EditorialNitric oxide-releasing aspirin: Will it say NO to atherothrombosis?☆
Introduction
In this issue of the journal, Lorusso et al. presented an elegant study [1], demonstrating an important aspect of the effect of nitric oxide-releasing aspirin (NCX-4016) on human vasculature: its vasodilatory effect on venous grafts used for coronary artery bypass grafting operation (CABG). It seems that NCX-4016 has significant vasodilatory properties by acting directly on vein grafts, an effect which is not modified by the well demonstrated functional abnormalities of vascular wall, observed in diabetes mellitus.
Despite its complicated chemical name, NCX-4016 is designed based on a simple but brilliant idea: to combine in a single molecule, the most widely used agent in cardiovascular disease, aspirin, and a donor of probably the most important signaling molecule in human vessels, nitric oxide (NO).
Section snippets
Aspirin: an old drug with great benefits in cardiovascular disease
Acetylosalicylic acid, or aspirin, was discovered during the 19th century [2], and despite its toxic effects on gastrointestinal tract [3] it became a first line agent against cardiovascular death, by preventing thrombotic events [4] and atherothrombosis in general [5], further to its well-known anti-inflammatory properties [2]. It is really interesting that the antithrombotic effect of aspirin is not due to salicylate but it is caused by the acetyl group on its molecule, which inhibits
Aspirin: any improvements to minimize side effects?
A promising alternative solution to minimize the side effects of aspirin on gastric mucosa without compromising its antithrombotic efficacy is a newly designed category of antithrombotic agents, the NO-releasing aspirin. Based on evidence that NO protects gastric mucosa by reducing microvascular ischemia [9], the NO-releasing aspirins may provide the solution to this problem.
NO-releasing aspirin NCX-4016: all in one molecule
NCX-4016 molecule is actually consisted of an aspirin group, a spacer joint by an ester linkage and an NO-releasing group [10]. When administered in vivo, esterases separate the aspirin moiety from the benzene spacer-NO complex, leading to the release of NO from this complex. The release of NO from NCX-4016 in vivo seems to be time- and concentration-dependent, since it possibly shares a common pathway with glycerol trinitrate, as implied by the presence of bidirectional cross-tolerance at the
References (21)
- et al.
Platelet-active drugs: the relationships among dose, effectiveness, and side effects
Chest
(2001) - et al.
Nitric oxide in mucosal defense: a little goes a long way
Gastroenterology
(2000) - et al.
A common pathway for nitric oxide release from NO-aspirin and glyceryl trinitrate
Biochem Biophys Res Commun
(2000) - et al.
Nitrosylhemoglobin, an unequivocal index of nitric oxide release from nitroaspirin: in vitro and in vivo studies in the rat by ESR spectroscopy
J Pharm Biomed Anal
(2001) - et al.
l-Arginine in coronary atherosclerosis
Int J Cardiol
(2000) - et al.
Co-administration of nitric oxide-aspirin (NCX-4016) and aspirin prevents platelet and monocyte activation and protects against gastric damage induced by aspirin in humans
J Am Coll Cardiol
(2004) - et al.
Cardiac medical therapy in patients after undergoing coronary artery bypass graft surgery: a review of randomized controlled trials
J Am Coll Cardiol
(2005) - Lorusso R, De Cicco G, Beghi C, Gherli T, Poli E, Corradi D., et al. Functional effects of nitric oxide-releasing...
- et al.
History of aspirin and its mechanism of action
Stroke
(1990) - et al.
Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis
BMJ
(2000)
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Invited Editorial on article entitled: “Functional effects of nitric oxide-releasing aspirin on vein conduits of diabetic patients undergoing CABG” by Lorusso et al., Published in the current issue of IJC.