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

被引:212
作者
Tsimikas, S
Lau, HK
Han, KR
Shortal, B
Miller, ER
Segev, A
Curtiss, LK
Witztum, JL
Strauss, BH
机构
[1] Univ Calif San Diego, Dept Med, Vasc Med Program, La Jolla, CA 92093 USA
[2] Hallym Univ, Dept Internal Med, Seoul, South Korea
[3] Univ Toronto, Scripps Res Inst, Dept Immunol, Toronto, ON, Canada
[4] Univ Toronto, Dept Med, Toronto, ON, Canada
[5] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
[6] Univ Toronto, St Michaels Hosp, Terrence Donnelly Heart Ctr, Ann & Roy Foss Intervent Res Program, Toronto, ON, Canada
关键词
angioplasty; atherosclerosis; antibodies; lipoproteins;
D O I
10.1161/01.CIR.0000130844.01174.55
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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(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.
引用
收藏
页码:3164 / 3170
页数:7
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