Nitric oxide, coagulation and cancer

Nitric Oxide (NO) is a well-known potent and rapid vasodilator and inhibitor of coagulation. Synthesized from an L-arginine precursor, NO is produced via the Nitric Oxide Synthase enzyme which is expressed constitutively in endothelial cells. Nitric oxide has a wide range of biological properties that maintain vascular homeostasis and protection of the vessel from injurious consequences. Thedecreased production of NO in pathological states causes deleterious effects, creating an endothelial dysfunction state with a wide variety of subsequent diverse biological effects. There is now evidence of the link between hypoxia and/or reduction of NO availability and coagulopathies. NO is also a modulator of various cancerrelated events and has anti-tumor properties. Cancer is a known hypercoagulable state and hypoxia is a typical feature of the tumor micro-environment. Cancer patients-particularly those with advanced or metastatic states-are at higher risk of developing venous and arterial thromboembolic events. The dichotomous nature of nitric oxide with regard to its tumorigenic and tumoricidal properties are at present under intense investigation. The transcendent field of nanotechnology has moved into the realm of NO donor therapy, though currently there are no commercially available carriers of NO. While nanotechnology is not quite at the translational research stage, it poses the greatest potential for storage and site-specific delivery of high concentrations of NO to tumors. In this chapter, we review the effects of NO on various hemostatic elements, the pro-tumoral and anti-tumoral effects of NO and finally shed some light on the link between NO, cancer and coagulopathies.