title: Platelet function in health and disease: from molecular mechanisms, redox considerations to novel therapeutic opportunities.
abstract: Increased oxidative stress appears to be of fundamental importance in the pathogenesis and development of several disease processes. Indeed, it is well known that reactive oxygen species (ROS) exert critical regulatory functions within the vascular wall, and it is, therefore, plausible that platelets represent a relevant target for their action. Platelet activation cascade (including receptor-mediated tethering to the endothelium, rolling, firm adhesion, aggregation, and thrombus formation) is tightly regulated. In addition to already well-defined platelet regulatory factors, ROS may participate in the regulation of platelet activation. It is already established that enhanced ROS release from the vascular wall can indirectly affect platelet activity by scavenging nitric oxide (NO), thereby decreasing the antiplatelet properties of endothelium. On the other hand, recent data suggest that platelets themselves generate ROS, which may evoke pro-thrombotic responses, triggering many biological processes participating in atherosclerosis initiation, progression, and complication. That oxidative stress may alter platelet function is conceivable when considering that antioxidants play a role in the prevention of cardiovascular disease, although the precise mechanism accounting for changes attributable to antioxidants in atherosclerosis remains unknown. It is possible that the effects of antioxidants may be a consequence of their enhancing or promoting the antiplatelet effects of NO derived from both endothelial cells and platelets. This review focuses on current knowledge regarding ROS-dependent regulation of platelet function in health and disease, and summarizes in vitro and in vivo evidence for their physiological and potential therapeutic relevance.
authors.affiliation: Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferroni
authors.forename: Natale
authors.initials: N
authors.lastname: Vazzana
authors.forename: Silvia
authors.initials: S
authors.lastname: Riondino
authors.forename: Chiara
authors.initials: C
authors.lastname: Cuccurullo
authors.forename: Fiorella
authors.initials: F
authors.lastname: Guadagni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide