Patterns of oxidized epitopes, but not NF-κB expression, change during atherogenesis in WHHL rabbits

被引:25
作者
Bräsen, JH
Häkkinen, T
Malle, E
Beisiegel, U
Ylä-Herttuala, S
机构
[1] Univ Kuopio, Dept Med, FIN-70211 Kuopio, Finland
[2] Univ Kuopio, AI Virtanen Inst, FIN-70211 Kuopio, Finland
[3] Humboldt Univ, Fac Med Charite, HELIOS, Klinikum Berlin,Franz Volhard Clin,Max Delbruck, Berlin, Germany
[4] Karl Franzens Univ Graz, Inst Med Biochem & Mol Biol, Graz, Austria
[5] Univ Hamburg Hosp, Dept Mol Cell Biol, Inst Med Biochem & Mol Biol, D-2000 Hamburg, Germany
基金
芬兰科学院; 奥地利科学基金会;
关键词
atherosclerosis; lipoprotein oxidation; modified lipoproteins; WHHL rabbit; pathology; immunohistochemistry;
D O I
10.1016/S0021-9150(02)00130-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Oxidative modification of lipoproteins plays an important role in atherogenesis. We investigated a variety of different oxidatively modified epitopes (malondialdehyde (MDA)-2, hydroxynonenal (HNE)-7, peroxynitrite, hypochlorite, EO-6) in parallel and compared normal vessel wall, early and advanced atherosclerotic lesions in WHHL rabbits. Early atherosclerotic lesions showed abundant intracellular staining in macrophages for all ox-epitopes, apo B and apo E; advanced lesions showed a more prominent peri- and extracellular staining for ox-epitopes, which tended to colocalize more with apo B than apo E. Hypochlorite-modified epitopes showed intense staining in all types of lesions, followed by MDA-2. Early and advanced atherosclerotic lesions differed significantly in that early stages revealed abundant cellular positivity for EO-6 and weak staining for HNE-7 modified proteins whereas the opposite was observed in advanced lesions. Nuclear factor-kappaB (NF-kappaB) was nearly exclusively detected in macrophages with no difference between early and advanced lesions. We conclude that hypochlorite-modified epitopes are abundantly present at all stages of atherogenesis. EO-6 might be a marker for early, HNE-7 a marker for advanced lesions. Colocalization of ox-epitopes with apolipoproteins further supports that oxidation of lipoproteins is one of the key mechanisms in atherogenesis. Chronic stable expression and activation of NF-kappaB could be a useful target for therapeutic interventions. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:13 / 21
页数:9
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