Novel Antioxidant Action of Aspirin May Contribute to Its Beneficial Cardiovascular Actions

Correspondence to Michael S. Wolin, PhD, Professor, Department of Physiology, New York Medical College, Valhalla, NY 10595. E-mail mike_wolin@nymc.edu

Key Words: aspirin • ferritin • endothelial cell • gene expression • antioxidant defense mechanism

In this issue of Circulation Research, Oberle et al¹ report a novel action of therapeutic doses of aspirin that may play a prominent role in the cardiovascular protective effects of this important drug. Investigation of an initial preliminary observation² that aspirin protected cultured endothelial cells against oxidative stress elicited by exposure to hydrogen peroxide resulted in evidence that it appears to function through increasing the expression of the cellular iron–binding protein ferritin. As discussed in the article by Oberle et al, evidence is emerging from clinical studies that increased cellular iron levels appear to be a risk factor in coronary artery disease. It is thought that iron can become an important contributor to enhancing the injury caused by oxidative stress as it is released from binding sites in cellular systems that normally use it for other catalytic or regulatory roles. Ferritin seems to bind iron in a manner which inhibits its ability to participate in oxidant injury. Thus, ferritin can be viewed as being a protective cellular antioxidant. When aspirin causes the elevation of ferritin, it is functioning in a manner which should reduce the tissue injury caused by oxidant stress.

Based on the data of Oberle et al,¹ previously identified actions of aspirin as an inhibitor of the biosynthesis of prostaglandins or as a scavenger of reactive radicals through its conversion to salicylic acid do not appear to contribute to the observed effects of aspirin on ferritin expression. In this study, the iron chelator desferrioxamine prevented the effects . . . [Full Text of this Article]