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PubMed2004

Elevated levels of low-density lipoprotein cholesterol, homocysteine, and lipoprotein(a) are associated with the occurrence of symptomatic bypass graft disease 1 year following coronary artery bypass graft surgery.

Severe coronary artery bypass graft disease occurs at a rate of approximately 16%-31% within the first year of surgery. Clinical and laboratory variables, including postoperative lipid profiles closest to the 1-year follow-up, lipoprotein(a) levels, and homocysteine levels, were assessed as predictors of early (< or = 1 year) symptomatic coronary artery bypass graft disease. Of 77 living consecutive patients (from the practice of one cardiologist) who underwent bypass surgery, 60 were asymptomatic at 1 year, and 17 had developed recurrent symptoms and had an angiogram that confirmed >50% lesion in at least one saphenous bypass graft. Using multivariate analysis, the strongest predictors of early symptomatic coronary artery bypass graft disease within 1 year of bypass surgery were elevated levels of low-density lipoprotein cholesterol (>100 mg/dL) (odds ratio [OR], 8:1; p=0.034), homocysteine (>10 micromol/L) (OR, 8:1; p=0.019), and lipoprotein(a) (>30 mg/dL) (OR, 4:1; p=0.011). Male gender was associated with a reduced risk (OR, 1:9; p=0.01) of symptomatic graft disease within 1 year of surgery. The authors conclude that low-density lipoprotein, homocysteine, and lipoprotein(a) levels are associated with symptomatic coronary artery bypass graft disease at 1 year after surgery.

Aged↗
PubMed1985

Changes in plasma lipoproteins from first day to third week of life in healthy breast-fed infants. I. Lipid and protein composition of lipoproteins.

Plasma lipoproteins were measured in seven healthy breast-fed infants three times during the first and on the third, sixth and twenty-first days of life. Plasma total beta-lipoprotein, very low density and low density lipoprotein increased three times during the first week of life. Plasma total apolipoprotein A-I and high density lipoprotein increased twice between the first and third week of life. These dramatic changes in plasma lipoprotein concentrations during the neonatal period can best be explained by the effect of feeding.

Age Factors↗
PubMed2006

Mutation of the maturase lipoprotein attenuates the virulence of Streptococcus equi to a greater extent than does loss of general lipoprotein lipidation.

Streptococcus equi is the causative agent of strangles, a prevalent and highly contagious disease of horses. Despite the animal suffering and economic burden associated with strangles, little is known about the molecular basis of S. equi virulence. Here we have investigated the contributions of a specific lipoprotein and the general lipoprotein processing pathway to the abilities of S. equi to colonize equine epithelial tissues in vitro and to cause disease in both a mouse model and the natural host in vivo. Colonization of air interface organ cultures after they were inoculated with a mutant strain deficient in the maturase lipoprotein (DeltaprtM(138-213), with a deletion of nucleotides 138 to 213) was significantly less than that for cultures infected with wild-type S. equi strain 4047 or a mutant strain that was unable to lipidate preprolipoproteins (Deltalgt(190-685)). Moreover, mucus production was significantly greater in both wild-type-infected and Deltalgt(190-685)-infected organ cultures. Both mutants were significantly attenuated compared with the wild-type strain in a mouse model of strangles, although 2 of 30 mice infected with the Deltalgt(190-685) mutant did still exhibit signs of disease. In contrast, only the DeltaprtM(138-213) mutant was significantly attenuated in a pony infection study, with 0 of 5 infected ponies exhibiting pathological signs of strangles compared with 4 of 4 infected with the wild-type and 3 of 5 infected with the Deltalgt(190-685) mutant. We believe that this is the first study to evaluate the contribution of lipoproteins to the virulence of a gram-positive pathogen in its natural host. These data suggest that the PrtM lipoprotein is a potential vaccine candidate, and further investigation of its activity and its substrate(s) are warranted.

Alleles↗
PubMed1987

Brucella outer membrane lipoprotein shares antigenic determinants with Escherichia coli Braun lipoprotein and is exposed on the cell surface.

In an enzyme-linked immunosorbent assay (ELISA), purified Brucella abortus and Escherichia coli peptidoglycan-linked lipoproteins gave a strong cross-reaction with sera from rabbits hyperimmunized with the heterologous lipoprotein. When smooth E. coli cells were used as ELISA antigens, the immunological cross-reaction was not observed unless the cells were treated to remove lipopolysaccharide and other outer membrane components. In contrast, intact cells from smooth strains of B. abortus and Brucella melitensis bound anti-lipoprotein immunoglobulin G, and the controls performed by ELISA showed that this reaction was not due to antibodies to the lipopolysaccharide, group 3 outer membrane proteins, or porins. Electron microscopy of cells labeled with antilipoprotein serum and protein A-colloidal gold showed specific labeling of smooth cells from both B. abortus and B. melitensis, even though unspecific labeling by nonimmune serum was observed with rough B. abortus. These results confirm the close similarity between E. coli and Brucella peptidoglycan-linked lipoproteins and show that, in contrast to E. coli, the lipoprotein of B. abortus and B. melitensis is partially exposed on the surface of smooth cells.

Antigens, Bacterial↗
PubMed1983

Inhibition of secretion of a mutant lipoprotein across the cytoplasmic membrane by the wild-type lipoprotein of the Escherichia coli outer membrane.

A globomycin-resistant mutant of Escherichia coli was found to produce a precursor of the major outer membrane lipoprotein (prolipoprotein), in which the glycine residue at position 14 within the signal peptide was replaced by an aspartic acid residue. The same mutation has been reported by Lin et al. (Proc. Natl. Acad. Sci. U.S.A. 175:4891-4895, 1978). The structural gene of the mutant prolipoprotein was inserted into an inducible expression cloning vehicle. When the mutant prolipoprotein was produced in lipoprotein-minus host cells, 82% of the unprocessed protein was found in the membrane fraction, with the remaining 18% localized in the soluble fraction. However, when the production of the mutant prolipoprotein was induced in the wild-type lpp+ host cells, only 31% of the mutant prolipoprotein was found in the membrane fraction, leaving the remaining 69% in the soluble, cytoplasmic fraction. In addition, the assembly of the wild-type lipoprotein in these cells was not affected, whether the mutant prolipoprotein was produced or not. These results suggest that secretions of both mutant and wild-type prolipoproteins utilize the same component(s) responsible for the initial stages of secretion across the cytoplasmic membrane. However, it appears that the wild-type lipoprotein has a higher affinity for these components than does the mutant lipoprotein.

Anti-Bacterial Agents↗
PubMed1986

Plasma lipoprotein cholesterol and triglycerides and lipoprotein lipase activity in epididymal white adipose tissue of rats fed high sucrose or high corn oil diets.

The present study was undertaken to compare plasma lipoprotein lipid composition, as well as white adipose tissue lipoprotein lipase activity, in rats fed purified diets high in either sucrose or corn oil. The experimental diets (65% of calories as sucrose or corn oil, 15% as the opposite nutrient, and 20% as casein) were given ad libitum for 4 weeks. An additional group was fed a nonpurified diet as a reference diet. Both sucrose and oil diets were spontaneously consumed in isocaloric amounts by the animals. Despite energy intakes that were 35% lower than that of the reference group, the sucrose and oil groups exhibited final body weights that were only 6 and 9% lower, respectively, than that of the reference group, and accumulated more fat in the epididymal depots. Postprandial as well as fasting total cholesterol levels were similar in the sucrose and oil groups, while the high-density lipoprotein to total cholesterol ratio was highest in the animals fed corn oil. In both the fasted and fed states, plasma total triglyceride levels were 73% higher in the sucrose group than in the corn oil group. The largest triglyceride differences due to diet were observed in the chylomicron + very-low-density lipoprotein fraction. The oil-fed rats accumulated large amounts of triglycerides in their livers. Postprandial lipoprotein lipase activity in epididymal adipose tissue was almost twice as high in the sucrose group as in the oil group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1981

Rat plasma lipoprotein inhibitors of lymphocyte proliferation: specific membrane receptor for very low density lipoproteins.

We have compared the inhibitory effects of plasma lipoproteins on DNA synthesis by phytohemagglutinin-stimulated rat lymphocytes. The order of suppressor potency was: very low density lipoproteins (VLDL) greater than low density lipoproteins much greater than high density lipoproteins. We have further demonstrated the presence of specific receptor sites for VLDL on rat spleen lymphocytes. The number of VLDL receptors was estimated at 31,000 by a modified Scatchard analysis. Our results suggest that in the normal physiologic state, the proliferation of circulating lymphocytes may be suppressed by the combined effects of plasma lipoproteins. Furthermore, it would appear that the binding of plasma VLDL to specific receptors on rat lymphocytes would be the initial physiological event in this inhibitory process.

Animals↗
PubMed2002

Value of HDL cholesterol, apolipoprotein A-I, lipoprotein A-I, and lipoprotein A-I/A-II in prediction of coronary heart disease: the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction.

OBJECTIVE: We have examined the association between the incidence of coronary heart disease (CHD) and plasma high density lipoprotein (HDL) cholesterol, apolipoprotein A-I (apoA-I), and 2 HDL fractions, lipoprotein A-I and lipoprotein A-I:A-II. METHODS AND RESULTS: These parameters were measured in subjects recruited in France and in Northern Ireland in the Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study, a prospective cohort study. Among the subjects free of CHD on entry, 176 in France and 113 in Northern Ireland suffered an ischemic attack (CHD patients) during the 5-year follow-up, whereas 6612 French and 2172 Northern Irish men showed no CHD symptoms (CHD-free subjects). All 4 HDL parameter levels were lower in CHD patients than in CHD-free subjects. After the cohort was divided into quintiles based on the distribution of HDL parameter levels, a significant (P<0.0001) linear increase in relative risk was observed for each HDL parameter level. However, regression logistic analyses showed that apoA-I was the strongest predictor (more powerful than HDL cholesterol) and that lipoprotein A-I and lipoprotein A-I:A-II did not supplement apoA-I in predicting CHD. CONCLUSIONS: Among the parameters related to HDL, apoA-I appears to be the strongest independent risk factor.

Angina Pectoris↗
PubMedDate not supplied

Double pre-beta lipoprotein. Isolation and characterization of the two population of very low density lipoproteins by zonal ultracentrifugation.

Two electrophoretic populations of very low density lipoprotein are frequently observed in both normal and hyperlipidemic human sera. This gives the appearance of two pre-beta bands, called the "double pre-beta lipoprotein phenomenon." The slow and fast bands forming the double pre-beta lipoprotein were isolated by ultracentrifugation in the zonal rotor under rate flotation conditions. On the basis of the effluent position, the slow band showed a lower flotation coefficient than the fast one. The lipid and apoprotein composition of the two very low density lipoprotein populations isolated by zonal ultracentrifugation was in close agreement with those obtained by preparative agarose gel electrophoresis. The slow and fast pre-beta fractions had the same triglyceride fatty acid composition. Both fractions contained only higher molecular weight apo B-100, while the slow fraction was relatively enriched in apo E and apo C-III. Since the slow pre-beta fraction showed the typical properties of the remnant particle, studying this fraction could clarify the possible relationship between remnant lipoproteins and atherogenesis. Zonal rotor ultracentrifugation may be useful to characterize remnant particles in normal and hyperlipidemic subjects.

Apoproteins↗
PubMed1970

A lipoprotein characterizing obstructive jaundice. II. Isolation and partial characterization of the protein moieties of low density lipoproteins.

The plasma low density lipoproteins (LDL) in biliary obstruction are characterized almost exclusively by the presence of the immunochemically distinct lipoprotein families, lipoprotein B (LP-B) and lipoprotein X (LP-X). It is suggested that LP-X, with its uniquely high content of unesterified cholesterol and phospholipid, is primarily responsible for the unusual lipid composition of LDL and the abnormal plasma lipid composition in obstructive jaundice. To show their protein moieties, we isolated LP-X and LP-B from the LDL in plasma obtained from patients with obstructive jaundice. A separation procedure was employed which combines ultracentrifugation, heparin precipitation, and ethanol fractionation. Whereas LP-B was characterized by the presence of apolipoprotein B (ApoB), intact LP-X contained a protein moiety of unique composition consisting of a mixture of albumin (approximately 40%) and the specific apolipoprotein, ApoX (60%). These two protein moieties were separated by preparative ultracentrifugation at d 1.21 g/ml of a solution of partially delipidized LP-X. LP-X thus comprises an albumin-lipoprotein complex in which the masked antigenic site of albumin can be revealed by partial or total delipidization. Apolipoprotein X, the characteristic nonalbumin protein moiety of intact or partially delipidized LP-X, was immunochemically different from ApoA, ApoB, albumin, gamma-globulins, and other serum proteins. The results of analytical ultracentrifugation and the immunochemical and electrophoretic properties of ApoX indicated it to be a complex protein consisting possibly of several nonidentical polypeptides. ApoX was characterized by its amino acid composition, and by serine and threonine as the major N-terminal and alanine as the major C-terminal amino acids. It has been suggested that ApoX is similar to, if not identical with, apolipoprotein C.

Alanine↗
PubMed2006

Effects of hepatic expression of the high-density lipoprotein receptor SR-BI on lipoprotein metabolism and female fertility.

The etiology of human female infertility is often uncertain. The sterility of high-density lipoprotein (HDL) receptor-negative (SR-BI(-/-)) female mice suggests a link between female infertility and abnormal lipoprotein metabolism. SR-BI(-/-) mice exhibit elevated plasma total cholesterol [with normal-sized and abnormally large HDL and high unesterified to total plasma cholesterol (UC:TC) ratio]. We explored the influence of hepatic SR-BI on female fertility by inducing hepatic SR-BI expression in SR-BI(-/-) animals by adenovirus transduction or stable transgenesis. For transgenes, we used both wild-type SR-BI and a double-point mutant, Q402R/Q418R (SR-BI-RR), which is unable to bind to and mediate lipid transfer from wild-type HDL normally, but retains virtually normal lipid transport activities with low-density lipoprotein. Essentially wild-type levels of hepatic SR-BI expression in SR-BI(-/-) mice restored to nearly normal the HDL size distribution and plasma UC:TC ratio, whereas approximately 7- to 40-fold overexpression dramatically lowered plasma TC and increased biliary cholesterol secretion. In contrast, SR-BI-RR overexpression had little effect on SR-BI(+/+) mice, but in SR-BI(-/-) mice, it substantially reduced levels of abnormally large HDL and normalized the UC:TC ratio. In all cases, hepatic transgenic expression restored female fertility. Overexpression in SR-BI(-/-) mice of lecithin:cholesterol acyl transferase, which esterifies plasma HDL cholesterol, did not normalize the UC:TC ratio, probably because the abnormal HDL was a poor substrate, and did not restore fertility. Thus, hepatic SR-BI-mediated lipoprotein metabolism influences murine female fertility, raising the possibility that dyslipidemia might contribute to human female infertility and that targeting lipoprotein metabolism might complement current assisted reproductive technologies.

Adenoviridae↗
PubMed1993

Elevated plasma low-density lipoprotein and high-density lipoprotein cholesterol levels in amenorrheic athletes: effects of endogenous hormone status and nutrient intake.

To determine the interactive effects of hormones, exercise, and diet on plasma lipids and lipoproteins, serum estrogen and progesterone levels, nutrient intake, and plasma lipid, lipoprotein, and apolipoprotein concentrations were measured in 24 hypoestrogenic amenorrheic and 44 eumenorrheic female athletes. When compared to eumenorrheic athletes, amenorrheic athletes had higher levels of plasma cholesterol (5.47 +/- 0.17 vs. 4.84 +/- 0.12 mmol/L, P = 0.003), triglyceride (0.75 +/- 0.06 vs. 0.61 +/- 0.03 mmol/L, P = 0.046), low-density lipoprotein (LDL; 3.16 +/- 0.15 vs. 2.81 +/- 0.09 mmol/L, P = 0.037), high-density lipoprotein (HDL; 1.95 +/- 0.07 vs. 1.73 +/- 0.05 mmol/L, P = 0.007), and HDL2 (0.84 +/- 0.06 vs. 0.68 +/- 0.04 mmol/L, P = 0.02) cholesterol. Plasma LDL/HDL cholesterol ratios, very low-density lipoprotein and HDL3 cholesterol, and apolipoprotein A-I and A-II levels were similar in the two groups. Amenorrheic athletes consumed less fat than eumenorrheic subjects (52 +/- 5 vs. 75 +/- 3 g/day, P = 0.02), but similar amounts of calories, cholesterol, protein, carbohydrate, and ethanol. HDL cholesterol levels in amenorrheic subjects correlated positively with the percent of dietary calories from fat (r = 0.42, n = 23, P = 0.045) but negatively with the percent from protein (r = -0.49, n = 23, P = 0.017). Thus, exercise-induced amenorrhea may adversely affect cardiovascular risk by increasing plasma LDL and total cholesterol. However, cardioprotective elevations in plasma HDL and HDL2 cholesterol may neutralize the risk of cardiovascular disease in amenorrheic athletes.

Adult↗
PubMed1999

Inter-relationships between small, dense low-density lipoprotein (LDL), plasma triacylglycerol and LDL apoprotein B in an atherogenic lipoprotein phenotype in free-living subjects.

A predominance of small, dense low-density lipoprotein (LDL) is a major component of an atherogenic lipoprotein phenotype, and a common, but modifiable, source of increased risk for coronary heart disease in the free-living population. While much of the atherogenicity of small, dense LDL is known to arise from its structural properties, the extent to which an increase in the number of small, dense LDL particles (hyper-apoprotein B) contributes to this risk of coronary heart disease is currently unknown. This study reports a method for the recruitment of free-living individuals with an atherogenic lipoprotein phenotype for a fish-oil intervention trial, and critically evaluates the relationship between LDL particle number and the predominance of small, dense LDL. In this group, volunteers were selected through local general practices on the basis of a moderately raised plasma triacylglycerol (triglyceride) level (>1.5 mmol/l) and a low concentration of high-density-lipoprotein cholesterol (<1.1 mmol/l). The screening of LDL subclasses revealed a predominance of small, dense LDL (LDL subclass pattern B) in 62% of the cohort. As expected, subjects with LDL subclass pattern B were characterized by higher plasma triacylglycerol and lower high-density lipoprotein cholesterol (<1.1 mmol/l) levels and, less predictably, by lower LDL cholesterol and apoprotein B levels (P<0.05; LDL subclass A compared with subclass B). While hyper-apoprotein B was detected in only five subjects, the relative percentage of small, dense LDL-III in subjects with subclass B showed an inverse relationship with LDL apoprotein B (r=-0.57; P<0.001), identifying a subset of individuals with plasma triacylglycerol above 2.5 mmol/l and a low concentration of LDL almost exclusively in a small and dense form. These findings indicate that a predominance of small, dense LDL and hyper-apoprotein B do not always co-exist in free-living groups. Moreover, if coronary risk increases with increasing LDL particle number, these results imply that the risk arising from a predominance of small, dense LDL may actually be reduced in certain cases when plasma triacylglycerol exceeds 2.5 mmol/l.

Adult↗
PubMed2000

Low levels of high density lipoproteins in Turks, a population with elevated hepatic lipase. High density lipoprotein characterization and gender-specific effects of apolipoprotein e genotype.

Turks have strikingly low levels of high density lipoprotein cholesterol (HDL-C) (10-15 mg/dL lower than those of Americans or Western Europeans) associated with elevated hepatic lipase mass and activity. Here we report that Turks have low levels of high density lipoprotein subclass 2 (HDL(2)), apoA-I-containing lipoproteins (LpA-I), and pre-beta-1 HDL and increased levels of HDL(3) and LpA-I/A-II particles (potentially an atherogenic lipid profile). The frequency distributions of HDL-C and LpA-I levels were skewed toward bimodality in Turkish women but were unimodal in Turkish men. The apoE genotype affected HDL-C and LpA-I levels in women only. In women, but not men, the varepsilon2 allele was strikingly more prevalent in those with the highest levels of HDL-C and LpA-I than in those with the lowest levels. The higher prevalence of the epsilon2 allele in these subgroups of women was not explained by plasma triglyceride levels, total cholesterol levels, age, or body mass index. The modulating effects of apoE isoforms on lipolytic hydrolysis of HDL by hepatic lipase (apoE2 preventing efficient hydrolysis) or on lipoprotein receptor binding (apoE2 interacting poorly with the low density lipoprotein receptors) may account for differences in HDL-C levels in Turkish women (the epsilon2 allele being associated with higher HDL levels). In Turkish men, who have substantially higher levels of hepatic lipase activity than women, the modulating effect of apoE may be overwhelmed. The gender-specific impact of the apoE genotype on HDL-C and LpA-I levels in association with elevated levels of hepatic lipase provides new insights into the metabolism of HDL.

Adult↗
PubMed2000

Increased low density lipoprotein degradation in aorta of irradiated mice is inhibited by preenrichment of low density lipoprotein with alpha-tocopherol.

We previously reported that upper thoracic exposure to ionizing radiation (IR) accelerates fatty streak formation in C57BL/6 mice and that such effects are inhibited by overexpression of the antioxidant enzyme CuZn-superoxide dismutase (SOD). Notably, IR-accelerated lesion formation is strictly dependent on a high fat diet (i.e., atherogenic lipoproteins) but does not involve alterations in circulating lipid or lipoprotein levels. We thus proposed that IR promotes changes in the artery wall that enhance the deposition of lipoprotein lipids. To address this hypothesis, we examined the effects of IR on aortic accumulation and degradation of low density lipoproteins (LDL). Ten-week-old C57BL/6 mice were exposed to a single (8-Gy) dose of (60)Co radiation to the upper thoracic area or were sham irradiated (controls) and were then placed on the high fat diet. Five days postexposure, the mice received either (125)I-labeled LDL ((125)I-LDL) (which was used to measure intact LDL) or (125)I-labeled tyramine cellobiose ((125)I-TC)-LDL (which was used to measure both intact and cell-degraded LDL) via tail vein injection. On the basis of trichloroacetic acid (TCA)-precipitable counts in retroorbital blood samples, > or =95% of donor LDL was cleared within 24 h and there were no differences in time-averaged plasma concentrations of the two forms of LDL among irradiated and control mice. Aortic values increased markedly within the first hour and thereafter exhibited a slow increase up to 24 h. There were no differences between irradiated and control mice at 1 h, when values primarily reflected LDL entry, but a divergence was observed thereafter. At 24 h, (125)I-TC-associated counts were 1.8-fold higher in irradiated mice (P = 0.10). In contrast, (125)I-LDL-associated counts were 30% lower in irradiated mice (P< 0.05), suggesting that most of the retained (125)I-TC was associated with LDL degradation products. Consistent with the proposed involvement of oxidative or redox-regulated events, IR-induced LDL degradation was lower in SOD-transgenic than wild-type mice (P<0.05). The importance of LDL oxidation was suggested by observations that IR-induced LDL degradation was significantly reduced by preenriching LDL with alpha-tocopherol. On the basis of these results, we propose that IR elicits SOD-inhibitable changes in the artery wall that enhance LDL oxidation and degradation leading to the deposition of LDL-borne lipids. These studies provide additional support for the role of oxidation in lipoprotein lipid deposition and atherogenesis and suggest that IR promotes an arterial environment that stimulates this process in vivo.

Animals↗
PubMed1979

Lipoprotein abnormalities in cholestasis. II. Isolation, characterization and clinical evaluation of an additional cholestatic lipoprotein (slow-migrating HDL).

An additional cholestatic lipoprotein with a slower mobility than the usual alpha-lipoprotein on polyacrylamide-gel disc-electrophoresis was found in the serum of patients with cholestasis. This abnormal lipoprotein was referred to as Slwo-migrating HDL (HDL-S), because it was mostly recovered in the high density lipoprotein (HDL) fraction after preparative ultracentrifugation. HDL-S was precipitated by dextran sulfate and Mg++ but did not react with either concanavalin A or anti-beta-lipoprotein serum. The main apoprotein of HDL-S was Apo A-I, and a trace of Apo E was also present. HDL-S was relatively enriched in free cholesterol and triglycerides and had a density in the range of 1.063 to 1.083. The appearance of HDL-S in serum or plasma was closely associated with chronic mild intrahepatic cholestasis, particularly as in primary biliary cirrhosis and related conditions.

Cholestasis, Intrahepatic↗
PubMed1988

Inhibition of vein graft intimal thickening by eicosapentanoic acid: reduced thromboxane production without change in lipoprotein levels or low-density lipoprotein receptor density.

Marine lipids containing omega-3 fatty acids (chiefly, eicosapentanoic acid [EPA] and docosahexanoic acid [DHA]) may inhibit the development of atherosclerotic vascular disease, but the mechanisms responsible for this putative beneficial effect are unknown. We investigated the effects of EPA and DHA in a canine model of accelerated vein graft arteriosclerosis during a 3-month period. Twenty-five dogs were divided into three dietary groups: group I (control), group II (2.5% cholesterol), and group III (2.5% cholesterol plus 2 gm EPA/day [as MaxEPA]). The effects of EPA on vein graft intimal thickening, platelet and vascular prostaglandin metabolism, lipid and lipoprotein receptor metabolism, and hematologic parameters were assessed. Cholesterol feeding caused a significant 54% increase in graft intimal thickness compared with control animals (124.9 +/- 50.4 vs 81.2 +/- 32.4 micron; p = 0.013), which was prevented by supplementation with EPA in group III (56.9 +/- 30.0 micron; p = 0.001 vs group II). Intimal thickness in group III was not significantly different from that of control. EPA supplementation was also associated with a 38% decline in serum thromboxane levels from 457.0 +/- 129.3 pg/0.1 ml in group II to 283.5 +/- 96.9 pg/0.1 ml in group III (p = 0.007). The alterations in lipoprotein metabolism associated with cholesterol feeding were not affected by EPA: in both groups II and III, serum cholesterol and high-density lipoproteins and liver cholesterol content were elevated and hepatic low-density lipoproteins (LDL) receptor content was reduced. There were no differences between the three groups in terms of vein graft or native vessel prostacyclin production, hematocrit, platelet count, or coagulation parameters. In this canine model, dietary supplementation with marine omega-3 fatty acids reduced the extent and magnitude of accelerated vein graft intimal thickening induced by hypercholesterolemia; moreover, this beneficial effect was associated with lower serum thromboxane production and appeared to be independent of alterations in lipoprotein metabolism or LDL receptor density.

Animals↗
PubMed1986

Uptake of canine beta-very low density lipoproteins by mouse peritoneal macrophages is mediated by a low density lipoprotein receptor.

The receptor on mouse peritoneal macrophages that mediates the uptake of canine beta-very low density lipoproteins (beta-VLDL) has been identified in this study as an unusual apolipoprotein (apo-) B,E(LDL) receptor. Ligand blots of Triton X-100 extracts of mouse peritoneal macrophages using 125I-beta-VLDL identified a single protein. This protein cross-reacted with antibodies against bovine apo-B,E(LDL) receptors, but its apparent Mr was approximately 5,000 less than that of the human apo-B,E(LDL) receptor. Binding studies at 4 degrees C demonstrated specific and saturable binding of low density lipoproteins (LDL), beta-VLDL, and cholesterol-induced high density lipoproteins in plasma that contain apo-E as their only protein constituent (apo-E HDLc) to mouse macrophages. Apolipoprotein E-containing lipoproteins (beta-VLDL and apo-E HDLc) bound to mouse macrophages and human fibroblasts with the same high affinity. However, LDL bound to mouse macrophages with an 18-fold lower affinity than to human fibroblasts. Mouse fibroblasts also bound LDL with a similar low affinity. Compared with the apo-B,E(LDL) receptors on human fibroblasts, the apo-B,E(LDL) receptors on mouse macrophages were resistant to down-regulation by incubation of the cells with LDL or beta-VLDL. There are three lines of evidence that an unusual apo-B,E(LDL) receptor on mouse peritoneal macrophages mediates the binding and uptake of beta-VLDL: LDL with residual apo-E removed displaced completely the 125I-beta-VLDL binding to mouse macrophages, preincubation of the mouse macrophages with apo-B,E(LDL) receptor antibody inhibited both the binding of beta-VLDL and LDL to the cells and the formation of beta-VLDL- and LDL-induced cholesteryl esters, and binding of 125I-beta-VLDL to the cells after down-regulation correlated directly with the amount of mouse macrophage apo-B,E(LDL) receptor as determined on immunoblots. This unusual receptor binds LDL poorly, but binds apo-E-containing lipoproteins with normal very high affinity and is resistant to down-regulation by extracellular cholesterol.

Animals↗