Vitamin E and macrophage cyclooxygenase regulation in the aged

Aging is associated with increased evidence of cardiovascular disease (CVD) . Atherosclerosis, a major cause of CVD, is an inflammatory process whose d evelopment is influenced by several proinflammatory mediators. Products of arachidonic acid metabolism, in particular, prostaglandin (PG) E-2 and thro mboxane (TX) A(2), play an important role in the development of atheroscler osis. We showed previously that the aged have higher PGE(2) production comp ared with their young counterparts. This age-associated increase in PGE(2) production is mainly a consequence of increased cyclooxygenase (COX) activi ty. We demonstrated further that increased COX activity in old mice is due to the increased expression of mRNA and protein for the inducible form of C OX, COX-2. Vitamin E has been shown to reduce PGE(2) production and risk of CVD. In aged mice, we showed that a vitamin E-induced decrease in PGE(2) p roduction is due to decreased COX activity. However, vitamin E had no effec t on COX mRNA and protein levels, indicating a post-translational regulatio n of COX by vitamin E. Further experiments indicated that vitamin E decreas es COX activity through reducing formation of peroxynitrite, a hydroperoxid e shown to be involved in the activation of COX-2, Other homologues of toco pherols were also effective in inhibiting COX activity, but their degree of inhibition varied. The varied potency to inhibit COX activity was not expl ained totally by differences in their antioxidant capacity. Vitamin E-induc ed inhibition of COX activity might contribute to its effect of reducing CV D risk.