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CLINICAL RESEARCH

Oxidized Low-Density Lipoprotein Autoantibodies, Chronic Infections, and Carotid Atherosclerosis in a Population-Based Study

Manuel Mayr, MD, PhD^_*,, Stefan Kiechl, MD, Sotirios Tsimikas, MD, FACC^||, Elizabeth Miller, BS^||, Joanna Sheldon, PhD, Johann Willeit, MD, Joseph L. Witztum, MD^|| and Qingbo Xu, MD, PhD^_*,,_*

^_* Department of Cardiac and Vascular Sciences
Protein Reference Unit, St. George's, University of London, London, United Kingdom
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria
Department of Neurology, Medical University Innsbruck, Innsbruck, Austria
^|| Department of Medicine, University of California San Diego, La Jolla, California

Manuscript received September 21, 2005; revised manuscript received January 3, 2006, accepted February 1, 2006.

^_* Reprint requests and correspondence: Dr. Qingbo Xu, Department of Cardiac and Vascular Science, St. George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom (Email: q.xu{at}sgul.ac.uk).

OBJECTIVES: We investigated whether associations exist between immune reactions to oxidized low-density lipoproteins (OxLDLs), chronic infections, and carotid atherosclerosis as quantified by ultrasound.

BACKGROUND: Atherosclerosis is a chronic immuno-inflammatory disease wherein both oxidized lipids and infectious agents are incriminated as possible contributors.

METHODS: We measured immunoglobulin (Ig)G and IgM autoantibody titers to copper-oxidized-LDL and malondialdehyde-LDL (OxLDL-AB), IgG and IgM apolipoprotein B-100-immune complexes (ApoB-IC), and titers of antibodies to Escherichia coli and chlamydial lipopolysaccharide (LPS), mycobacterial heat shock protein 65 (mHSP65), Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus and evaluated their relationship to cardiovascular risk factors, chronic infections, and incident/progressive carotid atherosclerosis in the Bruneck study.

RESULTS: The OxLDL-AB and ApoB-IC levels remained stable over time as indicated by strong correlations between 1995 and 2000 measurements (p < 0.001 each). Significant associations existed between all OxLDL markers and antibody titers to pathogens, especially to E. coli-LPS and mHSP65. Both OxLDL-AB and ApoB-IC levels showed a rise with increasing pathogen burden. Notably, OxLDL-ABs were also elevated in subjects with chronic infection as defined by clinical criteria. Titers of IgG, but not IgM, OxLDL-AB, or ApoB-IC inversely correlated with total cholesterol, LDL cholesterol, and apoB concentrations. The IgG OxLDL markers were positively and IgM markers were inversely associated with incident and progressive carotid atherosclerosis in univariate analyses but were not independent predictors in multivariate analyses.

CONCLUSIONS: Our study provides evidence for an association between human oxLDL markers and chronic infections. Moreover, in this population-based study, neither IgG nor IgM OxLDL autoantibodies were independently predictive of atherosclerosis progression in the carotid arteries.

Abbreviations and Acronyms   ApoB = apolipoprotein B   CMV = cytomegalovirus   Cu-OxLDL = copper-oxidized low-density lipoprotein   ELISA = enzyme-linked immunosorbent assay   HSP = heat shock protein   Ig = immunoglobulin   IMT = intima-media thickness   LDL = low-density lipoprotein   LPS = lipopolysaccharide   MDA = malondialdehyde   mHSP65 = mycobacterial heat shock protein 65   OxLDL-AB = autoantibodies to oxidized low-density lipoprotein   OxLDL = oxidized low-density lipoprotein

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