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G Bondjers

Publications and source records attributed to G Bondjers.

At least 73 records · Page 4Linked to original sources
PubMed1990

Effect of short-term beta blockade on serum lipid levels and on the interaction of LDL with human arterial proteoglycans.

In view of conflicting evidence suggesting that beta-blockers have an anti-atherogenic effect as well as induce a potentially atherogenic lipoprotein profile, the effects of a short term beta-blockade on serum lipoproteins were studied in 39 healthy volunteers. Because the interaction of LDL with arterial proteoglycans appears to play a role in lipoprotein accumulation during atherogenesis, the effects of metoprolol and atenolol on low density lipoprotein interaction with human aortic proteoglycans were included in the study. We could confirm that the beta-blockers caused a decrease in HDL cholesterol and an increase in triglycerides, both potentially undesirable effects. In addition, however they induced a significant decrease in the in vitro LDL affinity for arterial proteoglycans. Since there appears to be a strong association between LDL reactivity with proteoglycans and risk for myocardial infarction, this effect of the beta-blockers may be an anti-atherogenic effect which overrides other effects on the lipoprotein pattern.

Adult↗
PubMed1990

Transfer of lipoproteins from plasma to the cell populations of the normal and atherosclerotic arterial tissue.

It appears that retention of lipoproteins rather than increased influx is the basis for lipoprotein deposition in arterial tissue during atherogenesis. Binding of lipoproteins to arterial proteoglycans is mediated by a peptide sequence considered to be involved in the interaction between the lipoproteins and the lipoprotein receptor. Consequently, in the presence of an excess of arterial proteoglycan, receptor-mediated cellular uptake of LDL is inhibited. However, LDL which has been precipitated by proteoglycan and subsequently resolubilized is taken up more avidly than native LDL, both in macrophages and in smooth muscle cells. This appears to be due to selection by the proteoglycans of a more reactive fraction of LDL. This fraction has a smaller molecular size and less surface phospholipids. As smaller LDL particles also have a higher transfer rate into the arterial tissue they may be particularly atherogenic. Low density lipoproteins appear to be taken up with higher affinity by arterial macrophages than by smooth muscle cells. The selective transfer of the LDL to macrophages can be inhibited by alpha-tocopherol, suggesting that oxidative modification may be involved in this process. The role of foam cells in atherogenesis is discussed in the context of the energy requirements of the arterial wall.

Animals↗
PubMed1990

Molecular basis of the association of arterial proteoglycans with low density lipoproteins: its effect on the structure of the lipoprotein particle.

Modifications of low density lipoproteins (LDL) that enter the arterial intima appear to be responsible for their eventual extracellular and intracellular accumulation during atherogenesis. Some of these modifications seem to be the result of LDL association with intimal chondroitin sulphate-rich proteoglycans (CSPG). We have used frontal elution affinity chromatography, binding and competition experiments with synthetic segments of apoB-100 to better define the ligand regions for the LDL-CSPG complexes. The minimum structural requirement for recognition by the CSPG appears to be a hydrophilic nine-residue amino-acid segment with five lysine and arginine residues. Analysis of other similar regions in apoB-100 and other glycosaminoglycan-binding proteins suggest that besides a cluster of positively charged amino-acids, the presence of hydroxyl-containing residues favours the association with sulphated proteoglycans. With controlled proteolytic hydrolysis, we found that the interaction of LDL with CSPG modifies the surface accessibility of a apoB-100 segments containing arginine and lysine. Because these apoB-100 domains may also be involved in cell-receptor binding, the CSPG-induced modifications could be the structural explanation for the observed increase in cellular uptake of proteoglycan-modified LDL.

Amino Acid Sequence↗
PubMed1990

Treatment of familial hypercholesterolaemia: a controlled trial of the effects of pravastatin or cholestyramine therapy on lipoprotein and apolipoprotein levels.

The efficacy and safety of a new, selective inhibitor of cholesterol synthesis, pravastatin, and the bile acid-binding resin, cholestyramine, were compared in a randomized, double-blind study of 120 patients with familial hypercholesterolaemia. After a run-in period of 8-10 weeks with assessment of dietary habits, the patients were treated with pravastatin + placebo, placebo + cholestyramine, or placebo alone. Active pravastatin therapy was initiated with 10 mg b.i.d. for 6 weeks, and was increased to 20 mg b.i.d. for the following 6 weeks. Cholestyramine was given at 24 g d-1, or the highest tolerable dose. After 6 weeks of therapy, serum total and LDL cholesterol levels were reduced by 17% and 21%, respectively, on pravastatin treatment, whereas the corresponding reductions with cholestyramine treatment were 24% and 30%, respectively. With an increased dose of pravastatin, serum and LDL cholesterol concentrations were reduced by 23% and 28%, respectively, after 12 weeks; the effect of cholestyramine was unchanged. HDL cholesterol levels increased in response to pravastatin, by 7% and 9% after 6 and 12 weeks, respectively. Concomitant changes in the concentrations of apolipoproteins B and AI were observed. Three patients discontinued the study because of side-effects: two subjects were treated with pravastatin and one was given placebo. The prevalence of side-effects (including laboratory abnormalities) was 35% for pravastatin, 30% for placebo, and 53% (significantly higher) for cholestyramine. We conclude that pravastatin, in a 40 mg daily dose, is as effective as cholestyramine in lowering LDL cholesterol in familial hypercholesterolaemia. Since the frequency of side-effects is higher with cholestyramine, pravastatin offers a promising alternative for the therapy of this genetic disease.

Adult↗
PubMed1990

Experimental sympathetic activation causes endothelial injury in the rabbit thoracic aorta via beta 1-adrenoceptor activation.

Sympathetic activation appears to accelerate the development of atherosclerosis, an effect that may be inhibited by beta-receptor blockade. It is unclear, however, which mechanisms mediate this effect. In view of the significance attached to endothelial injury in the initial phases of atherogenesis, we decided to test whether sympathetic activation might lead to an increase in endothelial injury. Chloralose anesthesia was used to induce sympathetic activation and the presence of intracellular IgG as a criterion of endothelial cell injury. The beta 1-selective beta-blocker metoprolol was used to evaluate if the effect(s) of sympathetic activation might be mediated by beta 1-adrenoceptors. In normal rabbits, the frequency of injured endothelial cells in unbranched areas of the thoracic aorta was 0.23%, compared with 1.93% in circumostial areas. Chloralose anesthesia caused significant increases in blood pressure, heart rate, and plasma norepinephrine, that is, caused sympathetic activation, and led to an approximately fivefold increase in the number of injured cells both in unbranched and in circumostial areas. This increase was totally inhibited by metoprolol pretreatment, indicating that it was mediated by beta 1-receptors. These observations suggest one possible mechanism that may connect sympathetic activation with atherogenesis and explain why beta-blockade protects against atherosclerosis.

Anesthesia↗
PubMed1990

Interaction of LDL with human arterial proteoglycans stimulates its uptake by human monocyte-derived macrophages.

The aim of this work was to investigate the possible mechanisms for uptake by human monocyte-derived macrophages (HMDM) of low density lipoprotein (LDL) pretreated with human arterial chondroitin-6-SO4-rich proteoglycan (LDL-PG). HMDM were incubated with 125I-labeled tyramine cellobiose-labeled LDL-PG, native LDL, and acetylated LDL (Ac-LDL). The results showed that two to four times more LDL-PG than LDL was bound and internalized by the HMDM. Competition experiments showed that LDL-PG competed with native LDL for the apoB,E (LDL) receptor, but not for the Ac-LDL scavenger receptor. Both the LDL and LDL-PG uptake were reduced after preincubation of the macrophages with unlabeled native LDL, though to a lesser extent with LDL-PG. The specific binding of 125I-labeled LDL and 125I-labeled LDL-PG at 4 degrees C was both saturable and concentration-dependent. The dissociation constant (Kd) for binding was 8.6 x 10(-9) M for LDL and 9.4 x 10(-9) M for LDL-PG, but the maximum binding (Bmax) was 1.5-times higher for LDL-PG. Cholesterol derived from LDL-PG was less effective than native LDL in suppressing HMG-CoA reductase activity. The results indicate that the uptake of LDL-PG is mediated not only by the LDL-receptor, but also by another unspecific pathway, which may not be subjected to regulation. These results provide further support for the hypothesis that LDL modifications induced by arterial PG may contribute to the formation of foam cells.

Acetylation↗
PubMed1990

Hyperlipoproteinemia type I in a patient with active lipoprotein lipase in adipose tissue and indications of defective transport of the enzyme.

This paper presents a case of typical hyperlipoproteinemia type I in a young woman. Her serum triglycerides varied between 2 and 90 mmol/l and she had substantial amounts of apolipoprotein B-48 in fasting plasma. She had no detectable lipoprotein lipase (LPL) activity in post-heparin plasma (less than 0.2 percent of normal). Southern blot analysis suggested no major defect in her LPL gene and Northern blot analysis of adipose tissue RNA showed normal-sized LPL-mRNA. A 2-h [35S]methionine incorporation experiment with adipose tissue pieces in vitro showed that she produced normal-sized LPL and had LPL catalytic activity in the tissue. The amounts were, however, only 5-10% of control. No detectable LPL radioactivity or catalytic activity was released from patient tissue even in the presence of heparin in the incubations. Immunofluorescent staining of adipose tissue biopsies from the patient showed LPL immunoreactivity only in adipocytes and little or none within the capillaries. Treatment of immunoprecipitated labeled LPL with endoglycosidase H showed that the oligosaccharide chains on her enzyme were of the high-mannose type and not processed as in controls. Taken together the data suggest that the patient synthesizes a relatively normal LPL protein which is core-glycosylated and folded into active enzyme as in normal subjects, but is not effectively transported via the Golgi to the cell surface.

Adipose Tissue↗
PubMed1990

Differential uptake of proteoglycan-selected subfractions of low density lipoprotein by human macrophages.

Macrophages and arterial chondroitin sulfate proteoglycans (CSPG) are probably associated with extracellular and intracellular lipoprotein deposition during atherogenesis. We found that human arterial CSPG can be used to select subclasses from low density lipoprotein (LDL) with different structural properties and capacities to interact with human monocyte-derived macrophages (HMDM). Four subclasses, LDL(PG)1 to LDL(PG)4, in order of decreasing CSPG-complexing capacity, were prepared and characterized in terms of their ability to interact with HMDM. The LDL subclasses with highest avidity for CSPG, LDL(PG)1 and LDL(PG)2, were bound, internalized, and degraded more efficiently than those of lower avidity for CSPG. From LDL(PG)1 to LDL(PG)4, the gradual decrease in uptake by HMDM and decreasing avidity for CSPG were associated with a gradual decrease in isoelectric point (from 5.93 to 5.68) and an augmented ratio of surface polar lipid to core nonpolar components (from 0.35 to 0.54). Competition experiments indicated that the proteoglycan-selected subfractions shared the binding sites and uptake mechanisms of native LDL. The results suggest the existence of a structurally related gradation in the avidity of LDL subpopulations for cells and matrix components. The presence within LDL subpopulations of a differential capacity to interact with intimal extracellular and cellular elements could be associated with a similar heterogeneity in their atherogenic potential.

Binding Sites↗
PubMed1989

[Food and health].

Explore the source record for details and available documents.

Cardiovascular Diseases↗
PubMed1989

Human arterial smooth muscle cells in culture: inverse relationship between proliferation and expression of contractile proteins.

Human arterial smooth muscle cells (hASMC) from explants of the inner media of uterine arteries were studied in secondary culture. We had previously found that these cells depend on exogenous platelet-derived growth factor (PDGF) for proliferation in vitro. Deprivation of the serum mitogen(s) by culture in plasma-derived serum or bovine serum albumin (BSA) caused a true growth arrest that was reversible upon reexposure to the mitogen(s). When added to serum-containing medium, heparin caused a reversible growth arrest which could be competed for by increasing concentrations of serum. In the current study we used a set of smooth muscle-specific actin and myosin antibodies to study the expression of contractile proteins in stress fibers under indirect immunofluorescence on hASMC in culture. Even in sparse culture, growth-arrested hASMC expressed stress fibers containing these actin and myosin epitopes. This was true irrespective of whether growth arrest was achieved by culture in media containing only BSA or a combination of heparin and whole blood serum. hASMC proliferating in whole blood serum in sparse culture did not express such stress fibers, as judged by immunofluorescent staining. This was true also for cells that were restimulated to proliferate in serum after a growth arrest. Utilizing a monoclonal antibody against a nuclear antigen expressed in proliferating human cells, we were able to demonstrate an inverse relationship between the expression of this antigen and the SMC-specific contractile proteins, respectively. Under these culture conditions, the reversible transition between dedifferentiated and differentiated hASMC was almost complete and terminated about 1 wk after the change in culture condition. We conclude that hASMC in vitro respond to exogenous PDGF by proliferation and dedifferentiation as a single population of cells. We also conclude that this modulation is reversible, because the cells become uniformly quiescent and differentiated when the mitogenic stimulus is blocked or removed.

Actins↗
PubMed1989

Agarose isoelectric focusing of plasma low and very low density lipoproteins using the PhastSystem.

Human plasma lipoproteins, fractionated by density gradient ultracentrifugation, and very low density lipoproteins, subfractionated by cumulative rate centrifugation, were subjected to agarose isoelectric focusing in small format thin gels prepared in the laboratory for the commercially available PhastSystem (Pharmacia). From preparation of the gels to their staining, the procedure took less than 3 h. The pH gradient was found reproducible and the apparent average pI of individual low density lipoproteins could be measured with a coefficient of variation of less than 5% between and less than 2% within the same run. The method appears especially suitable for the exploration of charge properties of multiple lipoprotein samples, or other large macromolecules as low density lipoproteins and very low density lipoproteins, with considerable economy of time and reagents.

Cholesterol, LDL↗
PubMed1989

Apolipoprotein B in human aortic biopsies in relation to serum lipids and lipoproteins.

A total of 46 patients, aged 39-71 years (mean 57.7), were studied. Forty-eight percent of the patients were hyperlipidemic and 63% had earlier suffered a myocardial infarction. Biopsies from aorta were obtained during coronary bypass surgery. Apo B was extracted from the intima by incubation of the tissue in buffer, followed by collagenase digestion. Intimal apo B was quantified in an immunoradiometric assay. There were significant correlations between total or collagenase-extractable apo B and serum cholesterol (rs = 0.39, P less than 0.01), serum triglycerides (rs = 0.33, P less than 0.05), LDL cholesterol (rs = 0.33, P less than 0.05) and serum apo B (rs = 0.37, P less than 0.05). The correlations were strongest for the collagenase-extractable apo B, while no correlations were observed for the buffer-extractable intimal apo B. No significant correlations were found between intimal apo B and serum HDL, apo A-I, smoking habits, history of hypertension or sustained myocardial infarction. Follow-up data were available for 42 of the patients, with a mean follow-up period of 35.1 months. The patients were classified according to symptoms of angina pectoris at the time of follow-up. There were significantly lower levels of serum apo A-I in the patients with poorer clinical prognosis. In a linear multiple stepwise regression analysis, apo A-I and serum LDL were significantly and independently related to clinical prognosis (R2 = 0.31).

Adult↗
PubMed1989

Binding parameters and concentration modulate formation of complexes between LDL and arterial proteoglycans in serum.

The interactions of LDL with extracellular matrix proteoglycans apparently contribute to the accumulation of apo B-lipoproteins in atherogenesis. Serum LDL forms insoluble complexes with human arterial chondroitin sulfate proteoglycans (CSPG). While the amount of insolubilized LDL varies, serum from survivors of myocardial infarcts and ischaemic subjects shows higher values of CSPG-insolubilized LDL than serum from controls. In this study, we explored the relationship between the formation of LDL-CSPG complexes in serum and some LDL properties, using binding isotherms and characterization of isolated LDL from 12 healthy controls and 12 young myocardial infarct survivors. The amount of LDL insolubilized in serum from solutions of CSPG was found to be a function of the product Bt (total binding) x the amount of serum LDL-cholesterol. Furthermore, the Bt values for the isolated LDL from controls and patients could be predicted with more than 70% certainty by using a multiple regression model which included the cholesterol/protein ratio, protein/triglyceride ratio, isoelectric point and the affinity coefficient of the lipoprotein for CSPG. The results indicate that LDL-CSPG measurements in serum are dependent upon both LDL concentration and structural properties which are related to its tendency to form complexes with arterial CSPG.

Adult↗
PubMed1989

Lack of correlation between the apolipoprotein B XbaI polymorphism and blood lipid levels in a Swedish population.

The possible connections between the apolipoprotein B (apo B) XbaI polymorphism and the serum levels of total cholesterol, triglycerides, LDL, HDL and apo B have been investigated among 187 randomly selected subjects from Gothenburg, Sweden. The interferences of age and sex on the serum lipoproteins and apo B concentrations were considered. Using multiple regression analysis, we compared the different lipid levels and the levels of apo B with the genotypes X1X1, X1X2 and X2X2 (X1 = without the XbaI restriction site, X2 = with the site), with age and with sex and with those factors combined with each other. A significantly higher concentration of serum cholesterol and LDL among men than among women was found and total serum cholesterol, LDL and apo B were positively correlated with age. The allele frequency of the XbaI polymorphism in the sample was 0.45 for the allele without the XbaI restriction site. No correlation was found between the apo B genotypes and the levels of serum lipoproteins or apo B.

Adult↗
PubMed1989

Affinity of LDL to a human arterial proteoglycan among male survivors of myocardial infarction.

In the present study, the hypothesis that the affinity of LDL to arterial proteoglycans might discriminate myocardial infarction patients from controls were tested. The patients were 52 men who had sustained a myocardial infarction at an age of 50 years or less and the controls, selected from a random population sample, were matched to the patients for age and sex. Serum cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol and apoB discriminated patients from controls. In addition, LDL reactivity with arterial proteoglycans was significantly higher in patients than in controls. In a multiple regression analysis, with patient or control as the dependent variable, apoB levels, LDL proteoglycan reactivity and serum triglycerides appeared as independent contributors to the regression. These observations indicate that LDL reactivity with arterial proteoglycans is a new, highly significant factor which discriminates between young myocardial infarction patients and controls.

Adult↗