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Platelet NOX, a novel target for anti-thrombotic treatment

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Topic:

Theme Issue
New oral anticoagulants for stroke prevention in atrial fibrillation

DOI: https://doi.org/10.1160/TH13-10-0818
Issue: 2014: 111/5(May) pp. 781-1006
Pages: 817-823
Ahead of Print: 2014-01-09

Platelet NOX, a novel target for anti-thrombotic treatment

F. Violi (1), P. Pignatelli (1)

(1) I Clinica Medica, Department of Internal Medicine and Medical Specialties, Roma, Italy

Keywords

Platelets, oxidative stress, reactive oxygen species, NOX

Summary

There is a growing body of evidence to suggest that reactive oxidant species (ROS) including O2-, OH- or H2O2 act as second messengers to activate platelets via 1) calcium mobilisation, 2) nitric oxide (NO) inactivation, and 3) interaction with arachidonic to give formation of isoprostanes. Among the enzymes generating ROS formation NOX2, the catalytic core of NADPH oxidase (NOX), plays a prominent role as shown by the almost absent ROS production by platelets taken from patients with hereditary deficiency of NOX2. Experimental and clinical studies provided evidence that NOX2 is implicated in platelet activation. Thus, impaired platelet activation has been detected in patients with NOX2 hereditary deficiency. Similarly, normal platelets added with NOX2 specific inhibitors disclosed impaired platelet activation along with ROS down-regulation. Accordingly, animals prone to atherosclerosis treated with apocynin, a NOX inhibitor, showed reduced platelet adhesion and atherosclerotic plaque. Furthermore, a significant association between NOX2 up-regulation and platelet activation has been detected in patients at athero-thrombotic risk, but a cause-effect relationship needs to be established. These findings may represent a rationale to plan interventional trials with NOX inhibitors to establish if blocking NOX2 or other NOX isoforms may represent a novel anti-platelet approach.

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