Iron chelation improves endothelial function in patients with coronary artery disease

Background - Some epidemiological studies have shown that increased iron st ores are associated with increased cardiovascular events. Redox-active iron may contribute to lipid peroxidation, endothelial cell activation, and gen eration of reactive oxygen species (especially hydroxyl radical, via Fenton chemistry). Increased oxidative stress is associated with impaired action of endothelium-derived nitric oxide in patients with atherosclerosis. Methods and Results - To test the hypothesis that reducing vascular iron st ores would reverse endothelial dysfunction, we examined the effects of the iron chelator deferoxamine (500 mg intra-arterially over 1 hour) on vasomot or function in forearm resistance vessels of patients with coronary artery disease by venous occlusion plethysmography. Patients with coronary artery disease had impaired endothelium-dependent vasodilation in response to meth acholine compared with healthy control subjects (P <0.001). Deferoxamine in fusion decreased serum iron levels (P <0.001). Deferoxamine improved the bl ood flow response to methacholine in patients with coronary artery disease (P <0.01 by 2-way repeated-measures ANOVA) but had no effect on the respons e to sodium nitroprusside. In normal volunteers, deferoxamine had no effect on the response to methacholine. The nitric oxide synthase inhibitor N-G-m onomethyl-L-arginine abolished augmentation of the methacholine response as sociated with deferoxamine. The hydroxyl radical scavenger mannitol had no effect on the methacholine response. Conclusions-Deferoxamine improved nitric oxide-mediated, endothelium-depend ent vasodilation in patients with coronary artery disease. These results su ggest that iron availability contributes to impaired nitric oxide action in atherosclerosis.