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NOX2 up-regulation is associated with artery dysfunction in patients with peripheral artery disease.

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) (6g/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 p47(phox) 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.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Loffredo L,Carnevale R,Cangemi R,Angelico F,Augelletti T,Di Santo S,Calabrese CM,Della Volpe L,Pignatelli P,Perri L,Basili S,Violi F

doi

10.1016/j.ijcard.2012.01.069

subject

Has Abstract

pub_date

2013-04-30 00:00:00

pages

184-92

issue

1

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(12)00087-3

journal_volume

165

pub_type

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