Abstract 13335: Endothelial Function and Oxidative Stress in X-Linked, gp91phox Deficiency, Chronic Granulomatous Disease
Background: Chronic granulomatous disease (CGD) is an inherited phagocyte disorder caused by a defect of NADPH oxidase components and therefore diminishes superoxide generation, leading to severe and recurrent infections. In other words, patients with CGD have low levels of oxidative stress. A balance between ambient levels of superoxide and nitric oxide release plays a critical role in the maintenance of normal endothelial function.
Methods and Results: We evaluated flow-mediated vasodilation (FMD), an index of endothelial function, before and after bone-marrow transplantation in 2 patients with X-linked gp91phox, a component of NADPH oxidase, deficiency CGD and 128 healthy young men. The phenotype of X-linked CGD was X910. FMD was 8.6±3.7% (range 1.8% to 18.7%) in 128 healthy young men. FMD was 27.4% in case 1 and 26.0% in case 2. FMD in cases 1 and 2 before bone-marrow transplantation was higher than the maximum FMD in healthy young men. Serum malondialdehyde-modified low-density lipoprotein concentration and urinary excretion of 8-hydroxy-2′-deoxyguanosine, indices of oxidative stress, were markedly decreased in patients with X-linked CGD compared with healthy subjects. Bone-marrow transplantation attenuated FMD from 27.4% to 10.2% in case 1 and from 26.0% to 9.6% in case 2 and oxidative stress increased in cases 1 and 2 to levels of those in healthy subjects and plasma concentration or urinary excretion of nitrite/nitrate was not altered in both cases.
Conclusions: Increase in oxidative stress by bone-marrow transplantation attenuated FMD in patients with X-linked CGD. These findings suggest that superoxide generated by leukocyte NADPH oxidase plays an important role in endothelial function even under a normal condition without cardiovascular risk factors.
- © 2010 by American Heart Association, Inc.