Reactive oxygen species produced by the corrosion of Fe-based materials induce endothelial dysfunction

Abstract

Based on their good mechanical properties, bioresorbable Fe-based materials have been proposed during the last decade as candidate alloys for coronary stents. Previous investigations on the biocompatibility of metallic materials often overlooked the complexity of the biodegradation phenomenon. We document, for the first time, the generation of reactive oxygen species (ROS) during Fe-based materials corrosion and their deleterious impacts on endothelial function. ROS generation was evaluated by the terephtalic acid (TA) hydroxylation assay. The endothelium of rat aortic rings was directly exposed (6 h) by inserting an iron wire into the lumen in the presence/absence of catalase. Indirect exposure to iron wire was included to assess the potential role of solubilized iron ions. Nitric oxide (NO) production by rings was measured by EPR spin-trapping, and endothelium-dependent relaxation was assessed with the organ-bath method. Induction of oxidative stress in rings was assessed via the mRNA expression of the oxidative stress response gene heme oxygenase-1 (HO-1). Iron exhibited a strong potential to generate ROS in the TA assay. ROS generation, but not corrosion, was inhibited by catalase. Direct contact with iron significantly impaired endothelium-dependent relaxation of aortic rings. Direct contact with the material in the presence of catalase, or indirect contact did not affect endothelium function. NO production by isolated rat aortic rings was inhibited by ROS generated by the corrosion of iron, as indicated by the protective role of catalase. Expression of HO-1 was increased after direct exposure to iron, not to indirect exposure or in the presence of catalase. The demonstration of ROS production during corrosion, induction of oxidative stress, inhibition of NO production and consequent endothelium dysfunction raise concern about the biocompatibility of biodegradable Fe-based alloys for vascular implants.