Sialic acid content of low-density lipoprotein in women with coronary artery disease

A low sialic acid content in low-density lipoprotein (LDL) has been associated with coronary artery disease (CAD) in studies that have included mostly male subjects. We compared the sialic acid-to-apolipoprotein B ratios of total LDL and its subfractions in middle-aged women with CAD (CAD+, n = 22) with those ratios in healthy female control subjects (CAD-, n = 11). CAD+ subjects had a lower sialic acid ratio in total LDL and in its subfractions as compared with results in CAD- subjects. In total, light, and dense LDL, the sialic acid ratio was negatively correlated with the respective cholesterol and phospholipid concentrations, and in very dense LDL, it was negatively correlated with triglyceride concentration. In multivariate analysis, CAD and LDL cholesterol contributed to the explanation of the variability of LDL sialic acid ratios. In summary, a low sialic acid-to-apolipoprotein B ratio in LDL was associated with the presence of CAD in middle-aged women with mild to moderate hypercholesterolemia.     

Comparison of laboratory parameters as risk factors for the presence and the extent of coronary or carotid atherosclerosis: the significance of apolipoprotein B to apolipoprotein all ratio.

We compared several "new" risk factors (autoantibodies to oxidatively modified low density lipoprotein (LDL), sialic acid content of LDL, bilirubin and C-reactive protein) with "conventional" risk factors (apolipoprotein (apo) AI, AII and B, lipoprotein(a), triglycerides, and total, LDL and high density lipoprotein (HDL) cholesterol) for the presence and the extent of coronary or carotid atherosclerosis. Forty male patients with angiographically proven coronary atherosclerosis and 31 male patients with ultrasound-proven extracranial carotid atherosclerosis were compared to 40 age matched (53+/-5 years) healthy males as control subjects, with negative parental history of atherosclerosis, no clinical signs of systemic or organ-related ischemic disease and normal extracranial carotid arteries. The apo B/apo All ratio most powerfully indicated the presence and the extent of coronary or carotid atherosclerosis. Elevated lipoprotein(a) contributed significant additional information in the assessment of the atherosclerotic risk. Increase in C-reactive protein indicated the presence (but not the extent) of coronary or carotid atherosclerosis with a similar power as lipoprotein(a). Decreased values of total bilirubin indicated the presence of atherosclerosis only in smokers. Autoantibodies to oxidatively modified LDL additionally described the atherosclerotic process, but were less important than apolipoproteins, lipoprotein(a), C-reactive protein or bilirubin. Sialic acid content of LDL added no information to the parameters discussed above. We demonstrated that in male patients apolipoproteins, especially the apo B/apo All ratio, were better indicators of the presence and the extent of coronary or carotid atherosclerosis than C-reactive protein, bilirubin, autoantibodies to oxidatively modified LDL or sialic acid content of LDL.     

Serum and lipoprotein apolipoprotein B levels in normal subjects and patients with hyperlipoproteinaemia.

Apolipoprotein B (apo B) levels were measured by radioimmunoassay in the serum and lipoproteins from normal subjects and patients with hyperlipoproteinaemia. The total serum apo B concentration in normal subjects was 0.91 +/- 0.16 g/l (mean +/- S.D.); in type IIa hyperlipoproteinaemia it was 2.24 +/- 0.61 g/l; in type IIb, 3.05 +/- 1.24 g/l; in type IV, 2.24 +/- 0.99 g/l; and in type V, 1.30 +/- 0.16 g/l. In normal subjects 5.6 +/- 2.1% (mean +/- S.D.) of total apo B was present in very low density lipoproteins (VLDL) and 93 +/- 9% in low density lipoproteins (LDL). Corresponding values for type IIa were 3.8 +/- 1.9% and 93 +/- 3%, for type IIb, 9.9 +/- 7.5% and 91 +/- 1%, for type IV, 16.9 +/- 9.5% and 81 +/- 9%, and for type V, 38.4 +/- 11.0% and 52 +/- 8%. The ratio of cholesterol to apo B in serum was decreased in types IIa, IIb and IV, and increased in type V whereas the ratio of triglyceride to apo B in serum was decreased in type IIa, normal in type IIb and increased in types IV and V. The ratio of cholesterol to apo B in VLDL was increased in types IIa, IIb and V, but normal in type IV, whereas in LDL, this ratio was normal in types IIa and V but reduced in types IIb and IV. The ratio of triglycerides to apo B in VLDL was normal in types IIa, IIb and IV but raised in type V. In LDL, this ratio was increased in types IIb and IV but normal in types IIa and V.     

Effect of simvastatin on apoprotein B—containing lipoproteins in patients with diabetic nephropathy

Background: Diabetic patients with nephropathy usually have a more atherogenic lipoprotein profile than those without nephropathy, which may be associated with the substantially higher incidence of coronary heart disease (CHD) in this population. Simvastatin has been shown to significantly reduce the incidence of CHD events in diabetic patients.Objective: The purpose of this study was to evaluate the effect of simvastatin (10 mg/d) on atherogenic apoprotein (apo) B—containing lipoproteins in type 2 diabetic patients with nephropathy.Methods: Diabetic patients with nephropathy and a group of healthy control subjects matched for age, sex, and body weight were enrolled. Diabetic patients were administered simvastatin 10 mg/d for 6 months. Apo B—containing lipoproteins were sequentially separated by ultracentrifugation to yield very low-density lipoprotein (VLDL) (density <1.006 g/mL), intermediate-density lipoprotein (IDL) (1.006-1.019 g/mL), light low-density lipoprotein (LDL) (1.019-1.044 g/mL), and dense LDL (1.044-1.063 g/mL) fractions. Apo B in lipoproteins was measured by a sensitive enzyme-linked immunosorbent assay at baseline and after 6 months of simvastatin treatment.Results: A total of 18 patients with diabetic nephropathy and 36 matched controls were enrolled. The diabetic patients had significantly higher levels (P < 0.01) of total cholesterol, LDL cholesterol, triglycerides, and apo B compared with age- and weight-matched control subjects at baseline. The diabetic patients also had significantly higher levels (P < 0.05) of cholesterol and apo B in the VLDL, light LDL, and dense LDL fractions. Treatment with simvastatin for 6 months significantly reduced plasma total cholesterol by 21%, LDL cholesterol by 30%, and apo B by 25% (P < 0.001), but did not affect urinary albumin excretion. Simvastatin significantly decreased both triglyceride and cholesterol levels in VLDL by 18% (P < 0.05), and cholesterol and apo B in IDL by 22% (P < 0.05) and 26% (P < 0.01). Simvastatin decreased both the light and dense LDL subfractions to a similar extent, reducing cholesterol and apo B in light LDL by 27% (P < 0.001) and in dense LDL by 28% (P < 0.01) and 18% (P < 0.05), respectively. The light LDL/dense LDL ratio for apo B and for cholesterol were not altered by simvastatin therapy.Conclusions: The results of this study suggest that simvastatin may reduce levels of atherogenic apo B—containing lipoproteins and small dense LDL in diabetic patients with nephropathy.     

Efficacy of ciprofibrate in primary type II and IV hyperlipidemia: the Italian multicenter study

The 127 diet-resistant primary hyperlipidemic patients received 100 mg of ciprofibrate daily for 12 weeks. In the 63 patients with type IIa hyperlipidemia and 41 patients with type IIb hyperlipidemia, serum levels of total cholesterol, very-low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, very-low-density lipoprotein triglycerides, and apolipoprotein (apo) B decreased significantly and levels of high-density lipoprotein cholesterol and apo A-I increased significantly. Similar changes occurred in the 23 type IV patients, except that high-density lipoprotein cholesterol levels increased significantly and apo B levels did not change. No clinically significant side effects or drug-related abnormal laboratory test results were noted. It is concluded that ciprofibrate is a safe and potent hypolipidemic agent.     

Composition and immunoreactivity of serum low density lipoproteins (LDL) before and after LDL-apheresis on dextran sulfate-cellulose columns

The changes in low density lipoprotein (LDL) composition and immunoreactivity occurring after LDL-apheresis on dextran sulfate-cellulose columns (DSC) were investigated in 4 hypercholesterolemic patients. After apheretic treatment, serum levels of total cholesterol, triglycerides and apolipoprotein B (apo B) were decreased by 63, 80 and 65%, respectively, whereas the high density lipoprotein (HDL)-cholesterol remained unchanged. At the end of apheresis, LDL contained less triglycerides, more phospholipids and apo E and the ratio of LDL core lipid components, cholesteryl esters and triglycerides, to LDL surface lipid components, unesterified cholesterol and phospholipids was significantly lower. The post-apheretic LDL were characterized by the presence of subfractions slightly larger than those observed in the pre-apheretic LDL. The modifications of the composition and size of LDL after apheresis were accompanied by a relative increase in the immunoreactivity of 4G3 epitope, an apo B epitope located near the LDL-receptor binding site, with no change in the affinity of 1D1, an apo B epitope located in the amino-terminal region of the molecule. The changes in LDL composition, size and immunoreactivity following apheresis, suggest that postapheresis LDL could contain newly synthesized LDL, different from mature LDL. Thus, LDL-apheresis treatment could provide the opportunity to study the structural change of LDL during intravascular metabolism.     

Quantitative analysis of lipoproteins in hyperlipoproteinemias of type IIa, IIb and IV (author's transl)]

Cholesterol and triglyceride content of serum lipoprotein fractions isolated by ultracentrifugation have been studied in 33 healthy subjects and in 56 subjects affected by hyperlipoproteinemia of type IIa, IIb and IV. Patients with atherosclerotic disease were characterized by a general decrease of HDL cholesterol and by a negative correlation between HDL cholesterol and VLDL triglycerides; patients with type IIb and IV showed an increase of LDL lipoproteins. The increase of triglycerides in type IIb and IV was caused by elevation of VLDL triglycerides or LDL triglycerides, and the increase of cholesterol in type IIb is sometimes caused by elevation of VLDL cholesterol. It is evident that several subtypes exist within Fredrickson's classification. Patients with cerebral arterial disease when compared with patients affected by non-ischaemic disease, showed a negative and significant correlation between HDL cholesterol and total cholesterol.     

Significance of acidic sugar chains of apolipoprotein B-100 in cellular metabolism of low-density lipoproteins

We have elucidated the carbohydrate structures of the N-linked sugar chains of human and rabbit apolipoprotein B-100 (apo B-100), which is similar in composition to oligosaccharides (Arch Biochem Biophys 1989;273:197-205, Arteriosclerosis 1990; 10:386-93). We have also shown the negative correlation of the ratio of acidic sugar chains of apo B-100 to the serum cholesterol levels in Watanabe heritable hyperlipidemic rabbits (Atherosclerosis 1992;93:229-35). The acidity of sugar chains is determined by the existence of sialic acid residues at the terminal of oligosaccharides. In the present study we investigated N-linked sugar chains of apo B-100 from patients with coronary artery disease (CAD) who had moderate hypercholesterolemia (less than 400 mg/dL). There was no difference in the structure of their oligosaccharides and the ratio of acidic sugar chains of apo B-100 from CAD patients as compared with that from healthy individuals reported previously. To clarify the role of sialic acid residues in apo B-100 for lipoprotein metabolism, we studied cellular uptake of low-density lipoproteins (LDLs) treated with sialidase (desialylated LDL). Desialylated LDLs were taken up and degraded to a 2-fold greater degree than control LDL by human monocyte-derived macrophages and stimulated cholesterol esterification in these cells. These results indicate that sialic acid residues of apo B- 100 play an important role in cellular uptake and degradation of LDL.     

Activity of low-density lipoprotein receptors as estimated from concentrations of apolipoprotein B and C-II in serum

The correlation between low-density lipoprotein (LDL) receptor activity and concentrations of lipids and apolipoproteins in serum was examined in 12 subjects with heterozygous familial hypercholesterolemia (FH) and in four with non-FH type II hyperlipoproteinemia. Concentrations of high-density lipoprotein cholesterol and of apolipoproteins (apo) A-I, C-II, and C-III were significantly positively correlated with LDL receptor activity, whereas LDL receptor activity was significantly inversely correlated with LDL cholesterol and apo B concentrations, and with apo ratios B/A-I and B/A-II. Neither total serum cholesterol, triglyceride, phospholipid, apo A-I, nor apo E concentrations correlated significantly with LDL receptor activity. Multiple regression analysis, with LDL receptor activity as the dependent variable, revealed concentrations of apo B and apo C-II to be the principal determinant factors. To confirm this, we subsequently calculated the LDL receptor activities before and after administration of CS-514, an inhibitor of hydroxymethylglutaryl-CoA reductase (EC 1.1.1.88), which increases the hepatic LDL receptor activity and decreases the concentration of cholesterol in serum. This drug increased calculated LDL receptor activities significantly, with a significant decrease in serum cholesterol.     

Roles of apolipoproteins B and E in the cellular binding of very low density lipoproteins.

Apoproteins B and E both interact with cellular low density lipoprotein (LDL) apolipoprotein B and E (apo B,E)-receptors, and very low density lipoproteins (VLDL) contain both apo B and apo E. Our aim was to study the relative importance of apo B and apo E in the binding of VLDL subfractions to cells. Two monoclonal anti-LDL-apo B antibodies (464B1B3 and 464B1B6, 2a and 2b, respectively) and two anti-apo E antibodies (1506 A1.4 and 1907 F6.4) were used to inhibit lipoprotein-cell interactions. In confirmation of previous findings, the binding and degradation of 125I-LDL by human fibroblasts were inhibited approximately 90% by antibodies 2a or 2b or the antigen-binding fragments of 2a, whereas the cellular processing of 125I-VLDL3 (Sf20-60), 125I-VLDL2 (Sf60-120), and 125I-VLDL1 (Sf greater than 120) were inhibited by only approximately 50%, approximately 25%, and less than 10%, respectively. The VLDL1-3 and LDL-dependent intracellular esterification of cholesterol with [3H]oleate were inhibited to a similar extent. Other monoclonal anti-human apo B antibodies inhibited lipoprotein-cell interactions much less effectively and nonimmune IgG isolated from mouse serum did not inhibit at all. 20-fold excesses of LDL produced about the same patterns of inhibition of degradation of 125I-VLDL1-3 and LDL by cells as did antibodies 2a and 2b, whereas homologous unlabeled VLDL1-3 in like amounts inhibited the matched 125I-VLDL subfraction more effectively. Two anti-apo E monoclonal antibodies and a polyclonal anti-apo E antibody inhibited cell-mediated degradation of and lipoprotein-dependent cholesterol esterification by VLDL1 but not VLDL3 or LDL. The results suggest that receptor recognition sites on apo E in preference to sites on apo B mediate the cellular binding of hypertriglyceridemic VLDL1. However, the proportion of particles bound via apo B seems to increase as VLDL decreases in size toward LDL, and virtually all of LDL binding is mediated by apo B.     

Regulation of the production and catabolism of plasma low density lipoproteins in hypertriglyceridemic subjects. Effect of weight loss.

In subjects with hypertriglyceridemia, plasma concentrations of low density lipoprotein (LDL) cholesterol are often normal or reduced. Perturbations that alter plasma very low density lipoprotein (VLDL) concentrations are associated with opposite changes in plasma LDL levels. To determine the mechanisms regulating plasma LDL levels, we used 131I-VLDL and 125I-LDL to measure the fractional catabolic rates (FCR), production rates (PR), and rates of interconversion of apoprotein B (apo B) in VLDL, intermediate density lipoprotein, and LDL in six hypertriglyceridemic subjects pre- and post-weight reduction. [2-3H]glycerol was used to quantitate VLDL triglyceride PR. All data are presented as mean +/- SD. Percent ideal body weight fell from 132 +/- 17.9 to 119 +/- 15.9% in the group, P less than 0.05. After weight loss, plasma VLDL triglyceride (486.0 +/- 364.1 vs. 191.3 +/- 65.4 mg/dl, P less than 0.05) and VLDL apo B (32.2 +/- 12.0 vs. 14.8 +/- 6.8 mg/dl, P less than 0.05) concentrations were reduced. VLDL triglyceride PR also fell after weight reduction (56.6 +/- 39.0 vs. 28.6 +/- 23.1 mg/kg per h, P less than 0.05), as did VLDL apo B PR (47.9 +/- 41.4 vs. 19.0 +/- 14.1 mg/kg per d, P less than 0.05). Pre-weight loss, plasma LDL cholesterol and apo B levels were low-normal or reduced (64.0 +/- 12.6 and 58.4 +/- 11.9 mg/dl, respectively) despite normal or elevated LDL apo B PR (17.4 +/- 7.2 mg/kg per d). The reduced cholesterol and apo B levels were associated with increased FCRs (0.68 +/- 0.29 d-1) and reduced cholesterol/protein ratios (1.01 +/- 0.18) in LDL. The plasma levels of LDL cholesterol and apo B rose after weight reduction (84.8 +/- 24.9, P less than 0.05; and 69.5 +/- 14.3 mg/dl, P less than 0.05, respectively, vs. base line). These increased concentrations resulted from a combination of events. First, the FCR for LDL apo B fell in five of six subjects with a significant reduction for the group as a whole (0.48 +/- 0.11 d-1, P less than 0.05 vs. base line). Second, the cholesterol/protein ratio increased in all six subjects with a significantly greater mean after weight loss (1.25 +/- 0.27, P less than 0.05 vs. base line). In contrast, the LDL apo B PR fell or was essentially unchanged in the six subjects after weight loss (mean, 14.4 +/- 2.8 mg/kg per d; NS vs. pre-weight loss). The changes in LDL catabolism and composition were associated with changes in the source of LDL apo B. Pre-weight loss, 73.3% of LDL was derived from VLDL, while 26.7% was directly secreted into plasma. Post-weight reduction, VLDL-derived LDL fell to 46.8% of total, while direct secretion accounted for 53.2% of LDL production. These changes were significant; P < 0.95. Thus, all subjects had direct secretion of LDL apo B and the magnitude of this source of VLDL triglyceride secretion. These results indicate that the regulation of plasma LDL levels in hypertriglyceridemic subjects is quite complex and that the rise in LDL levels after weight loss results from reduction in the fractional catabolism of this lipoprotein. The fall in the FCR is associated with changes in the source of LDL and in its composition.     

The metabolism of low density lipoprotein in endogenous hypertriglyceridaemia.

The metabolism of low density lipoprotein (LDL) was studied in eighteen hypertriglyceridaemic patients by injecting autologous radioiodinated LDL. Over 95% of the label was bound to the protein moiety of LDL and therefore the metabolic data reflect the fate and distribution of LDL apoprotein (apo B). The hypertriglyceridaemic subjects included ten with Type V, five with Type IV, two with Type III and one with Type IIb hyperlipoproteinaemia. For comparison identical studies were carried out in seven normal subjects and five patients with heterozygous familial hyperbetalipoproteinaemia (Type IIa). The groups differed considerably in mean LDL-cholesterol concentration. The patients with Type V lipoprotein pattern had significantly lower LDL-cholesterol concentration (mean 0.754 g/1) than the normal group (mean 1.237 g/1). Raised LDL-cholesterol levels were observed in all patients with heterozygous familial hyperbetalipoproteinaemia. The synthetic rate of LDL-apoprotein was found to be similar in all three groups (hypertriglyceridaemic, normal and hypercholesterolaemic). The highest synthetic rate was observed in the patient with Type IIb pattern. However, the fractional catabolic rate (FCR) of LDL-apoprotein differed significantly. The highest mean FCR was found in the Type V group (0.65 +/- 0.17 day-1) compared with 0.41 +/- 0.09 day-1 in the normal group and 0.185 +/- 0.05 day-1 in the Type IIa group. A strong inverse correlation was found between FCR and LDL apoprotein concentration in the whole series (r = -0.90, p less than 0.001) as well as within the Type V group (r = -0.87, p less than 0.01). These data indicate that the low plasma levels of LDL frequently observed in patients with very high plasma triglyceride levels are due to a high removal rate of LDL in these patients rather than to abnormal LDL synthesis.     

Effect of captopril on high-density lipoprotein subfractions in patients with mild to moderate essential hypertension

Changes in serum lipids, apolipoproteins, and lipoproteins including high-density lipoprotein (HDL) subfractions following administration of captopril in patients with hypertension were studied. Captopril (25 mg twice daily) was administered over a 12-week period to 17 patients with mild to moderate essential hypertension. Captopril was observed to significantly reduce both systolic and diastolic blood pressure, as well as to increase HDL2- cholesterol (HDL2-C) and to decrease HDL3-cholesterol (HDL3-C); however, no significant changes in total HDL-C were recognized. Total cholesterol, low-density lipoprotein cholesterol, triglyceride, apolipoprotein (apo) A-I, apo A-II, apo B, apo C-II, apo C-III, and apo E did not change significantly. It is suggested that captopril monotherapy produces a favorable effect on HDL subfractions.     

Intercorrelations of lipoprotein subfractions and their covariation with lifestyle factors in healthy men

So far, little is known about the effect of nutrition and lifestyle on the composition of circulating lipoprotein subfractions. In the current study, we measured the correlations among physical activity, nutrient intake, smoking, body-mass index (BMI), and age with the concentration of triglycerides, cholesterol, phospholipids, and apolipoproteins (ApoA1, ApoA2 and ApoB) in subfractions of LDL and HDL in 265 healthy working men. Concentrations of cholesterol, phospholipids, and ApoB in small, dense atherogenic LDL particles (sdLDL) correlated negatively (p<0.001) with those of cholesterol, phospholipids, and ApoA1 in HDL2, respectively. Age correlated positively with sdLDL while increasing BMI correlated with an atherogenic shift of cholesterol, phospholipids, and ApoB from large, buoyant LDL (lbLDL) to sdLDL and decreasing concentrations of HDL2 constituents. Physical activity and alcohol intake correlated negatively with sdLDL constituents and positively with HDL2 components. Consumption of monounsaturated fatty acids (MUFA) correlated with a lower ratio of sdLDL to HDL2 cholesterol. A favorable lipoprotein subfraction profile linked to a reduced risk of cardiovascular disease in men was associated with physical activity, moderate alcohol consumption, and dietary intake of MUFA, which might be exploited in future interventions for prevention of age- and BMI-associated atherogenic shifts of lipoprotein subfractions.     

Increased catabolic rate of low density lipoproteins in humans with cholesteryl ester transfer protein deficiency.

The cholesteryl ester transfer protein (CETP) transfers lipids among lipoprotein particles and plays a central role in lipoprotein metabolism. Humans with genetic deficiency of CETP have both elevated HDL cholesterol and apolipoprotein A-I concentrations as well as decreased LDL cholesterol and apolipoprotein B levels. The present study was undertaken to elucidate the metabolic basis for the decreased LDL cholesterol and apo B levels in CETP deficiency. We conducted a series of in vivo apo B kinetic studies in tow unrelated homozygotes with CETP deficiency and in control subjects. A primed constant infusion of stable isotopically labeled phenylalanine was administered to the two CETP deficient subjects and control subjects and apo B kinetic parameters in VLDL, intermediate density lipoproteins, and LDL were obtained by using a multicompartmental model. The fractional catabolic rates (FCR) of LDL apo B were significantly increased in the CETP-deficient subjects (0.56 and 0.75/d) compared with the controls (mean FCR of 0.39/d). Furthermore, the production rates of apo B in VLDL and intermediate density lipoprotein were decreased by 55% and 81%, respectively, in CETP deficiency compared with the controls. In conclusion, CETP-deficient subjects were demonstrated to have substantially increased catabolic rates of LDL apo B as the primary metabolic basis for the low plasma levels of LDL apo B. This result indicates that the LDL receptor pathway may be up-regulated in CETP deficiency.     

Lipids, lipoproteins and apolipoproteins in the elderly

The lipoprotein components were studied in connection with a population study concerning the state of health and living habits of the elderly people in Turku, Finland. Serum levels of total cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1 (apo A1) and apolipoprotein B (apo B) of the 347 elderly people (aged 65 years or over) were measured and those of low density lipoprotein (LDL) cholesterol were calculated. The levels of total cholesterol, LDL cholesterol and apo B were significantly higher in females than in males, and the concentrations decreased with advancing age. The concentrations of HDL cholesterol and apo A1 were significantly higher in females than in males but age had no effect. Serum triglycerides behaved differently in males and females; in females age had a significant increasing effect whereas in males no age effect was observed. The apo A1/apo B ratio did not differ between males and females. Reference values of serum lipids, lipoproteins and apolipoproteins of the elderly are suggested.     

Relationship of apolipoprotein B levels to the number of risk factors for metabolic syndrome.

Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy. However, all lipoproteins containing apolipoprotein B (apo B) appear to be atherogenic. Preferred targets of therapy therefore may include either the cholesterol in all apo B-containing lipoproteins (non-high-density lipoprotein cholesterol [non-HDL-C]) or total apo B itself. Apo B can be measured by three methods: chemically, by nuclear magnetic resonance (NMR), and by immunoassay. This study compares the first two methods as a function of the number of metabolic risk factors in patients with metabolic syndrome. Plasma lipid, lipoprotein cholesterol, and apo B levels were measured in 274 adults with varying numbers of metabolic syndrome components. Low-density lipoprotein (LDL) particle sizes were measured by gel electrophoresis and by NMR. Total apo B was estimated chemically and by conversion of NMR lipoprotein particle number, assuming one apo B molecule per lipoprotein particle. As the number of metabolic syndrome components increased, apo B rose by both chemical and NMR methods, but by chemical methods, increases were in the triglyceride-rich fraction, whereas by NMR, they were in LDL. The correlation between total apo B measured by the two methods was only moderate (r = .73). Further, non-HDL-C was more highly correlated with total apo B measured chemically than either LDL-C or total apo B by NMR. Non-HDL-C correlates highly with total apo B in patients with metabolic syndrome and had advantages as a target of therapy over LDL-C or NMR apo B.     

Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo.

Previous data suggest that apolipoprotein (apo) CIII may inhibit both triglyceride hydrolysis by lipoprotein lipase (LPL) and apo E-mediated uptake of triglyceride-rich lipoproteins by the liver. We studied apo B metabolism in very low density (VLDL), intermediate density (IDL), and low density lipoproteins (LDL) in two sisters with apo CIII-apo AI deficiency. The subjects had reduced levels of VLDL triglyceride, normal LDL cholesterol, and near absence of high density lipoprotein (HDL) cholesterol. Compartmental analysis of the kinetics of apo B metabolism after injection of 125I-VLDL and 131I-LDL revealed fractional catabolic rates (FCR) for VLDL apo B that were six to seven times faster than normal. Simultaneous injection of [3H]glycerol demonstrated rapid catabolism of VLDL triglyceride. VLDL apo B was rapidly and efficiently converted to IDL and LDL. The FCR for LDL apo B was normal. In vitro experiments indicated that, although sera from the apo CIII-apo-AI deficient patients were able to normally activate purified LPL, increasing volumes of these sera did not result in the progressive inhibition of LPL activity demonstrable with normal sera. Addition of purified apo CIII to the deficient sera resulted in 20-50% reductions in maximal LPL activity compared with levels of activity attained with the same volumes of the native, deficient sera. These in vitro studies, together with the in vivo results, indicate that in normal subjects apo CIII can inhibit the catabolism of triglyceride-rich lipoproteins by lipoprotein lipase.