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

Item Type:Article
Title:Patterns of oxidized epitopes, but not NF-κB expression, change during atherogenesis in WHHL rabbits
Creators Name:Braesen, J.H. and Haekkinen, T. and Malle, E. and Beisiegel, U. and Ylae-Herttuala, S.
Abstract: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-{kappa}B (NF-{kappa}B) 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-{kappa}B could be a useful target for therapeutic interventions.
Keywords:Atherosclerosis, Lipoprotein Oxidation, Modified Lipoproteins, WHHL Rabbit, Pathology, Immunohistochemistry
Page Range:13-21
Date:January 2003
Official Publication:https://doi.org/10.1016/S0021-9150(02)00130-2
PubMed:View item in PubMed

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