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L L Rudel

Publications and source records attributed to L L Rudel.

At least 127 records · Page 7Linked to original sources
PubMed1978

Studies on the structure of low density lipoproteins isolated from Macaca fascicularis fed an atherogenic diet.

Cynomolgus monkeys, Macaca fascicularis, fed cholesterol-containing saturated-fat diets develop increased levels of high molecular weight plasma low density lipoproteins (LDL), associated with accelerated atherosclerosis. To study the composition and structure of these abnormal particles, LDL from monkeys, fed atherogenic and control diets, were characterized chemically and examined by differential scanning calorimetry and low-angle X-ray scattering. LDL from animals on the experimental diet showed an increase in molecular weight (4.0 to 7.0 x 10(6), experimental diet compared with 3.0 to 3.7 x 10(6), control diet) associated with a large increase in cholesterol ester content and concomitant smaller increases in protein, phospholipid, and free cholesterol. There was a strong positive correlation between molecular weight and the number of saturated and monounsaturated cholesterol esters in the particle. In contrast, particle content of polyunsaturated cholesterol esters remained constant despite large changes in total particle cholesterol esters.When examined by calorimetry and X-ray scattering, LDL from monkeys on both diets diplayed a reversible transition of cholesterol esters from an ordered smeticlike (layered) structure to a more disordered state. For all animals on the experimental diet, the peak temperature of the cholesterol-ester transition (42-48 degrees C) was above body temperature (39 degrees C), but below body temperature on the control diet (34-38.5 degrees C). In the experimental group, the transition temperature was correlated with the LDL molecular weight. However, after thermal disruption of LDL, liquid-crystalline transitions of LDL cholesterol esters were observed in the same temperature range as in the intact lipoprotein, which shows that changes in particle size had little effect on the cholesterol-ester transition temperature. Rather, the transition temperature was determined by the degree of saturation of the LDL cholesterol ester fatty acids and the LDL cholesterol ester: triglyceride ratio, both of which correlated with increased LDL molecular weight.The existence of smectic-like cholesterol ester in LDL at body temperature was clearly a discriminating feature between monkeys on control and experimental diets. Diet-induced changes in the lipid composition of precursor lipoproteins of LDL appeared to lead to the existence of smectic-like cholesterol ester in LDL above body temperature. The altered composition and structure of the core lipids of high molecular weight LDL probably account, in part, for the previously documented correlation between increased LDL molecular weight and atherosclerosis in this species.

Animals↗
PubMed1978

Male--female variability in the dietary cholesterol-induced hyperlipoproteinemia of cynomolgus monkeys (Macaca fascicularis).

The characteristics of dietary cholesterol-induced hyperlipoproteinemia were studied in adult Macaca fascicularis to determine if significant male--female differences could be identified. The plasma lipoproteins from individual animals were separated by agarose column chromatography and the resulting size populations of lipoproteins were chemically characterized. The distribution of constituents among the lipoprotein classes was determined. The lipoproteins that increased most significantly in response to dietary cholesterol were the low density lipoproteins (LDL) which were those of region III of the column elution profile. The LDL mass concentrations (in mg/dl of plasma) were not different between males and females. However, these lipoproteins showed a characteristic difference between males and females in response to dietary cholesterol. The primary response in the males was an increased LDL molecular weight. In females, the primary response was an increased number of LDL particles (measured as mumolar concentration). Thus, at the same LDL mass concentration, males had significantly larger LDL particles and yet fewer of them. Analysis of the chemical composition data showed that size differences between LDL of males and females was due primarily to the incorporation of more cholesteryl ester into the LDL particles from male animals; the content per LDL particle of free cholesterol, phospholipid, and protein showed the same proportionality to size for both sexes. Another significant difference between lipoproteins of males and females was in the extent to which the plasma HDL (identified in these studies as the lipoproteins of region IV of the elution profile) decreased in response to dietary cholesterol. Chemical composition differences were also noted. The HDL particles of males and of cholesterol-fed animals contained more cholesteryl ester than did HDL of females and control animals, respectively.

Animals↗
PubMed1977

Characterization of plasma low density lipoproteins on nonhuman primates fed dietary cholesterol.

LDL from animals of three nonhuman primate species, Macaca mulatta, Macaca fascicularis, and Cercopithecus aethiops, were studied. A standard preparation of 125I-LDL was added to isolated lipoprotein mixtures just prior to separation of plasma lipoproteins by agarose gel chromatography. A relative size index, rI, was determined by dividing the elution volume of the iodinated LDL by the elution volume of the sample LDL, both volumes being determined simultaneously during chromatographic elution. Comparison of rI with molecular weights measured by flotation equilibrium analysis in the analytical ultracentrifuge showed a linear relationship across a molecular weight range of 2.5-8.0 X 10(6), r = 0.985. A regression equation describing this relationship was used to calculate molecular weights of LDL from a group of M. fascicularis that were fed cholesterol-containing diets. In these animals, plasma cholesterol concentration ranged from 100 to over 700 mg/dl and was highly correlated with LDL molecular weight and with the micromolar concentration of the LDL. Using multiple regression analyses, the two variables of plasma LDL could be shown to account for 94% of the variation in plasma cholesterol concentration in the M. fascicularis of this study. Micromolar concentration and molecular weight of LDL were not correlated with each other, suggesting that in M. fascicularis at least two independent types of controls are operative in the response of plasma LDL to dietary cholesterol. The increase in LDL molecular weight was associated with a large increase in cholesteryl ester content and concomitant smaller increases in protein, phospholipid, and free cholesterol. As molecular weight increased, these components appeared to be added to the LDL particles together as discrete increments of fixed composition. The data are consistent with a spherical model of LDL structure with a core of cholesteryl ester and triglyceride and a 21.3 A-thick coat of phospholipid, free cholesterol, and protein.

Animals↗
PubMed1977

Separation and characterization of plasma lipoproteins of rhesus monkeys (Macaca mulatta).

A group of 14 adult male rhesus monkeys was maintained on a low cholesterol-high fat diet. Periodically, animals were fasted and blood samples were taken for characterization of the plasma lipoproteins. Complete separation of individual plasma lipoprotein classes was not achieved by traditional sequential ultracentrifugation techniques. Rather, initial separation of lipoprotein classes according to size was effected and density centrifugation was used subsequently for further separation. At least six lipoprotein fractions were identified, each of which was unique as defined by the properties of size, density (d), and electrophoretic mobility. These lipoprotein fractions were characterized by determination of chemical compositions and apoprotein patterns. The lipoproteins present in highest concentration in these monkeys were designated as region IV lipoproteins. This fraction had alpha-migration on agarose electrophoresis, 1.063 < d < 1.225, and the size, composition, and apoprotein pattern characteristic of HDL. No fewer than three fractions were identified with densities that overlapped the 1.019 < d < 1.063 range. Of these, the fraction designated as region III lipoproteins was present in highest concentration, had beta-migration by agarose electrophoresis, a predominant B apoprotein, and a chemical composition and size characteristic of LDL. Two larger subfractions, identified as region II lipoproteins, were separated from each other at a density of 1.050 g/ml. Agarose electrophoresis showed that the fraction with d < 1.050 had a migration intermediate between beta and pre-beta. The chemical composition and apoprotein pattern were consistent with the possibility that these lipoproteins were remnants of VLDL catabolism. The fraction with d > 1.050, had pre-beta mobility and a size and composition similar to the Lp(a) lipoprotein in plasma of human beings. At least two VLDL subfractions, identified as region I and IIa lipoproteins, were found although both were present in very low concentrations. Region I lipoproteins were larger and contained relatively more cholesteryl ester and more of the apoproteins that migrated with the mobility of apo-B and arg-rich apoprotein in SDS-polyacrylamide gel electrophoresis. Some of the region I lipoproteins were beta-migrating by agarose electrophoresis. These results suggested the possibility that a beta-migrating VLDL was present in these normal animals.

Animals↗
PubMed1974

Characterization of plasma lipoproteins separated and purified by agarose-column chromatography.

1. A simple method for isolation of individual human plasma lipoprotein classes is presented. In this technique, lipoproteins are removed from plasma at d1.225 by ultracentrifugation, after which they are separated and purified by agarose-column chromatography. 2. Three major classes are obtained after agarose-column chromatography. Separation between classes is excellent; more than 95% of the lipoproteins eluted from the column are recovered in the form of a purified lipoprotein class. 3. Each lipoprotein class was characterized immunologically, chemically, electrophoretically and by electron microscopy. A comparison of the properties of the column-isolated lipoproteins was made with very-low-density lipoproteins, low-density lipoproteins, and high-density lipoproteins separated by sequential ultracentrifugation at densities of 1.006, 1.063 and 1.21 respectively. 4. By each criterion, peak-I lipoproteins from the agarose column are the same as very-low-density lipoproteins, peak-II lipoproteins are the same as low-density lipoproteins, and peak-III lipoproteins are the same as high-density lipoproteins. Thus the lipoprotein classes isolated by both methods are similar if not identical. 5. The agarose-column separation technique offers the advantage of a two- to three-fold saving in time. In addition, the column-elution pattern serves as a recording of the size distribution of lipoproteins in plasma. 6. The most complete characterization is reported for human plasma lipoproteins. The results with rhesus-monkey and rabbit lipoproteins were identical.

Animals↗
PubMed1973

Exogenous cholesterol transport in rabbit plasma lipoproteins.

1. The appearance of exogenous cholesterol in free cholesterol and ester cholesterol of plasma chylomicra, very-low-density (VLD), low-density (LD) and high-density (HD) lipoproteins was studied in unanaesthetized rabbits after ingestion of a meal containing 5% fat and 0.08% [(3)H]cholesterol. 2. The specific radioactivity of ester cholesterol of VLD lipoproteins reached the highest value of any lipoprotein fraction and for each lipoprotein it increased at a faster rate and reached a higher maximum than that of free cholesterol; the maximum in VLD lipoproteins occurred later than in chylomicra. 3. The pattern of appearance of exogenous cholesterol in chylomicra and VLD lipoproteins of plasma was similar to the pattern previously observed in lymph. The specific radioactivity of ester cholesterol in plasma VLD lipoproteins was higher than that in chylomicra in spite of a larger pool size and dilution of cholesteryl esters from VLD lipoproteins produced by the liver. These results support the concept that during absorption the major portion of exogenous cholesterol is transported in VLD lipoproteins as ester cholesterol. 4. The specific radioactivity of ester cholesterol of chylomicra and VLD lipoproteins increased at a faster rate than that of LD and HD lipoproteins. However, the rate of increase and the absolute values of the specific radioactivity in LD and HD lipoproteins were identical. Since cholesteryl esters are thought not to exchange between lipoproteins, this observation supports the hypothesis that a result of VLD lipoprotein and chylomicron metabolism is the formation of LD and HD lipoproteins. 5. Results in vivo showed that the free cholesterol of individual plasma lipoproteins does not equilibrate within a period of 24h.

Journal Article↗
PubMed1973

Determination of cholesterol using o-phthalaldehyde.

A simple, rapid method for the determination of cholesterol in plasma and tissue using o-phthalaldehyde is presented. Comparison of this method with the FeCl(3) method gave identical results. However, the o-phthalaldehyde determination is three times more sensitive than the FeCl(3) determination (molar extinction coefficients of 11,610 and 33,440 for FeCl(3) and o-phthalaldehyde, respectively), it takes less time to complete, and the color developed is more stable. The o-phthalaldehyde method can be used to assay free and esterified cholesterol directly after thin-layer chromatographic separation.

Journal Article↗
PubMed1972

The transport of exogenous cholesterol in the rabbit. I. Role of cholesterol ester of lymph chylomicra and lymph very low density lipoproteins in absorption.

Thoracic lymph duct cannulations were performed shortly after a meal in rabbits trained to ingest a moderate fat, low cholesterol diet. A tracer dose of cholesterol-(3)H was administered to label exogenous (dietary) cholesterol during absorption. Sequential lymph samples were collected up to 24 hr postprandially, after which ultracentrifugal fractionation of lymph lipoproteins was carried out. The d < 1.006 lipoproteins were separated into two classes, chylomicra and very low density lipoproteins (VLDL).A comparison was made between chylomicra and VLDL of lymph in the transport of exogenous cholesterol after ingestion of a single meal. The per cent of exogenous cholesterol present in VLDL of sequential lymph collections progressively increased with time after a meal and by 18 hr had reached a value of 80% or greater. In chylomicra the per cent of exogenous cholesterol of sequential lymph collections progressively decreased. Therefore, exogenous cholesterol was preferentially transported in VLDL compared with chylomicra. Cholesterol ester specific activity (CESA) of lymph chylomicra and VLDL increased at a more rapid rate than free cholesterol specific activity (FCSA). CESA of VLDL was three times higher than FCSA at the maximum. Exogenous cholesterol which appeared in both chylomicra and VLDL was consistently 80% esterified. while the per cent of total cholesterol esterified decreased with time and was significantly lower than that for exogenous cholesterol from 6 to 24 hr postprandially. These results demonstrate preferential esterification of exogenous cholesterol during absorption and indicate that a mechanism exists within the intestinal mucosal cell to maintain both free and esterified exogenous cholesterol in a chemically distinct pool from endogenous cholesterol during incorporation into both chylomicra and VLDL.

Animals↗
PubMedDate not supplied

Dietary ethanol-induced modifications in hyperlipoproteinemia and atherosclerosis in nonhuman primates (Macaca nemestrina).

Male Macaca nemestrina were studied in an experiment with a 2 x 2 factorial design. Diets contained low vs high cholesterol levels (0.3 vs 1.0 mg/Kcal) and no ethanol or ethanol, as 36% of the calories substituted isocalorically for carbohydrate. After receiving their diets for 18 months, the monkeys had blood samples drawn for lipoprotein analyses, and then were killed for evaluation of the extent of atherosclerosis. Ethanol-fed groups had significantly increased concentrations of serum cholesterol, triglycerides, low density lipoprotein, and high density lipoprotein. The molecular weight of the low density lipoprotein particles was lower in ethanol-fed animals and the cholesterol esters of low density lipoprotein and high density lipoprotein contained relatively more cholesteryl linoleate and less cholesteryl oleate. Dietary cholesterol had the effect of increasing the concentration of low density lipoprotein (primarily via increasing the low density lipoprotein molecular weight) and decreasing the concentration of high density lipoprotein. Significant interactions were found between the effects of ethanol and cholesterol on high density lipoprotein and low density lipoprotein. Ethanol significantly decreased the cholesterol-induced atherosclerosis found in the aorta and coronary arteries. Highly significant correlations between coronary artery atherosclerosis and low density lipoprotein cholesterol ester pattern were found. In contrast, low density lipoprotein molar concentration (number of low density lipoprotein particles per liter of plasma) was not significantly correlated with coronary artery atherosclerosis. Different relationships with aortic atherosclerosis were found; low density lipoprotein molecular weight and cholesterol ester pattern were highly correlated, while high density lipoprotein concentration was not. The high correlations found between lipoprotein characteristics and atherosclerosis severity have been mediated through its effects on the plasma lipoproteins.

Animals↗
PubMedDate not supplied

Species, diet, and gender differences in plasma postheparin lipolytic activities in nonhuman primates. Relationships with plasma lipids and high density lipoproteins.

Studies were done in selected groups of nonhuman primates in which the diet (low fat and high fat as either polyunsaturated or saturated fat), gender, and species (African green monkeys and cynomolgus monkeys) were varied. Large differences in plasma lipid and lipoprotein concentrations were found among these groups, providing the opportunity to examine their relationships to postheparin lipolytic activities (PHLA) including lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL). PHLA was measured in plasma drawn 20 minutes after injection of heparin (100 units/kg). The assay was done with a radioactive triglyceride emulsion, and LPL and HTGL activities were estimated after 1 M NaCl inhibition of the former. LPL activity was high in both species of monkeys, and HTGL activity was low; the ratio of HTGL/LPL was consistently less than 0.5. The mean values for LPL activity did not vary significantly among experimental groups, but significant negative correlations between LPL activity and plasma triglyceride concentration were found. Statistically significant diet, species, and gender differences in HTGL activities were found. In high-fat-fed compared to low-fat-fed animals, HTGL activities were higher, and high density lipoprotein (HDL) cholesterol concentrations and the percentages of HDL2b were also higher. African green monkeys had consistently higher HTGL activities than cynomolgus monkeys and had higher concentrations of HDL cholesterol and a greater proportion of HDL as the larger HDL2b subfraction. Significantly lower HTGL activities were found in females compared to males fed the low-fat diets, and females had a significantly greater proportion of total HDL in the HDL2b subfraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Effect of dietary fish oil on coronary artery and aortic atherosclerosis in African green monkeys.

Studies were carried out for 2.5 to 3 years in adult male African green monkeys (grivet subspecies) fed diets containing 22% of calories as lard or fish oil with 40% of calories as fat and 0.75 mg cholesterol/Kcal to determine if isocaloric substitution of menhaden fish oil for lard affects coronary artery atherosclerosis. The average total plasma cholesterol concentrations during the experimental period were significantly lower for the fish-oil group (231 +/- 37 mg/dl) compared to the lard group (360 +/- 44 mg/dl), but this difference did not become apparent until after 5 months of experimental diet consumption. High density lipoprotein cholesterol concentrations were 30% lower (p less than 0.01) for the fish-oil group also (57 +/- 5 vs. 82 +/- 6 mg/dl). Plasma triglyceride concentrations were low for both groups, but after about 5 months of diet consumption, they were higher for the animals fed fish oil (25 +/- 2 mg/dl) compared to their lard-fed counterparts (15 +/- 1 mg/dl). Coronary artery intimal area (in this case a measure of early atherosclerotic lesion size) was low in all animals but was significantly less (p less than 0.03) for the fish oil vs. lard groups (0.01 +/- 0.002 vs. 0.03 +/- 0.009 mm2). More atherosclerosis was found in other arteries, and a trend was seen of less atherosclerosis in the thoracic aorta and common carotid arteries of the fish-oil group. The size of lesions in the abdominal aorta was similar between diet groups, but microscopic examination of arteries of the lard group revealed relatively more cholesterol monohydrate crystals compared to the arteries of the fish-oil group. Chemical analysis showed that there was less esterified cholesterol (1.46 +/- 0.71 vs. 3.43 +/- 0.74 mg/g, p = 0.04) and free cholesterol (3.7 +/- 2.15 vs. 7.05 +/- 1.68 mg/g, p = 0.08) in the abdominal aortas taken from the animals fed fish oil. There was a significant correlation between low density lipoprotein (LDL) cholesteryl ester (CE) fatty acid ratio (i.e., saturated + monounsaturated/polyunsaturated species) and the amount of esterified (r = 0.59) and free (r = 0.63) cholesterol in the abdominal aortas. Compared to the lard group, animals fed fish oil had significantly lower LDL CE melting temperatures (26 +/- 1 vs. 38 +/- 1 degree C) and significantly smaller LDL particles (2.68 +/- 0.10 vs. 3.25 +/- 0.38 g/mumol). Therefore, the potentially antiatherogenic effects of dietary fish oil include its ability to decrease the concentration, size, CE content, and CE melting temperature of plasma LDL.

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