Abstract 15021: Ascorbic Acid Infusion Blunts Cd40l up-Regulation in Patients Undergoing Coronary Stent
Background: A significant increase of sCD40L has been observed after procedure in patients undergoing coronary stenting. Several studies have shown that the increase of CD40L after stenting is an important hallmark of poor vascular outcome. Interestingly, in patients undergoing stenting, a significant increase of oxidative stress has been also reported. We had demonstrated that intravenous infusion of ascorbic acid in healthy subjects is associated with a significant decrease of oxidative stress dependent sCD40L release. Aim. To reduce the increase of oxidative stress and sCD40L during stenting procedure using ascorbic acid infusion.
Methods: Fifty-six patients undergoing elective coronary stenting were randomly allocated to intravenous infusion of the antioxidant ascorbic acid or placebo. Platelet CD40L, plasma levels of soluble CD40L and of 8-hydroxy-2′-deoxyguanosine, a marker of oxidative stress, were measured before and after coronary stenting. In vitro study, aimed to reproduce the ischemic event, evaluated reactive oxidant species and CD40L expression in platelets exposed to anoxia-reoxygenation.
Results: Placebo-treated patients showed an increase of platelet CD40L, soluble CD40L and 8-hydroxy-2′-deoxyguanosine compared to baseline values. Patients given ascorbic acid showed no change of soluble CD40L and platelet CD40L but a significant decrease of 8-hydroxy-2′-deoxyguanosine. After 60 and 120 minutes, soluble CD40L, platelet CD40L and 8-hydroxy-2′-deoxyguanosine were significantly lower in the ascorbic acid-treated group compared to the placebo-treated one. A significant correlation between platelet CD40L and soluble CD40L and between soluble CD40L and 8-hydroxy-2′-deoxyguanosine was observed. Platelets, in vitro exposed to anoxia-reoxygenation, had a burst of ROS and an up-regulation of CD40L that were inhibited by ascorbic acid or by specific inhibitor of NADPH oxidase.
Conclusions: We showed that platelet CD40L up-regulation, occurs precociously after coronary stenting, is oxidative stress-mediated and could be dependent upon NADPH oxidase activation. Ascorbic acid may represent a simple and cheap approach to counteract coronary stenting-related platelet activation.
- © 2010 by American Heart Association, Inc.