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Biomedical subjects

S Stender

Publications and source records attributed to S Stender.

At least 91 records · Page 5Linked to original sources
PubMed1987

In vivo transfer of cholesterol from plasma into human aortic tissue.

It has recently become possible to measure the in vivo flux of cholesteryl ester from plasma into human aortic tissue by use of labeled cholesterol in patients undergoing reconstructive aortic surgery. For the ascending thoracic aorta without visible atherosclerotic lesions the influx was 4.5 +/- 1.4 nmol X cm-2 X day-1 (means +/- SEM, n = 9). For the abdominal aorta with severe atherosclerosis the influx of cholesteryl ester was 45 +/- 5 nmol X cm-2 X day-1 (n = 12). In both types of tissues the influx of cholesteryl ester from HDL was 2-3 times higher than the influx of cholesteryl ester from LDL and VLDL compared with the concentration of these fractions in plasma. This is in accordance with an aortic influx-mechanism which depends on the sizes and the concentration of the lipoproteins in plasma. The transfer of plasma lipoproteins into human aortic tissue shows a number of similarities with the transfer of plasma lipoproteins into the aortic wall of cholesterol-fed rabbits and also with the transfer of other plasma macromolecules across various capillaries. The cholesterol content in intima-media tissue without lesions corresponded in some of the patients to less than one year of continuous influx of cholesteryl ester from plasma. This time is short compared with the age of the patients. It suggests that removal of cholesterol from the aortic wall represents a major importance in prevention of cholesterol accumulation in that tissue.

Aorta↗
PubMed1987

Severe hypertriglyceridemia, large lipoproteins and protection against atherosclerosis.

Alloxan-diabetic cholesterol-fed rabbits exhibiting severe hypertriglyceridemia are protected against atherosclerosis. In such rabbits most of the plasma cholesterol is found in lipoproteins with a diameter of 75 nm or larger. In the present report it is hypothesized, that due to their large sizes, the lipoproteins of the severely hypertriglyceridemic diabetic rabbits are not able to penetrate the endothelial layer of the arteries. Therefore, the macrophages and smooth muscle cells of the intima will only come in contact with relatively small amounts of cholesterol-carrying lipoproteins. Consequently, cellular accumulation of cholesterol, which is a necessary step in the formation of an atherosclerotic lesion, will be retarded. There are certain parallels between hypertriglyceridemic cholesterol-fed alloxan-diabetic rabbits and humans with familial lipoprotein lipase deficiency, familial apolipoprotein C-II deficiency and insulin-dependent diabetes mellitus in the ketoacidotic state. Based on reports about patients with these metabolic disorders, we suggest that cholesterol in very large lipoproteins also in humans is less atherogenic than cholesterol in smaller lipoproteins.

Animals↗
PubMed1986

Effect of verapamil on accumulation of free and esterified cholesterol in the thoracic aorta of cholesterol-fed rabbits.

In order to investigate the effect of the calcium antagonist verapamil on atherogenesis in cholesterol-fed rabbits, 3 groups of 11 animals were fed a 2% cholesterol-enriched diet for 10 weeks. One group received verapamil in a daily dose of 16 mg/kg orally plus 2 mg/kg subcutaneously. This dosage resulted in plasma concentrations of verapamil in the same range as the usual therapeutic levels in humans. Another group received verapamil in a daily dose of 8 mg/kg orally and 0.5 mg/kg subcutaneously. The third group received placebo capsules orally and isotonic saline subcutaneously. Total cholesterol concentrations in plasma over the 10 weeks were 37 +/- 4, 42 +/- 4 and 45 +/- 3 mM (mean +/- SE) in the high verapamil-, in the low verapamil- and in the placebo group, respectively. These values were not significantly different. The distribution of cholesterol between HDL, LDL and VLDL in plasma was similar in the 3 groups. The high verapamil group had a significantly (P less than 0.05) lower concentration of cholesterol in the thoracic aorta than the placebo group (29 +/- 5 vs 43 +/- 9 mumol/g wet weight). The low verapamil group and the placebo group had the same aortic cholesterol concentrations. Neither dosage of verapamil affected the permeability of the aortic endothelium to plasma lipoproteins and albumin, as measured by use of radioactive tracers at the end of the experiment.

Animals↗
PubMed1984

In vivo influx of free and esterified plasma cholesterol into human aortic tissue without atherosclerotic lesions.

In order to determine the in vivo influx of plasma cholesterol into human aortic intimamedia tissue, specimens of the ascending aortic wall without visible atherosclerosis were obtained from patients undergoing aortic valve replacement. Before the operation the patients were intravenously injected with autologous plasma in which the lipoproteins were labeled with radioactive cholesterol. The influence of the duration of the exposure time (0.3-114 h) and of the distribution of radioactivity between free and esterified cholesterol in plasma on the amount of radioactivity found in the arterial wall was studied by the simultaneous use of 3H- and 14C-cholesterol. It was shown that the influx of free and esterified cholesterol into the intima-media layer of the tissue could be calculated from a set of linear equations that relate the labeled sterols in the tissue to the average specific activities in plasma. In nine patients between 50 and 70 yr of age with 4.2-5.9 mM total cholesterol in plasma, the influx of free cholesterol and of esterified cholesterol was 1.2-8.8 and 1.0-12.5 nmol X cm-2 X d-1, respectively. Both hydrolysis and esterification of the sterol fractions in the aortic tissue and exchange of free cholesterol between the plasma lipoproteins and the tissue were demonstrated. The cholesterol content of the intima-media layer was 0.6-2.3 mumol X cm-2. This corresponds to the influx of esterified cholesterol during a period of only 0.1-3.5 yr, which is short compared with the lifespan of the patient. Our data thus suggest that removal of esterified cholesterol from aortic tissue without visible atherosclerosis represents a major importance for the cholesterol concentration in the tissue.

Adult↗
PubMed1982

The in vivo transfer of free and esterified cholesterol from plasma into the arterial wall of hypercholesterolemic rabbits.

With a new technique based on the simultaneous use of 3H and 14C-cholesterol, the fluxes of free and esterified cholesterol into the thoracic aorta of the hypercholesterolemic rabbits have been measured. By additional use of 3H-leucine as tracer for apoproteins, it was shown that esterified cholesterol in plasma enters the arterial tissue mainly as part of a lipoprotein influx. In contrast, only between 20 and 90% of the influx of free cholesterol could be accounted for by an influx of plasma lipoproteins. The excess probably represents an exchange of free cholesterol between the plasma lipoproteins and the intimal surface of the artery. Some 5-40% of the esterified cholesterol which had entered the artery during a 3-6 hours period was hydrolyzed in the artery during that period, whereas only negligible amounts of newly-entered free cholesterol was esterified. The arterial influx of very low, low and high density lipoproteins or albumin was determined in the same animal. The influx of each fraction was expressed as an intimal clearance, i.e., the influx divided by its plasma concentration. The intimal clearances of these macromolecules decreased linearly with the logarithm of their diameters. This suggests that the arterial influx of plasma lipoproteins and of albumin proceed by the same mechanism, which involves a steric hindrance for these macromolecules in the influx pathway.

Animals↗
PubMed1981

In vivo influx, tissue esterification and hydrolysis of free and esterified plasma cholesterol in the cholesterol-fed rabbit.

The influx of free and esterified cholesterol into various tissues of cholesterol-fed rabbits is calculated from the tissue [3H] cholesterol and [14C] cholesterol content - corrected for radioactivity in contaminating plasma - after a 3--6 h exposure to in vivo-labeled plasma. The plasma free cholesterol was labeled primarily with 3H and the esterified cholesterol with 14C or vice versa. The influx calculation is based on total 3H and 14C in tissues and two linear equations that take into account esterification and hydrolysis of sterol fractions by the tissues. The influx of esterified cholesterol into tissue samples from aorta, heart, small intestine and lung was 10--80 nmol-g--1-h--1, whereas the influx into adrenal, spleen and liver was from 400--2500 nmol--g-1--h-1. The influx of free cholesterol was considerably higher than expected if free and esterified cholesterol had entered the tissues together as part of plasma lipoproteins. This excess of free cholesterol influx can be ascribed to cholesterol exchange between plasma lipoproteins and tissues, which in several tissues amounted to more than 80% of the total free cholesterol influx. From tissue free and esterified cholesterol radioactivity, one can calculate that 20--70% of the newly entered esterified cholesterol was hydrolyzed by various tissues and that most tissues esterified less than 10% of newly entered cholesterol during the experimental period. However, esterification of plasma cholesterol by adrenals averaged 50% of that taken up during a 3-6 h period.

Animals↗
PubMed1980

Effect of chronic uremia on plasma lipids and the aortic accumulation of cholesterol in hypercholesterolemic rabbits.

14 rabbits were made uremic by extensive cauterization and subsequent removal of the contralateral kidney, resulting in a mean plasma creatinine concentration four times the value observed in a sham-operated control group. The animals were killed after 10 weeks of uremia. During the last 7 weeks the rabbits were fed an individually adjusted amount of cholesterol in order to maintain the same elevated level of plasma cholesterol in both groups. The triglyceride concentration was four times higher in the uremic than in the control group. In spite of the same average level of total plasma cholesterol the uremic rabbits had a lower concentration of cholesterol in the VLDL-fraction than the controls. None of the aortas had intimal lesions macroscopically. There were no significant differences between the two groups in the 48-hour accumulation of radioactive cholesterol or in the amount of free and esterified cholesterol in the aortas. Thus, no significant effect on cholesterol accumulation by uremia in the aorta of hypercholesterolemic rabbits was demonstrated.

Animals↗
PubMed1979

Arterial entrance and metabolism of free and esterified plasma cholesterol measured in vivo in experimental animals by a dual isotope method.

The arterial walls of 3 cholesterol-fed rabbits were exposed for 3--4 hours in vivo to homologous cholesterol-labelled plasma with a 20-fold higher [3H/14C] ratio in esterified cholesterol (EC) than in free cholesterol (FC). The [3H/14C] ratio in total cholesterol (TC) in the thoracic aorta was 0.6--0.9 times the ratio prevailing in TC in plasma. This corresponds to a transfer from plasma into the arterial wall of relatively more FC, with the low ratio, than EC with the higher ratio. The [3H/14C] ratio in FC in the arterial wall was 1.4--2.0 times the ratio in FC in plasma. This corresponds to hydrolysis of some of the entered EC, adding cholesterol with the high ratio to FC with the lower ratio. The [3H/14C] ratio in EC in the arterial wall was 0.1--1.1 times the ratio in EC in plasma. This corresponds to no esterification in the arterial wall of entered FC. The same method applied to normolipidemic cockerels gave similar results. In a kinetic model the arterial influx from plasma of FC and EC combined (lipoprotein influx) corresponded in both groups to 20--90 nl plasma per cm2 arterial surface per hour with subsequent hydrolysis of 10--50% of the entered EC. The arterial influx of FC without EC (influx by exchange) accounted for 10--25% of the total influx of cholesterol in the rabbits and 40--70% in the cockerels.

Animals↗
PubMed1978

The effect in vitro of ionizing irradiation and small rises in temperature on the uptake and release of labelled lipids by the human erythrocyte membrane.

1. The effect of X-irradiation (50 000 rad) and an increase in temperature from 37 to 42 degrees C on the synthesis, uptake and release of labelled lipids by erythrocytes was studied in plasma incubations in vitro. 2. Both irradiation and a rise in temperature resulted in an inhanced synthesis of [32P]phosphatidic acid in the erythrocytes. 3. The uptake by the erythrocytes of 14C- and 3H-labelled cholesterol, [14C, 32P]phosphatidylethanolamine and [14C, 32P]phosphatidylcholine from plasma lipoproteins was increased by a rise in temperature but not by irradiation. These labelled lipids were apparently taken up in the ratio in which they were found in plasma. They were not released from the erythrocytes in the same manner.

Cholesterol↗
PubMed1978

Uptake of labelled free and esterified cholesterol from plasma by the aortic intima--media tissue measured in vivo in three animal species.

Hyperlipemic stilboestrol-treated cockerels, cholesterol-fed rabbits and minipigs, as well as normolipemic cockerels and rabbits were injected intravenously with homologous plasma of corresponding lipid concentration labelled in vivo with radioactive cholesterol. The ratios between labelled free cholesterol and labelled esterified cholesterol in the intima--media from the thoracic aorta of these 5 groups of animals were respectively 1-, 2-, 8-, 2- and 20-fold greater than the corresponding average tracer ratio in plasma during the uptake period of 4--6 h. The intima--media tissue in the coronary arteries studied in one minipig contained 2--5 times more labelled cholesterol per mg wet weight than corresponding aortic tissue. This arterial uptake of labelled cholesterol in the minipigs was measured concomitantly with the uptake of phosphatidylcholine and plasma protein labelled in vivo. The uptake for these various tracers in the minipig suggested entry of labelled free and esterified cholesterol into the arterial wall, mainly as part of the plasma lipoproteins, with subsequent hydrolysis in the arterial wall of some of the cholesterol ester. In the stilboestrol-treated cockerels hydrolysis of cholesterol ester seems to be absent. The relatively higher uptake in the minipig of the labelled plasma protein (albumin) than of the lipoprotein (as traced by its lipids) suggests a molecular weight-dependent arterial entry of these plasma macromolecules.

Animals↗
PubMed1977

Glucosamine and experimental atherosclerosis. Increased wet weight and changed composition of cholesterol fatty acids in aorta of rabbits fed a cholesterol-enriched diet with added glucosamine.

Three groups of each 12 rabbits were fed a cholesterol-enriched diet. Glucosamine was added in amounts of 0.5% and 2.0% (w/w) to the diet of two of the groups, while the third group served as a control group. The amount of cholesterol in the diet was individually adjusted, so that all rabbits experimental period. Glucosamine did not affect the concentration response of serum cholesterol to dietary cholesterol or the amount of free and esterified cholesterol in the inner aorta. It did, however, cause an increase in the wet weight of the inner aorta with a corresponding decrease in the concentration of aortic cholesterol. Furthermore a decrease in the ratio between mono-unsaturated and di-unsaturated fatty acids of the cholesterol esters of serum and inner aorta were observed in the animals which received glucosamine.

Animals↗