record for details and available documents.
In 36 patients with primary hyperlipoproteinemia of type II B or IV the effect of bezafibrate, a new derivate of clofibrate, has been compared with the effect of clofibrate. In an open cross-over-study the effect of 1.5 g clofibrate p.d. has been compared with that of 450 mg bezafibrate p.d. for several months. The effect of bezafibrate on plasma triglyceride concentration and plasma cholesterol concentration was more pronounced than that of clofibrate. This difference was statistically significantly only in the concentration of plasma triglycerides of type IV patients. It is obvious that the difference between bezafibrate and clofibrate would have been more pronounced if the dose of bezafibrate had been in the optimal range. Serious side-effects caused by bezafibrate could not be observed.
50 patients with different types of hyperlipoproteinaemia were treated with a combination of Mg-chlorophenoxyisobutyrate (700 mg) and mesoinositol-hexanicotinate (500 mg) (Atroplex) twice daily. 7 patients had type IIa, 39 patients type IIb or IV and 4 patients type V. After a period of one month without any treatment the patients were treated during two months. While the effects of this combination on cholesterol of type IIa patients was poor, the drug had an excellent lipid-lowering effect in the patients with type IIb, IV and V. After 14 days' treatment the plasma cholesterol and triglyceride levels in patients of type IIb or IV were significantly lowered. This effect became even more pronounced after one-month treatment. There was no significant difference between the effect of one-month treatment and that of two-month treatment. About two-thirds of the patients of type IIb or IV were responders. No serious side effects could be observed during our study.
Lp(a) was isolated and labeled by reductive alkylation. Radioactivity only entered the protein moiety of the lipoprotein. No change in the immunological or physicochemical properties of Lp(a) was noted after the radiomethylation. After incubation of labeled Lp(a) with whole serum for 24 h in vitro, more than 99% of the radioactivity of the incubated sample was found in Lp(a). In 4 subjects Lp(a) was injected intravenously. A linear decline of the specific activity of Lp(a) in the serum was found when it was plotted semilogarithmically against time. Half-lives of Lp(a) in the serum were 35, 38, 53 and 58 h. In one subject, the "soluble" and the "insoluble" apoproteins of Lp(a) showed the same half-life as the whole Lp(a) molecule. This suggests that no exchange of Lp(a) apoproteins with lipoproteins of other density classes took place. At different times after the injection of Lp(a), 3--8% of the radioactivity of the serum was found in Lp B, and less than 2% of the radioactivity was detectable in VLDL and the fraction having a density of greater than 1.110 g/ml.
In eleven patients with chronic renal insufficiency treated by intermittent haemodialysis and in ten normal subjects, hepatic and extrahepatic triglyceride lipase activity of post heparin plasma was selectively measured, utilizing the different sensitivity of both enzymes to inhibition by protamine sulphate. In uraemic patients, hepatic triglyceride lipase activity was significantly decreased and extrahepatic triglyceride lipase activity was normal when compared with the control group. The uraemic subjects showed a moderate hypetriglyceridaemia; their serum cholesterol level, however, was normal. The high triglyceride concentration was due to an increase of very low density lipoproteins and low density lipoproteins of the density between 1.006 and 1.019 g/ml (LDL1). The concentration of low density lipoproteins of the density between 1.019 and 1.063 g/ml (LDL2) was decreased. LDL2 were relatively rich in triglycerides when compared with LDL2 from the control group.
The PAH extraction of the kidneys was determined separately on each side after catheterisation of both renal veins and the femoral artery during PAH infusion in eleven patients with normal or diminished renal function due to bilateral renal disease and in five patients with only one kidney with normal or diminished renal function. A significant positive correlation was found between PAH extraction and inulin clearance and a significant negative correlation between PAH extraction and the log of the serum creatinine. PAH extraction is a suitable method for quantitative evaluation of right and left renal function.
40 patients with essential hypertension of varying degrees were treated with prazosin for up to 6 months. Both in severe (n=10) and in moderately severe (n=28) hypertension a significant decrease of the systolic and diastolic blood pressure was observed after only one month of treatment. This effect was even more evident after 3 and 6 months. 18 patiets showed orthostatic disorders at the beginning of treatment which in all cases disappeared after several weeks. No side effects were observed which could be attributed with certainty to prazosin.
The role of genetic variation at the 3' end of the apolipoprotein B gene locus in the development of coronary heart disease and the regulation of the serum levels of various lipoproteins was studied by using two common restriction fragment length polymorphisms detected with the enzymes Xba I and EcoR I. A group of 106 male patients with coronary heart disease and 118 matched controls of Austrian origin were investigated. The frequency of the R2 allele of the EcoR I polymorphism at cDNA position 12,669 defined by the absence of the polymorphic EcoR I cutting site was significantly higher among patients than among controls. The controls with the R2 allele had significantly higher levels of total triglycerides, very low density lipoprotein (VLDL) triglycerides, and VLDL cholesterol than did the controls without this allele. Among the patients, the R2 allele was associated with higher serum VLDL apolipoprotein B levels. The chemical composition of VLDL in individuals with different genotypes for the EcoR I polymorphism did not differ significantly. For the Xba I polymorphism at cDNA position 7673, no correlation with coronary risk could be demonstrated. Patients and controls homozygous for the X2 allele characterized by the presence of the polymorphic Xba I cutting site showed a higher total and low density lipoprotein cholesterol level than did subjects with the genotype X1X1 or X1X2. This difference, however, was not statistically significant. These findings indicate that the R2 allele of the EcoR I polymorphism is associated with the occurrence of coronary heart disease and that variation at the 3' end of the apo B gene is involved in the regulation of VLDL metabolism.