on June 7, 2004
Published online before print June 7, 2004, doi: 10.1161/01.CIR.0000130844.01174.55
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on May 14, 2003
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. * To whom correspondence should be addressed. E-mail: stsimikas{at}ucsd.edu.
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.
Revised on March 4, 2004
Accepted on March 17, 2004
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
Sotirios Tsimikas MD*,
Key words: angioplasty • atherosclerosis • antibodies • lipoproteins
This article has been cited by other articles:
 |
|
 |
|
  S. Tsimikas High-Dose Statins Prior to Percutaneous Coronary Intervention: A Paradigm Shift to Influence Clinical Outcomes in the Cardiac Catheterization Laboratory J. Am. Coll. Cardiol., December 1, 2009; 54(23): 2164 - 2166. [Full Text] [PDF]
|
|
|
|
|
|
A. E. Fraley, G. G. Schwartz, A. G. Olsson, S. Kinlay, M. Szarek, N. Rifai, P. Libby, P. Ganz, J. L. Witztum, S. Tsimikas, et al. Relationship of oxidized phospholipids and biomarkers of oxidized low-density lipoprotein with cardiovascular risk factors, inflammatory biomarkers, and effect of statin therapy in patients with acute coronary syndromes: Results from the MIRACL (Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering) trial. J. Am. Coll. Cardiol., June 9, 2009; 53(23): 2186 - 2196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tsimikas, P. Clopton, E. S. Brilakis, S. M. Marcovina, A. Khera, E. R. Miller, J. A. de Lemos, and J. L. Witztum Relationship of Oxidized Phospholipids on Apolipoprotein B-100 Particles to Race/Ethnicity, Apolipoprotein(a) Isoform Size, and Cardiovascular Risk Factors: Results From the Dallas Heart Study Circulation, April 7, 2009; 119(13): 1711 - 1719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hartvigsen, M.-Y. Chou, L. F. Hansen, P. X. Shaw, S. Tsimikas, C. J. Binder, and J. L. Witztum The role of innate immunity in atherogenesis J. Lipid Res., April 1, 2009; 50(Supplement): S388 - S393. [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]
|
|
|
|
 |
|
 P. W.F. Wilson Progressing From Risk Factors to Omics Circ Cardiovasc Genet, December 1, 2008; 1(2): 141 - 146. [Full Text] [PDF]
|
|
|
|
|
|
C. Bergmark, A. Dewan, A. Orsoni, E. Merki, E. R. Miller, M.-J. Shin, C. J. Binder, S. Horkko, R. M. Krauss, M. J. Chapman, et al. A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma J. Lipid Res., October 1, 2008; 49(10): 2230 - 2239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Merki, M. J. Graham, A. E. Mullick, E. R. Miller, R. M. Crooke, R. E. Pitas, J. L. Witztum, and S. Tsimikas Antisense Oligonucleotide Directed to Human Apolipoprotein B-100 Reduces Lipoprotein(a) Levels and Oxidized Phospholipids on Human Apolipoprotein B-100 Particles in Lipoprotein(a) Transgenic Mice Circulation, August 12, 2008; 118(7): 743 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Choi, A. Chae, E. Miller, M. Messig, F. Ntanios, A. N. DeMaria, S. E. Nissen, J. L. Witztum, and S. Tsimikas Relationship Between Biomarkers of Oxidized Low-Density Lipoprotein, Statin Therapy, Quantitative Coronary Angiography, and Atheroma Volume Observations From the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) Study. J. Am. Coll. Cardiol., July 1, 2008; 52(1): 24 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C. Briley-Saebo, P. X. Shaw, W. J.M. Mulder, S.-H. Choi, E. Vucic, J. G. S. Aguinaldo, J. L. Witztum, V. Fuster, S. Tsimikas, and Z. A. Fayad Targeted Molecular Probes for Imaging Atherosclerotic Lesions With Magnetic Resonance Using Antibodies That Recognize Oxidation-Specific Epitopes Circulation, June 24, 2008; 117(25): 3206 - 3215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ky, A. Burke, S. Tsimikas, M. L. Wolfe, M. G. Tadesse, P. O. Szapary, J. L. Witztum, G. A. FitzGerald, and D. J. Rader The Influence of Pravastatin and Atorvastatin on Markers of Oxidative Stress in Hypercholesterolemic Humans J. Am. Coll. Cardiol., April 29, 2008; 51(17): 1653 - 1662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Brasen, O. Leppanen, M. Inkala, T. Heikura, M. Levin, F. Ahrens, J. Rutanen, H. Pietsch, D. Bergqvist, A.-L. Levonen, et al. Extracellular Superoxide Dismutase Accelerates Endothelial Recovery and Inhibits In-Stent Restenosis in Stented Atherosclerotic Watanabe Heritable Hyperlipidemic Rabbit Aorta J. Am. Coll. Cardiol., December 4, 2007; 50(23): 2249 - 2253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Morikawa, Y. Kawai, K. Arakawa, T. Kumamoto, I. Miyamori, H. Akao, M. Kitayama, K. Kajinami, J.-D. Lee, H. Takeshita, et al. Serum deoxyribonuclease I activity can be used as a novel marker of transient myocardial ischaemia: results in vasospastic angina pectoris induced by provocation test Eur. Heart J., December 2, 2007; 28(24): 2992 - 2997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tsimikas, L. D. Tsironis, and A. D. Tselepis New Insights Into the Role of Lipoprotein(a)-Associated Lipoprotein-Associated Phospholipase A2 in Atherosclerosis and Cardiovascular Disease Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2094 - 2099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Parastatidis, L. Thomson, D. M. Fries, R. E. Moore, J. Tohyama, X. Fu, S. L. Hazen, H. F.G. Heijnen, M. K. Dennehy, D. C. Liebler, et al. Increased Protein Nitration Burden in the Atherosclerotic Lesions and Plasma of Apolipoprotein A-I Deficient Mice Circ. Res., August 17, 2007; 101(4): 368 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kiechl, J. Willeit, M. Mayr, B. Viehweider, M. Oberhollenzer, F. Kronenberg, C. J. Wiedermann, S. Oberthaler, Q. Xu, J. L. Witztum, et al. Oxidized Phospholipids, Lipoprotein(a), Lipoprotein-Associated Phospholipase A2 Activity, and 10-Year Cardiovascular Outcomes: Prospective Results From the Bruneck Study Arterioscler Thromb Vasc Biol, August 1, 2007; 27(8): 1788 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Pulido, J. P. McConnell, L. M. Peterson, W. E. Highsmith, R. J. Lennon, S. C. Bryant, P. B. Berger, and V. Somers Relationship Between Age-Related Macular Degeneration-Associated Variants of Complement Factor H and LOC387715 With Coronary Artery Disease Mayo Clin. Proc., March 1, 2007; 82(3): 301 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tsimikas, E. S. Brilakis, R. J. Lennon, E. R. Miller, J. L. Witztum, J. P. McConnell, K. S. Kornman, and P. B. Berger Relationship of IgG and IgM autoantibodies to oxidized low density lipoprotein with coronary artery disease and cardiovascular events J. Lipid Res., February 1, 2007; 48(2): 425 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tsimikas, M. Aikawa, F. J. Miller Jr, E. R. Miller, M. Torzewski, S. R. Lentz, C. Bergmark, D. D. Heistad, P. Libby, and J. L. Witztum Increased Plasma Oxidized Phospholipid:Apolipoprotein B-100 Ratio With Concomitant Depletion of Oxidized Phospholipids From Atherosclerotic Lesions After Dietary Lipid-Lowering: A Potential Biomarker of Early Atherosclerosis Regression Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 175 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Watson Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Lipidomics: a global approach to lipid analysis in biological systems J. Lipid Res., October 1, 2006; 47(10): 2101 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Feletou and P. M. Vanhoutte Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture) Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H985 - H1002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hartmann, C. von Birgelen, G. S. Mintz, M. G. Stoel, H. Eggebrecht, H. Wieneke, M. Fahy, T. Neumann, J. van der Palen, H. W. Louwerenburg, et al. Relation Between Lipoprotein(a) and Fibrinogen and Serial Intravascular Ultrasound Plaque Progression in Left Main Coronary Arteries J. Am. Coll. Cardiol., August 1, 2006; 48(3): 446 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mayr, S. Kiechl, S. Tsimikas, E. Miller, J. Sheldon, J. Willeit, J. L. Witztum, and Q. Xu Oxidized Low-Density Lipoprotein Autoantibodies, Chronic Infections, and Carotid Atherosclerosis in a Population-Based Study J. Am. Coll. Cardiol., June 20, 2006; 47(12): 2436 - 2443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tsimikas, S. Kiechl, J. Willeit, M. Mayr, E. R. Miller, F. Kronenberg, Q. Xu, C. Bergmark, S. Weger, F. Oberhollenzer, et al. Oxidized Phospholipids Predict the Presence and Progression of Carotid and Femoral Atherosclerosis and Symptomatic Cardiovascular Disease: Five-Year Prospective Results From the Bruneck Study J. Am. Coll. Cardiol., June 6, 2006; 47(11): 2219 - 2228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rodenburg, M. N. Vissers, A. Wiegman, E. R. Miller, P. M. Ridker, J. L. Witztum, J. J.P. Kastelein, and S. Tsimikas Oxidized Low-Density Lipoprotein in Children With Familial Hypercholesterolemia and Unaffected Siblings: Effect of Pravastatin J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1803 - 1810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Gomes and E. Buffolo Coronary stenting and inflammation: implications for further surgical and medical treatment. Ann. Thorac. Surg., May 1, 2006; 81(5): 1918 - 1925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tsimikas, J. T. Willerson, and P. M. Ridker C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J. Am. Coll. Cardiol., April 18, 2006; 47(8 Suppl): C19 - C31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Giannitsis and H. A. Katus Mirror, mirror on the wall: the quest for the earliest marker of myocardial ischaemia Eur. Heart J., November 2, 2005; 26(22): 2349 - 2350. [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]
|
|
|
|
|
|
L. J. van Tits, J. de Graaf, A. F. Stalenhoef, S. Tsimikas, J. L. Witztum, E. R. Miller, W. J. Sasiela, M. Szarek, A. G. Olsson, and G. G. Schwartz Letter Regarding Article by Tsimikas et al, "High-Dose Atorvastatin Reduces Total Plasma Levels of Oxidized Phospholipids and Immune Complexes Present on Apolipoprotein B-100 in Patients With Acute Coronary Syndromes in the MIRACL Trial" * Response Circulation, May 10, 2005; 111(18): e284 - e285. [Full Text] [PDF]
|
|
|
|
|
|
M. Schneider, J. L. Witztum, S. G. Young, E. H. Ludwig, E. R. Miller, S. Tsimikas, L. K. Curtiss, S. M. Marcovina, J. M. Taylor, R. M. Lawn, et al. High-level lipoprotein [a] expression in transgenic mice: evidence for oxidized phospholipids in lipoprotein [a] but not in low density lipoproteins J. Lipid Res., April 1, 2005; 46(4): 769 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Torzewski, P. X. Shaw, K.-R. Han, B. Shortal, K. J. Lackner, J. L. Witztum, W. Palinski, and S. Tsimikas Reduced In Vivo Aortic Uptake of Radiolabeled Oxidation-Specific Antibodies Reflects Changes in Plaque Composition Consistent With Plaque Stabilization Arterioscler Thromb Vasc Biol, December 1, 2004; 24(12): 2307 - 2312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tsimikas, J. L. Witztum, E. R. Miller, W. J. Sasiela, M. Szarek, A. G. Olsson, G. G. Schwartz, and for the Myocardial Ischemia Reduction with Aggress High-Dose Atorvastatin Reduces Total Plasma Levels of Oxidized Phospholipids and Immune Complexes Present on Apolipoprotein B-100 in Patients With Acute Coronary Syndromes in the MIRACL Trial Circulation, September 14, 2004; 110(11): 1406 - 1412. [Abstract] [Full Text] [PDF]
|
|