Patterns of oxidized epitopes, but not NF-kappa B expression, change during atherogenesis in WHHL rabbits.
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.
Bräsen
Jan Hinrich
JH
HELIOS Klinikum-Berlin, Franz Volhard Clinic at the Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University, Berlin, Germany.
Häkkinen
Tomi
T
Malle
Ernst
E
Beisiegel
Ulrike
U
Ylä-Herttuala
Seppo
S
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000939:Epitopes / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D008315:Malondialdehyde / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism*; D010084:Oxidation-Reduction; D011817:Rabbits
D000447:Aldehydes; D000939:Epitopes; D009566:Nitrates; C039642:peroxynitric acid; D008315:Malondialdehyde; D006997:Hypochlorous Acid; C027576:4-hydroxy-2-nonenal