ASPIRIN INCREASES FERRITIN SYNTHESIS IN ENDOTHELIAL-CELLS - A NOVEL ANTIOXIDANT PATHWAY

Aspirin has recently been shown to increase endothelial resistance to oxidative damage, However, the mechanism underlying aspirin-induced cy toprotection is still unknown. Using cultured cells, the present study investigates the effect of aspirin on the expression of ferritin, a c ytoprotective protein that sequesters free cytosolic iron, the main ca talyst of oxygen radical formation. In bovine pulmonary artery endothe lial cells, aspirin at low antithrombotic concentrations (0.03 to 0.3 mmol/L) induced the synthesis of ferritin protein in a time-and concen tration-dependent fashion up to 5-fold over basal levels, whereas ferr itin H (heavy chain) mRNA remained unaltered. Aspirin-induced cytoprot ection from hydrogen peroxide toxicity was mimicked by exogenous iron- free apoferritin but not iron-loaded ferritin, demonstrating the antio xidant function of newly synthesized ferritin under these conditions. Ferritin induction by aspirin was specific in that other nonsteroidal anti-inflammatory drugs such as salicylic acid, indomethacin, or diclo fenac failed to alter ferritin protein levels. Aspirin-induced ferriti n synthesis was abrogated in the presence of the iron chelator desferr ioxamine, pointing to an interaction of aspirin with iron-responsive a ctivation of ferritin translation. Together, our results suggest induc tion of ferritin as a novel mechanism by which aspirin may prevent end othelial injury in cardiovascular disease, eg, during atherogenesis.