Abstract 5090: Nadph Oxidase-mediated Arterial Dysfunction in Patients With Peripheral Arterial Disease
BACKGROUND. Peripheral arterial disease (PAD) is a clinical setting characterized by endothelial dysfunction and atherosclerosis. NADPH oxidase is believed to modulate arterial tone and oxidative stress but its role in PAD is still unclear.
OBJECTIVE. The aim of this study was to evaluate whether NADPH oxidase is implicated in determining reduced FMD and to assess if the administration of an antioxidant was able to improve arterial dilatation and gp91phox, the catalytic core of NADPH oxidase, serum levels in PAD patients.
METHODS. We performed a cross-sectional study comparing flow-mediated dilation, oxidative stress, by serum levels of 8-Hydroxy-2-deoxy-2-deoxyguanosine (8-OHdG), and NO generation, by serum levels of nitrite/nitrate (NOx), and serum gp91phox in a population of PAD patients (n=25; mean age: 63.7±7.9 years) and controls (n=40; mean age: 64.2±11.2 years). In the second part, we performed an interventional cross-over study in PAD patients to assess if the infusion of an antioxidant, propionyl-L-carnitine (PLC), vs placebo, was able to improve endothelial dysfunction and serum gp91phox levels in 20 PAD patients.
RESULTS. Compared with controls, patients with PAD had enhanced gp91phox (mean±S.E.: 21.3±3.6 vs 71.7±14; p<0.001) and 8-OHdG serum levels (mean±SD: 2.4+1.2 vs. 4.24+3.11 ng/mL; P<0.001), reduced NOx (mean±SD:17.02+6.11 vs.11.28+6.02 mM; P<0.001), and lowered FMD (mean±SD: 10.34+2.14 vs. 6.69+2.95%; P<0.001). General linear model analysis for repeated measures showed that PLC infusion was associated with an increase of FMD (from 6.6±0.6 to 11.1±1.2%, F=9.98, p=0.005) and with a reduction of serum gp91phox (from 88.2±13 to 38.6±5.9, F=9.98, p=0.006). No changes were observed after placebo treatment.
CONCLUSIONS. This study shows that in PAD patients, gp91phox is overexpressed and may contribute to reduce FMD.