This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holvoet, P. Articles by Collen, D. Search for Related Content PubMed PubMed Citation Articles by Holvoet, P. Articles by Collen, D.

(Circulation. 1998;98:1487-1494.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

Oxidized LDL and Malondialdehyde-Modified LDL in Patients With Acute Coronary Syndromes and Stable Coronary Artery Disease

Paul Holvoet, PhD; Johan Vanhaecke, MD, PhD; Stefaan Janssens, MD, PhD; Frans Van de Werf, MD, PhD; ; Désiré Collen, MD, PhD

From the Center for Molecular and Vascular Biology (P.H., D.C.) and Department of Cardiology (J.V., S.J., F.V.d.W.), University of Leuven, Belgium.

Correspondence to P. Holvoet, PhD, Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O&N, Herestraat 49, B-3000 Leuven, Belgium. E-mail paul.holvoet{at}med.kuleuven.ac.be

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background—The association between oxidative modifications of LDL and coronary artery disease (CAD) is suspected but not established. Therefore, the association between plasma levels of oxidized LDL and malondialdehyde (MDA)-modified LDL and acute coronary syndromes and stable CAD was investigated.

Methods and Results—The study population contained 63 patients with acute coronary syndromes (45 with acute myocardial infarction and 18 with unstable angina pectoris), 35 nontransplanted patients with angiographically confirmed stable angina, 28 heart transplant patients with posttransplant CAD, 79 heart transplant patients without CAD, and 65 control subjects. After correction for age, sex, and LDL and HDL cholesterol, plasma levels of oxidized LDL and MDA-modified LDL were significantly higher in patients with CAD than in individuals without CAD (r²=0.57 and r²=0.26, respectively; both P=0.0001). Plasma levels of MDA-modified LDL were significantly higher in patients with acute coronary syndromes than in individuals with stable CAD (r²=0.65; P=0.0001) and were associated with increased levels of troponin I and C-reactive protein (r²=0.39 and r²=0.34, respectively; both P=0.0001). Plasma levels of oxidized LDL were not associated with increased levels of troponin I and C-reactive protein (r²=0.089 and r²=0.063, respectively).

Conclusions—Elevated plasma levels of oxidized LDL are associated with CAD. Elevated plasma levels of MDA-modified LDL suggest plaque instability and may be useful for the identification of patients with acute coronary syndromes.

Key Words: lipoproteins • coronary disease • angina • diagnosis • plaque

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Subendothelial accumulation of foam cells plays a key role in the initiation of atherosclerosis.^{1 2} These foam cells, which may be generated by the uptake of oxidized LDL and/or malondialdehyde (MDA)-modified LDL by macrophages via scavenger receptors,³ accumulate in fatty streaks that evolve to more complex fibrofatty or atheromatous plaques.⁴ Oxidized LDL may also be involved in atherogenesis by inducing smooth muscle cell proliferation⁵ and smooth muscle foam cell generation.

An association between LDL oxidation and atherogenesis was first suggested by experiments showing that oxidized LDL caused injury to endothelial cells⁶ and was further supported by studies showing a protective effect of antioxidants against progression of atherosclerosis.⁷ With the use of a specific ELISA for oxidized LDL, an association between the extent of coronary artery disease (CAD) in heart transplant patients and plasma levels of oxidized LDL was recently established, suggesting that oxidized LDL may be a marker of CAD.⁸ Previously, elevated levels of MDA-modified LDL were detected in the plasma of acute myocardial infarction (AMI) patients but not patients with stable angina.⁹

We wanted to compare plasma levels of oxidized and MDA-modified LDL in patients with acute coronary syndromes and patients with stable CAD and to study the association between oxidized LDL and MDA-modified LDL, respectively, and troponin I, a marker of ischemic syndromes,^{10 11} and C-reactive protein, a marker of inflammation.¹²

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Patients and Blood Sampling
A total of 270 individuals were studied: 63 consecutive patients with acute coronary syndromes, 35 patients with stable CAD, 107 posttransplant patients, and 65 control subjects. Patients with acute coronary syndromes had ischemic chest discomfort with ST-segment elevation or depression of >0.5 mm or T-wave inversion of >1 mm. In 45 patients, elevated creatine kinase (CK)-MB levels (and 3% of total CK) were present at entry or in the samples taken at 6 to 8 hours after enrollment, indicating AMI. In 18 patients, no CK-MB elevations were found, and these patients were classified as having unstable angina. Thirty-five patients with angiographically documented CAD and no clinical signs of ischemia within the previous month were considered to have stable CAD.

One hundred seven posttransplant patients (47 patients got a heart transplant for dilated cardiomyopathy and 60 patients for end-stage CAD), who have been described in more detail elsewhere,⁸ were reincluded. Twenty-eight of these patients had angiographically determined posttransplant CAD.

Sixty five control subjects (31 men, 34 women; age, 52±1.3 years) without a history of atherosclerotic cardiovascular disease were studied (Table 1).

View this table: [in this window] [in a new window]   Table 1. Characteristics of Control Subjects, CAD Patients, and Heart Transplant Patients

Venous blood samples⁸ were taken in the fasting state in control subjects, patients with stable angina, and posttransplant patients. In patients with acute coronary syndromes, blood samples were taken on admission before the start of treatment.

Lipoproteins: Isolation and Modification
LDL was isolated from pooled plasma of fasting normolipidemic donors by density gradient ultracentrifugation.¹³ MDA-modified and copper-oxidized LDL was prepared as described elsewhere.^{14 15}

Assays
An mAb-4E6–based ELISA was used for the quantification of oxidized LDL in plasma.^{8 16 17 18} Plasma levels of MDA-modified LDL were measured in an mAb-1H11–based ELISA.⁹ Total cholesterol, HDL cholesterol, and triglycerides were measured by enzymatic methods (Boehringer Mannheim). LDL cholesterol values were calculated with the Friedewald formula. Troponin I levels were measured on a Beckman ACCESS immunoanalyzer by use of commercially available monoclonal antibodies (Sanofi). C-reactive protein levels were measured in a commercial immunoassay (Boehringer), and plasma levels of D-dimer were measured in ELISA as described previously.¹⁹

Immunodetection of Oxidized and MDA-Modified LDL in Coronary Atherosclerotic Lesions
Coronary arteries were collected from cardiac explants and treated as described elsewhere.⁹ Sections were developed with either mAb-4E6 or mAb-1H11 (final concentration, 1 µg/mL). Immunostaining of smooth muscle cells and monocytes or macrophages was performed with a murine monoclonal antibody against human -actin (clone 1A4; Sigma Chemical Co) or a rat monoclonal antibody against the common leukocyte antigen/CD45 (clone 30F11.1; Pharmingen).

Statistical Analysis
Control subjects and patients were compared by nonparametric Kruskal-Wallis ANOVA followed by Dunnet's multiple comparison test in the Prism statistical program (Graph Pad Software). Plasma levels of oxidized LDL and MDA-modified LDL in patients with normal or elevated levels of troponin I, C-reactive protein, or D-dimer and in patients with and without peripheral vascular disease were compared by the Mann-Whitney test. Discontinuous parameters were compared by ² analysis. Multiple regression analysis, with SAS software, was performed to evaluate the association between angiographically detected CAD (independent variable) and oxidized LDL or MDA-modified LDL (response) after controlling for age, sex, LDL cholesterol, and HDL cholesterol; it was also used to study the interaction with heart transplantation. For patients with angiographically confirmed CAD, multiple regression analysis was performed to study the association between acute coronary syndromes, troponin I, C-reactive protein, or D-dimer (independent variables) and oxidized LDL or MDA-modified LDL (response) after controlling for age, sex, LDL cholesterol, and HDL cholesterol.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Plasma levels of oxidized LDL were 0.71±0. 033 mg/dL (mean±SEM) in 65 control subjects, 1.8-fold higher (P<0.01) in heart transplant patients with angiographically normal coronary arteries, 3.7-fold higher (P<0.001) in patients with stable angina pectoris, 4.0-fold higher (P<0.001) in patients with unstable angina pectoris, 4.8-fold higher (P<0.001) in patients with AMI, and 3.5-fold higher (P<0.001) in patients with posttransplant CAD (Figure 1). Plasma levels of oxidized LDL were independent of sex but correlated with age (Figure 2). In individuals with CAD, however, there was no correlation between plasma levels of oxidized LDL and age. Plasma levels of total cholesterol, LDL cholesterol, and triglycerides in control subjects and patients were very similar, whereas HDL cholesterol levels in nontransplanted CAD patients were significantly lower than in control subjects and the other patient groups (Table 1). Plasma levels of oxidized LDL were independent of LDL cholesterol levels but correlated inversely with HDL cholesterol levels (Figure 2). Plasma levels of oxidized LDL were very similar in 21 CAD patients with clinical evidence of peripheral vascular disease and 105 patients without peripheral vascular disease (3.11± 0.27 and 2.89±0.095 mg/dL, respectively).

View larger version (24K): [in this window] [in a new window]   Figure 1. Individual values of oxidized LDL and MDA-modified LDL in control subjects; nontransplanted patients with stable angina and unstable angina and AMI; and heart transplant patients without and with posttransplant CAD.

View larger version (37K): [in this window] [in a new window]   Figure 2. Plasma levels of oxidized LDL and MDA-modified LDL vs age, sex, LDL cholesterol, and HDL cholesterol, respectively.

Plasma levels of MDA-modified LDL were 0.37±0.017 mg/dL in control subjects, similar in patients with stable angina pectoris and heart transplant patients without and with posttransplant CAD, 2.6-fold higher (P<0.001) in patients with unstable angina pectoris, and 3.1-fold higher (P<0.001) in AMI patients (Figure 1). Plasma levels of MDA-modified LDL were independent of sex and LDL cholesterol levels and correlated weakly with age (Figure 2). In individuals with CAD, however, there was no correlation between plasma levels of MDA-modified LDL and age. Plasma levels of MDA-modified LDL did not correlate with LDL cholesterol and correlated weakly with HDL cholesterol (Figure 2). Plasma levels of MDA-modified LDL were very similar in 21 CAD patients with and 105 patients without clinical evidence of peripheral vascular disease (0.96± 0.14 versus 0.73±0.042 mg/dL).

Plasma levels of troponin I were 0.025±0.0031 ng/mL in control subjects, very similar in patients with stable angina and heart transplant patients without and with posttransplant CAD, and 14.8- and 27.2-fold higher in patients with unstable angina and AMI, respectively (Table 1). At a cutoff value of 0.1 ng/mL, exceeding the 99^th percentile of distribution in individuals without CAD, 40 of 45 AMI patients (89%) had increased troponin I levels compared with 10 of 18 patients with unstable angina (55%), 2 of 35 patients with stable CAD (5.7%), 2 of 28 patients with posttransplant CAD (7.1%), and 2 of 144 individuals without CAD (0.7%). In agreement with previously published data,^{10 11} troponin I was found to be a marker of acute coronary syndromes (Table 2). Plasma levels of oxidized LDL were 3.26±0.14 mg/dL in CAD patients with increased troponin I levels compared with 2.66±0.11 mg/dL in CAD patients with normal troponin I levels (P<0.01) (Figure 3). Corresponding values of MDA-modified LDL were 1.10±0.061 and 0.54±0.039 mg/dL, respectively (P<0.0001) (Figure 3).

View this table: [in this window] [in a new window]   Table 2. Distribution of Troponin I, C-Reactive Protein, and D-Dimer in Patients With Acute Coronary Syndromes, Patients With Stable Angina, and Individuals Without CAD

View larger version (37K): [in this window] [in a new window]   Figure 3. Plasma levels of oxidized LDL and MDA-modified LDL in CAD patients with normal and elevated levels of troponin I, C-reactive protein, and D-dimer, respectively.

Plasma levels of C-reactive protein were 0.34±0.033 mg/dL in control subjects, similar in patients with stable CAD and heart transplant patients without and with posttransplant CAD, and 5.3- and 6.5-fold higher in patients with unstable angina and AMI, respectively (Table 1). At a cutoff value of 0.5 mg/dL, 39 AMI patients (97%), 10 patients with unstable angina (56%), 5 patients with stable angina (14%), 2 patients with posttransplant CAD (7.1%), and 2 individuals without CAD (1.4%) had increased levels of C-reactive protein. In agreement with previously published data,¹² C-reactive protein was found to be a marker of acute coronary syndromes (Table 2). Plasma levels of oxidized LDL were 3.21±0.14 mg/dL in CAD patients with increased levels of C-reactive protein compared with 2.71±0.11 mg/dL in patients with normal levels (P<0.01) (Figure 3). Corresponding values of MDA-modified LDL were 1.05±0.059 and 0.55±0.043 mg/dL, respectively (P<0.0001) (Figure 3).

Plasma levels of D-dimer were 13±0.86 µg/dL in control subjects, similar in patients with stable angina and heart transplant patients without and with posttransplant CAD, 2.8-fold higher in patients with unstable angina, and 4.4-fold higher in AMI patients (Table 1). At a cutoff value of 40 µg/dL, 22 AMI patients (49%), 8 patients with unstable angina (44%), 11 patients with stable angina (31%), 1 patient with posttransplant CAD (3.6%), and 1 individual without CAD (0.7%) had increased plasma levels of D-dimer. In agreement with earlier published data,²⁰ D-dimer was found to be a marker of acute coronary syndromes (Table 2). Plasma levels of oxidized LDL were 3.17±0.18 mg/dL in patients with increased D-dimer levels compared with 2.81±0.10 mg/dL in patients with normal D-dimer levels (P=NS). Corresponding values of MDA-modified LDL were 0.94±0.091 and 0.69±0.042 mg/dL, respectively (P<0.01) (Figure 3).

Multiple regression analysis was performed to evaluate the association between angiographically detected CAD and plasma levels of oxidized LDL and MDA-modified LDL. The analysis contained 144 patients without CAD (65 control subjects and 79 heart transplant patients with angiographically normal coronary arteries) and 126 individuals with CAD. After correction for age, sex, LDL cholesterol, and HDL cholesterol, CAD was associated with elevated plasma levels of oxidized LDL (r²=0.57; P=0.0001) and, to a lesser extent, elevated plasma levels of MDA-modified LDL (r²=0.26; P=0.0001). Multiple regression analysis was performed on the subgroups of CAD patients to study the association between acute coronary syndromes and plasma levels of oxidized LDL and MDA-modified LDL. The analysis contained 63 patients with stable CAD (35 nontransplanted and 28 transplanted patients) and 63 patients with acute coronary syndromes. Elevated plasma levels of MDA-modified LDL were associated with acute coronary syndrome, increased troponin I, and increased C-reactive protein but not with increased D-dimer (Table 3). Differences between plasma levels of oxidized LDL in patients with stable CAD and patients with acute coronary syndromes were less pronounced (Table 3). Plasma levels of oxidized LDL and MDA-modified LDL were similar in nontransplanted and transplanted patients with stable CAD.

View this table: [in this window] [in a new window]   Table 3. Multiple Regression Analysis of Association Between Acute Coronary Syndromes and Plasma Levels of Oxidized LDL or MDA-modified LDL

Figure 4 shows representative sections of coronary arteries obtained from the cardiac explants of CAD patients. mAb-4E6 immunostained oxidized LDL in nonthrombotic human coronary atherosclerotic plaques (Figure 4a, 4b, 4e, and 4f). Oxidized LDL was associated with smooth muscle foam cells in the fibrous cap (Figure 4b and 4f) and was present in the necrotic core (not shown). In contrast, mAb-1H11 detected only very small amounts of immunoreactive material associated with macrophages in the shoulder areas (Figure 4d), whereas no immunoreactive material was detected in the necrotic core of nonthrombotic plaques (Figure 4h).

View larger version (121K): [in this window] [in a new window]   Figure 4. Representative sections of coronary arteries isolated from cardiac explants of patients with end-stage ischemic heart disease. mAb-4E6 immunostained oxidized LDL in nonthrombotic human coronary atherosclerotic plaques (a, b, e, f). Oxidized LDL was associated with smooth muscle foam cells (immunostained with cell-specific mAb-1A4) in fibrous cap (b, f) or was present in necrotic core (not shown). In contrast, mAb-1H11 detected only very small amounts of immunoreactive material in nonthrombotic atherosclerotic lesions (c, d, g, h). Immunostaining was associated with macrophage foam cells (immunostained with cell-specific mAb-30F11) in shoulder areas (d) or was absent (h).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
The present study demonstrates that plasma levels of oxidized LDL are significantly elevated in CAD patients and that these levels are very similar in patients with stable CAD and in patients with acute coronary syndromes, suggesting that their increases are independent of plaque instability. The presence of oxidized LDL in nonthrombotic plaques and the lack of correlation between plasma levels of oxidized LDL and LDL cholesterol suggest that increased plasma levels of oxidized LDL in association with CAD may be due to their back-diffusion from the vessel wall. In contrast, plasma levels of MDA-modified LDL were significantly higher in patients with acute coronary syndromes than in patients with stable CAD, suggesting that increases in plasma levels of MDA-modified LDL are dependent on the ischemic syndromes in patients with unstable angina pectoris or AMI. The association between MDA-modified LDL and troponin I, a marker of ischemic syndromes, further supports this hypothesis. Furthermore, the increase in MDA-modified LDL was associated more with inflammation (with C-reactive protein as marker) than with thrombotic syndromes (with D-dimer as marker). These data thus suggest that elevated levels of MDA-modified LDL may be markers of plaque instability.

Different mechanisms for the oxidation of LDL have been proposed. Copper ion–induced in vitro oxidation of LDL results in the release of hydroperoxides that are converted to reactive aldehydes (eg, MDA and 4-hydroxynonenal).^{21 22} Interaction of these aldehydes with lysine residues in the apolipoprotein B-100 moiety renders the LDL more negatively charged, which results in a decreased affinity for the LDL receptor and an increased affinity for scavenger receptors.³ Endothelial cells, monocytes, macrophages, lymphocytes, and smooth muscle cells are all capable of enhancing the rate of metal ion–induced in vitro oxidation of LDL,²³ and different enzymes may be involved.^{24 25 26 27 28} Myeloperoxidase, secreted by activated phagocytes, may be a catalyst for the initiation of lipid peroxidation in LDL independent of free metal ions.²⁹ Previously, we isolated oxidized LDL from the plasma of patients with posttransplant CAD.⁸ The characteristics suggested that it did not originate from extensive metal ion–induced oxidation of LDL but that it might be generated by cell-associated oxidative enzymatic activity in the arterial wall. Previously, it was demonstrated in animal models that the oxidation of LDL indeed occurs in the arterial wall and not in the blood.^{17 18}

The causal role of oxidized LDL is suspected but not established.^{30 31 32 33} The observed association between CAD and plasma levels of oxidized LDL, measured in a specific ELISA, suggests that the assay may be a useful tool to investigate the causal role of oxidized LDL in atherosclerotic cardiovascular disease in a prospective study.

Previously, we have also isolated MDA-modified LDL from the plasma of AMI patients.⁹ It was concluded that it did not originate from extensive metal ion–induced oxidation of LDL but that it may be generated by MDA released by oxidation of arachidonic acid present in LDL.^{34 35 36} Ischemic injury may result not only in the activation of the cyclooxygenase-dependent pathway of prostaglandin synthesis in endothelial cells³⁷ but also in increased production of F₂-isoprostanes, non–cyclooxygenase-derived prostaglandin F₂–like compounds,^{38 39} that are strong inducers of platelet activation. Activated platelets may then produce large amounts of aldehydes, further enhancing the modification of LDL. The present very significant association between plasma levels of MDA-modified LDL and markers of necrosis (troponin I) or inflammation (C-reactive protein) further supports the hypothesis that the generation of MDA-modified LDL is associated with ischemic injury rather than with the extent of coronary atherosclerosis. The very low reactivity of the monoclonal antibody mAb-1H11 with nonthrombotic atherosclerotic plaques indeed suggests that MDA-modified LDL, in contrast with oxidized LDL, is not released continuously from atherosclerotic plaques. Hammer et al⁴⁰ recently characterized a monoclonal antibody, mAb-OB/O9, that is specific for LDL modified with aldehydes that can be released by activated platelets. It may be used to further investigate the role of activated platelets in the oxidative modification of LDL.

In conclusion, the present study demonstrates the association between elevated plasma levels of oxidized LDL and CAD clinically expressed in stable CAD and acute coronary syndromes. Elevated levels of MDA-modified LDL, however, are associated with acute coronary syndrome. A prospective investigation of the role of MDA-modified LDL and/or oxidized LDL in the progression of coronary atherosclerosis and/or the development of atherothrombosis appears to be warranted.

	Acknowledgments

 
This work was supported in part by a grant from the Nationaal Fonds voor Geneeskundig Wetenschappelijk Onderzoek (project 3.0103.92) and by the Interuniversitaire Attractiepolen (Program 4/34). Dr Vanhaecke holds the Michael Ondetti Chair in Cardiology. We are grateful to Drs W. Daenen, W. Flameng, and P. Sergeant for providing coronary arteries of the cardiac explants; to H. Bernar and M. Landeloos for technical assistance; and to Dr K. Bogaerts of the Biostatistical Center for Clinical Trials, University of Leuven, for statistical analysis. We thank K. Roels (Analis, Gent, Belgium) for measuring levels of troponin I.

	Footnotes

 
Presented in part at the 70th Scientific Sessions of the American Heart Association, Orlando, Fla, November 9–12, 1997, and published in abstract form (Circulation. 1997;96[suppl I]:I-417).

Received March 23, 1998; revision received June 11, 1998; accepted June 13, 1998.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Gerrity RG. The role of the monocyte in atherogenesis, I: transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol. 1981;103:181–190.[Abstract]

2. Schaffner T, Taylor K, Bartucci EJ, Fischer-Dzoga K, Beeson JH, Glagov S, Wissler, RW. Arterial foam cells with distinctive immunomorphologic and histochemical features of macrophages. Am J Pathol. 1980;100:57–80.[Abstract]

3. Brown MS, Goldstein JL. Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem. 1983;52:223–261.[Medline] [Order article via Infotrieve]

4. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809.[Medline] [Order article via Infotrieve]

5. Heery JM, Kozak M, Stafforini DM, Jones DA, Zimmerman GA, McIntyre TM, Prescott SM. Oxidatively modified LDL contains phospholipids with platelet-activating factor-like activity and stimulates the growth of smooth muscle cells. J Clin Invest. 1995;96:2322–2330.

6. Penn MS, Chisolm GM. Oxidized lipoproteins, altered cell function and atherosclerosis. Atherosclerosis. 1994;108:S21–S29.

7. Steinberg D. Clinical trails of antioxidants in atherosclerosis: are we doing the right thing? Lancet. 1995;346:36–38.[Medline] [Order article via Infotrieve]

8. Holvoet P, Stassen JM, Van Cleemput J, Collen D, Vanhaecke J. Correlation between oxidized low density lipoproteins and coronary artery disease in heart transplant patients. Arterioscler Thromb Vasc Biol. 1998;18:100–107.[Abstract/Free Full Text]

9. Holvoet P, Perez G, Zhao Z, Brouwers E, Bernar H, Collen D. Malondialdehyde-modified low density lipoproteins in patients with atherosclerotic disease. J Clin Invest. 1995;95:2611–2619.

10. Adams JE, 3d, Bodor GS, Davila-Roman VG, Delmez JA, Apple FS, Ladenson JH, Jaffe AS. Cardiac troponin: a marker with high specificity for cardiac injury. Circulation. 1993;88:101–106.[Abstract/Free Full Text]

11. Antman EM, Tanasijevic MJ, Thompson B, Schactman M, McCabe CH, Cannon CP, Fischer GA, Fung AY, Thompson C, Wybenga D, Braunwald E. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med. 1996;335:1388–1389.[Free Full Text]

12. Oltrona L, Merlini PA, Pezzano A. C-reactive protein and serum amyloid A protein in unstable angina. N Engl J Med. 1995;332:399–400.

13. Havel RJ, Eder HA, Bragdon JH. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human sera. J Clin Invest. 1995;34:1345–1353.

14. Haberland MD, Fogelman AM, Edwards PA. Specificity of receptor-mediated recognition of malondialdehyde-modified low density lipoproteins. Proc Natl Acad Sci U S A. 1982;79:1712–1716.[Abstract/Free Full Text]

15. Steinbrecher UP. Oxidation of low density lipoprotein results in derivatization of lysine residues of apolipoprotein B by lipid peroxide decomposition products. J Biol Chem. 1987;262:3603–3608.[Abstract/Free Full Text]

16. Holvoet P, Donck J, Landeloos M, Brouwers E, Luijtens K, Arnout J, Lesaffre E, Vanrenterghem Y, Collen D. Correlation between oxidized low density lipoproteins and von Willebrand factor in chronic renal failure. Thromb Haemost. 1996;76:663–669.[Medline] [Order article via Infotrieve]

17. Holvoet P, Collen D. ßVLDL hypercholesterolemia relative to LDL hypercholesterolemia is associated with higher levels of oxidized lipoproteins and a more rapid progression of coronary atherosclerosis in rabbits. Arterioscler Thromb Vasc Biol. 1997;17:2376–2382.[Abstract/Free Full Text]

18. Holvoet P, Theilmeier G, Shivalkar B, Flameng W, Collen D. LDL hypercholesterolemia is associated with accumulation of oxidized LDL, atherosclerotic plaque growth, and compensatory vessel enlargement in coronary arteries of miniature pigs. Arterioscler Thromb Vasc Biol. 1998;18:415–422.[Abstract/Free Full Text]

19. Declerck PJ, Mombaerts P, Holvoet P, De Mol M, Collen D. Fibrinolytic response and fibrin fragment D-dimer levels in patients with deep vein thrombosis. Thromb Haemost. 1987;58:1024–1029.[Medline] [Order article via Infotrieve]

20. Hoffmeister HM, Jur M, Wendel HP, Heller W, Seipel L. Alterations of coagulation and fibrinolytic and kallikrein-kinin systems in the acute and post-acute phases in patients with unstable angina pectoris. Circulation. 1995;91:2520–2527.[Abstract/Free Full Text]

21. Esterbauer H, Jurgens G, Quehenberger Q, Koller E. Autooxidation of human low density lipoprotein: loss of polyunsaturated fatty acids and vitamin E and generation of aldehydes. J Lipid Res. 1987;28:495–509.[Abstract]

22. Steinbrecher UP, Parthasarathy S, Leake DS, Witztum JL, Steinberg D. Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci U S A. 1984;81:3883–3887.[Abstract/Free Full Text]

23. Parthasarathy S, Wieland E, Steinberg D. A role for endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein. Proc Natl Acad Sci U S A. 1989;86:1046–1050.[Abstract/Free Full Text]

24. Ravalli S, Marboe CC, D'Agati VD, Michler RE, Sigal E, Cannon PJ. Immunohistochemical demonstration of 15-lipoxygenase in transplant coronary artery disease. Arterioscler Thromb Vasc Biol. 1995;15:340–348.[Abstract/Free Full Text]

25. Folcik VA, Nivar-Aristy RA, Krajewski LP, Cathcart MK. Lipoxygenase contributes to the oxidation of lipids in human atherosclerotic plaques. J Clin Invest. 1995;96:504–510.

26. Sparrow CP, Olszewski J. Cellular oxidative modification of low density lipoprotein does not require lipoxygenases. Proc Natl Acad Sci U S A. 1992;89:128–131.[Abstract/Free Full Text]

27. Menschikowski M, Kasper M, Lattke P, Schiering A, Schiefer S, Stockinger H, Jaross W. Secretory group II phospholipase A₂ in human atherosclerotic plaques. Atherosclerosis. 1995;118:173–181.[Medline] [Order article via Infotrieve]

28. Aviram M, Maor I. Phospholipase D-modified low density lipoprotein is taken up by macrophages at increased rate: a possible role for phosphatidic acid. J Clin Invest. 1993;91:1942–1952.

29. Savenkova ML, Mueller DM, Heinecke JW. Tyrosyl radical generated by myeloperoxidase is a physiological catalyst for the initiation of lipid peroxidation in low density lipoprotein. J Biol Chem. 1994;269:20394–20400.[Abstract/Free Full Text]

30. Steinberg D. Lewis A. Conner Memorial Lecture. Oxidative modification of LDL and atherogenesis. Circulation. 1997;95:1062–1071.[Free Full Text]

31. Holvoet P, Collen D. Thrombosis and atherosclerosis. Curr Opin Lipidol. 1997;8:320–328.[Medline] [Order article via Infotrieve]

32. Murugesan G, Chisolm GM, Fox PL. Oxidized low density lipoprotein inhibits the migration of aortic endothelial cells in vitro. J Cell Biol. 1993;120:1011–1019.[Abstract/Free Full Text]

33. Chen CH, Nguyen HH, Weilbaecher D, Luo S, Gotto AM Jr, Henry PD. Basic growth factor reverses atherosclerotic impairment of human coronary angiogenesis-like responses in vitro. Atherosclerosis. 1995;116:261–268.[Medline] [Order article via Infotrieve]

34. Haberland ME, Olch CL, Fogelman AM. Role of lysines in mediating interaction of modified low density lipoproteins with the scavenger receptor of human monocyte macrophages. J Biol Chem. 1984;259:11305–12311.[Abstract/Free Full Text]

35. Fogelman MA, Shechter I, Seager J, Hokom M, Child JS, Edwards PA. Malondialdehyde modification of low density lipoproteins leads to cholesterylesters accumulation in human monocyte-macrophages. Proc Natl Acad Sci U S A. 1980;77:2214–2218.[Abstract/Free Full Text]

36. Hoff HF, O'Neill J, Chisolm III GM, Cole TB, Quehenberger O, Esterbauer H, Jürgens G. Modification of low density lipoprotein with 4-hydroxynonenal induces uptake by macrophages. Arteriosclerosis. 1989;9:538–549.[Abstract/Free Full Text]

37. Farber HW, Barnett HF. Differences in prostaglandin metabolism in cultured aortic and pulmonary arterial endothelial cells exposed to acute and chronic hypoxia. Circ Res. 1991;68:1446–1457.[Abstract/Free Full Text]

38. Morrow JD, Awad JA, Boss HJ, Blair IA, Roberts LJ. Non-cycloogenase-derived prostanoids (F₂-isoprostanes) are formed in situ on phospholipids. Proc Natl Acad Sci U S A. 1992;89:10721–10725.[Abstract/Free Full Text]

39. Lynch SM, Morrow JD, Roberts LJII, Frei B. Formation of non-cyclooxygenase-derived prostanoids (F₂-isoprostanes) in plasma of low density-lipoprotein exposed to oxidative stress in vitro. J Clin Invest. 1994;93:998–1004.

40. Hammer A, Kager G, Dohr G, Rabl H, Ghassempur I, Jürgens G. Generation, characterization, and histochemical application of monoclonal antibodies selectively recognizing oxidatively modified apoB-containing serum lipoproteins. Arterioscler Thromb Vasc Biol. 1995;15:704–713.Plasma levels of malondialdehyde (MDA)-modified LDL were significantly higher in patients with acute coronary syndromes than in individuals with stable coronary artery disease (r²=0.65; P=0.0001) and were associated with increased levels of troponin I and C-reactive protein (r²=0.39 and r²=0.34, respectively; both P=0.0001). Thus, plasma levels of MDA-modified LDL appear to be a marker of acute coronary syndromes, clinically presenting as unstable angina pectoris or acute myocardial infarction. In contrast, elevated plasma levels of oxidized LDL are associated with both stable and unstable coronary artery disease.[Abstract/Free Full Text]

This article has been cited by other articles:

				J. Bausenwein, H. Serke, K. Eberle, J. Hirrlinger, P. Jogschies, F. A. Hmeidan, V. Blumenauer, and K. Spanel-Borowski Elevated levels of oxidized low-density lipoprotein and of catalase activity in follicular fluid of obese women Mol. Hum. Reprod., February 1, 2010; 16(2): 117 - 124. [Abstract] [Full Text] [PDF]

				D. De Keyzer, S.-A. Karabina, W. Wei, B. Geeraert, D. Stengel, J. Marsillach, J. Camps, P. Holvoet, and E. Ninio Increased PAFAH and Oxidized Lipids Are Associated With Inflammation and Atherosclerosis in Hypercholesterolemic Pigs Arterioscler Thromb Vasc Biol, December 1, 2009; 29(12): 2041 - 2046. [Abstract] [Full Text] [PDF]

				B. Zhang, A. Matsunaga, D. L. Rainwater, S.-i. Miura, K. Noda, H. Nishikawa, Y. Uehara, K. Shirai, M. Ogawa, and K. Saku Effects of rosuvastatin on electronegative LDL as characterized by capillary isotachophoresis: the ROSARY Study J. Lipid Res., September 1, 2009; 50(9): 1832 - 1841. [Abstract] [Full Text] [PDF]

				A. F. De Vecchi, F. Bamonti, C. Novembrino, S. Ippolito, L. Guerra, S. Lonati, S. Salini, C. S. Aman, E. Scurati-Manzoni, and G. Cighetti Free and total plasma malondialdehyde in chronic renal insufficiency and in dialysis patients Nephrol. Dial. Transplant., August 1, 2009; 24(8): 2524 - 2529. [Abstract] [Full Text] [PDF]

				G. Flores-Mateo, P. Carrillo-Santisteve, R. Elosua, E. Guallar, J. Marrugat, J. Bleys, and M.-I. Covas Antioxidant Enzyme Activity and Coronary Heart Disease: Meta-analyses of Observational Studies Am. J. Epidemiol., July 15, 2009; 170(2): 135 - 147. [Abstract] [Full Text] [PDF]

				A. Asai, F. Okajima, K. Nakagawa, D. Ibusuki, K. Tanimura, Y. Nakajima, M. Nagao, M. Sudo, T. Harada, T. Miyazawa, et al. Phosphatidylcholine hydroperoxide-induced THP-1 cell adhesion to intracellular adhesion molecule-1 J. Lipid Res., May 1, 2009; 50(5): 957 - 965. [Abstract] [Full Text] [PDF]

				B. Scazzocchio, R. Vari, M. D'Archivio, C. Santangelo, C. Filesi, C. Giovannini, and R. Masella Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases J. Lipid Res., May 1, 2009; 50(5): 832 - 845. [Abstract] [Full Text] [PDF]

				T. E. Brinkley, B. J. Nicklas, A. M. Kanaya, S. Satterfield, E. G. Lakatta, E. M. Simonsick, K. Sutton-Tyrrell, S. B. Kritchevsky, and for the Health, Aging, and Body Composition Study Plasma Oxidized Low-Density Lipoprotein Levels and Arterial Stiffness in Older Adults: The Health, Aging, and Body Composition Study Hypertension, May 1, 2009; 53(5): 846 - 852. [Abstract] [Full Text] [PDF]

				P. Martinez-Miguel, V. Raoch, C. Zaragoza, J. M. Valdivielso, M. Rodriguez-Puyol, D. Rodriguez-Puyol, and S. Lopez-Ongil Endothelin-converting enzyme-1 increases in atherosclerotic mice: potential role of oxidized low density lipoproteins J. Lipid Res., March 1, 2009; 50(3): 364 - 375. [Abstract] [Full Text] [PDF]

				L. P. van der Zwan, T. Teerlink, J. M. Dekker, R. M. A. Henry, C. D. A. Stehouwer, C. Jakobs, R. J. Heine, and P. G. Scheffer Circulating oxidized LDL: determinants and association with brachial flow-mediated dilation J. Lipid Res., February 1, 2009; 50(2): 342 - 349. [Abstract] [Full Text] [PDF]

				R. Kato, C. Mori, K. Kitazato, S. Arata, T. Obama, M. Mori, K. Takahashi, T. Aiuchi, T. Takano, and H. Itabe Transient Increase in Plasma Oxidized LDL During the Progression of Atherosclerosis in Apolipoprotein E Knockout Mice Arterioscler Thromb Vasc Biol, January 1, 2009; 29(1): 33 - 39. [Abstract] [Full Text] [PDF]

				E. R. Rietzschel, M. Langlois, M. L. De Buyzere, P. Segers, D. De Bacquer, S. Bekaert, L. Cooman, P. Van Oostveldt, P. Verdonck, G. G. De Backer, et al. Oxidized Low-Density Lipoprotein Cholesterol Is Associated With Decreases in Cardiac Function Independent of Vascular Alterations Hypertension, September 1, 2008; 52(3): 535 - 541. [Abstract] [Full Text] [PDF]

				M. R. Langlois, E. R. Rietzschel, M. L. De Buyzere, D. De Bacquer, S. Bekaert, V. Blaton, G. G. De Backer, T. C. Gillebert, and on behalf of the Asklepios Investigators Femoral Plaques Confound the Association of Circulating Oxidized Low-Density Lipoprotein With Carotid Atherosclerosis in a General Population Aged 35 to 55 Years: The Asklepios Study Arterioscler Thromb Vasc Biol, August 1, 2008; 28(8): 1563 - 1568. [Abstract] [Full Text] [PDF]

				T. Thum and J. Borlak LOX-1 Receptor Blockade Abrogates oxLDL-induced Oxidative DNA Damage and Prevents Activation of the Transcriptional Repressor Oct-1 in Human Coronary Arterial Endothelium J. Biol. Chem., July 11, 2008; 283(28): 19456 - 19464. [Abstract] [Full Text] [PDF]

				P. Holvoet, D.-H. Lee, M. Steffes, M. Gross, and D. R. Jacobs Jr Association Between Circulating Oxidized Low-Density Lipoprotein and Incidence of the Metabolic Syndrome JAMA, May 21, 2008; 299(19): 2287 - 2293. [Abstract] [Full Text] [PDF]

				P. Castilla, A. Davalos, J. L. Teruel, F. Cerrato, M. Fernandez-Lucas, J. L. Merino, C. C. Sanchez-Martin, J. Ortuno, and M. A Lasuncion Comparative effects of dietary supplementation with red grape juice and vitamin E on production of superoxide by circulating neutrophil NADPH oxidase in hemodialysis patients Am. J. Clinical Nutrition, April 1, 2008; 87(4): 1053 - 1061. [Abstract] [Full Text] [PDF]

				R. Cangemi, L. Loffredo, R. Carnevale, L. Perri, M. P. Patrizi, V. Sanguigni, P. Pignatelli, and F. Violi Early decrease of oxidative stress by atorvastatin in hypercholesterolaemic patients: effect on circulating vitamin E Eur. Heart J., January 1, 2008; 29(1): 54 - 62. [Abstract] [Full Text] [PDF]

				M. Grau, M. Guxens, I. Subirana, M. Fito, M.-I. Covas, B. Jacquemin, J. Sunyer, T. Lanki, S. Picciotto, T. Bellander, et al. South-to-North gradient in lipid peroxidation in men with stable coronary artery disease in Europe Eur. Heart J., December 1, 2007; 28(23): 2841 - 2849. [Abstract] [Full Text] [PDF]

				B. J. Arsenault, I. Lemieux, J.-P. Despres, N. J. Wareham, R. Luben, J. J.P. Kastelein, K.-T. Khaw, and S. M. Boekholdt Cholesterol levels in small LDL particles predict the risk of coronary heart disease in the EPIC-Norfolk prospective population study Eur. Heart J., November 2, 2007; 28(22): 2770 - 2777. [Abstract] [Full Text] [PDF]

				C. G. C. Vinagre, E. S. Ficker, C. Finazzo, M. J. N. Alves, K. de Angelis, M. C. Irigoyen, C. E. Negrao, and R. C. Maranhao Enhanced removal from the plasma of LDL-like nanoemulsion cholesteryl ester in trained men compared with sedentary healthy men J Appl Physiol, October 1, 2007; 103(4): 1166 - 1171. [Abstract] [Full Text] [PDF]

				J. Pincemail, S. Vanbelle, U. Gaspard, G. Collette, J. Haleng, J.P. Cheramy-Bien, C. Charlier, J.P. Chapelle, D. Giet, A. Albert, et al. Effect of different contraceptive methods on the oxidative stress status in women aged 40 48 years from the ELAN study in the province of Liege, Belgium Hum. Reprod., August 1, 2007; 22(8): 2335 - 2343. [Abstract] [Full Text] [PDF]

				P. W. B. Nanayakkara, C. van Guldener, P. M. ter Wee, P. G. Scheffer, F. J. van Ittersum, J. W. Twisk, T. Teerlink, W. van Dorp, and C. D. A. Stehouwer Effect of a Treatment Strategy Consisting of Pravastatin, Vitamin E, and Homocysteine Lowering on Carotid Intima-Media Thickness, Endothelial Function, and Renal Function in Patients With Mild to Moderate Chronic Kidney Disease: Results From the Anti-Oxidant Therapy in Chronic Renal Insufficiency (ATIC) Study Arch Intern Med, June 25, 2007; 167(12): 1262 - 1270. [Abstract] [Full Text] [PDF]

				S. Musaad and E. N. Haynes Biomarkers of Obesity and Subsequent Cardiovascular Events Epidemiol. Rev., May 10, 2007; (2007) mxm005v1. [Abstract] [Full Text] [PDF]

				R. Klein, B. E. K. Klein, M. D. Knudtson, M. F. Cotch, T. Y. Wong, K. Liu, G. L. Burke, M. F. Saad, D. R. Jacobs Jr, and A. R. Sharrett Subclinical Atherosclerotic Cardiovascular Disease and Early Age-Related Macular Degeneration in a Multiracial Cohort: The Multiethnic Study of Atherosclerosis Arch Ophthalmol, April 1, 2007; 125(4): 534 - 543. [Abstract] [Full Text] [PDF]

				S. Baba, N. Osakabe, Y. Kato, M. Natsume, A. Yasuda, T. Kido, K. Fukuda, Y. Muto, and K. Kondo Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans Am. J. Clinical Nutrition, March 1, 2007; 85(3): 709 - 717. [Abstract] [Full Text] [PDF]

				D. Segers, F. Helderman, C. Cheng, L. C.A. van Damme, D. Tempel, E. Boersma, P. W. Serruys, R. de Crom, A. F.W. van der Steen, P. Holvoet, et al. Gelatinolytic Activity in Atherosclerotic Plaques Is Highly Localized and Is Associated With Both Macrophages and Smooth Muscle Cells In Vivo Circulation, February 6, 2007; 115(5): 609 - 616. [Abstract] [Full Text] [PDF]

				J. W. Gaubatz, B. K. Gillard, J. B. Massey, R. C. Hoogeveen, M. Huang, E. E. Lloyd, J. L. Raya, C.-y. Yang, and H. J. Pownall Dynamics of dense electronegative low density lipoproteins and their preferential association with lipoprotein phospholipase A2 J. Lipid Res., February 1, 2007; 48(2): 348 - 357. [Abstract] [Full Text] [PDF]

				W. Koenig and N. Khuseyinova Biomarkers of Atherosclerotic Plaque Instability and Rupture Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 15 - 26. [Abstract] [Full Text] [PDF]

				T. Wu, W. C. Willett, N. Rifai, I. Shai, J. E. Manson, and E. B. Rimm Is Plasma Oxidized Low-Density Lipoprotein, Measured With the Widely Used Antibody 4E6, an Independent Predictor of Coronary Heart Disease Among U.S. Men and Women? J. Am. Coll. Cardiol., September 5, 2006; 48(5): 973 - 979. [Abstract] [Full Text] [PDF]

				G. N. Fredrikson, G. Berglund, R. Alm, J.-A. Nilsson, P. K. Shah, and J. Nilsson Identification of autoantibodies in human plasma recognizing an apoB-100 LDL receptor binding site peptide J. Lipid Res., September 1, 2006; 47(9): 2049 - 2054. [Abstract] [Full Text] [PDF]

				N. Duerrschmidt, O. Zabirnyk, M. Nowicki, A. Ricken, F. A. Hmeidan, V. Blumenauer, J. Borlak, and K. Spanel-Borowski Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1-Mediated Autophagy in Human Granulosa Cells as an Alternative of Programmed Cell Death Endocrinology, August 1, 2006; 147(8): 3851 - 3860. [Abstract] [Full Text] [PDF]

				P. Castilla, R. Echarri, A. Davalos, F. Cerrato, H. Ortega, J. L. Teruel, M. F. Lucas, D. Gomez-Coronado, J. Ortuno, and M. A Lasuncion Concentrated red grape juice exerts antioxidant, hypolipidemic, and antiinflammatory effects in both hemodialysis patients and healthy subjects Am. J. Clinical Nutrition, July 1, 2006; 84(1): 252 - 262. [Abstract] [Full Text] [PDF]

				D. Macut, S. Damjanovic, D. Panidis, N. Spanos, B. Glisic, M. Petakov, D. Rousso, A. Kourtis, J. Bjekic, and N. Milic Oxidised low-density lipoprotein concentration - early marker of an altered lipid metabolism in young women with PCOS. Eur. J. Endocrinol., July 1, 2006; 155(1): 131 - 136. [Abstract] [Full Text] [PDF]

				B. Mackness, R. Quarck, W. Verreth, M. Mackness, and P. Holvoet Human Paraoxonase-1 Overexpression Inhibits Atherosclerosis in a Mouse Model of Metabolic Syndrome Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1545 - 1550. [Abstract] [Full Text] [PDF]

				P. Holvoet, P. C. Davey, D. De Keyzer, M. Doukoure, E. Deridder, M.-L. Bochaton-Piallat, G. Gabbiani, E. Beaufort, K. Bishay, N. Andrieux, et al. Oxidized Low-Density Lipoprotein Correlates Positively With Toll-Like Receptor 2 and Interferon Regulatory Factor-1 and Inversely With Superoxide Dismutase-1 Expression: Studies in Hypercholesterolemic Swine and THP-1 Cells Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1558 - 1565. [Abstract] [Full Text] [PDF]

				T. Naruko, M. Ueda, S. Ehara, A. Itoh, K. Haze, N. Shirai, Y. Ikura, M. Ohsawa, H. Itabe, Y. Kobayashi, et al. Persistent High Levels of Plasma Oxidized Low-Density Lipoprotein After Acute Myocardial Infarction Predict Stent Restenosis Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 877 - 883. [Abstract] [Full Text] [PDF]

				P. Holvoet, E. Macy, M. Landeloos, D. Jones, J. S. Nancy, F. Van de Werf, and R. P. Tracy Analytical Performance and Diagnostic Accuracy of Immunometric Assays for the Measurement of Circulating Oxidized LDL Clin. Chem., April 1, 2006; 52(4): 760 - 764. [Abstract] [Full Text] [PDF]

				E. J. Armstrong, D. A. Morrow, and M. S. Sabatine Inflammatory Biomarkers in Acute Coronary Syndromes: Part III: Biomarkers of Oxidative Stress and Angiogenic Growth Factors Circulation, February 28, 2006; 113(8): e289 - e292. [Full Text] [PDF]

				T. Weinbrenner, H. Schroder, V. Escurriol, M. Fito, R. Elosua, J. Vila, J. Marrugat, and M.-I. Covas Circulating oxidized LDL is associated with increased waist circumference independent of body mass index in men and women Am. J. Clinical Nutrition, January 1, 2006; 83(1): 30 - 35. [Abstract] [Full Text] [PDF]

				M. Gritters, M. P. C. Grooteman, M. Schoorl, M. Schoorl, P. C. M. Bartels, P. G. Scheffer, T. Teerlink, C. G. Schalkwijk, M. Spreeuwenberg, and M. J. Nube Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis Nephrol. Dial. Transplant., January 1, 2006; 21(1): 153 - 159. [Abstract] [Full Text] [PDF]

				J. George, D. Wexler, A. Roth, T. Barak, D. Sheps, and G. Keren Usefulness of anti-oxidized LDL antibody determination for assessment of clinical control in patients with heart failure Eur J Heart Fail, January 1, 2006; 8(1): 58 - 62. [Abstract] [Full Text] [PDF]

				S. Takai, D. Jin, M. Muramatsu, K. Kirimura, H. Sakonjo, and M. Miyazaki Eplerenone Inhibits Atherosclerosis in Nonhuman Primates Hypertension, November 1, 2005; 46(5): 1135 - 1139. [Abstract] [Full Text] [PDF]

				H. Scholz, W. Sandberg, J. K. Damas, C. Smith, A. K. Andreassen, L. Gullestad, S. S. Froland, A. Yndestad, P. Aukrust, and B. Halvorsen Enhanced Plasma Levels of LIGHT in Unstable Angina: Possible Pathogenic Role in Foam Cell Formation and Thrombosis Circulation, October 4, 2005; 112(14): 2121 - 2129. [Abstract] [Full Text] [PDF]

				L. Wehlin, M. Lofdahl, J. Lundahl, and M. Skold Reduced Intracellular Oxygen Radical Production in Whole Blood Leukocytes From COPD Patients and Asymptomatic Smokers Chest, October 1, 2005; 128(4): 2051 - 2058. [Abstract] [Full Text] [PDF]

				R. Hirano-Ohmori, R. Takahashi, Y. Momiyama, H. Taniguchi, A. Yonemura, S. Tamai, K. Umegaki, H. Nakamura, K. Kondo, and F. Ohsuzu Green Tea Consumption and Serum Malondialdehyde-Modified LDL Concentrations in Healthy Subjects J. Am. Coll. Nutr., October 1, 2005; 24(5): 342 - 346. [Abstract] [Full Text] [PDF]

				L. Cominacini, M. Anselmi, U. Garbin, A. Fratta Pasini, C. Stranieri, M. Fusaro, C. Nava, P. Agostoni, D. Keta, P. Zardini, et al. Enhanced Plasma Levels of Oxidized Low-Density Lipoprotein Increase Circulating Nuclear Factor-Kappa B Activation in Patients With Unstable Angina J. Am. Coll. Cardiol., September 6, 2005; 46(5): 799 - 806. [Abstract] [Full Text] [PDF]

				C. Meisinger, J. Baumert, N. Khuseyinova, H. Loewel, and W. Koenig Plasma Oxidized Low-Density Lipoprotein, a Strong Predictor for Acute Coronary Heart Disease Events in Apparently Healthy, Middle-Aged Men From the General Population Circulation, August 2, 2005; 112(5): 651 - 657. [Abstract] [Full Text] [PDF]

				S. Tsimikas, E. S. Brilakis, E. R. Miller, J. P. McConnell, R. J. Lennon, K. S. Kornman, J. L. Witztum, and P. B. Berger Oxidized Phospholipids, Lp(a) Lipoprotein, and Coronary Artery Disease N. Engl. J. Med., July 7, 2005; 353(1): 46 - 57. [Abstract] [Full Text] [PDF]

				K. L. Moreau, K. M. Gavin, A. E. Plum, and D. R. Seals Ascorbic Acid Selectively Improves Large Elastic Artery Compliance in Postmenopausal Women Hypertension, June 1, 2005; 45(6): 1107 - 1112. [Abstract] [Full Text] [PDF]

				K. Zorn-Pauly, P. Schaffer, B. Pelzmann, E. Bernhart, G. Wei, P. Lang, G. Ledinski, J. Greilberger, B. Koidl, and G. Jurgens Oxidized LDL induces ventricular myocyte damage and abnormal electrical activity-role of lipid hydroperoxides Cardiovasc Res, April 1, 2005; 66(1): 74 - 83. [Abstract] [Full Text] [PDF]

				T. M. van Himbergen, M. Roest, J. de Graaf, E. H. J. M. Jansen, H. Hattori, J. J. P. Kastelein, H. A. M. Voorbij, A. F. H. Stalenhoef, and L. J. H. van Tits Indications that paraoxonase-1 contributes to plasma high density lipoprotein levels in familial hypercholesterolemia J. Lipid Res., March 1, 2005; 46(3): 445 - 451. [Abstract] [Full Text] [PDF]

				S. Saevarsdottir, O. O. Oskarsson, T. Aspelund, G. Eiriksdottir, T. Vikingsdottir, V. Gudnason, and H. Valdimarsson Mannan binding lectin as an adjunct to risk assessment for myocardial infarction in individuals with enhanced risk J. Exp. Med., January 3, 2005; 201(1): 117 - 125. [Abstract] [Full Text] [PDF]

				J. T. Wu and L. L. Wu Association of Soluble Markers with Various Stages and Major Events of Atherosclerosis Ann. Clin. Lab. Sci., January 1, 2005; 35(3): 240 - 250. [Abstract] [Full Text] [PDF]

				P.-Y. Chang, S.-C. Lu, T.-C. Su, S.-F. Chou, W.-H. Huang, J. D. Morrisett, C.-H. Chen, C.-S. Liau, and Y.-T. Lee Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation J. Lipid Res., November 1, 2004; 45(11): 2116 - 2122. [Abstract] [Full Text] [PDF]

				Y. Shoenfeld, R. Wu, L. D. Dearing, and E. Matsuura Are Anti-Oxidized Low-Density Lipoprotein Antibodies Pathogenic or Protective? Circulation, October 26, 2004; 110(17): 2552 - 2558. [Full Text] [PDF]

				R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]

				T. Weinbrenner, M. Fito, R. d. l. Torre, G. T. Saez, P. Rijken, C. Tormos, S. Coolen, M. F. Albaladejo, S. Abanades, H. Schroder, et al. Olive Oils High in Phenolic Compounds Modulate Oxidative/Antioxidative Status in Men J. Nutr., September 1, 2004; 134(9): 2314 - 2321. [Abstract] [Full Text] [PDF]

				T. Matsumoto, H. Takashima, N. Ohira, Y. Tarutani, Y. Yasuda, T. Yamane, S. Matsuo, and M. Horie Plasma level of oxidized low-density lipoprotein is an independent determinant of coronary macrovasomotor and microvasomotor responses induced by bradykinin J. Am. Coll. Cardiol., July 21, 2004; 44(2): 451 - 457. [Abstract] [Full Text] [PDF]

				M. J. Jarvisalo, T. Lehtimaki, and O. T. Raitakari Determinants of Arterial Nitrate-Mediated Dilatation in Children: Role of Oxidized Low-Density Lipoprotein, Endothelial Function, and Carotid Intima-Media Thickness Circulation, June 15, 2004; 109(23): 2885 - 2889. [Abstract] [Full Text] [PDF]

				P. Holvoet, S. B. Kritchevsky, R. P. Tracy, A. Mertens, S. M. Rubin, J. Butler, B. Goodpaster, and T. B. Harris The Metabolic Syndrome, Circulating Oxidized LDL, and Risk of Myocardial Infarction in Well-Functioning Elderly People in the Health, Aging, and Body Composition Cohort Diabetes, April 1, 2004; 53(4): 1068 - 1073. [Abstract] [Full Text] [PDF]

				I. Eskurza, K. D. Monahan, J. A. Robinson, and D. R. Seals Ascorbic acid does not affect large elastic artery compliance or central blood pressure in young and older men Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1528 - H1534. [Abstract] [Full Text] [PDF]

				I. Eskurza, K. D. Monahan, J. A. Robinson, and D. R. Seals Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing J. Physiol., April 1, 2004; 556(1): 315 - 324. [Abstract] [Full Text] [PDF]

				N. Haseruck, W. Erl, D. Pandey, G. Tigyi, P. Ohlmann, C. Ravanat, C. Gachet, and W. Siess The plaque lipid lysophosphatidic acid stimulates platelet activation and platelet-monocyte aggregate formation in whole blood: involvement of P2Y1 and P2Y12 receptors Blood, April 1, 2004; 103(7): 2585 - 2592. [Abstract] [Full Text] [PDF]

				T. Thum and J. Borlak Mechanistic Role of Cytochrome P450 Monooxygenases in Oxidized Low-Density Lipoprotein-Induced Vascular Injury: Therapy Through LOX-1 Receptor Antagonism? Circ. Res., January 9, 2004; 94 (1): e1 - e13. [Abstract] [Full Text] [PDF]

				J. E Upritchard, C. R. Schuurman, A. Wiersma, L. B. Tijburg, S. A. Coolen, P. J Rijken, and S. A Wiseman Spread supplemented with moderate doses of vitamin E and carotenoids reduces lipid peroxidation in healthy, nonsmoking adults Am. J. Clinical Nutrition, November 1, 2003; 78(5): 985 - 992. [Abstract] [Full Text] [PDF]

				H. Itabe, M. Mori, Y. Fujimoto, Y. Higashi, and T. Takano Minimally Modified LDL Is an Oxidized LDL Enriched with Oxidized Phosphatidylcholines J. Biochem., September 1, 2003; 134(3): 459 - 465. [Abstract] [Full Text] [PDF]

				E. Rother, R. Brandl, D. L. Baker, P. Goyal, H. Gebhard, G. Tigyi, and W. Siess Subtype-Selective Antagonists of Lysophosphatidic Acid Receptors Inhibit Platelet Activation Triggered by the Lipid Core of Atherosclerotic Plaques Circulation, August 12, 2003; 108(6): 741 - 747. [Abstract] [Full Text] [PDF]

				P. Holvoet, T. B. Harris, R. P. Tracy, P. Verhamme, A. B. Newman, S. M. Rubin, E. M. Simonsick, L. H. Colbert, and S. B. Kritchevsky Association of High Coronary Heart Disease Risk Status With Circulating Oxidized LDL in the Well-Functioning Elderly: Findings From the Health, Aging, and Body Composition Study Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): 1444 - 1448. [Abstract] [Full Text] [PDF]

				M. Kosch, A. Levers, M. Fobker, M. Barenbrock, R. M. Schaefer, K.-H. Rahn, and M. Hausberg Dialysis filter type determines the acute effect of haemodialysis on endothelial function and oxidative stress Nephrol. Dial. Transplant., July 1, 2003; 18(7): 1370 - 1375. [Abstract] [Full Text] [PDF]

				G. N. Fredrikson, B. Hedblad, G. Berglund, R. Alm, M. Ares, B. Cercek, K.-Y. Chyu, P. K. Shah, and J. Nilsson Identification of Immune Responses Against Aldehyde-Modified Peptide Sequences in ApoB Associated With Cardiovascular Disease Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 872 - 878. [Abstract] [Full Text] [PDF]

				G. N. Fredrikson, I. Soderberg, M. Lindholm, P. Dimayuga, K.-Y. Chyu, P. K. Shah, and J. Nilsson Inhibition of Atherosclerosis in ApoE-Null Mice by Immunization with ApoB-100 Peptide Sequences Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 879 - 884. [Abstract] [Full Text] [PDF]

				S. Kopprasch, J. Pietzsch, E. Kuhlisch, and J. Graessler Lack of Association between Serum Paraoxonase 1 Activities and Increased Oxidized Low-Density Lipoprotein Levels in Impaired Glucose Tolerance and Newly Diagnosed Diabetes Mellitus J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1711 - 1716. [Abstract] [Full Text] [PDF]

				A. Mertens, P. Verhamme, J. K. Bielicki, M. C. Phillips, R. Quarck, W. Verreth, D. Stengel, E. Ninio, M. Navab, B. Mackness, et al. Increased Low-Density Lipoprotein Oxidation and Impaired High-Density Lipoprotein Antioxidant Defense Are Associated With Increased Macrophage Homing and Atherosclerosis in Dyslipidemic Obese Mice: LCAT Gene Transfer Decreases Atherosclerosis Circulation, April 1, 2003; 107(12): 1640 - 1646. [Abstract] [Full Text] [PDF]

				M Uno, K T Kitazato, K Nishi, H Itabe, and S Nagahiro Raised plasma oxidised LDL in acute cerebral infarction J. Neurol. Neurosurg. Psychiatry, March 1, 2003; 74(3): 312 - 316. [Abstract] [Full Text] [PDF]

				M. Sanada, Y. Higashi, K. Nakagawa, M. Tsuda, I. Kodama, M. Kimura, K. Chayama, and K. Ohama A Comparison of Low-Dose and Standard-Dose Oral Estrogen on Forearm Endothelial Function in Early Postmenopausal Women J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1303 - 1309. [Abstract] [Full Text] [PDF]

				R. De Caterina, F. Cipollone, F. P. Filardo, M. Zimarino, W. Bernini, G. Lazzerini, T. Bucciarelli, A. Falco, P. Marchesani, R. Muraro, et al. Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F2-Isoprostane Formation in Hypercholesterolemic Subjects: No Further Effect of Vitamin E Circulation, November 12, 2002; 106(20): 2543 - 2549. [Abstract] [Full Text] [PDF]

				S. Kopprasch, J. Pietzsch, E. Kuhlisch, K. Fuecker, T. Temelkova-Kurktschiev, M. Hanefeld, H. Kuhne, U. Julius, and J. Graessler In Vivo Evidence for Increased Oxidation of Circulating LDL in Impaired Glucose Tolerance Diabetes, October 1, 2002; 51(10): 3102 - 3106. [Abstract] [Full Text] [PDF]

				K. Nishi, H. Itabe, M. Uno, K. T. Kitazato, H. Horiguchi, K. Shinno, and S. Nagahiro Oxidized LDL in Carotid Plaques and Plasma Associates With Plaque Instability Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1649 - 1654. [Abstract] [Full Text] [PDF]

				P. Verhamme, R. Quarck, H. Hao, M. Knaapen, S. Dymarkowski, H. Bernar, J. Van Cleemput, S. Janssens, J. Vermylen, G. Gabbiani, et al. Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs Cardiovasc Res, October 1, 2002; 56(1): 135 - 144. [Abstract] [Full Text] [PDF]

				J. T. Cvetkovic, S. Wallberg-Jonsson, E. Ahmed, S. Rantapaa-Dahlqvist, and A. K. Lefvert Increased levels of autoantibodies against copper-oxidized low density lipoprotein, malondialdehyde-modified low density lipoprotein and cardiolipin in patients with rheumatoid arthritis Rheumatology, September 1, 2002; 41(9): 988 - 995. [Abstract] [Full Text] [PDF]

				G. Theilmeier, P. Verhamme, S. Dymarkowski, H. Beck, H. Bernar, M. Lox, S. Janssens, M.-C. Herregods, E. Verbeken, D. Collen, et al. Hypercholesterolemia in Minipigs Impairs Left Ventricular Response to Stress: Association With Decreased Coronary Flow Reserve and Reduced Capillary Density Circulation, August 27, 2002; 106(9): 1140 - 1146. [Abstract] [Full Text] [PDF]

				G. Theilmeier, R. Quarck, P. Verhamme, M.-L. Bochaton-Piallat, M. Lox, H. Bernar, S. Janssens, M. Kockx, G. Gabbiani, D. Collen, et al. Hypercholesterolemia impairs vascular remodelling after porcine coronary angioplasty Cardiovasc Res, August 1, 2002; 55(2): 385 - 395. [Abstract] [Full Text] [PDF]

				J. Hulthe and B. Fagerberg Circulating Oxidized LDL Is Associated With Subclinical Atherosclerosis Development and Inflammatory Cytokines (AIR Study) Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1162 - 1167. [Abstract] [Full Text] [PDF]

				K. Tanaga, H. Bujo, M. Inoue, K. Mikami, K. Kotani, K. Takahashi, T. Kanno, and Y. Saito Increased Circulating Malondialdehyde-Modified LDL Levels in Patients With Coronary Artery Diseases and Their Association With Peak Sizes of LDL Particles Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 662 - 666. [Abstract] [Full Text] [PDF]

				M. de Lorgeril, P. Salen, P. Defaye, P. Mabo, and F. Paillard Dietary prevention of sudden cardiac death Eur. Heart J., February 2, 2002; 23(4): 277 - 285. [Full Text] [PDF]

				M. Mori, H. Itabe, Y. Higashi, Y. Fujimoto, M. Shiomi, M. Yoshizumi, Y. Ouchi, and T. Takano Foam cell formation containing lipid droplets enriched with free cholesterol by hyperlipidemic serum J. Lipid Res., November 1, 2001; 42(11): 1771 - 1781. [Abstract] [Full Text] [PDF]

				A. MERTENS and P. HOLVOET Oxidized LDL and HDL: antagonists in atherothrombosis FASEB J, October 1, 2001; 15(12): 2073 - 2084. [Abstract] [Full Text] [PDF]

				B. de Geest and D. Collen Antibodies against oxidized LDL for non-invasive diagnosis of atherosclerotic vascular disease Eur. Heart J., September 1, 2001; 22(17): 1517 - 1518. [PDF]

				C. Monaco, F. Crea, G. Niccoli, F. Summaria, D. Cianflone, R. Bordone, G. Bellomo, and A. Maseri Autoantibodies against oxidized low density lipoproteins in patients with stable angina, unstable angina or peripheral vascular disease; pathophysiological implications Eur. Heart J., September 1, 2001; 22(17): 1572 - 1577. [Abstract] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holvoet, P. Articles by Collen, D. Search for Related Content PubMed PubMed Citation Articles by Holvoet, P. Articles by Collen, D.