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F A Kummerow

Publications and source records attributed to F A Kummerow.

At least 55 records · Page 3Linked to original sources
PubMed1994

Combined effects of magnesium deficiency and an atherogenic level of low density lipoprotein on uptake and metabolism of low density lipoprotein by cultured human endothelial cells. II. Electron microscopic data.

The effects of magnesium deficiency on low density lipoprotein (LDL) transport by cultured endothelial cells with a high concentration of LDL (2 mg of LDL cholesterol/ml) were investigated by electron microscopy and by counting the radioactivity of [3H]-LDL transported across an endothelial monolayer grown on culture plate inserts. Electron microscopic examination showed that the number of pits/vesicles in the apical side was time-dependently increased for 24 h in both magnesium-deficient and magnesium-sufficient groups with the exception of 1 h under magnesium sufficiency. The number of pits/vesicles in the basal side was also increased for 8 h in both groups, though there was a decrease at 24 h in the two groups. No difference between either magnesium group at the same time point was statistically significant. [3H]-LDL transport was also time-dependently increased in both magnesium-deficient and magnesium-sufficient groups. In contrast to the results obtained by electron microscopy, the amount of LDL transported under magnesium deficiency was much larger for 24 h than under magnesium sufficiency. Differences in LDL transport between magnesium groups were statistically significant at 4 and 8 h. This finding indicates that magnesium deficiency increases LDL transport across the endothelial monolayer. The increase may be due to energy-dependent movement across endothelial cells, energy-independent movement between cells, or both. However, we conclude that magnesium deficiency increases the energy-dependent LDL transport to some degree since intercellular gap formations were rarely observed in either magnesium group. This LDL transported to the subendothelial space may lead to LDL accumulation and initiate atherosclerosis.

Arteriosclerosis↗
PubMed1994

Tissue lipid peroxidation may be triggered by increased formation of bilirubin in vivo.

Following the administration of phenylhydrazine, cadmium chloride and ethanol to rats there was a marked increase in the concentration of liver lipid peroxides and a sharp decline in GSH levels. The oxidative stress generated by the action of these toxic compounds led to the induction of liver heme oxygenase, which exhibited a 3-fold increase in activity over the control value. Patients with various forms of liver disorders showed increased levels of plasma lipid peroxides as well as hyperbilirubinemia. In view of the known ability of bilirubin to cause lipid peroxidation in illuminated erythrocyte membranes, the results of the present paper suggest that in severely impaired liver, as in some liver diseases, lipid peroxides may be also produced by a mechanism involving heme oxygenase.

Animals↗
PubMed1994

Effect of dietary magnesium deficiency with/without cholesterol supplementation on phospholipid content in liver, plasma and erythrocytes of rabbits.

The effect of magnesium deficiency with/without supplementary cholesterol on phospholipid content in liver, plasma and erythrocytes was investigated in New Zealand White male rabbits. After the rabbits had been fed a low magnesium and/or high cholesterol diet for seven weeks, the phospholipid content in liver, plasma and erythrocytes was measured. Dietary magnesium deficiency produced a marked elevation of total phospholipid and certain individual phospholipids in the rabbit liver. The elevation was accentuated by cholesterol supplementation. In the plasma, a low magnesium intake enhanced plasma phosphatidylcholine, phosphatidic acid, phosphatidylinositol, and sphingomyelin, but an activated conversion from phosphatidylethanolamine to phosphatidylcholine made the increase in phospholipid insignificant. On the other hand, a low magnesium intake restricted the increase in magnitude of phospholipid caused by cholesterol supplementation. In the erythrocytes, total phospholipid, phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine were decreased by a low magnesium and/or a high cholesterol intake. We suggest that the increased contents of total phospholipid and/or certain individual phospholipids in the livers and plasma resulted from the enhanced synthesis of phospholipid in the liver by low magnesium intake. A decreased utilization of food by low magnesium diet limited the magnitude of plasma phospholipid increase produced by cholesterol supplementation.

Animals↗
PubMed1994

Alterations of Ca++ uptake and lipid content in cultured human arterial smooth muscle cells treated with 26-hydroxycholesterol.

The effects of 26-hydroxycholesterol on 45Ca++ uptake, [14C]cholesterol uptake, [14C] acetate incorporation and the concentrations of 26-hydroxycholesterol and cholesterol in the plasma membrane were studied in cultured human smooth muscle cells isolated from umbilical arteries. The results showed that: (1) 26-hydroxycholesterol enhanced markedly 45Ca++ uptake and the enhancement was not diminished by nifedipine; (2) 26-hydroxycholesterol decreased cholesterol content in plasma membrane by inhibiting cholesterol uptake and synthesis, and [14C]cholesterol uptake was not LDL-receptor dependent; (3) 26-hydroxycholesterol induced a shift of [14C] acetate from cholesterol into phospholipid synthesis, but the radioactive incorporation into triglyceride and cholesterol ester was inhibited by 26-hydroxycholesterol; and (4) 26-hydroxycholesterol inserted itself into the plasma membrane. We suggested that 26-hydroxycholesterol changes the composition of membrane lipids with a consequential alteration of membrane permeability to Ca++.

Biological Transport↗
PubMed1993

Plasma lipid physical properties in swine fed margarine or butter in relation to dietary magnesium intake.

Plasma lipids obtained from swine which had been fed butter or margarine at two dietary magnesium (Mg) levels indicated that the level of dietary Mg was more significant to plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels than was the presence of butter or margarine. At 270 mg Mg/kg, which is considered adequate for swine, there was a significant difference in the plasma TC between swine fed margarine and those fed butterfat (105 and 126 mg %, respectively). Plasma LDL-C was higher in swine fed butter than in those fed margarine (88 and 71 mg %, respectively). In swine fed an additional 247 mg Mg/kg, however, there was no significant difference in plasma TC between those fed margarine or butter. Although at 247 mg Mg/kg, however, there was no significant difference in plasma TC between those fed margarine or butter. Although at 247 mg Mg/kg plasma LDL-C was higher in swine fed margarine and HDL-C was higher in those fed butter, there were no significant differences in the order parameters of LDL and HDL. Studies in which the influences of dietary fats on plasma cholesterol were first noted were carried out on liquid diets deficient in Mg. Mg, a cofactor in the enzymes involved in desaturation of saturated fatty acids, is also necessary in desaturation of linoleic to arachidonic acid.

Animals↗
PubMed1993

Cytotoxicity of oxysterols on cultured smooth muscle cells from human umbilical arteries.

The lethal effect of 25- and 26-hydroxycholesterol on smooth muscle cells derived from human umbilical arteries was investigated. The extent of cellular death corresponded with increasing oxysterol concentrations and incubation times. Incubation of the cells with 0.5, 2.5, or 10 micrograms/ml of 25- or 26-hydroxycholesterol revealed a proportionality between the degree of cellular death and oxysterol concentration over the 5 days of the experiment. Correlation coefficients among the degree of cellular death, the exposing period, and oxysterol concentration were significantly different (P < 0.05). However, none of these changes were noted in the smooth muscle cells cultured for 5 days in a medium containing the same concentration of cholesterol or 0.5% ethanol. An increase in the concentration of either serum or cholesterol in the culture medium did not significantly reduce the cytotoxicity of 2.5 micrograms/ml of 26-hydroxycholesterol. The results of this study suggest that oxysterols have an injurious effect on arterial cells, and that the injurious effect could not be altered by cholesterol, which was present at a serum concentration 12 times higher than that of oxysterols.

Cell Death↗
PubMed1993

Modifying effect of 26-hydroxycholesterol on low-magnesium-induced atherosclerotic changes in the cultured human arterial smooth muscle cell.

This study investigated the modifying effect of 26-hydroxycholesterol (26-OHC) on low-Mg(2+)-induced atherosclerotic changes in human arterial smooth muscle cells. Cells were exposed to a medium containing a concentration of 142, 332, 665 and 949 microM Mg2+ (as control) for the designed periods. Half the cells were simultaneously exposed to 10 micrograms/ml of 26-OHC. The results showed that the cytotoxicity of low Mg2+ and the stimulating effect of low Mg2+ on cytosolic free Ca2+ level and 45Ca2+ uptake were accentuated by 26 microns OHC. The significant increase of [3H]thymidine incorporation by Mg2+ level at and lower than 332 was, however, counteracted by 26-OHC. While an increased [3H]leucine incorporation occurred only at a level of 665 microM Mg2+, an additional increase of [3H]leucine incorporation also occurred at a level of 142 microM Mg2+ in the presence of 26-OHC. We suggest that 26-OHC could modify the atherogenic effect of low Mg2+.

Arteriosclerosis↗
PubMed1992

Decreased uptake of low density lipoprotein by LLC-PK cells cultured at low magnesium concentration.

LLC-PK cells grown in tissue culture on medium containing normal or deficient amounts of magnesium were presented with 125I-low density lipoprotein (LDL) and the uptake determined. Total LDL uptake by Mg-deficient cells decreased as the magnesium concentration decreased. The receptor binding of LDL and the internalization of LDL by the Mg-deficient cells were reduced. Degradation of LDL by Mg-deficient cells, when corrected for the reduced uptake, was less affected.

Animals↗
PubMed1992

Effect of magnesium deficiency on 15-hydroxyeicosatetraenoic acid in cultured human umbilical arterial endothelial cells.

Effects of magnesium deficiency on the production of 15-hydroxyeicosatetraenoic acid (15-HETE) and cytosolic free calcium concentration in human umbilical arterial endothelial cells were studied by radioimmunoassay. 15-HETE release by endothelial cells incubated with normal magnesium media (900 microM Mg2+) for 24 h was 2.2 +/- 0.3 ng/mg protein. 15-HETE release gradually increased in proportion to decrease of magnesium. Low magnesium media (180 microM Mg2+) caused an increase in 15-HETE release in a time-dependent manner. Cytosolic free calcium concentration of endothelial cells in normal magnesium media fluctuated between 129.4 nM and 134.2 nM during a 24 h period. Low magnesium media (180 microM Mg2+) caused a time-dependent rise in cytosolic free calcium concentration which is consistent with a time-dependent increase in H-HETE release. High magnesium medium (1800 microM Mg2+) did not have any effect on cytosolic free calcium concentration or 15-HETE production. In conclusion, 15-HETE release by endothelial cells was stimulated by increase in cytosolic free calcium concentration induced by magnesium deficient media. It is suggested that magnesium deficiency induces atherosclerosis via increase in 15-HETE production.

Calcium↗
PubMed1992

Effect of 25-hydroxycholesterol on cytotoxicity and prostacyclin production in cultured human umbilical arterial endothelial cells.

The effect of cholesterol or 25-hydroxycholesterol on DNA synthesis and prostacyclin synthesis by cultured human umbilical arterial endothelial cells was investigated. Cells incubated with 25-hydroxycholesterol showed an increased rate of cell death, decreased [3H]-thymidine incorporation and increased prostacyclin production as compared to either the control or the pure cholesterol group. 25-hydroxycholesterol caused a concentration- and time-dependent increase in prostacyclin synthesis. The intracellular free calcium concentration of endothelial cells incubated with 25-hydroxycholesterol was markedly increased in a time-dependent manner. Calcium uptake by endothelial cells incubated with 25-hydroxycholesterol for 24 h was markedly increased. It is suggested that 25-hydroxycholesterol may depress DNA synthesis and increase prostacyclin synthesis via an elevation in the intracellular free calcium concentration of endothelial cells.

Calcium↗
PubMed1991

Neuropeptide Y stimulates prostacyclin production in porcine vascular endothelial cells.

We investigated the effects of neuropeptide Y on the prostacyclin production of cultured porcine aortic endothelial cells by measuring the stable metabolite of prostacyclin, 6-keto-prostaglandin F1 alpha, by radioimmunoassay. Neuropeptide Y induced dose- and time-dependent stimulation of prostacyclin production by cultured porcine aortic endothelial cells. The lowest stimulatory concentration of neuropeptide Y was 10(-8) M and maximal response, a 2.8 fold rise, was obtained with 10(-6) M. The stimulation lasted at least 24 h. The effect was associated with the stimulation of arachidonic acid release. Our data suggest that neuropeptide Y may inhibit the development of atherosclerosis by stimulating prostacyclin synthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

The effect of cholesterol on the accumulation of intracellular calcium.

Cholesterol/egg phosphatidylcholine (PC) liposomes (1:1 or 4:1, M/M), in which the absolute amount of PC was adjusted to be the same, were incubated with cultured bovine arterial smooth muscle cells for up to 8 h at 37 degrees C. The effect of increased cellular cholesterol on the accumulation of intracellular calcium in these cells was studied. The results indicate that the intracellular calcium content, measured by Fura-2/AM, was increased 2.3-fold by incubation with 4:1, cholesterol/PC liposomes. Kinetic analysis using 45Ca2+ indicated that the increased calcium influx was due to increase of pool size, not from a change of rate constant. (Ca2+ + Mg2+)-ATPase activity was decreased by 4:1, cholesterol/PC liposomes. The molar ratio of cholesterol/phospholipids in the cell membranes was directly proportional to that in liposomes. No change in phospholipid composition was noted. We suggest that the accumulation of intracellular calcium was a composite result due to the altering effect of inserted cholesterol on surface area, and to direct interactions between cholesterol and the proteins of the Ca2+ channel and (Ca2+ + Mg2+)-ATPase.

Animals↗
PubMed1991

The effect of 25-hydroxycholesterol on accumulation of intracellular calcium.

Liposomes prepared with 25-hydroxycholesterol and egg phosphatidylcholine (PC) were incubated with bovine arterial smooth muscle cells for 8 h at 37 degrees C. Cells incubated in the absence of liposomes or with liposomes containing cholesterol and PC were used as controls. The results indicated that calcium accumulated in the smooth muscle cells incubated in the presence of 25-hydroxycholesterol containing liposomes in an amount proportional to the time of incubation. The calcium accumulation, as indicated by kinetic analysis, resulted from an increased compartment size. (Ca(2+)+Mg2+)-ATPase exhibited decreased activity after pretreatment with 25-hydroxycholesterol containing liposomes and the increased intracellular calcium content was directly proportional to the decreased (Ca(2+) + Mg2+)-ATPase activity. When lipids in the cell membrane were examined, a failure to change the cholesterol/phospholipids ratio in the membrane was noted. The 25-hydroxycholesterol content in the membrane determined by HPLC did not increase. An increase in sphingomyelin and a decrease in phosphatidylethanolamine and acidic phospholipids in the membrane was noted. We suggest that the accumulation of intracellular calcium comes from both an increase of calcium influx and a decrease of (Ca(2+) + Mg2+)-ATPase activity, which may be the consequence of changes in membrane phospholipid composition.

Animals↗
PubMed1991

Influence of 26-hydroxycholesterol on the composition and function of gel-filtered platelets.

The influence of 26-hydroxycholesterol (26-OH-CHOL) on the structure and function of gel-filtered rat platelets, as a model membrane, was studied in vitro. Its influence on structure was determined by a fatty acid and a phospholipid analysis of the platelet lipids and on function by the cytoplasmic calcium concentration of the platelets exposed to increasing concentrations of 26-OH-CHOL for various periods of time. The intracellular free calcium (Ca2+)i of the gel-filtered rat platelets was monitored by a fluorescent probe (quin 2) after incubation in a 37 degrees C water bath with 1 mM Ca2+ and 20 microM quin 2/AM. The presence of 26-OH-CHOL in the incubation media changed both the phospholipid composition and the mixed fatty acid composition in the membrane and increased the intracellular free Ca2+ level of the platelets. As the incubation of platelets with cholesterol (CHOL) or esterified 26-OH-CHOL did not increase intracellular Ca2+ levels, these results indicate that the hydrophilic free 26-hydroxy group in 26-OH-CHOL may have influenced the enzymes catalyzing the synthesis of the phospholipid in the platelet membrane so as to allow it to become more and more "leaky" to Ca2+. Such a fundamental change in membrane structure and function may be responsible for the development of atherosclerosis in the intimal layer of the coronary arteries.

Animals↗
PubMed1991

Dietary fat and plasma lipid physical properties in swine.

Changes in the lipid composition of swine lipoprotein were induced by feeding highly saturated or highly unsaturated diets. The diet higher in oleic acid, even when this was a highly unsaturated diet, resulted in a lower order parameter (more fluid) than in the other diets, as has been observed by others. This difference could be detected in whole unfractionated lipoprotein and in isolated high-density lipoprotein. Changes in order parameter with changes in cholesterol/triglyceride, reported by others, were not observed, possibly because of the weighted average effect of measuring whole plasma lipoprotein.

Animals↗
PubMed1990

Effects of a dietary magnesium deficiency and excess vitamin D3 on swine coronary arteries.

The effect of a moderate magnesium (Mg) deficiency on coronary arteries of 61 swine, fed various levels of vitamin D3, was studied by light and electron microscopy. The effect of subnormal Mg intake on vitamin D3-induced intimal lesions of the arteries showed a trend towards increased damage. The degree of cell degeneration and intimal thickening, which was induced by high vitamin D intakes, was as great in swine whose diet was low in Mg and moderately high in vitamin D as it was in those on twice as much vitamin D. Also, the degree of arterial calcification was intensified by inadequate Mg intake at the two higher vitamin D intakes. Present findings indicate that suboptimal dietary Mg, in combination with an excess of vitamin D, has an additive effect in the initiation of ultrastructural changes in the coronary arteries. Extension of the study is indicated to ascertain the extent to which further reduction of Mg intake can potentiate vitamin-D-induced coronary lesions.

Animals↗