Gasomediators (•NO, CO, and H2S) and their role in hemostasis and thrombosis

Hemostasis is a group of mechanisms used to prevent the outflow of blood from its vessels, and to ensure its liquidity and flow within them. The system incorporates aspects of the blood vessel wall (mainly the intima), the clotting process, together with its factors (i.e. fibrinogen) and coagulation inhibitors, as well as fibrinolysis, blood platelets and the phagocyte system. The modulation of hemostasis is associated with the pathogenesis of cardiovascular diseases, such as thrombosis. The study examines the action of three selected gasomediators, nitric oxide ((NO)-N-center dot), carbon monoxide (CO) and hydrogen sulfide (H2S), on hemostasis and thrombosis, although these gasses are also involved in a multitude of other physiological functions. (NO)-N-center dot inhibits blood platelet activation, relaxes blood vessels and, as a free radical chain, may rapidly react with superoxide anion (O-2(-center dot)) in blood platelets to form peroxynitrite (ONOO-). ONOO- is a reactive nitrating and nitrosating agent which induces oxidative/nitrative stress in blood platelets and plasma. Moreover, ONOO- changes the structure and function of fibrinogen and proteins associated with fibrinolysis. Recently, proteomic studies have provided unequivocal evidence that human platelets lack any expression of nitric oxide synthase isoforms. Other studies have demonstrated that CO and H2S, reduce blood platelet reactivity. Moreover, H2S has been reported to demonstrate anticoagulatory activity, and CO may act not only as an anticoagulant, but also aprocoagulant. This review article summarizes current knowledge of the biological roles of gasomediators (NO, CO, H2S) in hemostasis and in cardiovascular diseases. (C) 2015 Elsevier B.V. All rights reserved.