European Heart Journal Advance Access originally published online on February 13, 2007
European Heart Journal 2007 28(5):608-612; doi:10.1093/eurheartj/ehl533
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Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease
1 IV Divisione di Clinica Medica, Department of Experimental Medicine and Pathology, University of Rome ‘La Sapienza’, Viale del Policlinico 155, Roma 00161, Italy
2 Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy
Received 18 May 2006; revised 30 December 2006; accepted 18 January 2007; online publish-ahead-of-print 13 February 2007.
* Corresponding author: Tel: +39 06 4461933; fax: 39 06 49970893. E-mail address: francesco.violi{at}uniroma1.it
Aims To investigate the existence of a relationship among flow-mediated dilation (FMD), nitric oxide (NO), and oxidative stress in patients with peripheral arterial disease (PAD), and to assess if the administration of an antioxidant was able to improve arterial dilatation.
Methods and results We performed a cross-sectional study comparing FMD, 8-Hydroxy-2-deoxy-2-deoxyguanosine (8-OHdG), a marker of oxidative stress, and nitrite/nitrate (NOx) serum levels in a population of 25 PAD patients and 40 controls. In the second part of the study, 21 PAD patients were randomly allocated to a treatment sequence of 7 days of i.v. infusion of placebo or 6 g/day propionyl-L-carnitine (PLC) in a cross-over design. Compared with controls, patients with PAD had enhanced 8-OHdG serum levels (2.4 ± 1.2 vs. 4.24 ± 3.11 ng/mL; P < 0.001), reduced NOx (17.02 ± 6.11 vs. 11.28 ± 6.02 µM; P < 0.001), and lowered FMD (10.34 ± 2.14 vs. 6.69 ± 2.95; P < 0.001).
PLC infusion was associated with an increase of FMD [from 6.6 ± 0.6 to 11.1 ± 1.2% (mean ± SE), P = 0.004] and NOx (from 14.5 ± 1.4 to 17.1 ± 1.2 µM; +18%, P = 0.012) and a decrease of 8-OHdG (from 3.62 ± 0.37 to 2.64 ± 0.32 ng/mL; –27%, P < 0.001). No changes were observed after placebo treatment.
Conclusion This study shows that in PAD patients, oxidative stress is implicated in determining reduced FMD.
Key Words: Peripheral vascular disease • Flow-mediated dilation • Nitric oxide • Oxidative stress • Propionylcarnitine
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