15-Lipoxygenase Preferentially Oxygenates a Subfraction of Human Low Density Lipoprotein
The 15-lipoxygenase is high level expressed in foamy macrophages of atherosclerotic lesions but is absent in the normal vessel wall1–4. In cholesterol fed rabbits specific lipoxygenase products have been detected in the developing lesions suggesting the in vivo action of the enzyme5. Since these products appear to correlate with lipid deposition in the vessel wall a causal relation between lipoxygenase expression and atherogenesis may be concluded. In more advanced human lesions the pattern of oxygenated lipids is more unspecific suggesting a massive non-enzymatic lipid peroxidation in later stages of atherogenesis6. However, even in older lesions a small share of specific lipoxygenase product has been detected recently suggesting that the 15-lipoxygenase may also be of pathophysiological importance in later stages of atherogenesis7. Although the role of the enzyme in atherogenesis is far from clear the capability of 15-lipoxygenase of oxidising LDL into an atherogenic form8,9 led to the hypothesis that the enzyme in vivo may act pro-atherogenic by oxidising native LDL which is subsequently taken up by macrophages via scavenger receptor(s) mediated pathways10. There are, however, several unsolved problems as to the mechanism of the lipoxygenase catalysed LDL oxidation in vivo, in particular the question whether there is a direct physical contact of the 15-lipoxygenase with LDL in the lesion or whether the 15-lipoxygenase catalysed oxygenation of membrane lipids leads to the formation of radical intermediates which in turn may induce the extracellular LDL oxidation.
KeywordsAtherosclerotic Lesion Hydroxy Fatty Acid Foam Cell Formation Human Atherosclerotic Lesion Direct Physical Contact
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