Abstract
Objective
Oxidative stress seems to play a role in impairing flow-mediated dilation (FMD) in
patients with peripheral artery disease (PAD) but the underlying mechanism is still
undefined. We evaluated whether NOX2, the catalytic core of NADPH oxidase, the most
important producer of reactive oxidant species (ROS), is implicated in impairing FMD.
Methods
We measured FMD, urinary isoprostanes, a marker of oxidative stress, nitric oxide
generation by serum levels of nitrite/nitrate (NOx), and serum levels of soluble NOX2-derived
peptide (sNOX2-dp), a marker of NOX2 activation, in 50 PAD patients and 50 controls.
Also, we performed an interventional cross-over study to assess if propionyl-l-carnitine (PLC) (6 g/day), vs. placebo, was able to affect FMD via an oxidative stress-mediated mechanism.
Results
Compared to controls, patients with PAD had enhanced sNOX2-dp and isoprostanes and
reduced NOx and FMD. Multiple linear regression analysis showed that FMD was independently
associated with sNOX2-dp. After PLC infusion FMD increased while sNOX2-dp and isoprostanes
significantly decreased; no changes were observed after placebo. In vitro study by
incubating platelets or white cells with PLC demonstrated a significant inhibition
of p47phox translocation on cellular surface and ROS generated by NOX2 activation.
Conclusion
This study suggests that in PAD patients ROS generated by NOX2 contribute to reduce
FMD and that the administration of an antioxidant is able to improve arterial dilatation
via NOX2 inhibition.
Keywords
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Article info
Publication history
Published online: February 15, 2012
Accepted:
January 22,
2012
Received in revised form:
November 23,
2011
Received:
July 31,
2011
Identification
Copyright
© 2012 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
