12/15-lipoxygenase, oxidative modification of LDL and atherogenesis

Lipoxygenases comprise a family of non-heme iron-containing dioxygenases that stereospecifically insert molecular oxygen into free or esterified polyunsaturated fatty acids. The dual specificity 12/15-lipoxygenases have been implicated in the oxidative modification of low-density lipoproteins and foam cell formation primarily based on in vitro studies. Recent in vivo data obtained with 12/15-lipoxygenase-deficient mice crossbred to apolipoprotein E-deficient mice have established a proatherogenic role for this pathway. In contrast, previous experiments with macrophage expressing 15-lipoxygenase transgenic rabbits have suggested an anti-atherogenic role. Possible explanations are presented that may elucidate these differences.