chapter  31
Catheter-based delivery of NOS gene Stefan Janssens
Pages 8

Nitric oxide is a structurally simple heterodiatomic molecule, synthesized from L-arginine by the catalytic reaction of a class of enzymes called nitric oxide synthases (NOS). NO is short-lived and its synthesis involves a complex array of biochemical interactions which, in turn, participate in a wide variety of physiological functions, including neurotransmission, cellular communication, inflammation, and regulation of vascular tone.1 In the cardiovascular system, NO has an important role in basic homeostasis by way of mediating vasorelaxation and attenuating platelet and leukocyte activation. In addition, NO also mediates essential cellular functions in the vessel wall including smooth muscle migration, proliferation, and apoptosis, as well as endothelial cell growth.2 NO interacts with several intracellular molecular targets, one of which is soluble guanylate cyclase (sGC), a heterodimer consisting of and subunits, linked by disulfide bonds. Binding of NO to the heme-Fe group in sGC stimulates conversion of guanosine 5′- triphosphate GTP to the intracellular second messenger cyclic GMP, which, in turn, mediates the vasorelaxation, regulation of apoptosis, migration, and proliferation of smooth muscle

cells by binding to a cyclic GMP-dependent protein kinase (Figure 31.1).