Key result
S-nitrosothiols exhibit selective antithrombotic properties potentially mediated by differences in cell surface denitrosating enzymes and amino acid transporters between platelets and vascular cells.
S-nitrosothiols represent a potential class of selective antithrombotic agents with novel mechanisms of action that may not require transmembrane delivery of nitric oxide.
May support selective antithrombotic development; leaves open clinical translation pending prospective trials.
S-nitrosothiols have a number of potential clinical applications, among which their use as antithrombotic agents has been emphasized. This is largely because of their well-documented platelet inhibitory effects, which show a degree of platelet selectivity, although the mechanism of this remains undefined. Recent progress in understanding how nitric oxide (NO)-related signalling is delivered into cells from stable S-nitrosothiol compounds has revealed a variety of pathways, in particular denitrosation by enzymes located at the cell surface, and transport of intact S-nitrosocysteine via the amino acid transporter system-L (L-AT). Differences in the role of these pathways in platelets and vascular cells may in part explain the reported platelet-selective action. In addition, emerging evidence that S-nitrosothiols regulate key targets on the exofacial surfaces of cells involved in the thrombotic process (for example, protein disulphide isomerase, integrins and tissue factor) suggests novel antithrombotic actions, which may not even require transmembrane delivery of NO.
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Gordge et al. (2010) conducted a review in Thrombosis. S-nitrosothiols was evaluated. S-nitrosothiols exhibit selective antithrombotic properties potentially mediated by differences in cell surface denitrosating enzymes and amino acid transporters between platelets and vascular cells.
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