Acid Low Density Lipoprotein Research Articles

Decreased resistance against in vitro oxidation of LDL from patients with familial defective apolipoprotein B-100.

Familial defective apolipoprotein B-100 (FDB) is caused by a mutation in the receptor-binding region of apolipoprotein B-100, the structural protein of the low-density lipoprotein (LDL) particle. We studied the effect of this mutation on the composition and susceptibility to oxidative modification of LDL in patients with FDB. Twenty Dutch carriers of the mutation identified in a family study were matched with 20 unaffected siblings of similar age and sex. The mean concentration of LDL cholesterol was 5.19 +/- 0.94 versus 2.9 +/- 0.5 mmol/L in control subjects (P < .0001). Measurement of LDL oxidizability in vitro by continuously monitoring conjugated-diene absorbance showed that LDL from FDB patients was significantly less resistant against oxidation (lag time, 90 +/- 22 minutes versus 108 +/- 21 minutes; P < .05); furthermore, the maximal rate of diene production and total diene production were also significantly increased. Analysis of the chemical composition revealed an increased relative content of cholesteryl esters and reduced content of protein in the LDL of FDB patients (cholesterol-to-protein ratio, 1.54 +/- 0.24 versus 1.25 +/- 0.23; P < .01). The relative amount of arachidonic acid in LDL was increased and that of stearic acid was decreased. The vitamin E (alpha-tocopherol) content per gram of LDL protein was similar to that in control subjects. The relative amount of cholesteryl esters and protein in LDL as well as the fatty acid composition were significantly correlated with LDL oxidizability. Thus, compositional factors in LDL resulting in increased susceptibility to oxidative modification may contribute to the increased risk of premature vascular disease in FDB.

Fatty acid composition and the oxidation of low-density lipoproteins.

The effect of the fatty acid composition of low-density lipoprotein (LDL) on copper-ion-catalyzed oxidation of isolated LDL was examined in 18 normolipidemic men. The decrease in LDL linoleic acid concentration (delta L) during oxidation was found to be strongly correlated with initial LDL linoleic acid concentration (r = 0.976, n = 18, P < 0.001), whereas the production of thiobarbituric acid reacting substances (TBARS) was not. The concentration of oleic acid in LDL was then increased significantly (mean increase 20%, P < 0.05) in 8 male volunteers by a daily dietary supplement of rapeseed oil/muesli for 4 weeks. The mean delay before copper-ion-catalyzed production of conjugated dienes (the lag phase) was significantly (P < 0.001) greater in LDL isolated after the study period (67 min) than that of before the study period (40 min). The rate of formation of conjugated dienes, delta L and TBARS production during oxidation of LDL was not significantly altered by the rapeseed oil/muesli supplement. These results suggest that the linoleic acid content of LDL is a determinant of individual variability in LDL oxidation, and that a rapeseed oil/muesli dietary supplement reduces the susceptibility of LDL to oxidation.

Separation of the dietary fat and cholesterol influences on plasma lipoproteins of rhesus monkeys

In order to isolate the effects of the type of dietary fat from those of dietary cholesterol on the circulating pool of cholesterol, plasma lipoproteins were characterized in juvenile rhesus monkeys fed semipurified diets containing 31% of calories as corn oil or coconut oil. Half the diets contained 300 mg of cholesterol per 1000 kcal. The fatty acids of cholesteryl esters and phospholipids varied significantly with dietary fat such that saturated and monounsaturated fatty acids replaced polyunsaturated fatty acids in low-density lipoproteins (LDL) and high density-lipoproteins of rhesus monkeys fed coconut oil. Dietary cholesterol alone induced small but significant increases in the cholesteryl ester: triglyceride ratio in both very low-density lipoproteins and LDL. Whereas neither saturated fat (coconut oil) nor cholesterol alone substantially altered the plasma cholesterol concentration or lipoprotein profile, together these dietary components interacted synergistically to produce a significant elevation in plasma cholesterol. This was due primarily to a significant rise in the cholesteryl ester fraction of LDL, disproportionate to any change in LDL protein concentration. The data are consistent with current hypotheses that relate parameters of LDL turnover and clearance to their macromolecular structure and physicochemical characteristics.

Utilization of free fatty acids complexed to human plasma lipoproteins by mammalian cell suspensions

The purpose of this study was to determine whether lipoprotein-bound free fatty acid could be utilized by isolated mammalian cells. Ehrlich ascites tumor cells were incubated in vitro with radioactive free fatty acids that were bound to human plasma lipoproteins. Under these conditions, lipoprotein-bound free fatty acids were readily taken up by the cells. After 2 min of incubation with free fatty acids bound to low density lipoproteins, most of the radioactivity that was associated with the cells was in the form of free fatty acids. As the incubation continued, increasing amounts of radioactivity were incorporated into CO(2) and cell lipids, particularly phospholipids. Most of the free fatty acid uptake was the result of fatty acid transfer from low density lipoproteins to the cell, not from irreversible incorporation of the intact free fatty acid-low density lipoprotein complex. Fatty acid uptake increased as the ratio of free fatty acid to low density lipoprotein was raised. When albumin was added to the medium, free fatty acid uptake decreased. A large percentage of the newly incorporated cellular radioactivity was released into the medium if the cells were exposed subsequently to a solution containing albumin. Most of the released radioactivity was in the form of free fatty acid. The results with this experimental model suggest that lipoprotein-bound free fatty acid, like albumin-bound free fatty acid, is readily available for uptake by isolated cells. The mechanism of free fatty acid utilization by the Ehrlich cell is similar when either low density lipoprotein or serum albumin serves as the fatty acid carrier.