Accumulation of cholesteryl esters and triglycerides in cultured macrophages incubated with plasma very low density lipoproteins from rats fed on casein or soybean protein diets containing moderate levels of cholesterol

Even when administered at a comparatively low level, dietary cholesterol produces significant changes in the properties of plasma lipoproteins in rats, particularly the d less than or equal to 1.006 g/ml fraction (VLDL). The occurrence of these changes is promoted by dietary casein. To test the hypothesis that these dietary-induced perturbations might include properties influencing lipoprotein-cell interactions of relevance to atherogenesis, cultured mouse peritoneal macrophages were incubated with VLDL isolated from male rats fed on diets containing either 0, 0.25 or 0.5% cholesterol with casein or soybean protein, respectively, as the sole source of protein. No increase in cholesteryl ester content, and a comparatively small rise in triglyceride content, was observed in macrophages incubated with VLDL from rats fed on cholesterol-free diets. In contrast, a significant and apparently saturable cellular accumulation of cholesteryl esters as well as triglycerides was produced by VLDL from cholesterol-fed rats. The curves showing cellular lipid accumulation versus VLDL-protein (or VLDL-cholesterol) content in the cell medium indicated different cellular affinity for VLDL from casein-fed rats in comparison with VLDL from soybean protein-fed rats. The apoprotein composition of VLDL differed between groups of rats fed on different types of dietary protein with higher proportions of apo C's in the casein-fed rats. In addition, cholesterol feeding resulted in increased proportions of apo A-I and apo A-IV in the plasma VLDL fraction.     

Effects of alcohol and cholesterol feeding on lipoprotein metabolism and cholesterol absorption in rabbits

Alcohol fed to rabbits in a liquid formula at 30% of calories increased plasma cholesterol by 36% in the absence of dietary cholesterol and by 40% in the presence of a 0.5% cholesterol diet. The increase was caused almost entirely by VLDL, IDL, and LDL. Cholesterol feeding decreased the fractional catabolic rate for VLDL and LDL apoprotein by 80% and 57%, respectively, and increased the production rate of VLDL and LDL apoprotein by 75% and 15%, respectively. Alcohol feeding had no effect on VLDL apoprotein production but increased LDL production rate by 55%. The efficiency of intestinal cholesterol absorption was increased by alcohol. In the presence of dietary cholesterol, percent cholesterol absorption rose from 34.4+/-2.6% to 44.9+/-2.5% and in the absence of dietary cholesterol, from 84.3+/-1.4% to 88.9+/-1.0%. Increased cholesterol absorption and increased LDL production rate may be important mechanisms for exacerbation by alcohol of hypercholesterolemia in the cholesterol-fed rabbit model.     

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Summary Cholesterol absorption and metabolism and LDL and HDL kinetics were investigated in 11 hypercholesterolaemic non-insulin-dependent diabetic men off and on a hypolipidaemic treatment with sitostanol ester, (3 g sitostanol daily) dissolved in rapeseed oil margarine, by a double-blind crossover study design. Serum total, VLDL and LDL cholesterol and apoprotein B fell significantly by 6±2, 12±6, 9±3 and 6±2%, mean ±SEM, and HDL cholesterol was increased by 11±4% (p<0.05) by sitostanol ester. LDL cholesterol and apoprotein B were significantly decreased in the dense (1.037–1.055 g/ml), but not light, LDL subfraction due to a significantly diminished transport rate for LDL apoprotein B, while the fractional catabolic rate was unchanged. HDL kinetics, measured with autologous apoprotein AI, was unaffected by sitostanol ester. Cholesterol absorption efficiency was markedly reduced from 25±2 to 9±2% (p<0.001) during sitostanol ester followed by proportionately decreased serum plant sterol proportions. Cholesterol precursor sterol proportions in serum, fecal neutral sterol excretion, and cholesterol synthesis, cholesterol transport, and biliary secretion were all significantly increased by sitostanol ester. We conclude that the sitostanol ester-induced decrease in cholesterol absorption compensatorily stimulated cholesterol synthesis, had no effect on fractional catabolic rate, but decreased transport rate for LDL apoprotein B so that serum total, VLDL and LDL cholesterol levels were decreased. Dietary rapeseed oil margarine rich in sitostanol ester was well tolerated, appears to be safe from the nutritional point of view and effective for lowering VLDL and LDL cholesterol and increasing HDL cholesterol in hypercholesterolaemic non-insulin-dependent diabetic subjects.Abbreviations Apo apoprotein - NIDDM non-insulin-dependent diabetes mellitus - VLDL very low density lipoprotein - IDL intermediate density lipoprotein - LDL low density lipoprotein - HDL high density lipoprotein - FCR fractional catabolic rate - TR transport rate Presented in part at the 65th Scientific Sessions of the American Heart Association, New Orleans, November 1992 (Circulation 1992; 86[Suppl I]: I-404)     

Intermediate density lipoprotein-apolipoprotein B turnover in rabbits fed semipurified diets containing casein or soy protein

The aim of this study was to investigate the underlying causes of elevated levels of intermediate density lipoprotein (IDL) in rabbits fed casein compared to soy protein in a cholesterol-free, semipurified diet. Kinetic studies were carried out in which homologous, radiolabelled IDL was injected into casein- and soy protein-fed animals after a period of 7 months on diet. Total plasma cholesterol and IDL cholesterol and protein were significantly higher in animals fed casein compared to those fed soy protein. The fractional catabolic rate of IDL-apolipoprotein B was significantly lower in casein-fed animals but the difference in mean values for the production rate did not reach statistical significance. The effect of feeding casein on IDL can be attributed to its reduced efficiency of removal from the plasma.     

Influence of dietary minerals on apolipoprotein B metabolism in rabbits fed semipurified diets containing casein

Rabbits were fed semipurified casein diets containing either 4% or 2.5% mineral mix for 8 weeks. Both groups maintained weight throughout the experimental period. The plasma total cholesterol concentration was significantly higher after 4 weeks on diet and slightly higher after 8 weeks in animals fed the lower level of minerals. Plasma IDL- and LDL-cholesterol concentrations after 4 weeks and HDL-cholesterol concentrations after 8 weeks were significantly higher in animals fed the 2.5% compared to those fed the 4% mineral mix. Kinetic experiments showed that in rabbits fed the lower level, the fractional catabolic and production rates of VLDL-apo B were lower and a greater proportion of IDL-apo B was derived from sources other than VLDL compared to the animals fed the higher level. LDL-apo B kinetics were not significantly different between the 2 groups. These data suggest that a reduction in dietary minerals enhances casein-induced hypercholesterolemia.     

Direct synthesis of low-density lipoprotein apoprotein B in the miniature pig

The metabolism of apoprotein B (apo B) was investigated in five miniature pigs following the injection of radiolabeled, very low-density lipoproteins (VLDL). The fractional catabolic rate (FCR) for VLDL apoprotein B was 0.71 +/- 0.10 h-1 (mean +/- SE), the rate of flux was 0.77 +/- 0.05 mg h-1 kg-1, and the pool size of apoprotein B averaged 1.26 +/- 0.20 mg kg-1. Examination of precursor-product relationships between VLDL and low-density lipoprotein (LDL) apoprotein B illustrated that a significant proportion (greater than 80%) of LDL apo B was derived from some source other than VLDL catabolism. In further experiments (n = 4), 125I-VLDL and 131I-LDL were simultaneously injected into miniature pigs. The fractional catabolic rate of LDL apo B averaged 0.055 +/- 0.008 h-1 and the flux rate 0.73 +/- 0.07 mg h-1 kg-1. These dual-label studies allowed us to calculate that an average of 16% of VLDL apoprotein B was converted to LDL and thus the remainder was cleared directly from the circulation. Simultaneous injection of radiolabeled homologous and human VLDL indicated that the catabolism of the two tracers was qualitatively similar. However, human VLDL apo B exhibited a slower fractional catabolic rate (0.42 v 0.71 h-1 P less than 0.05) and reduced rate of conversion to LDL. Therefore, low-density lipoproteins in the pig are largely produced by direct secretion into the circulation, independent of VLDL catabolism. Apo B metabolism in miniature pigs is similar to that of cynomologous and squirrel monkeys, and rats, but differs from normal humans in whom all LDL apo B is derived from VLDL catabolism.     

Apolipoprotein B metabolism in normal,type IV,and type V hyperlipoproteinemic subjects

Apolipoprotein B (apoB) metabolism was investigated in four normal, three type IV, and three type V hyperlipoproteinemic subjects. Following injection of autologous radioiodinated very low density lipoprotein (VLDL) the rate of clearance of the apoprotein from this particle and its subsequent appearance in low density lipoprotein (LDL) was measured by frequent apoB specific activity determinations over an 11-day period. The resultant data were analyzed using the SAAM 27 computer program. In the normal subjects, more than 95% of the injected VLDL apoB was rapidly transferred to the LDL density range and accounted for all LDL apoB synthesis in that group. The plasma VLDL apoB concentration in the type IV group was, on average, five times the normal level. This resulted primarily from a doubling of the VLDL apoB synthetic rate associated with a defective or saturated catabolic mechanism. Only 60% of this material subsequently appeared in LDL, while the remainder was catabolized via an LDL-independent pathway. The turnover parameters of LDL apoB were normal in the type IV patients. Type V hyperlipoproteinemic subjects exhibited a 12- to 35-fold increase in plasma VLDL apoB concentration over normal. This again derived from increased VLDL apoB synthesis in the presence of defective removal of the apoprotein; the fractional catabolic rate of VLDL apoB in this group was 14% of the normal value. However, in contrast to the type IV patient data, more than 85% of the apoB in type V VLDL eventually appeared in LDL whose turnover rate was raised as a result of an increase in its catabolism; the fractional catabolic rate of LDL apoB in type V patients was four-fold above normal. The plasma LDL apoB pool size was substantially reduced in these subjects. This study shows that in hyperlipoproteinemic pheno-types IV and V there exist multiple anomalies of apoB metabolism affecting both VLDL and LDL.     

Effects of casein and soy protein on hepatic and serum lipids and lipoprotein lipid distributions in the rat

Rats fed a semipurified diet containing casein developed higher levels of circulating triglycerides and cholesterol than animals fed a soy protein-containing diet. The increased serum lipid levels in non-fasted rats were associated largely with the d less than 1.006 g/ml lipoprotein particles (e.g. chylomicrons or very low density-like lipoproteins). In addition, casein-fed rats exhibited higher levels of circulating insulin and depressed hepatic 7 alpha-hydroxylase levels compared to soy-fed rats. Supplementation of the casein diet with arginine, to give an arginine/lysine ratio comparable to that in the soy diet, resulted in a reduction of d less than 1.006 g/ml lipids, a reduction in serum insulin levels and an elevation in hepatic 7 alpha-hydroxylase activity. Supplementation of the soy diet with lysine also resulted in modification of these parameters toward those observed with casein diets, albeit the effects were less dramatic. The results suggest that the hyperlipidemia associated with feeding casein-based diet is associated with decreased rates of clearance of chylomicron-like lipoproteins and their component triglycerides and cholesterol. Furthermore, this is largely prevented by addition of arginine to diets containing casein as the sole protein source.     

Intestinal apolipoprotein B-48 synthesis and lymphatic cholesterol transport are lower in swine fed high fat, high cholesterol diet with soy protein than with casein

Effects of dietary proteins on intestinal lipoproteins were studied in 8 Yorkshire swine fed a high fat, high cholesterol diet with either casein or soy protein. After 5 weeks of feeding, the casein group exhibited moderately elevated levels of serum cholesterol (334 +/- 46 mg/dl). The soy protein group showed significantly less hypercholesterolemia as compared to the casein group (122 +/- 8 mg/dl). Swine were subjected to cannulation of mesenteric lymph duct under halothane anesthesia. A single dose of 250 microCi [14C]cholesterol and 10 mCi [3H]leucine was infused into the upper jejunum 2 h after one-fifth of daily food was given. The 3-h lymphatic transport of cholesterol in casein-fed swine was significantly higher than in those fed soy protein. Triglyceride transport values were similar in the 2 groups. The [3H]leucine incorporation study revealed that transport of apo B-48 bore a significant positive relationship to transport of cholesterol in both chylomicron and VLDL fractions of mesenteric lymph. A greater apo B-48 secretion with higher specific activity was probably responsible for the greater transport of cholesterol in chylomicrons in casein-fed than in soy protein-fed swine. Similarly, the transport of lymph VLDL cholesterol in swine fed casein or soy protein paralleled the amount of accompanying apo B-48. Dietary proteins probably influence the intestinal synthesis of apo B-48 which in turn affects cholesterol transport into the lymphatics.     

Effects of excess dietary L-cystine on the rat plasma lipoproteins

The effects of excess dietary cystine on the cholesterol and protein contents of rat plasma lipoproteins are described. 5% L-cystine was added to a semisynthetic diet containing 23% casein and 0.05% cholesterol, to the same diet enriched with 1% cholesterol or containing tristearin instead of lard. Rats were fed the diets during 2 months. The addition of cystine led to an increase in the plasma cholesterol level of the rats fed with the basal diet (from 0.92 to 1.56 mg/ml). But it produced a reduction of this level in cholesterol-fed rats (from 1.71 to 1.49 mg/ml). These different changes in the total plasma cholesterol level are explained by the specific effects of cystine on each lipoprotein: whatever the diet, cystine supplementation reduced the chylomicron and VLDL cholesterol contents and increased that of LDL (especially LDL2: density 1.040-1.063) and HDL. This study allowed us to compare 2 conditions which lead to hypercholesterolemia but which have opposite effects on hepatic cholesterogenesis: the supplementation of the same basal diet with 1% cholesterol or 5% cystine. In cholesterol-fed rats, the major part (49%) of plasma cholesterol was found in the chylomicrons and VLDL while the LDL2 cholesterol content was low (0.07 mg/ml plasma). Conversely, cystine-fed rats had a low chylomicron and VLDL plasma content (both enriched in apoprotein E), whereas up to 33% of the plasma cholesterol were carried by LDL2. Thus the production of LDL2 in cholesterol and cystine-fed rats could be related to hepatic cholesterogenesis.     

Plasma lipid and lipoprotein cholesterol levels in swine. Modification of protein-induced response by added cholesterol and soy fiber

Piglets, aged 8 weeks and weighing 12-18 kg, were fed semi-purified casein or soy protein diets, with or without cholesterol and soy hull fiber, for 2 months. In addition to observing the effects of the dietary treatments on growth, the modification of the primary hypocholesterolemic action of soy protein by cholesterol and soy fiber was studied. Pigs fed the soy protein or casein diets grew normally with no difference in weight gain. Plasma triglyceride and phospholipid levels, as well as several plasma metabolic indices examined, were not significantly affected by dietary treatment. However, plasma total cholesterol was higher (but not significantly) in pigs fed casein than in those fed soy protein alone. Cholesterol feeding induced markedly significant (P less than 0.05) hypercholesterolemia with either protein source, compared to feeding the proteins without added cholesterol. Dietary soy fiber fed simultaneously with cholesterol decreased the cholesterol-induced hypercholesterolemia, but the reduction was significantly greater (P less than 0.05) with soy protein than with casein in the diet. Analyses of the lipoprotein cholesterol indicated that LDL cholesterol was much more sensitive to the changes induced by feeding cholesterol and soy fiber than either HDL or VLDL cholesterol. These findings suggest a beneficial role of dietary soy fiber in hypercholesterolemia.     

Relationship between metabolism and composition of low density lipoproteins in rabbits on semi-purified diet

The metabolism of 125I-labelled apoprotein of low density lipoproteins was studied in rabbits fed either commercial or semi-purified, cholesterol-free, diet. The rise in apo-LDL intravascular pool size observed in the semi-purified group is accompanied by a marked decrease in the fractional catabolic rate and an increase in the total catabolic rate. The semi-purified diet induces an increase in the cholesterol ester/triglyceride ratio of the LDL which is normalized by cholestyramine therapy. The concomitant alterations in both LDL metabolism and lipid composition raise the possibility that enrichment of LDL in cholesterol esters is a consequence of the delayed LDL clearance from the plasma.     

Long-term feeding of casein or soy protein with or without cholesterol in Mongolian gerbils. II. Plasma lipid and liver cholesterol responses

Male Mongolian gerbils (Meriones unguiculatus) were fed casein or soy protein in the presence and absence of dietary cholesterol for 15 months. Diets resembled the average North American diet in energy contributions from protein, fat and carbohydrate, cholesterol content and fatty acid profile. At month 0, 3, 6, 9, 12 and 15, plasma samples were analyzed for total cholesterol (TC), HDL cholesterol (HDLC) and triglyceride (TG) concentrations. Plasma LDL cholesterol (LDLC) was estimated indirectly. Liver TC was also determined at these time points. Comparisons of protein source and cholesterol level were averaged over the 15 month period. Casein-fed gerbils had significantly higher plasma TC and TG levels and lower HDLC levels (as a percent of TC) compared to soy-fed animals, independent of the presence or absence of dietary cholesterol. LDLC was significantly elevated in casein-fed gerbils only when cholesterol was present in the diet. Elevations in plasma TC levels were reflected by elevations in liver TC. Despite plasma lipid elevations that are consistent with the development of atherosclerosis (AS) and coronary heart disease (CHD) in humans, hyperlipidemic gerbils do not develop AS. Further characterization of gerbil lipid metabolism responses to dietary alterations aimed at the prevention of CHD in humans is necessary to elucidate the mechanism for the gerbil's resistance to AS.     

Normocholesterolemic dysbetalipoproteinemia with xanthomatosis.

A patient is described who has marked palmar xanthomatosis associated with a normal concentration of plasma cholesterol. Analysis of xanthomas revealed them to contain large quantities of cholesterol with both intra- and extracellular lipids. Examination of plasma lipoproteins showed them to be consistent with a pattern of dysbetalipoproteinemia (Type III hyperlipoproteinemia). VLDL had beta-mobility on electrophoresis, a high cholesterol/triglyceride ratio, and increased apoprotein B. However, arginine-rich apoprotein was not increased in VLDL, in contrast to hypercholesterolemic patients with the Type III pattern. Nevertheless, the E3 subfraction of the arginine-rich apoprotein was virtually absent, which is characteristic of dysbetalipoproteinemia. Cholesterol and bile acid synthesis were in the normal range. Thus, of particular interest was the development of severe xanthomatosis without hypercholesterolemia in this patient. Therefore, tissue accumulation of cholesterol was apparently the result of a qualitative abnormality in lipoproteins and not due to an excess of plasma cholesterol.     

Serum lipids, lipoprotein composition and liver cholesterol in genetically obese Zucker rats fed semipurified diets containing either casein or soy protein

The effect of semipurified diets containing either casein or soy protein on serum lipids, lipoprotein composition and liver cholesterol was studied in genetically obese Zucker rats. The ingestion of a cholesterol-enriched semipurified diet containing casein resulted in elevated levels of serum cholesterol and phospholipids compared to the feeding of a soy protein diet. No differences in serum triglycerides were observed. Differences in serum cholesterol and phospholipids were mainly reflected in the very low density lipoproteins and low density lipoproteins and to a minor extent in the high density lipoproteins. Liver cholesterol paralleled the levels of cholesterol in the serum, the rats fed casein exhibited markedly higher levels of liver cholesterol than those fed soy protein. Furthermore, the rats fed casein also had enlarged livers. Thus, this study clearly shows the differential cholesterolemic effect of dietary casein and soy protein in genetically obese Zucker rats.     

Accelerated turnover of very low density lipoprotein triglycerides in chronic alcohol users. A possible mechanism for the up-regulation of high density lipoprotein by ethanol

The concentration of high density lipoproteins (HDL) is related to the catabolism of triglyceride-rich lipoproteins. In order to elucidate the mechanisms by which alcohol increases plasma HDL levels we measured the turnover kinetics of very low density lipoprotein (VLDL) triglycerides in 10 alcoholic men without liver disease and in nonalcoholic control men matched for age, weight and plasma VLDL triglyceride level. The study was repeated in the alcoholics after a 2-week abstinence period. The alcoholic men had elevated HDL cholesterol but reduced low density lipoprotein (LDL) cholesterol as compared to the controls. The fractional catabolic rate and the total turnover (production) rate of VLDL triglycerides were both significantly increased (P less than 0.05) in the alcoholic men before abstinence. After withdrawal of alcohol both the synthetic rate and the catabolic rate of VLDL triglycerides returned to normal and the HDL (HDL2 and HDL3) cholesterol fell. The per cent decrease in HDL2 cholesterol during abstinence was positively correlated to the respective fall of VLDL triglyceride fractional catabolic rate (r = +0.51). The results suggest that the absence of hypertriglyceridemia and the elevated levels of HDL in regular alcohol users may be partly based on increased metabolic clearance of VLDL particles and on subsequent accelerated transfer of the VLDL surface components to HDL.     

Modulation of very low-density lipoprotein secretion by dietary protein is age-dependent in rats

The Triton WR-1339 technique was used in order to study age-dependent changes of the rate of very low-density lipoprotein (VLDL) lipid secretion in rats consuming either casein or soy protein isolate. There was a significantly higher influx of lipoprotein cholesterol and triglycerides into the plasma compartment (of fasted animals) after a casein than after a soy diet, both in 10-week-old animals (cholesterol: 0.78 +/- 0.06 vs. 0.52 +/- 0.03 mmol X 1(-1) X h-1) and 25-week-old animals (cholesterol: 0.50 +/- 0.07 vs. 0.32 +/- 0.05 mmol X 1(-1) X h-1), but secretion rates diminished with age. The higher secretion rates following casein were paralleled by higher serum cholesterol levels in the fasted younger animals and also, though to a lesser degree, in the fed animals. These data contribute further evidence to our earlier proposal that dietary protein may induce different serum lipid levels by the modulating rate of lipid influx into the plasma compartment.     

Effect of olive oil-fried sardine consumption on cholesterol content in the serum, lipoproteins, spleen and adipose tissue of hypercholesterolemic rats

BACKGROUND: The information about the effect of fried-oily fish consumption on cholesterol metabolism is rather scarce. AIM: To test the effect of olive oil-fried sardine consumption on cholesterol content in the serum, lipoproteins, spleen and adipose tissue of hypercholesterolemic rats. METHODS: Hypercholesterolemia was induced for 3 weeks by a casein + olive diet containing cholesterol and bovine bile (COC). Rats were later switched for 2 weeks to diets containing casein + olive oil (CO), olive oil-fried sardines (S), and olive oil-fried sardines-cholesterol-bovine bile (SC) while one rat group continued on the COC diet. Cholesterol was determined in serum, lipoproteins, adipose tissue and spleen. RESULTS: The SC diet markedly blocked the hypercholesterolemic induction of the cholesterol-raising agents. Dietary cholesterol withdrawal decreased serum cholesterol levels, with the S diet inducing the highest decrease in serum and VLDL + LDL-cholesterol levels. Cholesterol withdrawal decreased spleen total cholesterol content and weight but the S diet was unable to reduce spleen cholesterol content (micromol/g) more than CO diet. Adipose tissue of S rats displayed the lowest cholesterol values. Cholesterol (mmol/g) of adipose tissue correlated very significantly with total serum cholesterol (r = 0.9225, p < 0.0001) and VLDL + LDL-cholesterol (r = 0.9313, p < 0.0001). CONCLUSIONS: Cholesterol in adipose tissue was very sensitive to variations in plasma cholesterol. Consumption of fried sardines interacts with cholesterol withdrawal, accelerating serum cholesterol normalization and reduction of cholesterol levels in adipose tissue.     

Catabolism of apoprotein A-1 of HDL in normal and nephrotic rats

High density lipoprotein was isolated from the plasma of control and puromycin aminonucleoside nephrotic rats and labeled with ¹²⁵I. It was injected into control and nephrotic rats and the plasma analyzed after 3 min, 5 hr, and 20 hr. High density lipoprotein was isolated and the specific activity of apo A-I determined following apoprotein separation using SDS-polyacrylamide gel electrophoresis. The distribution of labeled apoproteins was determined in whole plasma by SDS-gel filtration column chromatography and the plasma concentration of apo A-I was calculated from its specific activity and the total plasma apo A-I radioactivity. A 3 min to 5 or 20 hr fractional catabolic rate was calculated. When multiplied by the plasma concentration of apo A-I, an estimate of the absolute catabolic rate was obtained. When injected into normal animals, the high density lipoprotein apo A-I had similar catabolic rates whether derived from control or nephrotic rat plasma, averaging 65 and 48 μg of apoprotein per ml of plasma per hr at 5 or 20 hr, respectively. Labeled HDL was injected into nephrotic rats of varying degrees of severity. The moderately nephrotic rats with plasma cholesterol levels averaging 177 mg/dl had apo A-I levels that were 3.6 times that of controls (1799 ± 195 μg/ml) and 2.4-fold increases in apo A-I catabolic rates (134 ± 28.9 μg/ml plasma/hr). The severely nephrotic rats with cholesterol concentrations averaging 396 mg/dl had apo A-I levels 7.1 times that of the controls (3533 ± 220 μg/ml) while the catabolic rate was 2.7 times the control rate (153 ± 19.5 μg/ml/hr), which was not a significant increase beyond that of the moderately nephrotic group. It was concluded that compositional differences of HDL resulting in an increased proportion of apo A-I, as in nephrotic rat plasma, do not affect apo A-I metabolism. The high levels of apo A-I in the plasma of nephrotic rats is due to increased hepatic synthesis that results in an expansion of the pool size and saturation of catabolic pathways. Small increases in apo A-I synthesis lead to large increases in the plasma concentration, an observation that may be important in the regulation of HDL levels that are known to be correlated with a decreased incidence of atherosclerosis.     

Arterial blood derived low density lipoprotein increases platelet aggregation and macrophage cholesterol content in comparison to lipoprotein derived from veinous blood

We studied the biochemical and biological properties of plasma lipoproteins taken from blood derived from either the aorta or femoral vein of patients with normal coronary arteriography. There were no significant differences in concentrations of cholesterol, triglycerides, apoprotein A-1 and apoprotein B derived from either source. The cholesterol content of very low density lipoprotein (VLDL) and high density lipoprotein (HDL) was similar in both aortic and venous blood. The low density lipoprotein (LDL) concentration, however, was significantly higher in the aortic blood sample. Arterial LDL significantly enhanced in vitro platelet aggregation when compared to venous LDL. (p less than 0.02). When incubated with mouse peritoneal macrophages (MPM) arterial LDL and VLDL caused an increased cholesterol accumulation and enhanced cholesterol esterification within these macrophages. The venous lipoproteins had little effect. The differences noted in the arterial lipoproteins in composition and biological function when compared to venous lipoproteins might be related to the much higher incidence of atherosclerosis found in the arterial tree.