Reactive Oxygen Species

Abstract

Abstract-Platelets participate not only in thrombus formation but also in the regulation of vessel tone, the development of atherosclerosis, angiogenesis, and in neointima formation after vessel wall injury. It is not surprising, therefore, that the 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, such as nitric oxide (NO), prostacyclin (PGI 2 ), and adenosine, reactive oxygen species (ROS) participate in the regulation of platelet activation. Although exogenously derived ROS are known to affect the regulation of platelet activation, recent data suggest that the platelets themselves generate ROS. Intracellular ROS signaling in activated platelets could be of significant relevance after transient platelet contact with the vessel wall, during the recruitment of additional platelets, and in thrombus formation. This review discusses the potential cellular and enzymatic sources of ROS in platelets, their molecular mechanisms of action in platelet activation, and summarizes in vitro and in vivo evidence for their physiological and potential therapeutic relevance. Key Words: platelets Ⅲ reactive oxygen species Ⅲ NAD(P)H-oxidase Ⅲ aggregation Ⅲ adhesion Ⅲ thrombus formation P latelet interaction with the vessel wall serves numerous physiological and pathophysiological functions. This is reflected by the fact that platelets release growth factors, 1 lipid mediators, 2,3 and cytokines. 4 Consequently, the regulation of platelet activity plays a role not only for thrombus formation and the regulation of vascular tone 5 but also for the vascular pathophysiology of angiogenesis and inflammation. Moreover, platelets participate in the development of atherothrombotic disease by promoting atherosclerotic lesion 6 and neointima formation. 7 Not surprisingly, the activation of platelets is regulated and modulated by numerous factors, blood-borne and cell-derived. Most of these factors are relatively well-characterized. 8 However, in recent time, several publications have suggested that reactive oxygen species (ROS) represent a new modulator of platelet activity. It has been known for some time that ROS exert critical regulatory functions within the vascular wall and it is therefore plausible that platelets represent a relevant target for their action.Within the vessel wall (where endothelial cells, vascular smooth muscle cells, and fibroblasts express a variety of ROS-generating enzymes), there is a constant, low-quantity flux of ROS. 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 the endothelium. 9 In addition to their exposure to ROS derived from the vascular wall, platelets themselves also can generate ROS, and there is some evidence for a more direct role of ROS in the control of platelet activi...

Oxidation of proteins: Basic principles and perspectives for blood proteomics

“…Platelets are exposed to ROS generated by the endothelial cells of the vessel walls; in addition, there is evidence that platelets can themselves produce ROS. Lastly, under inflammatory conditions, platelets are exposed the phagocyte-dependent, acute production of ROS [164].…”

An investigation of the antiplatelet effects of succinobucol (AGI-1067)

“…This may be either a direct effect of oxidant stress on the platelet [13] or an indirect effect through destruction of labile endothelium-derived vasodilators such as nitric oxide [14]. However, the direct effects of reactive oxygen species (ROS) on platelets are inconsistent with previous studies reporting both pro-and anti-aggregatory effects when platelets are exposed to exogenous ROS [15]. Oxidant stress generated either by platelets themselves via several intracellular sources [16] or by the artery wall can also modulate vascular tone [17] and this has implications for blood flow and thrombus formation within blood vessels.…”

Antiplatelet and Antithrombotic Activities of Lindera obtusiloba Extract in vitro and in vivo

“…The balance between oxidative stress and platelet production of NO plays a key role in the process of platelet recruitment, which is an important phase of platelet activation at the site of vascular injury (Freedman et al, 1997). It is recently reported that reactive oxygen species (ROS) influence platelet function and coagulation, and are associated with the pathogenesis of cardiovascular disease (Krotz et al, 2004;Gorlach, 2005;Arthur et al, 2008). In addition, polyphenols exert an antioxidant effect via inhibition of O2 − (superoxide) generation and suggest that this effect could result in enhanced NO bioavailability and inhibit platelet recruitment (Pignatelli et al, 2006).…”