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Biomedical subjects

S Stender

Publications and source records attributed to S Stender.

103 records · Page 6Linked to original sources
PubMedDate not supplied

A nicotinic acid ester and experimental atherosclerosis: no significant effect of treatment with niceritrol (pentaerythritoltetranicotinate) on cholesterol in aorta of rabbits previously fed with cholesterol-enriched diet.

The influence of niceritrol on cholesterol in serum, liver and inner aorta of 115 rabbits was studied during a period where a cholesterol-enriched diet was given and during two succeeding periods after which cholesterol addition to the diet was discontinued. Niceritrol given together with cholesterol for 6 weeks reduced significantly the concentration of cholesterol in serum and liver, but not in the inner aorta. During 16 weeks decrease of serum cholesterol after discontinuation of cholesterol feeding no significant effect of niceritrol was observed on the decrease in serum and liver cholesterol or on the concentration of cholesterol in inner aorta. When serum cholesterol had normalized 16 weeks after discontinuation of cholesterol feeding, addition of niceritrol to the diet for the following 16 weeks did not significantly affect the concentration of cholesterol in liver and inner aorta. Animals in all groups were injected intravenously with an equal amount of [3H] cholesterol 3 weeks before discontinuing cholesterol feeding. Niceritrol did not significantly affect the amount of accumulated labelled cholesterol in inner aorta. The present results indicated that niceritrol had no significant effects on metabolism of cholesterol in inner aorta of the hypercholesterolemic and previously hypercholesterolemic rabbits.

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PubMedDate not supplied

Transfer of plasma lipoprotein components and of plasma proteins into aortas of cholesterol-fed rabbits. Molecular size as a determinant of plasma lipoprotein influx.

The arterial influx of esterified and free cholesterol from low density lipoproteins and very low density lipoproteins in 20 hypercholesterolemic rabbits was measured simultaneously by the use of lipoproteins labeled in vivo with [3H]- and [14C]-cholesterol. The simultaneous arterial influx of either [3H]-leucine-labeled very low density lipoproteins, low density lipoproteins, high density lipoproteins, or plasma proteins was also measured in each rabbit. The arterial influx was calculated as intimal clearance, i.e., the influx of a given fraction divided by its plasma concentration. The intimal clearance of low density lipoprotein esterified cholesterol was equal to that for the apolipoproteins of that fraction, which is compatible with an arterial influx of intact low density lipoprotein molecules. The intimal clearance of very low density apolipoprotein or cholesteryl ester was less than that for low density lipoprotein, whereas high density lipoprotein and albumin clearances exceeded low density lipoprotein clearance by 1.5- to 3-fold. The intimal clearances of plasma proteins, high density, low density, and very low density lipoproteins decreased linearly with the logarithm of the macromolecular diameter. This indicates that the arterial influx of three plasma lipoprotein fractions and of plasma proteins proceeds by similar mechanisms. Apparently the relative intimal clearances of lipoproteins are more dependent on their size relative to pores or vesicular diameters at the plasma-artery interface than on specific interactions between lipoproteins and the arterial intimal surface.

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PubMedDate not supplied

Different efflux pathways for high and low density lipoproteins from porcine aortic intima.

To study the efflux of high (HDL) and low (LDL) density lipoproteins from the arterial wall in vivo, a surgical model in pigs was used. An isolated segment of the lesion-free thoracic aorta was pulse labeled from the lumen of the artery with 3H-cholesteryl ester labeled HDL and 14C-cholesteryl ester labeled LDL. Subsequently, the labeled aortic segment was exposed to cold chase in vivo. The transfer of HDL cholesteryl ester from plasma into intima expressed as intimal clearance was three to seven times greater than that of LDL cholesteryl ester. At least 50%, but possibly as much as 95%, of the HDL cholesteryl ester that entered the arterial intima during a period of 4 hours penetrated the arterial wall beyond the internal elastic lamina. In contrast, less than 15% of the LDL cholesteryl ester that entered the arterial intima in the same period penetrated beyond the luminal layer. After 24 hours of cold chase in vivo, more than 80% of both labeled HDL esterified cholesterol and labeled LDL esterified cholesterol had disappeared from the arterial wall. Transmural profiles after 9 hours of cold chase showed that labeled HDL was present throughout the entire arterial wall, whereas labeled LDL in quantitative amounts was present only in the luminal layer. The results suggest that the most important efflux route for HDL esterified cholesterol is through the vasa vasorum and lymphatics in the outer media and adventitia, whereas LDL esterified cholesterol predominantly leaves intima via the lumen of the artery.

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PubMedDate not supplied

Comparison of cholesteryl ester transfer from chylomicrons and other plasma lipoproteins to aortic intima media of cholesterol-fed rabbits.

Lymph chylomicrons labeled with 14C-cholesterol and plasma very low and intermediate density lipoproteins (d less than 1.019) labeled with 3H-cholesterol were injected simultaneously into recipient cholesterol-fed rabbits. The cholesteryl ester of chylomicron origin (14C) found in the tissues 1 to 4 hours after the injection is the sum of both direct and indirect uptake of chylomicron cholesteryl ester. The direct uptake of chylomicron cholesteryl ester is defined as occurring in situ during the interaction between chylomicrons and lipoprotein lipase in endothelial cells. The indirect uptake of chylomicron cholesteryl ester results from the uptake of chylomicron remnants and of other plasma lipoproteins which become labeled during the degradation of the injected chylomicrons by net lipid transfer or by exchange. The indirect contribution of chylomicron cholesteryl ester to tissues was calculated from tissue 3H-cholesteryl ester derived from injected plasma d less than 1.019 lipoproteins. In rabbits fed 0.5 g cholesterol daily for 40-60 days, with plasma cholesterol concentrations between 20 and 30 mM (800-1200 mg/dl), less than 1% of the cholesteryl ester influx into aortic intima media and less than 10% in liver was derived from the direct uptake of chylomicron cholesteryl ester.

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PubMedDate not supplied

No effect of nifedipine on atherogenesis in cholesterol-fed rabbits.

It was recently reported that the calcium antagonist nifedipine suppresses aortic cholesterol accumulation in cholesterol-fed rabbits without reducing hypercholesterolemia. We extended this study on plasma lipoprotein levels and aortic influx of cholesteryl ester. We gave 40 mg per day of nifedipine orally to 17 rabbits fed a 2% cholesterol diet for 8 weeks. For the same period of time 15 control rabbits received placebo capsules and the same diet. During the study, total cholesterol, HDL, LDL, and VLDL cholesterol concentrations in plasma were not significantly different in the experimental and control animals. At the end of the study we found no difference in the two groups in accumulation of cholesterol in the intima media of the proximal thoracic aorta, the distal thoracic aorta, and the corresponding media layers. Furthermore, aortic influx of free cholesterol, cholesteryl ester, and albumin from plasma measured by radioactive tracers was not significantly affected by nifedipine.

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PubMedDate not supplied

In vivo flux of plasma cholesterol into human abdominal aorta with advanced atherosclerosis.

To measure the flux of free and esterified cholesterol from plasma into abdominal aortic tissue that had severe atherosclerotic lesions, we intravenously injected two autologous plasma samples containing radioactive cholesterol into patients scheduled for reconstructive arterial surgery. After the injections, blood samples were collected for calculation of the exposure of arterial tissue to labeled free and esterified plasma cholesterol. When tissue specimens were removed a few days after the injection, the aortic influx was determined by the simultaneous use of two differently labeled species of cholesterol. The flux of free and esterified cholesterol into 51 tissue specimens from the abdominal aorta of 12 normocholesterolemic patients was 41 +/- 3 and 45 +/- 3 nmol X cm-2 X day-1 (mean +/- SE), respectively, with 7% to 30% hydrolysis and 8% to 24% esterification of the labeled sterols in the atherosclerotic tissue. The influx was up to 100 times greater than the influx into nonatherosclerotic ascending aorta previously measured in other patients. The cholesterol content of the atherosclerotic tissue corresponded to 16 +/- 3 months (mean +/- SE) of continuous cholesteryl ester influx. Unless counteracted by cholesteryl ester efflux from the plaque, this influx provides enough cholesteryl ester from plasma to cause rapid lesion progression.

Aged↗
PubMedDate not supplied

In vivo transfer of cholesteryl ester from high and low density plasma lipoproteins into human aortic tissue.

For the study of cholesteryl ester transfer from different plasma lipoproteins into human aortic tissue, patients scheduled for reconstructive aortic surgery were intravenously injected with autologous in vitro labeled lipoproteins 20 to 24 hours before aortic intima-media samples were obtained during the operation. The injectate contained high density lipoproteins (d greater than 1.063) labeled with 3H-cholesteryl ester and lipoproteins of lower density (d less than 1.063) labeled with 14C-cholesteryl ester or lipoproteins with the opposite labeling. In 16 aortic tissue samples (some with visible atherosclerosis) from 11 normocholesterolemic patients, the aortic influx of total cholesteryl ester was 1 to 50 nmol x cm-2 x day-1. Some 39% +/- 3% (mean +/- SEM) of the influx was derived from high density lipoproteins, which in plasma accounted for only 22% +/- 2% (mean +/- SEM) of the esterified cholesterol. The findings suggest that: 1) esterified cholesterol from the two lipoprotein fractions in plasma enter the aortic intima by the same mechanism, and 2) influx of cholesteryl ester from the smaller, high density lipoproteins is greater than influx from the larger, lower density lipoproteins considering their concentrations in plasma. In some patients, the cholesterol content in the intima-media tissue with no visible atherosclerosis corresponded to only a few months of continuous cholesteryl ester influx. This time is short considering the age of the patients and, therefore, indicates that removal of esterified cholesterol from the intima-media is of major importance in preventing cholesterol deposition in the arterial wall.

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PubMedDate not supplied

Antiatherogenic effect of olive and corn oils in cholesterol-fed rabbits with the same plasma cholesterol levels.

Two groups of 18 rabbits were fed isocaloric, cholesterol-enriched diets for 8 weeks. The diet for one group was supplemented with 5% corn oil. The concentration of cholesterol in plasma was determined weekly and the amount of cholesterol in the diet was adjusted individually so that each rabbit had a mean plasma cholesterol concentration of about 45 mM during the experimental period. The aortic cholesterol concentrations were 122 +/- 29 and 193 +/- 38 (mean +/- SEM) mumol/g protein for the corn-oil group and the control group, respectively (p less than 0.05). In a similar experiment, each of 36 rabbits was given a mean plasma cholesterol level of about 20 mM over a period of 12 weeks. One-third of the rabbits received 10% to 15% corn oil, another third 10% to 15% olive oil, while the last third served as a control group. The aortic cholesterol concentrations were 98 +/- 25, 57 +/- 9, and 131 +/- 32 mumol/g protein, respectively. The value for the olive-oil group was significantly (p less than 0.01) lower than the value for the control group. The triglyceride concentrations and the distributions of cholesterol between HDL, LDL, and VLDL in plasma showed no significant differences between the plant-oil groups and their control groups. This suggests that plant oils have a direct effect on the aortic cholesterol metabolism.

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PubMedDate not supplied

Reduced atherogenesis in cholesterol-fed diabetic rabbits. Giant lipoproteins do not enter the arterial wall.

In cholesterol-fed rabbits, alloxan-diabetes has an anti-atherogenic effect, which is associated with severe elevation of plasma triglyceride concentrations. To study this effect, we measured lipoprotein sizes and aortic permeability coefficients for cholesteryl ester and for albumin in hypertriglyceridemic diabetic cholesterol-fed rabbits and in normotriglyceridemic cholesterol-fed rabbits. With the same high cholesterol concentration in plasma, hypertriglyceridemic diabetic rabbits had 70% of plasma cholesterol in very large lipoproteins (diameter greater than 75 nm), whereas normotriglyceridemic rabbits had only about 10% of plasma cholesterol in these giant lipoproteins. The aortic permeability coefficients for cholesteryl ester in hypertriglyceridemic diabetic cholesterol-fed rabbits was only 10% to 50% of that in normotriglyceridemic cholesterol-fed rabbits. Aortic permeability coefficients for albumin did not differ significantly between the hypertriglyceridemic and normotriglyceridemic rabbits. The results suggest that the large size of a major fraction of plasma lipoproteins in the hypertriglyceridemic diabetic cholesterol-fed rabbits is responsible for the relatively low aortic permeability coefficient for cholesteryl ester from plasma and hence for reduced atherogenesis in these animals.

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