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Thromb Haemost 2007; 98(02): 413-419
DOI: 10.1160/TH06-10-0561
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Evaluation of antibodies to oxidized low-density lipoprotein and assessment of C-reactive protein in acute coronary syndrome and stable coronary artery disease

Pal Soltesz
1   Intensive Care Unit and
,
Katalin Veres
1   Intensive Care Unit and
,
Renata Laczik
1   Intensive Care Unit and
,
Henrietta Der
1   Intensive Care Unit and
,
Istvan Csipo
2   Regional Immune Laboratory, University of Debrecen, Medical and Health Science Center, Institute for Internal Medicine, 3rd Department of Medicine; Debrecen, Hungary
,
Orsolya Timar
1   Intensive Care Unit and
,
Edit Szomjak
1   Intensive Care Unit and
,
Gyula Szegedi
1   Intensive Care Unit and
,
Peter Szodoray
1   Intensive Care Unit and
› Author Affiliations Financial support:This study was supported by grants from the Hungarian National Research Fund (OTKA T 46517) and János Bolyai research fellow competition.
Further Information

Publication History

Received 04 October 2006

Accepted after resubmission 17 May 2007

Publication Date:
28 November 2017 (online)

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Summary

The aim was to measure the level of antibodies to oxidized LDL (oxLDL) and C-reactive protein (CRP) in the serum of patients with acute coronary syndrome (ACS). The results were correlated with data obtained from patients with stable coronary artery disease (stable CAD) and healthy controls.Thirty-three patients with ACS and 62 stable CAD patients were enrolled in the study. Fifty healthy individuals served as controls.The evaluation of anti-oxLDL autoantibodies was performed by ELISA, while CRP levels were measured by turbidimetry. The level of antibodies to oxLDL was significantly higher in both groups of patients with ACS and stable CAD compared to controls.The comparison between the acute and stable groups showed that anti-oxLDL levels were higher in the acute group,but because of high SD, the difference was not significant. By performing group analysis, anti-oxLDL levels were found to be significantly higher in ACS patients with unstable clinical state (circulatory insufficiency, malignant arrhythmias, recurring ischemic pain, need for urgent coronary intervention and death). CRP level in patients with ACS was significantly higher than in those with stable CAD. A positive correlation was found between anti-oxLDL antibodies and CRP levels both in patients with ACS and stable CAD. The association between the two biomarkers was stronger in the ACS group. In conclusion, our findings support the notion that the presence of antibodies to oxLDL, a plaquespecific antigen, plays a major role as a predictor of complicated manifestations of ACS.

Keywords

Atherosclerosis - coronary artery disease - antibodies to oxidized LDL - C-reactive protein
 

  • References

  • 1 Biasucci LM, Santamaria M, Liuzzo G. Inflammation, atherosclerosis and acute coronary syndrome. Minerva Cardioangiol 2002; 50: 475-486.
    PubMedSearch in Google Scholar
  • 2 George J, Afek A, Gilburd B. et al. Induction of early atherosclerosis in LDL-receptor-deficient mice immunized with beta2-glycoprotein I. Circulation 1998; 98: 1108-1115.
    CrossrefPubMedSearch in Google Scholar
  • 3 Goon PK, Boos CJ, Stonelake PS. et al. Detection and quantification of mature circulating endothelial cells using flow cytometry and immunomagnetic beads: a methodological comparison. Thromb Haemost 2006; 96: 45-52.
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Sherer Y, Shoenfeld Y. Immunomodulation for treatment and prevention of atherosclerosis. Auto-immun Rev 2002; 1: 21-27. Review.
    CrossrefPubMedSearch in Google Scholar
  • 5 Veres K, Lakos G, Kerényi A. et al. Antiphospholipid antibodies in acute coronary syndrome: implications for pathogenesis and prognosis. Lupus 2004; 13: 423-427.
    CrossrefPubMedSearch in Google Scholar
  • 6 Berliner JA, Subbanagounder G, Leitinger N. et al. Evidence for a role of phospholipid oxidation products in atherogenesis. Trends Cardiov Med 2001; 11: 142-147.
    PubMedSearch in Google Scholar
  • 7 Parthasarathy S, Wieland E, Steinberg D. A role of endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein. Proc Natl Acad Sci USA 1989; 86: 1046-1050.
    CrossrefPubMedSearch in Google Scholar
  • 8 Wu R, Nityanand S, Berglund L. et al. Antibodies against cardiolipin and oxidatively modified LDL in 50-year-old men predict myocardial infarction. Arterioscler Thromb Vasc Biol 1997; 17: 3159-3163.
    CrossrefPubMedSearch in Google Scholar
  • 9 Salonen JT, Yla Herttuala S, Yamamoto R. et al. Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet 1992; 339: 883-887.
    CrossrefPubMedSearch in Google Scholar
  • 10 George J, Ahmed A, Patnaik M. et al. The prediction of coronary atherosclerosis employing artificial neural networks. Clin Cardiol 2000; 23: 453-456.
    CrossrefPubMedSearch in Google Scholar
  • 11 George J, Harats D, Bakshi E. et al. Anti-oxidized low density lipoprotein antibody determination as a predictor of restenosis following percutaneous transluminal coronary angioplasty. Immunol Lett 1999; 68: 263-266.
    CrossrefPubMedSearch in Google Scholar
  • 12 Miyakis S, Lockshin MD, Atsumi T. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome(APS). J Thromb Haemost 2006; 4: 295-306.
    CrossrefPubMedSearch in Google Scholar
  • 13 Vaarala O. Antibodies to oxidised LDL. Lupus 2000; 9: 202-205.
    CrossrefPubMedSearch in Google Scholar
  • 14 Hasunuma Y, Matsuura E, Makita Z. et al. Involvement of beta 2-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages. Clin Exp Immunol 1997; 107: 569-573.
    CrossrefPubMedSearch in Google Scholar
  • 15 Tuomisto K, Jousilahti P, Sundvall J. et al. C-reactive protein, interleukin-6 and tumor necrosis factor alpha as predictors of incident coronary and cardiovascular events and total mortality. A population-based, prospective study. Thromb Haemost 2006; 95: 511-518.
    Thieme ConnectPubMedSearch in Google Scholar
  • 16 De Maria AN, Ben-Yehuda O, Berman D. et al. Highlights of the Year in JACC 2003. J Am Coll Cardiol 2003; 42: 2156-2166.
    CrossrefPubMedSearch in Google Scholar
  • 17 Ikonomidis I, Lekakis J, Kremastinos DT. Inflammatory markers for risk stratification in primary prevention of cardiovascular disease: time for a “multi-marker” approach?. Thromb Haemost 2006; 95: 397-398.
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Labarrere CA, Zaloga GP. C-reactive protein: from innocent bystander to pivotal mediator of atherosclerosis. Am J Med 2004; 117: 499-507.
    CrossrefPubMedSearch in Google Scholar
  • 19 Stemme S, Faber B, Holm J. et al. T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. Proc Natl Acad Sci 1995; 92: 3893-3897.
    CrossrefPubMedSearch in Google Scholar
  • 20 Shoenfeld Y, Wu R, Dearing L. et al. Are anti-oxidized low-density lipoprote in antibodies pathogenic or protective?. Circulation 2004; 110: 2552-2558.
    CrossrefPubMedSearch in Google Scholar
  • 21 George J, Afek A, Gilburd B. et al. Hyperimmunization of apo-E-deficient mice with homologous malondialdehyde low-density lipoprotein suppresses early atherogenesis. Atherosclerosis 1998; 138: 147-152.
    CrossrefPubMedSearch in Google Scholar
  • 22 Caligiuri G, Nicoletti A, Poirier B. et al. Protective immunity against atherosclerosis carried by Bcells of hypercholesterolemic mice. J Clin Invest 2002; 109: 745-753.
    CrossrefPubMedSearch in Google Scholar
  • 23 Shoji T, Nishizawa Y, Fukumoto M. et al. Inverse relationship between circulating oxidized low density lipoprotein(oxLDL) andanti-oxLDL antibody levels in healthy subjects. Atherosclerosis 2000; 148: 171-177.
    CrossrefPubMedSearch in Google Scholar
  • 24 Fukumoto M, Shoji T, Emoto M. et al. Antibodies against oxidized LDL and carotidarteryintima-media thickness in a healthy population. Arterioscler Thromb Vasc Biol 2000; 20: 703-707.
    CrossrefPubMedSearch in Google Scholar
  • 25 Ylä-Herttuala S, Palinski W, Butler SW. et al. Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL. Arterioscler Thromb 1994; 14: 32-40.
    CrossrefPubMedSearch in Google Scholar
  • 26 Bergmark C, Wu R, de Faire U. et al. Patients with early-onset peripheral vascular disease have increased levels of autoantibodies against oxidized LDL. Arterioscler Thromb Vasc Biol 1995; 15: 441-445.
    CrossrefPubMedSearch in Google Scholar
  • 27 Libby P. Inflammation in atherosclerosis. Nature 2002; 420: 868-874.
    CrossrefPubMedSearch in Google Scholar
  • 28 Wu R, Lefvert AK. Autoantibodies against oxidized low density lipoproteins (oxLDL): characterization of antibody isotope, subclass, affinity and effect on the macrophage uptake of oxLDL. Clin Exp Immunol 1995; 102: 174-180.
    PubMedSearch in Google Scholar
  • 29 Virella G, Atchley D, Koskinen S. et al. Proatherogenic and proinflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL. Clin Immunol 2002; 105: 81-92.
    CrossrefPubMedSearch in Google Scholar
  • 30 Ameli S, Hultgardh-Nilsson A, Regnstrom J. et al. Effect of immunization with homologous LDL and oxidized LDL on early atherosclerosis in hypercholesterolemic rabbits. Arterioscler Thromb Vasc Biol 1996; 16: 1074-1079.
    CrossrefPubMedSearch in Google Scholar
  • 31 Vaarala O, Puurunen M, Manttari M. et al. Antibodies to prothrombin imply a risk of myocardial infarction in middle-aged men. Thromb Haemost 1996; 75: 456-459.
    Thieme ConnectPubMedSearch in Google Scholar
  • 32 Vaarala O. Antiphospholipid antibodies and atherosclerosis. Lupus 1996; 5: 442-447. Review.
    CrossrefPubMedSearch in Google Scholar
  • 33 Auer J, Berent R, Lassing E. et al. C-reactive protein and coronary artery disease. Jpn Heart J 2002; 43: 607-619.
    CrossrefPubMedSearch in Google Scholar
  • 34 Mirat J, Raguz M, Romic Z. et al. Inflammation markers in acute coronary syndrome. Acta Med Croatica 2004; 58: 115-117.
    PubMedSearch in Google Scholar
  • 35 Szodoray P, Timar O, Veres K. et al. Th1/Th2 imbalance, measured by circulating and intracytoplasmic inflammatory cytokines- immunological alterations in acute coronary syndrome and stable coronary artery disease. Scand J Immunol 2006; 64: 336-344.
    CrossrefPubMedSearch in Google Scholar