Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes.
OBJECTIVE
This study was conducted to test the hypothesis that plasma markers of oxidized low-density lipoprotein (OxLDL) reflect acute coronary syndromes (ACS).


BACKGROUND
Oxidized LDL contributes to the pathogenesis of atherosclerosis, but its role in ACS is not established.


METHODS
Serial plasma samples were prospectively obtained from patients with an acute myocardial infarction (MI) (n = 8), unstable angina (UA) (n = 15), stable coronary artery disease (CAD) (n = 17), angiographically normal coronary arteries (n = 8), and from healthy subjects (n = 18), at entry into the study, hospital discharge (MI group only), and at 30, 120, and 210 days. Chemiluminescent enzyme-linked immunosorbent assay was used to quantitate plasma levels of: 1) immunoglobulin (Ig)M and IgG OxLDL autoantibody titers (presented as a mean OxLDL autoantibody titer by averaging the results of four distinct epitopes); 2) LDL-autoantibody immune complexes (LDL-IC); and 3) minimally OxLDL measured by antibody E06 (OxLDL-E06), as determined by the content of oxidized phospholipids (OxPL) per apolipoprotein B-100.


RESULTS
Baseline OxLDL IgG autoantibody levels were higher in the MI group (p < 0.0001). At 30-day follow-up, the mean IgM OxLDL titers increased by 48% (p < 0.001) and 20% (p < 0.001), and IgM LDL-IC increased by 60% (p < 0.01) and 26% (p < 0.01) in the MI and UA groups, respectively. The OxLDL-E06 levels increased by 54% (p < 0.01) in the MI group at hospital discharge and by 36% at 30 days. No significant changes in any OxLDL markers were noted in the other groups. The OxLDL-E06 levels strongly paralleled the acute rise in lipoprotein(a), or Lp(a), in the MI group, suggesting that toxic OxPL are preferentially bound to Lp(a). Oxidized LDL-E06 also correlated extremely well with Lp(a) in the entire cohort of patients (r = 0.91, p < 0.0001).


CONCLUSIONS
Circulating OxLDL-specific markers strongly reflect the presence of ACS, implying immune awareness to newly exposed oxidation-specific epitopes and possible release of OxLDL in the circulation. The OxLDL-E06 measurements provide novel insights into plaque rupture and the potential atherogenicity of Lp(a).
Tsimikas
Sotirios
S
Department of Medicine, University of California at San Diego, 9500 Gilman Drive, BSB 1080, La Jolla, CA 92093-0682, USA. stsimikas@ucsd.edu
Bergmark
Claes
C
Beyer
Reinaldo W
RW
Patel
Raj
R
Pattison
Jennifer
J
Miller
Elizabeth
E
Juliano
Joseph
J
Witztum
Joseph L
JL
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000276:immunology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013577:Syndrome; D013997:Time Factors
D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein