title: Platelet NOX, a novel target for anti-thrombotic treatment.
abstract: 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.
authors.affiliation: Prof. Francesco Violi, I Clinica Medica, Viale del Policlinico 155, Roma, 00161, Italy, Tel.: +39 064461933, Fax: +39 0649970103, E-mail: francesco.violi@uniroma1.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
mesh_terms: D000818:Animals; D001778:Blood Coagulation Disorders / Q000188:drug therapy* / Q000235:genetics; D001792:Blood Platelets / Q000502:physiology*; D017700:Embolism, Cholesterol / Q000188:drug therapy* / Q000235:genetics; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D058990:Molecular Targeted Therapy; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D015539:Platelet Activation / Q000187:drug effects / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005343:Fibrinolytic Agents; D017382:Reactive Oxygen Species; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human
keywords: NOX; Platelets; oxidative stress; reactive oxygen species