Clinical Chemistry
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Clinical Chemistry 50: 589-595, 2004. First published January 15, 2004; 10.1373/clinchem.2003.029207
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
clinchem.2003.029207v1
50/3/589    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hattori, H.
Right arrow Articles by Miller, N. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hattori, H.
Right arrow Articles by Miller, N. E.
Related Collections
Right arrow Lipids, Lipoproteins, and Cardiovascular Risk Factors
(Clinical Chemistry. 2004;50:589-595.)
© 2004 American Association for Clinical Chemistry, Inc.

Lipids, Lipoproteins, and Cardiovascular Risk Factors

Association of Coronary Heart Disease with Pre-ß-HDL Concentrations in Japanese Men

Hiroaki Hattori1, Takeshi Kujiraoka1, Tohru Egashira1, Eiji Saito2, Takayuki Fujioka2, Sadao Takahashi3, Mayumi Ito1, Jackie A. Cooper4, Irina P. Stepanova5, M. Nazeem Nanjee5,a and Norman E. Miller5,1

1 Department of Advanced Medical Technology and Development, BML, Kawagoe, Saitama, Japan.2 Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.3 Third Department of Internal Medicine, Fukui Medical University, Fukui, Japan.4 Medical Research Council Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, London, UK.5 Cardiovascular Biochemistry Unit, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London, UK.

aAddress correspondence to this author at: Metabolism Research Laboratory, Department of Cardiovascular Genetics, University of Utah College of Medicine, Rm. 218, 410 Chipeta Way, Salt Lake City, UT 84108. Fax 801-581-6862; e-mail nazeem{at}ucvg.med.utah.edu.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background: In individuals heterozygous for ABCA1 transporter mutations, defective reverse cholesterol transport (RCT) causes low HDL-cholesterol and premature coronary heart disease (CHD). However, the extent to which impaired RCT underlies premature CHD in others with low HDL-cholesterol is not known. The primary acceptors of cell cholesterol are a minor subclass of lipid-poor pre-ß-HDLs. These are generated during remodeling of {alpha}-HDLs, which account for almost all HDL-cholesterol. We studied the strength of the association of CHD with pre-ß-HDL concentrations in Japanese men.

Methods: Blood was collected from 42 men with clinical CHD and 44 healthy controls 40–70 years of age. Pre-ß-HDL was assayed by crossed immunoelectrophoresis.

Results: Cases had lower HDL-cholesterol (-23%), total apolipoprotein A-I (-26%), and pre-ß-HDL (-55%; all P <0.001) concentrations; lower pre-ß-HDL:{alpha}-HDL ratios (-45%; P <0.001); and higher plasma triglycerides (20%; P <0.03) than the controls. On stepwise logistic regression, CHD was associated most strongly with pre-ß-HDL concentrations. On ROC analysis, pre-ß-HDL concentration discriminated between cases and controls better than any other lipoprotein measurement. When plasma was incubated for 16 h at 37 °C, mean (SD) pre-ß-HDL increased by 47 (36)% in controls, but was unchanged in cases (group difference, P <0.001).

Conclusions: Our results suggest that inefficient RCT, secondary to a low pre-ß-HDL concentration and production rate in plasma, contributes to premature CHD in Japanese men with low HDL-cholesterol.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The risk of coronary heart disease (CHD) 2 is inversely related to plasma HDL-cholesterol (1). Studies in transgenic animals have shown that HDLs have antiatherogenic activity (2)(3), but the mechanism for this activity is not known. HDLs play a central role in reverse cholesterol transport (RCT) (4), but it is not clear that this explains their impact in CHD (5)(6). Some HDL-cholesterol is derived from triglyceride-rich lipoproteins (TGRLs) (7), and little comes from arterial macrophages (8). In rodents, plasma HDL-cholesterol is not a reliable indicator of the efficiency of RCT (9)(10). Furthermore, HDLs have other potentially antiatherogenic properties. These include protection of LDLs from oxidative modification, inhibition of platelet aggregation, and suppression of adhesion molecule expression in endothelium (11)(12).

The HDLs are a heterogeneous family of lipoproteins. Nascent HDLs, secreted by the liver and small intestine, are discoidal and devoid of core lipids (4). Once in the plasma, they are rapidly converted by lecithin:cholesterol acyltransferase (LCAT) into spheroidal particles with a cholesteryl ester (CE)-rich core. These have {alpha} electrophoretic mobility, comprise the majority of plasma HDLs, and account for almost all HDL-cholesterol. The primary acceptors of unesterified cholesterol (UC) and phospholipid from the ABCA1 transporters of peripheral cells are a minor subclass of small lipid-free or lipid-poor HDLs that have pre-ß electrophoretic mobility (4)(13). Remodeling of these pre-ß0-HDLs yields discoidal pre-ß1- and pre-ß2-HDLs (4)(13). Esterification of UC in pre-ß2-HDLs by LCAT converts them into CE-rich {alpha}-HDLs. CEs are delivered from {alpha}-HDLs to hepatocytes by selective uptake by SR-B1 receptors (14), and in humans they are also indirectly delivered after transfer to apolipoprotein (apo) B-containing lipoproteins (7).

The rate-limiting factor for UC efflux appears to vary according to the cell type and conditions. The notion proposed by Glomset and Norum (15), after experiments with erythrocytes, that LCAT activity is rate-limiting probably applies only to the transfer of UC to {alpha}-HDLs from cells that are exposed directly to plasma because tissue fluids have little LCAT activity (16). Efflux of UC from cells to pre-ß0-HDLs in tissue fluids exceeds its esterification, leading to accumulation of UC-rich discoidal HDLs in lymph (16)(17). For this pathway of RCT, which presumably applies to arterial smooth muscle and macrophages, ABCA1 transporter function (4)(18)(19) and pre-ß-HDL concentration (20)(21) appear to play critical roles in regulating UC efflux.

Pre-ß0-HDLs are generated during the remodeling of {alpha}-HDLs in plasma. One mechanism is catalyzed by phospholipid transfer protein (PLTP), which transfers phospholipids from TGRLs to {alpha}-HDLs and induces their fusion, releasing lipid-poor or lipid-free apo A-I (22). In a separate mechanism, CE transfer protein (CETP) transfers triglycerides from TGRLs to {alpha}-HDLs in exchange for CEs, followed by hydrolysis of HDL triglycerides by hepatic and other endothelial lipases (23).

Individuals heterozygous for ABCA1 transporter mutations have diminished UC efflux to apo A-I from their fibroblasts in cell culture, low plasma HDL-cholesterol, and premature CHD (18)(24). These findings have established that inefficient RCT by HDLs is a causal factor in atherogenesis in such individuals. However, because ABCA1 transporter mutations are rare and a common genetic variation at the locus contributes only slightly to typical variations in HDL-cholesterol (25)(26), they provide no guidance on the extent to which RCT underlies the association between HDL-cholesterol and CHD in the general population. To address this question, we have tested by case–control study the hypothesis that clinically manifested CHD is associated more strongly with pre-ß-HDL concentration than with HDL-cholesterol in Japanese men.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
clinical procedures
Fasting blood samples were collected into chilled glass tubes containing disodium EDTA (1 g/L) from 42 men with CHD and 44 healthy men 40–70 years of age. Individuals taking lipid-lowering drugs, beta-blockers, steroids, calcium-channel blockers, or thiazide diuretics were excluded, as were those with liver, renal, or endocrine disease. The body mass index for all participants was <32 kg/m2. Diagnosis of CHD was by history of first myocardial infarction 3 or more months earlier (electrocardiography and enzymes, with or without coronary angiography; 20 individuals) or new angina pectoris confirmed by angiography. Cases were consecutive patients attending the Third Department of Internal Medicine, Fukui Medical University, who conformed with the selection criteria. Controls were randomly selected from apparently healthy men (based on medical history and interview) working in the same locality. The mean (SD) ages were 58.2 (7.3) years for the cases and 52.5 (7.0) years for the controls. One patient was excluded retrospectively because of a plasma triglyceride value of 7.3 mmol/L. The study was approved by an ethics committee of Nihon University, and all individuals gave informed consent.

laboratory procedures
Samples from cases and controls were processed in an identical manner. Blood was centrifuged for 15 min at 1700g and 4 °C immediately after collection. Multiple aliquots of plasma were taken and transferred directly to a -70 °C freezer. All assays were performed within 3 months. Cholesterol, triglycerides, and HDL-cholesterol were assayed in a Hitachi automated analyzer, by commercial enzymatic assays (Daiichi Pure Chemical Co.). HDL-cholesterol was assayed after precipitation of other lipoproteins with dextran sulfate and MgCl2. LDL-cholesterol was calculated according to Friedewald et al. (27). Plasma total apo A-I and apo B concentrations were quantified by immunoturbidimetry with commercial assays (Daiichi).

Apo A-I in pre-ß- and {alpha}-migrating particles was quantified by crossed immunoelectrophoresis (28). Samples were thawed at 4 °C to prevent significant remodeling of HDLs in vitro. In the first dimension, nondenaturing, nonsieving charge-based electrophoresis was performed through a 1% low electroendosmosis agarose slab gel. The second dimension was through the same type of gel impregnated with goat anti-human apo A-I antiserum (Octo), polyethylene glycol 6000, and Tween 20 (to denature the particles). After reactants were removed by soaking the gels in 150 mmol/L NaCl and pressing and drying them, antigen–antibody complexes were visualized with Coomassie Blue R250. The proportions of apo A-I in the pre-ß- and {alpha}-regions were quantified by cutting and weighing magnified images of the gels, and their absolute values calculated from plasma total apo A-I. The inter- and intraassay CV for pre-ß apo A-I concentration were <5%. This assay measures total apo A-I in all pre-ß-HDL particles of different sizes, is unaffected by storage of plasma at -70 °C for several months, and has been shown in two independent studies to give results that are in excellent agreement with those obtained by high-performance size-exclusion chromatography (28)(29).

When human plasma is incubated in vitro, the pre-ß-HDL concentration decreases at first, reaching zero or almost zero after 2 or 3 h, because initial conversion of pre-ß-HDLs to {alpha}-HDLs, which is catalyzed by LCAT, exceeds the rate of pre-ß-HDL production from {alpha}-HDLs, which is catalyzed by PLTP (20)(30). Thereafter, production of pre-ß-HDLs from {alpha}-HDLs exceeds consumption, and the pre-ß-HDL concentration increases for several hours. To obtain a measure of HDL remodeling in plasma, we assayed total pre-ß apo A-I before and after a 16-h incubation at 37 °C. The incubations were started immediately after the samples were thawed at 4 °C. Examples of crossed immunoelectropherograms are shown in Fig. 1 .



View larger version (43K):
[in this window]
[in a new window]
  		Figure 1. Crossed immunoelectropherograms of plasma samples before and after incubation for 16 h at 37 °C in four healthy individuals, illustrating the extent of variation of the induced change in pre-ß apo A-I concentration.

statistical analyses
Case–control comparisons were performed both on the raw data and after adjusting the data to mean age, using regression models to estimate the effects. Triglyceride concentrations were log-transformed. Regression models were used to identify the variables with which the pre-ß apo A-I concentration was associated. In stepwise regression, at each stage the most strongly associated variable was entered into the model until no variables made further contributions. The criterion for entry was significance at the 5% level. Coefficients thus obtained estimate the absolute changes in the dependent variable that are associated with a one-unit change in the independent variable. The product of the coefficient and the SD of an independent variable is the change in the dependent variable associated with the 1 SD change.

Associations of the different measurements with CHD were estimated by logistic regression. Results are expressed as odds ratios for a 1 SD change in the variable. SDs were estimated from the control data. To describe the powers of variables to differentiate between cases and controls, a series of cut-points across the range of each variable was used to classify those with CHD as true positives or false negatives and controls as true negatives or false positives. ROC curves were constructed by plotting sensitivity (true-positive rate) against 1 - specificity (false-positive rate) at each cut-point (31). The higher a curve lies above the line of chance, the better the variable is as a discriminator. Thus, the area under the curve provides a measure of the predictive accuracy of a variable, with possible values ranging from 0.5 for a variable with 0 accuracy to 1.0 for a variable that discriminates perfectly.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The plasma lipid, HDL subclass, and apolipoprotein concentrations are listed in Table 1 . Cases had higher triglyceride concentrations; lower HDL-cholesterol, total apo A-I, and pre-ß apo A-I concentrations; and lower pre-ß apo A-I:{alpha} apo A-I ratios than the controls. Adjusting for age had no significant effect on these results. In both cases and controls, the pre-ß apo A-I concentration was positively correlated with HDL-cholesterol (Fig. 2 ).


View this table:
[in this window]
[in a new window]
  		Table 1. Mean (SD) plasma lipids, apolipoproteins, and pre-ß apo A-I in cases and controls.



View larger version (18K):
[in this window]
[in a new window]
  		Figure 2. Relationship between pre-ß apo A-I concentration and HDL-cholesterol concentration in CHD cases and controls.

The cases and controls also differed in the effect of incubation of plasma on pre-ß-HDLs. In all but three of the control samples, the pre-ß apo A-I concentration had increased after 16 h of incubation [absolute change, 124 (96) mg/L; percentage change, 47.3 (35.8)%; P <0.01]. In contrast, in the samples from the cases, the response was more variable, and we observed overall no statistically significant change in pre-ß-HDL [8.3 (51) mg/L and 3.9 (40.4)%]. This case–control difference was highly significant (P <0.001). These results are illustrated in Figs. 1Up and 3 .



View larger version (33K):
[in this window]
[in a new window]
  		Figure 3. Concentrations of pre-ß apo A-I in plasma samples from CHD cases and controls before and after incubation for 16 h at 37 °C.

The horizontal lines indicate the means; the error bars indicate the SE.

The results of univariate logistic regression and ROC analyses are presented in Table 2 . The lipoprotein measurement most strongly associated with CHD by both methods of statistical analysis was the pre-ß apo A-I concentration, followed by the incubation-induced change in pre-ß apo A-I. The area under the ROC curve for baseline pre-ß apo A-I was significantly greater than that under any other curve (vs triglycerides, LDL-cholesterol, and HDL-cholesterol, all P <0.002; vs total apo A-I, P <0.03). Examples of some of the ROC curves are shown in Fig. 4 . Adjustment for age had no significant effect on these results.


View this table:
[in this window]
[in a new window]
  		Table 2. Results of univariate ROC analysis (area under the curve) and logistic regression analysis (odds ratio).



View larger version (23K):
[in this window]
[in a new window]
  		Figure 4. ROC curves for pre-ß apo A-I concentration, incubation-induced change in pre-ß apo A-I concentration, HDL-cholesterol, and LDL-cholesterol.

The diagonal line is the ROC curve of a hypothetical variable with no discriminating power.

On stepwise logistic regression, CHD was again most strongly associated with baseline pre-ß apo A-I concentration [odds ratio = 0.01 (95% confidence interval, 0.001–0.07); P <0.001]. CHD was also independently associated with LDL-cholesterol [3.70 (1.32–10.35); P = 0.01] and age [1.96 (1.08–3.56); P = 0.03]. The odds ratios for pre-ß apo A-I and LDL-cholesterol are for a 1 SD increase; that for age is for an increase of 5 years.


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Most previous studies of the relationships between CHD and HDL subclasses separated particles by density or by apolipoprotein content (e.g., those with and without apo A-II). These divisions were largely empirical because they were not based on complete knowledge of the functions of different subclasses. Furthermore, the subclasses were themselves heterogeneous, being composed of different types of particles. This probably explains why the results obtained in such studies were inconsistent and provided little insight into the mechanism of the protective effect of HDL (32).

Studies in transgenic mice have shown that arterial macrophages contribute little to HDL-cholesterol (8) and that the plasma HDL-cholesterol concentration is not a reliable indicator of the rate of flux of cholesterol from peripheral tissues to the liver (9)(10). Plasma HDL-cholesterol is influenced by the lipolysis of TGRLs, by the transfer of CEs to apo B-containing lipoproteins via CETP (7), and by the activity of the ABCA1 transporter in liver cells (19). For these reasons, no conclusion can be drawn about the contribution of RCT to protection against atherosclerosis in the general population from the inverse relationship between CHD incidence and HDL-cholesterol.

The most striking finding of this study was the strength of the negative association of CHD with pre-ß apo A-I concentration. This was stronger than the association of CHD with HDL-cholesterol or any other lipoprotein measurement and was independent of all other variables and age. In addition, the ability of pre-ß apo A-I to discriminate between cases and controls, as measured by ROC analysis, was greater than that of any other measurement. Although pre-ß-HDLs represent only a small proportion of total HDLs and account for only a trace of plasma HDL-cholesterol, they are important physiologically because they include the initial acceptors of UC from cells (4)(13). Therefore, our findings suggest that the antiatherogenic action of HDLs is related, at least in part, to their role in RCT and that this contributes to the inverse relationship of CHD risk with plasma HDL-cholesterol in the general population. In clinical practice the accuracy of CHD risk prediction might be improved by measurement of pre-ß apo A-I. However, a longitudinal study will be needed to confirm or refute this possibility.

Although the sample sizes in this study were small relative to those of a prospective study, it was adequately powered. We had 80% power at the 5% level to detect a difference of 0.6 SD in any variable between cases and controls. The observed differences were much greater than this: ~1 SD for HDL-cholesterol and 2 SD for pre-ß-HDL. The number of individuals does not affect the interpretation of the area under ROC curves. It does affect the precision of the estimate, however, for which reason we have presented confidence intervals for all estimates. Taking into account the numbers of participants, the estimates of SE were 2.5% for a ROC area of 0.95 for pre-ß-HDLs and 5.2% for an area of 0.76 for HDL-cholesterol. We had 90% power at the 5% significance level to detect a 20% difference between the areas under two ROC curves (assuming areas of 0.95 and 0.75).

There are two published CHD case–control studies of pre-ß-HDLs. Miida et al. (33) found significantly higher concentrations in cases. However, they studied only 20 individuals in each group, both of mixed gender, and provided little information about clinical procedures, selection criteria, or drug therapy. Asztalos et al. (34) found no significant difference in pre-ß apo A-I concentrations between 76 cases and 79 controls. However, in this study the cases were very heterogeneous, including patients with a history of myocardial infarction, coronary artery bypass graft surgery, transluminal coronary angioplasty, documented disease on coronary angiography, or angina with a positive stress test. Apart from the fact that individuals on lipid-lowering drugs were excluded, no other information was provided about drug therapy, except that an unspecified number of the cases were taking beta-blockers. Furthermore, Asztalos et al. used arbitrary cutoff values for body mass index and lipoproteins and applied these differentially to cases and controls. In the controls, LDL-cholesterol had to be between the 10th and 90th centiles, HDL-cholesterol had to be >250 mg/L and below the 95th centile, triglycerides had to be below the 95th centile, and body mass index had to be <32 kg/m2. In the cases, no cutoffs were used for LDL or HDL, but that for triglycerides was 4000 mg/L and that for body mass index was 35 kg/m2. With the exception of one individual who was excluded on the basis of an extremely high triglyceride concentration, we did not use cutoffs and applied all selection criteria equally to cases and controls.

An additional consideration when comparing the outcome of our study with those of Miida et al. (33) and Asztalos et al. (34) is that whereas we quantified apo A-I under denaturing conditions, both of the above studies used nondenaturing two-dimensional agarose/polyacrylamide gradient gel electropheresis followed by Western blotting with polyclonal anti-apo A-I. Although this is an excellent qualitative procedure, it has never been shown to accurately quantify pre-ß apo A-I, and to our knowledge has never been cross-referenced with an alternative procedure for assaying pre-ß-HDLs. Because affinities of polyclonal antibodies for apo A-I are affected by its conformation, which differs among HDL subclasses (13), assays on nondelipidated particles might not be quantitative. None of the two-dimensional polyacrylamide gradient gel electropheresis/Western blotting methods described to date involves treatment of the particles before, during, or after the electrotransfer process with an agent that would ensure normalization of apo A-I epitopes in different HDLs. Also to be considered is the possibility that some HDLs may be lost during the electrotransfer step. Although treatment of the membrane with glutaraldehyde (34) should prevent losses after electrotransfer, some losses may already have occurred. We have shown in two independent studies that the pre-ß apo A-I concentration measured by our assay over a wide range of values in plasma and lymph is in good agreement with that obtained by high-performance size-exclusion chromatography (28)(29).

In conclusion, we present evidence that the metabolic basis of the low pre-ß-HDL concentration in our CHD cases may have been a low net production rate in plasma. Whereas pre-ß apo A-I increased by a mean of almost 50% when control plasma was incubated for 16 h, no change was observed in samples from the cases. The change in pre-ß-HDL during incubation is the net effect of two opposing processes: conversion of pre-ß-HDLs to {alpha}-HDLs, catalyzed by LCAT, and production of new pre-ß-HDLs during the remodeling of {alpha}-HDLs. Initially, the former process exceeds the latter, lowering the pre-ß-HDL concentration (20)(30). After 2 or 3 h, the opposite is the case, leading to a progressive accumulation of pre-ß-HDLs. Theoretically, the case–control difference in incubation-induced change could have been attributable to one or more of at least three factors: low PLTP activity (reducing the production of pre-ß-HDLs from {alpha}-HDLs), high LCAT activity (increasing the conversion of pre-ß-HDLs to {alpha}-HDLs), and/or a difference in particle composition (affecting either process). Low CETP activity might also have contributed, although the importance of CETP activity in the determination of pre-ß-HDL concentration is not clear (35). Notwithstanding the fact that a 16-h incubation of plasma in vitro is far removed from the physiologic situation in vivo, our findings raise the possibility that there is an abnormality of HDL remodeling in many patients with CHD and low HDL-cholesterol. Additional work will be needed to determine its nature and to confirm that it precedes the onset of CHD.


   Acknowledgments
 
I.P.S. was a Wellcome Trust Traveling Research Fellow. N.E.M. was British Heart Foundation Professor of Cardiovascular Biochemistry.


   Footnotes
 
1 Current address: Molecular Pathology Laboratory, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.

2 Nonstandard abbreviations: CHD, coronary heart disease; RCT, reverse cholesterol transport; TGRL, triglyceride-rich lipoprotein; LCAT, lecithin:cholesterol acyltransferase; CE, cholesteryl ester; UC, unesterified cholesterol; apo, apolipoprotein; PLTP, phospholipid transfer protein; and CETP, cholesteryl ester transfer protein.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Gordon DJ, Rifkind BM. High-density lipoprotein: the clinical implications of recent studies. N Engl J Med 1989;321:1311-1316.[Web of Science][Medline] [Order article via Infotrieve]
  2. Plump AS, Scott CJ, Breslow JL. Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein E-deficient mouse. Proc Natl Acad Sci U S A 1994;91:9607-9611.[Abstract/Free Full Text]
  3. Tangirala RK, Tsukamoto K, Chun SH, Usher D, Pure E, Rader DJ. Regression of atherosclerosis induced by liver-directed gene transfer of apolipoprotein A-I in mice. Circulation 1999;100:1816-1822.[Abstract/Free Full Text]
  4. Young SG, Fielding CJ. The ABCs of cholesterol efflux. Nat Genet 1999;22:316-338.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  5. Tall AR, Wang N, Mucksavage P. Is it time to modify the reverse cholesterol transport model?. J Clin Invest 2001;108:1273-1275.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  6. Von Eckardstein A, Nofer JR, Assmann G. High density lipoproteins and arteriosclerosis: role of cholesterol efflux and reverse cholesterol transport. Arterioscler Thromb Vasc Biol 2001;21:13-27.[Abstract/Free Full Text]
  7. Tall A. Plasma lipid transfer proteins. Annu Rev Biochem 1995;64:235-257.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  8. Haghpassand M, Bourassa PA, Francone OL, Aiello RJ. Monocyte/macrophage expression of ABCA1 has minimal contribution to plasma HDL levels. J Clin Invest 2001;108:1315-1320.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  9. Osono Y, Woollett LA, Marotti KR, Melchior GW, Dietschy JM. Centripetal cholesterol flux from extrahepatic organs to the liver is independent of the concentration of high density lipoprotein-cholesterol in plasma. Proc Natl Acad Sci U S A 1996;93:4114-4119.[Abstract/Free Full Text]
  10. Jolley CD, Woollett LA, Turley SD, Dietschy JM. Centripetal cholesterol flux to the liver is dictated by events in the peripheral organs and not by the plasma high density lipoprotein or apolipoprotein A-I concentration. J Lipid Res 1998;39:2143-2149.[Abstract/Free Full Text]
  11. Nofer JR, Kehrel B, Fobker M, Levkau B, Assmann G, von Eckardstein A. HDL and arteriosclerosis: beyond reverse cholesterol transport. Atherosclerosis 2002;161:1-16.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  12. Mackness MI, Mackness B, Durrington PN, Fogelman AM, Berliner J, Lusis AJ, et al. Paraoxonase and coronary heart disease. Curr Opin Lipidol 1998;9:319-324.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  13. Fielding CJ, Fielding PE. Molecular physiology of the reverse cholesterol transport. J Lipid Res 1995;36:211-228.[Abstract]
  14. Krieger M. Charting the fate of the "good cholesterol": identification and characterization of the high-density lipoprotein receptor SR-BI. Annu Rev Biochem 1999;68:523-558.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  15. Glomset JA, Norum KR. The metabolic role of lecithin: cholesterol acyltransferase: perspectives from pathology. Adv Lipid Res 1973;11:1-65.
  16. Dory L, Sloop CH, Boquet LM, Hamilton RL, Roheim PS. Lecithin: cholesterol acyltransferase-mediated modification of discoidal peripheral lymph lipoproteins. Proc Natl Acad Sci U S A 1983;80:3489-3493.[Abstract/Free Full Text]
  17. Nanjee M N, Cooke CJ, Wong J, Hamilton RL, Olszewski WL, Miller NE. Composition and ultrastructure of size subclasses of normal human peripheral lymph lipoproteins. J Lipid Res 2001;42:639-648.[Abstract/Free Full Text]
  18. Marcil M, Brooks-Wilson A, Clee SM, Roomp K, Zhang LH, Lu L, et al. Mutations in the ABCA1 gene in familial HDL deficiency with defective cholesterol efflux. Lancet 1999;354:1341-1346.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  19. Basso F, Freeman L, Knapper CL, Remaley A, Stonik J, Neufeld EB, et al. Role of the hepatic ABCA1 transporter in modulating intrahepatic cholesterol and plasma HDL-cholesterol concentrations. J Lipid Res 2003;44:296-302.[Abstract/Free Full Text]
  20. Kawano M, Miida T, Fielding CJ, Fielding PE. Quantitation of pre ß-HDL-dependent and nonspecific components of the total efflux of cellular cholesterol and phospholipid. Biochemistry 1993;32:5025-5028.[CrossRef][Medline] [Order article via Infotrieve]
  21. Lee M, von Eckardstein A, Lindstedt L, Assmann G, Kovanen PT. Depletion of pre ß1 LpA1 and LpA4 particles by mast cell chymase reduces cholesterol efflux from macrophage foam cells induced by plasma. Arterioscler Thromb Vasc Biol 1999;19:1066-1074.[Abstract/Free Full Text]
  22. Huuskonen J, Olkkonen VM, Jauhiainen M, Ehnholm C. The impact of phospholipid transfer protein (PLTP) on HDL metabolism. Atherosclerosis 2001;155:269-281.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  23. Clay MA, Newnham HH, Forte TM, Barter PJ. Cholesteryl ester transfer protein and hepatic lipase activity promote shedding of apo A-I from HDL and subsequent formation of discoidal HDL. Biochim Biophys Acta 1992;1124:52-58.[Medline] [Order article via Infotrieve]
  24. Clee SM, Kastelein JJ, van Dam M, Marcil M, Roomp K, Zwarts KY, et al. Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes. J Clin Invest 2000;106:1263-1270.[Web of Science][Medline] [Order article via Infotrieve]
  25. Brousseau ME, Bodzioch M, Schaefer EJ, Goldkamp AL, Kielar D, Probst M, et al. Common variants in the gene encoding ATP-binding cassette transporter 1 in men with low HDL cholesterol levels and coronary heart disease. Atherosclerosis 2001;154:607-611.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  26. Clee SM, Zwinderman AH, Engert JC, Zwarts KY, Molhuizen HO, Roomp K, et al. Common genetic variation in ABCA1 is associated with altered lipoprotein levels and a modified risk for coronary heart disease. Circulation 2001;103:1198-1205.[Abstract/Free Full Text]
  27. Friedewald WT, Levy RI, Frederickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma without the use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.[Abstract]
  28. Nanjee MN, Cooke CJ, Olszewski WL, Miller NE. Concentrations of electrophoretic and size subclasses of apolipoprotein A-I containing particles in human peripheral lymph. Arterioscler Thromb Vasc Biol 2000;20:2148-2155.[Abstract/Free Full Text]
  29. Nanjee MN, Brinton E. Very small apolipoprotein A-I-containing particles from human plasma: isolation and quantification by high-performance size-exclusion chromatography. Clin Chem 2000;46:207-223.[Abstract/Free Full Text]
  30. Kunitake ST, Mendel CM, Hennessy LK. Interconversion between apolipoprotein A-I-containing lipoproteins of pre-ß and {alpha} electrophoretic mobilities. J Lipid Res 1992;33:1807-1816.[Abstract]
  31. Hanley JA, McNeil BJ. The meaning and use of the area under the receiver operating characteristic (ROC) curve. Radiology 1982;143:29-36.[Abstract/Free Full Text]
  32. Barter PJ, Rye K-A. High density lipoproteins and coronary heart disease. Atherosclerosis 1996;121:1-12.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  33. Miida T, Nakamura Y, Inano K, Matsuto T, Yamaguchi T, Tsuda T, et al. Preß1-high density lipoprotein increases in coronary artery disease. Clin Chem 1996;42:1992-1995.[Abstract/Free Full Text]
  34. Asztalos BF, Roheim PS, Milani RL, Lefevre M, McNamara JR, Horvath KV, et al. Distribution of apo A-I-containing HDL subpopulations in patients with coronary heart disease. Arterioscler Thromb Vasc Biol 2000;20:2670-2676.[Abstract/Free Full Text]
  35. Lie J, de Crom R, Jauhiainen M, van Gent T, van Heperen R, Scheek L, et al. Evaluation of phospholipid transfer protein and cholesteryl ester transfer protein as contributors to the generation of preß-high-density lipoproteins. Biochem J 2001;360:379-385.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]



The following articles in journals at HighWire Press have cited this article:


Home page
 Clin. Chem.Home page
M. Suzuki, H. Wada, S. Maeda, K. Saito, S. Minatoguchi, K. Saito, and M. Seishima
Increased Plasma Lipid-Poor Apolipoprotein A-I in Patients with Coronary Artery Disease
Clin. Chem., January 1, 2005; 51(1): 132 - 137.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
clinchem.2003.029207v1
50/3/589    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hattori, H.
Right arrow Articles by Miller, N. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hattori, H.
Right arrow Articles by Miller, N. E.
Related Collections
Right arrow Lipids, Lipoproteins, and Cardiovascular Risk Factors

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS