Intermediate Lipoprotein Research Articles

Evidence of How rs7575840 Influences Apolipoprotein B–Containing Lipid Particles

Recent genome-wide association studies identified a variant rs7575840 in the apolipoprotein B (APOB) gene region as associated with low-density lipoprotein (LDL) cholesterol. However, the underlying functional mechanism of this variant, which resides 6.5 kb upstream of APOB, has remained unknown. Our objective was to investigate rs7575840 for association with refined apoB-containing lipid particles, for replication in a Mexican population, and for its underlying functional mechanism. Our data show that rs7575840 is associated with serum apoB levels (P=4.85×10(-10)) and apoB-containing lipid particles, very small very-low-density lipoprotein, intermediate lipoprotein, and LDL particles (P=2×10(-5) to 9×10(-7)) in the Finnish Metabolic Syndrome in Men study sample (n=7710). Fine mapping of the APOB region using 43 single-nucleotide polymorphisms replicated the association of rs7575840 with apoB in a Mexican study sample (n=2666, P=3.33×10(-5)). Furthermore, our transcript analyses of adipose RNA samples from 175 subjects in the Finnish Metabolic Syndrome in Men study indicate that rs7575840 alters expression of APOB (P=1.13×10(-10)) and a regional noncoding RNA (BU630349) (P=7.86×10(-6)) in adipose tissue. It has been difficult to convert genome-wide association study associations into mechanistic insights. Our data show that rs7575840 is associated with serum apoB levels and apoB-containing lipid particles, as well as influencing expression of APOB and a regional transcript BU630349 in adipose tissue. We thus provide evidence how a common genome-wide significant single-nucleotide polymorphism, rs7575840, may affect serum apoB, LDL cholesterol, and total cholesterol levels.

Exercise and Lipids: How Much Exercise Is Adequate to Increase HDL and Lower Triglycerides

The association of elevated cholesterol and coronary artery disease is evident in so many epidemiological studies that the National Heart, Lung, and Blood Institute consider this association as causal. More explicitly, elevated plasma cholesterol and triglycerides are the identified culprits. Cholesterol is transported to target organs via the blood stream, which is mostly hydrophobic in nature. For the fatty cholesterol to travel through blood it must attach to a lipoprotein. There are several major ones that we pay attention to: the low-density lipoprotein (LDL; the “bad cholesterol”), highdensity lipoprotein (HDL; “good cholesterol”), verylow-density lipoprotein (VLDL), and triglycerides. VLDL, originating in the liver, interacts with lipoprotein lipase, resulting in hydrolysis of triglycerides to form intermediate lipoproteins and LDL. Cholesterol attaches to LDL and is transported from the liver to various organs/tissue in the body. If the blood level of the LDL complex is elevated, it sets up ideal conditions for plaque formation, leading to atherosclerosis. On the other hand, HDL picks up LDL circulating in the blood stream and transports it to the liver, thereby lowering serum cholesterol levels to reduce the risk of atherosclerotic plaque formation. Triglycerides are thought to be an independent risk factor according to a meta-analysis of 17 studies, which is the best evidence to date of the role triglycerides play in cardiovascular disease. According to the National Cholesterol Education Program Expert Panel (2002), plasma levels of lipoproteins that reduce the risk for coronary artery disease are as follows: LDL 60 mg/dL, total cholesterol (TC) <200 mg/dL, and triglyceride (TG) <150 mg/dL.

Liver-specific Inactivation of the Abetalipoproteinemia Gene Completely Abrogates Very Low Density Lipoprotein/Low Density Lipoprotein Production in a Viable Conditional Knockout Mouse

Conventional knockout of the microsomal triglyceride transfer protein large subunit (lMTP) gene is embryonic lethal in the homozygous state in mice. We have produced a conditional lMTP knockout mouse by inserting loxP sequences flanking exons 5 and 6 by gene targeting. Homozygous floxed mice were born live with normal plasma lipids. Intravenous injection of an adenovirus harboring Cre recombinase (AdCre1) produced deletion of exons 5 and 6 and disappearance of lMTP mRNA and immunoreactive protein in a liver-specific manner. There was also disappearance of plasma apolipoprotein (apo) B-100 and marked reduction in apoB-48 levels. Wild-type mice showed no response, and heterozygous mice, an intermediate response, to AdCre1. Wild-type mice doubled their plasma cholesterol level following a high cholesterol diet. This hypercholesterolemia was abolished in AdCre1-treated lMTP-/- mice, the result of a complete absence of very low/intermediate/low density lipoproteins and a slight reduction in high density lipoprotein. Heterozygous mice showed an intermediate lipoprotein phenotype. The rate of accumulation of plasma triglyceride following Triton WR1339 treatment in lMTP-/- mice was <10% that in wild-type animals, indicating a failure of triglyceride-rich lipoprotein production. Pulse-chase experiments using hepatocytes isolated from wild-type and lMTP-/- mice revealed a failure of apoB secretion in lMTP-/- animals. Therefore, the liver-specific inactivation of the lMTP gene completely abrogates apoB-100 and very low/intermediate/low density lipoprotein production. These conditional knockout mice are a useful in vivo model for studying the role of MTP in apoB biosynthesis and the biogenesis of apoB-containing lipoproteins.

Intermediate Lipoproteins, Atherosclerosis, and Gofman

To the Editor: I was keenly disappointed that Dr Hodis and his coworkers ( Circulation . 1997;95:2022–2026) failed to refer to Gofman and his work on the relationship between the intermediate lipoproteins (SF 12 to 20) and atherosclerosis. This failure is especially egregious because Gofman’s work and Hodis and his coworkers’ work were both …

Biliary excretion of chylomicron remnant cholesterol in the rat: responses to the expansion of their plasma pool and promoting role of stimulated bile-acid synthesis.

1. Chylomicron remnants, the intermediate intestinal lipoproteins carrying the bulk of dietary cholesterol, are actively taken up and degraded in the hepatocytes, releasing cholesterol which can be excreted in bile. To study this pathway, a mass of remnants, leading to a consistent rise in hepatic cholesterol, was administered as an intravenous bolus in rats with chronic bile fistula equilibrated by water, electrolyte and taurocholate infusions, and changes in biliary lipids and bile acids were evaluated for up to 24 h in comparison with baseline. 2. A mean 16% increase in the net output of bile acids was observed at each time interval after lipoprotein injection, accounting for a 24h cumulative excretion of approximately one-third of the administered cholesterol mass. These changes did not reach statistical significance however. The cholesterol output and concentrations of all biliary lipids did not vary either. Without taurocholate replacement, remnants injection was followed by a 15-20% decrease in bile acid and bile lipid secretion, presumably due to an insufficient hepatic bile-acid flux. 3. When [3H]cholesterol-labelled remnants were administered at the same mass in the chronic equilibrated bile fistula model, 21% of injected radioactivity was excreted in 24h, distributing mostly in acidic rather than neutral sterols (20.02 +/- 1.85 compared with 1.07 +/- 0.04), with an acidic to neutral sterol mean ratio of 16. 4. To exclude interfering effects from the administered cholesterol mass and chronic bile fistula, 3H-labelled remnants were also studied as a cholesterol trace injected in rats with acute bile fistula.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate on low density lipoprotein in rabbits

The hypolipidemic effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) on cholesterol diet-fed rabbits were studied. EPA-E (300 mg/kg, p.o. x 4 weeks) decreased total cholesterols in the lipoprotein fractions of very low-density lipoprotein and intermediate lipoprotein+low-density lipoprotein (LDL), but not in high-density lipoprotein. Furthermore, the properties of LDL were investigated in rabbits given EPA-E (300 mg/kg, p.o. x 2 weeks). EPA-E had no influence on the lipid composition in LDL, and the cholesterol accumulation into macrophages was not increased by the incubation with EPA-E-treated LDL. However, the omega 3 polyunsaturated fatty acids contents of LDL were increased by the administration of EPA-E. EPA-E-treated LDL was also studied on the binding to the hepatic membranes. The binding of EPA-E-treated LDL to the hepatic membranes was higher than that of ordinary LDL. These results suggest that EPA-E causes a modification of LDL, such that EPA-E has an enhancing effect on the hepatic uptake of LDL. These effects may contribute to the hypolipidemic action of EPA-E.

Serum lipoproteins of rabbits fed semi‐purified diets varying in protein and carbohydrate source

AbstractThe effect of dietary protein and carbohydrate type on the composition and properties of serum lipoproteins in rabbits was studied. The animals were pair‐fed either casein‐sucrose and soy protein‐sucrose or casein‐dextrose and soy protein‐dextrose‐containing low fat, low cholesterol, semi‐purified diets for 84 days. Main effects due to protein and carbohydrate type were observed to be altered lipoprotein class compositions. These effects were due primarily to the presence of casein which resulted in cholesterol‐rich, triglyceride‐poor lipoproteins among all isolated classes. Increases in serum low and high density lipoprotein cholesterol and protein concentrations, as well as lipoprotein total mass, were also observed with casein feeding. Carbohydrate effects due to dietary sucrose were elevated high density lipoprotein phospholipid and protein concentrations, independent of protein source. When casein was included, sucrose‐containing diets resulted in increased intermediate density lipoprotein cholesterol; when soy protein was used, low density lipoprotein cholesterol elevations were observed. Dietary interactions were also found especially between casein and sucrose, resulting in increased intermediate lipoprotein mass and total lipoprotein concentrations. Comparisons of lipoprotein class particle size among rabbits indicated similar particle diameters among animals in all dietary groups. Evidence that casein feeding caused increased lipoprotein particle number in addition to compositional differences was obtained. It was concluded that lipoprotein structure within a given class is maintained in spite of compositional variations due to dietary protein or carbohydrate source.

Distribution of lipids and apolipoproteins in human plasma by vertical spin ultracentrifugation

A study on the fractionation of human plasma into various lipoprotein classes was performed by single spin vertical ultracentrifugation. Detailed apolipoprotein (A-I, A-II, B, C-III, and E) and lipid (cholesterol, cholesterol ester, and triacylglycerol) analyses were performed on the fractions obtained by single spin vertical ultracentrifugation. ApoB was located primarily in the low-density lipoprotein (LDL) fraction whereas Lp(a) was detected in the fractions extending into the high-density lipoprotein region. The distributions of ApoA-I and ApoA-II varied among individuals, suggesting heterogeneity in the composition of HDL, and this was confirmed by the distributions of ApoC-III, ApoD, and ApoE. ApoC-III and ApoD were associated primarily with HDL 3 while ApoE showed the most variation among subjects, spreading across the entire density spectrum. Distributions of cholesterol and cholesterol ester coincided with the elution of major apolipoproteins A-I and B while the distribution of triacylglycerol was variable. An immunoassay for lecithin:cholesterol acyltransferase (LCAT) demonstrated that the majority of LCAT was present in the high- to very high-density lipoprotein region, but LCAT was also detected in LDL and the immunoreactivity extended into the very low-density lipoprotein region. The presence of apolipoproteins A-I and A-II, as well as LCAT in the intermediate lipoprotein density region (LDL 1) was consistent with these species representing lipolytic remnants. This study indicated that rapid (3 h) single spin vertical ultracentrifugation offers insights into the heterogeneity of lipoproteins and offers a useful tool for monitoring perturbations of the plasma lipid transport system. In conjunction with immunosorbers, immunoassays, and micro lipid analyses, this procedure offers a method to isolate and characterize various lipoprotein subspecies.

Secretion of cholesteryl-ester-rich lipoproteins by the perfused livers of rabbits fed a wheat-starch-casein diet

Rabbits fed a cholesterol-free semi-synthetic wheat-starch-casein diet had a high plasma cholesterol concentration; most of the cholesterol was associated with low-density lipoproteins (LDL). Chemical analyses of plasma lipoproteins revealed that very-low-density lipoproteins (VLDL), intermediate lipoproteins and LDL from casein-fed rabbits contained more cholesteryl ester than that of lipoproteins isolated from chow-fed animals. The fatty acid composition of cholesteryl esters of plasma lipoproteins showed that there were higher contents of oleic acid than linoleic acids in lipoproteins from casein-fed rabbits. Lipoproteins isolated from liver perfusates of casein-fed rabbits had higher cholesteryl oleate content than lipoproteins from chow-fed rabbit liver perfusates. There was a marked increase in secretion of apolipoproteins from perfused livers of casein-fed rabbits. We conclude that the high levels of plasma cholesterol in casein-fed rabbits are of hepatic origin and that one of the hypercholesterolemic actions of dietary casein in rabbits is the induction of hepatic synthesis and secretion of cholesteryl-ester-rich lipoproteins.

Human plasma carboxyl esterase-catalyzed triolein hydrolysis. Existence of promoting factor in serum.

The possibility that some factor in serum changes the substrate specificity of purified human plasma carboxyl esterase, which hydrolyzes the short chain fatty acid ester, tributyrin, was investigated. The purified carboxyl esterase from human plasma hydrolyzed 48 mmol of tributyrin/mg of protein/h, monoolein at 1560 mumol of released fatty acids/mg of protein/h, diolein at 133 mumol of released fatty acids/mg of protein/h, and triolein at less than 10 mumol of released fatty acids/mg of protein/h. When human serum was applied to phenyl-Sepharose, a triolein hydrolysis-promoting factor (THPF) for purified carboxyl esterase was bound to the gel and was eluted with water. This partially purified human serum THPF enhanced carboxyl esterase-catalyzed triolein hydrolysis about 30-fold, diolein hydrolysis 2-fold, and monoolein hydrolysis 1.5-fold. Hydrolysis of triolein in very low density lipoproteins (d less than 1.006) and intermediate lipoproteins (1.006 less than d less than 1.019) by carboxyl esterase was also enhanced by addition of THPF. THPF activity was reduced by treatment of delipidation, but resistant to trypsin treatment or heating at 50 degrees C. These results indicated that serum carboxyl esterase can hydrolyze the long chain fatty acid ester, triolein, in the presence of triolein hydrolysis-promoting factor in serum.

血清Carboxyl esteraseに対してLipase活性を発現させる因子の存在について

The possibility that some factor in serum changes the substrate specificity of purified human plasma carboxyl esterase, which hydrolyzes the short chain fatty acid ester, tributyrin, was investigated. The purified carboxyl esterase from human plasma hydrolyzed 48 mmol of tributyrin/mg of protein/h, monoolein at 1560 mumol of released fatty acids/mg of protein/h, diolein at 133 mumol of released fatty acids/mg of protein/h, and triolein at less than 10 mumol of released fatty acids/mg of protein/h. When human serum was applied to phenyl-Sepharose, a triolein hydrolysis-promoting factor (THPF) for purified carboxyl esterase was bound to the gel and was eluted with water. This partially purified human serum THPF enhanced carboxyl esterase-catalyzed triolein hydrolysis about 30-fold, diolein hydrolysis 2-fold, and monoolein hydrolysis 1.5-fold. Hydrolysis of triolein in very low density lipoproteins (d less than 1.006) and intermediate lipoproteins (1.006 less than d less than 1.019) by carboxyl esterase was also enhanced by addition of THPF. THPF activity was reduced by treatment of delipidation, but resistant to trypsin treatment or heating at 50 degrees C. These results indicated that serum carboxyl esterase can hydrolyze the long chain fatty acid ester, triolein, in the presence of triolein hydrolysis-promoting factor in serum.

肝性リパーゼ阻害因子がみられIII型高脂血症を呈したWeber-Christian病の一例

Hyperlipidemia (Type III) was observed in a patient of Weber-Christian disease. Apo E-III deficiency was not observed. Post-heparin hepatic triglyceride lipase activity was low, but detectable. When the amount of post-heparin plasma was decreased to less than 20μl, the hepatic triglyceride lipase activity was higher than at more than 30μl. Inhibitory effect on hepatic triglyceride lipase was observed in intermediate lipoprotein fractions (1.017<d<1.063). Semipurified inhibitory factor inhibited triolein hydrolyzing activity of hepatic triglyceride lipase, but did not inhibited tributyrin hydrolyzing activity. These results may suggest that the inhibitor interacts with interface recognition site of hepatic triglyceride lipase, but not catalytic site.

Zonal rotor ultracentrifugation: a proposal for improving the effectiveness of the procedure

A methodological variant of the zonal ultracentrifugation technique for the separation of plasma lipoproteins is described. The modification consists of (1) preloading the rotor with water and (2) using a different gradient former, and altering the gradient profile during the second step. This variant permits the detection of an intermediate lipoprotein even in healthy individuals and in cord blood.

家族性異常リポ蛋白血症の研究

Familial dyslipoproteinemias were reviewed from the viewpoint of six-step metabolism of human serum lipoproteins proposed for comprehension of various aspects of complicated serum lipoprotein metabolism. The six steps of lipoprotein metabolism consists of (i) synthesis of triglyceride-rich lipoproteins in digestive organs, (ii) conversion of triglyceride-rich lipoproteins to intermediate lipoproteins (IDL) through hydrolysis of triglycerides, (iii) transformation of IDL to LDL by hydrolysis of the remaining triglycerides, (iv) catabolism of LDL and release of cholesterol by LDL pathway in peripheral cells, (v) removal and esterification of cholesterol from cell membrane by HDL and LCAT, and (vi) catabolism of HDL in the liver lysosome and the excretion of cholesterol into the bile. The first three steps of these metabolic processes are related to the energy metabolism of the human body, while the last three to the structural metabolism of tisrues and organs.In reviewing familial dyslipoproteinemias, abetalipoproteinemia, C-II deficiency, LPL deficiency, and Type IV and V hypertriglyceridemia have common characteristics of accumulation of triglycerides in parenchymal cells of organs, while broad beta disease, Type II hyperlipidemia, LCAT deficiency and HDL deficiency cause accumulation of esterified cholesterol in the scavenger cells of arteries, skin, and the other peripheral tissues.The six-step theory of human serum lipoproteins, thus, shed a new light on understanding the relationship between serum lipoprotein and tissue reaction, and enables to provide a tool for an integrated approach toward the role of human lipoproteins in whole-body metabolism.

VLDLからLDLへの中間体のうつ滞する高脂血症について

VLDLからLDLへの中間体のうつ滞する高脂血症について

B-2. VLDLからLDLへの中間体のうっ滞を示す高脂血症についての考察

B-2. VLDLからLDLへの中間体のうっ滞を示す高脂血症についての考察

Atherogenic hyperlipoproteinemia induced by cholesterol feeding in the Patas monkey

Patas monkeys were studied for 2 years on three dietary regimes: (1) commercial chow (control diet); (2) semipurified diet plus lard (fat-fed); and (3) semipurified diet plus lard and cholesterol (cholesterol-fed). The control and fat-fed animals had similar lipoproteins which were equivalent to the human very low density, low density (LDL), and high density lipoproteins. An additional lipoprotein referred to as LDL-II appeared to be equivalent to the human Lp(a). The cholesterol-fed animals developed accelerated atherosclerosis associated with a hypercholesterolemia which was characterized by (1) the appearance of beta-migrating lipoproteins (B=VLDL) in the d less than 1.006, (2) an increase in the intermediate lipoproteins and LDL, and (3) the appearance of LDL-II which contained a prominence of the arginine-rich apoprotein. The arginine-rich apoprotein was also a prominent component of the B-VLDL and intermediate lipoproteins. Characterization of this apoprotein revealed that it contained 11.5 mol % arginine, had a molecular weight of approximately 34 000, and coelectrophoresed with the arginine-rich apoprotein of man, dog, swine, rat, and rabbit.

Changes in the composition and physico-chemical characteristics of serum lipoproteins during ethanol-induced lipaemia in alcoholic subjects

The effect upon serum lipids and lipoproteins of a large intake of ethanol (180 g in 6 hr) has been studied during the ensuing 24 hr in 21 subjects. These were all men who were habituated to heavy drinking but who were shown to be normolipaemic when maintained on a normal diet with a restricted intake of alcohol. In all the subjects studied, ingestion of this amount of ethanol induced an acute hypertriglyceridaemia which varied in intensity between individuals, with increases ranging from 26% to 377% above the basal value. On the other hand, no significant change occurred in plasma cholesterol. In addition to measurements of triglycerides and cholesterol, the plasma from all the subjects were examined by electrophoresis in agarose and polyacrylamide gels with photometric scanning of the gels. In a subgroup of ten of the subjects, the plasma lipoproteins were separated into very low density (VLDL), lowdensity (LDL), and high-density (HDL) fractions, which were also analyzed biochemically and by electrophoresis. Following ethanol ingestion, a mean increase of about twofold in triglyceride content, and a decrease in the cholesterol/triglyceride ratio was observed in VLDL, LDL, and HDL. The triglyceride/protein ratio decreased in VLDL and increased in LDL. On electrophoresis of the intact sera following ethanol ingestion visible particulate fat and a band which failed to permeate the gel (‘chylomicron-like band‘) was observed in five out of ten subjects and eight out of these ten subjects showed a prominent prebetalipoprotein (pre-beta) band. This component was found to be present in the lipoprotein fraction of density > 1.006 Kg/l. Examination of this fraction from basal specimens revealed a pre-beta band in only two of the ten subjects and the intensity of this band increased in the corresponding fractions from the same subjects after ethanol ingestion. In an additional four subjects no pre-beta was detected in this fraction before ethanol but appeared after ethanol ingestion. No attempt has been made to characterize further the component with these characters but it is suggested that it is probably an intermediate lipoprotein (ILDL), that is, a lipoprotein with characteristics intermediate between VLDL and LDL.

Interaction of rat plasma very low density lipoprotein with lipoprotein lipase-rich (postheparin) plasma.

Incubation of 125I-labeled very low density lipoprotein (VLDL) with lipoprotein lipase-rich (postheparin) plasma obtained from intact or supradiaphragmatic rats resulted in the transfer of more than 80% of apoprotein C from VLDL to high density lipoprotein (HDL), whereas apoprotein B was associated with lipoprotein of density less than 1.019 g/ml (intermediate lipoprotein). The transfer of 125I-labeled apoprotein C from VLDL to HDL increased with time and decreased in proportion to the amount of VLDL in the incubation system. A relationship was established between the content of triglycerides and apoprotein C in VLDL, whereas the amount of apoprotein C in VLDL was independent of that of other apoproteins, especially apoprotein B. The injection of heparin to rats preinjected with 125I-labeled VLDL caused apoprotein interconversions similar to those observed in vitro. The intermediate lipoprotein was relatively rich in apoprotein B, apoprotein VS-2, cholesterol, and phospholipids and poor in triglycerides and apoprotein C. The mean diameter of intermediate lipoprotein was 269 A (compared with 427 A, the mean Sf rate was 30.5 (compared with 115), and the mean weight was 7.0 X 10(6) daltons (compared with 23.1 X 10(6)). From these data it was possible to calculate the mass of lipids and apoproteins in single lipoprotein particles. The content of apoprotein B in both particles was virtually identical, 0.7 X 10(6) daltons. The relative amount of all other constituents in intermediate lipoprotein was lower than in VLDL: triglycerides, 22%; free cholesterol, 37%; esterified cholesterol, 68%; phospholipids, 41%; apoprotein C, 7%, and VS-2 apoprotein, 60%. The data indicate that (a) one and only one intermediate lipoprotein is formed from each VLDL particle, and (b) during the formation of the intermediate lipoprotein all lipid and apoprotein components other than apoprotein B leave the density range of VLDL to a varying degree. Whether these same changes occur during the clearance of VLDL in vivo is yet to be established.

Swine lipoproteins and atherosclerosis. Changes in the plasma lipoproteins and apoproteins induced by cholesterol feeding

Cholesterol feeding in miniature swine resulted in a hypercholesterolemia with a distinctive hyperlipoproteinemia and the subsequent development of atherosclerosis. Alterations in the type and distribution of plasma lipoproteins induced by cholesterol feeding were as follows: (a) the occurrence of beta-migrating lipoproteins (B-VLDL) as well as very low density lipoproteins in the d less than 1.006 ultracentrifugal fraction; (b) an increased prominence of the intermediate lipoproteins (d = 1.006-1.02); (c) an increased prominence of low density lipoproteins; and (d) the occurrence of a distinctive lipoprotein with alpha mobility which was referred to as HDLc (cholesterol induced). Characterization of the various plasma lipoproteins included chemical composition, size by electron microscopy, and apoprotein content. The B-VLDL resembled the beta-migrating lipoproteins of human Type III hyperlipoproteinemia and contained a prominent protein equivalent to the arginine-rich apoprotein in addition to the B apoprotein, apo-A-I, and the fast-migrating apoproteins (apo-C). The HDLc were rich in cholesterol, ranged in size from 100 to 240 A in diameter, and contained the arginine-rich apoprotein and apo-A0I but lacked the B apoprotein. The arginine-rich apoproteins isolated from B-VLDL and HDLc by gel chromatography were similar in amino acid analyses, with glutamic acid as their amino-terminal residue. The occurrence of a spectrum of cholesterol-rich lipoproteins which contained the arginine-rich apoprotein with the occurrence of accelerated atherosclerosis suggested an interesting, although speculative, association.