Published online before print June 7, 2004, doi: 10.1161/01.CIR.0000130844.01174.55
(Circulation. 2004;109:3164-3170.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Percutaneous Coronary Intervention Results in Acute Increases in Oxidized Phospholipids and Lipoprotein(a)
Short-Term and Long-Term Immunologic Responses to Oxidized Low-Density Lipoprotein
From the Department of Medicine, University of California, San Diego (S.T., B.S., E.R.M., J.L.W.); the Department of Internal Medicine, Hallym University, Seoul, Korea (K.-R.H.); and the Department of Immunology, The Scripps Research Institute (L.K.C.), and the Departments of Medicine and Laboratory Medicine and Pathobiology (H.K.L) and the Ann and Roy Foss Interventional Research Program, Terrence Donnelly Heart Centre, St Michael’s Hospital (A.S., B.H.S.), University of Toronto, Ontario, Canada.
Correspondence to Sotirios Tsimikas, MD, Vascular Medicine Program, Department of Medicine, University of California San Diego, 9500 Gilman Drive, BSB 1080, La Jolla, CA 92093-0682. E-mail stsimikas{at}ucsd.edu
Received May 14, 2003; de novo received December 27, 2003; revision received March 4, 2004; accepted March 17, 2004.
Background— This study was performed to assess whether oxidized low-density lipoprotein (OxLDL) levels are elevated after percutaneous coronary intervention (PCI).
Methods and Results— Patients (n=141) with stable angina pectoris undergoing PCI had serial venous blood samples drawn before PCI, after PCI, and at 6 and 24 hours, 3 days, 1 week, and 1, 3, and 6 months. Plasma levels of OxLDL-E06, a measure of oxidized phospholipid (OxPL) content on apolipoprotein B-100 detected by antibody E06, lipoprotein(a) [Lp(a)], autoantibodies to malondialdehyde (MDA)-LDL and copper-oxidized LDL (Cu-OxLDL), and apolipoprotein B-100-immune complexes (apoB-IC) were measured. OxLDL-E06 and Lp(a) levels significantly increased immediately after PCI by 36% (P<0.0001) and 64% (P<0.0001), respectively, and returned to baseline by 6 hours. In vitro immunoprecipitation of Lp(a) from selected plasma samples showed that almost all of the OxPL detected by E06 was bound to Lp(a) at all time points, except in the post-PCI sample, suggesting independent release and subsequent reassociation of OxPL with Lp(a) by 6 hours. Strong correlations were noted between OxLDL-E06 and Lp(a) (r=0.68, P<0.0001). MDA-LDL and Cu-OxLDL autoantibodies decreased, whereas apoB-IC levels increased after PCI, but both returned to baseline by 6 hours. Subsequently, IgM autoantibodies increased and peaked at 1 month and then returned to baseline, whereas IgG autoantibodies increased steadily over 6 months.
Conclusions— PCI results in acute plasma increases of Lp(a) and OxPL and results in short-term and long-term immunologic responses to OxLDL. OxPL that are released or generated during PCI are transferred to Lp(a), suggesting that Lp(a) may contribute acutely to a protective innate immune response. In settings of enhanced oxidative stress and chronically elevated Lp(a) levels, the atherogenicity of Lp(a) may stem from its capacity as a carrier of proinflammatory oxidation byproducts.
Key Words: angioplasty • atherosclerosis • antibodies • lipoproteins
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