Nitric oxide insufficiency, platelet activation, and arterial thrombosis.
Nitric oxide (NO) was originally discovered as a vasodilator product of the endothelium. Over the last 15 years, this vascular mediator has been shown to have important antiplatelet actions as well. By activating guanylyl cyclase, inhibiting phosphoinositide 3-kinase, impairing capacitative calcium influx, and inhibiting cyclooxygenase-1, endothelial NO limits platelet activation, adhesion, and aggregation. Platelets are also an important source of NO, and this platelet-derived NO pool limits recruitment of platelets to the platelet-rich thrombus. A deficiency of bioactive NO is associated with arterial thrombosis in animal models, individuals with endothelial dysfunction, and patients with a deficiency of the extracellular antioxidant enzyme glutathione peroxidase-3. This enzyme catalyzes the reduction of hydrogen and lipid peroxides, which limits the availability of these reactive oxygen species to react with and inactivate NO. The complex biochemical reactions that underlie the function and inactivation of NO in the vasculature represent an important set of targets for therapeutic intervention for the prevention and treatment of arterial thrombotic disorders.
Loscalzo
J
J
Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, USA. jloscalz@bu.edu
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000172:deficiency* / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology
D020030:Nitric Oxide Donors; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D009569:Nitric Oxide; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase