Generation of plasma oxidized LDL in the early stages of atherogenesis

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Deposition of lipid peroxidation products was found in intimal and medial regions in aortas of apoE-knockout mice at 10 week old in which very little atherosclerotic lesion was formed. The protein profiles of the two aortic tissues, aortic origin and aortic arch which are prone to atherosclerotic lesion formation, and thoracic and abdominal aortas which form atherosclerotic lesions much later, were examined. We found that peroxiredoxin 2(Prx2), an anti-oxidative stress enzyme, and SM22, a marker for smooth muscle cell differentiation, were reduced expressions in the athero-prone tissues, suggesting a possibility that athero-prone tissue reduces its anti-oxidative stress potential and increase smooth muscle differentiation status. In aortic origin, Prx2 expression was high at 4 weeks of age and lower at 10 and 20 weeks of age. At sites of medial layer with high expression of Prx2, migration of macrophages into adjacent intima was scarcely observed. When a few macrophages are present in intima, the adjacent medial tissue has very low expression of Prx2. It is possible that transmigration of macrophages into intima may be facilitated by reduction of medial Prx2 expression. In the lesions with intimal thickening with a number of accumulated macrophages Prx2 expression increased in both medial and intimal tissues. Accumulation of inflammatory cells in intima could enhance Prx2 expression in media. From these observations, in the very early stages of atherogenesis in mouse aortas, decrease in anti-oxidative enzyme Prx2 expression could increase oxidative stress in the tissues and induce lipid peroxidation. Such a temporal change would be important event as a trigger of the early steps of atherogenesis.