title: Nox-2 up-regulation and platelet activation: Novel insights.
abstract: Platelet activation is a key step in the onset of cardiovascular complications in patients affected by systemic atherosclerosis. Among other mechanisms, oxidative stress seems to play a crucial role in platelet activation. Reactive Oxidant Species (ROS) including O2(-), OH(-) or H2O2 act as second messenger to activate platelets via (1) calcium mobilization, (2) nitric oxide inactivation and (3) through the interaction with arachidonic acid to give formation of isoprostanes. One important source of ROS is represented by platelet NADPH oxidase. Growing data from experimental and clinical studies provide evidence that Nox2, the catalytic core of the NADPH oxidase system, is implicated in platelet activation. Accordingly, an impaired platelet activation has been described in patients with genetically determined Nox2 deficiency. Moreover, platelets added with specific inhibitors of Nox2 revealed impaired platelet activation, along with ROS down-production. Similar results were seen in animals treated with apocynin, a Nox inhibitor, showed reduced platelet adhesion and atherosclerotic plaque. A significant association between Nox2 and platelet activation has been detected in patients with atherosclerotic diseases. The observed up-regulation of Nox2 with subsequent isoprostanes over-production in patients with cardiovascular diseases suggests the need to explore the potential benefit of targeting Nox2 as part of a holist anti-atherothrombotic strategy in patients with systemic atherosclerosis.
authors: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors: Daniele
authors: D
authors: Pastori
authors: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors: Pasquale
authors: P
authors: Pignatelli
authors: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy; Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
authors: Roberto
authors: R
authors: Carnevale
authors: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. Electronic address: francesco.violi@uniroma1.it.
authors: Francesco
authors: F
authors: Violi
mesh_terms: D000818:Animals; D006801:Humans; D019255:NADPH Oxidases / Q000737:chemistry / Q000378:metabolism*; D015539:Platelet Activation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D017382:Reactive Oxygen Species; D019255:NADPH Oxidases
keywords: Isoprostanes; Nox; Oxidative stress; Platelets; Reactive oxygen species