Targeting Phosphodiesterases in Anti-platelet Therapy
There are two primary modes of platelet inhibition: blockade of membrane receptors or neutralization of intracellular pathways. Both means of inhibition have proven benefits in the prevention and resolution of atherothrombotic events. With regard to intracellular inhibition, phosphodiesterases (PDEs) are fundamental for platelet function. Platelets possess several PDEs (PDE2, PDE3 and PDE5) that catalyze the hydrolysis of cyclic adenosine 3′-5′-monophosphate (cAMP) and cyclic guanosine 3′-5′-monophosphate (cGMP), thereby limiting the levels of intracellular nucleotides. PDE inhibitors, such as cilostazol and dipyridamole, dampen platelet function by increasing cAMP and cGMP levels. This review focuses on the roles of PDE inhibitors in modulating platelet function, with particular attention paid to drugs that have anti-platelet clinical indications.
KeywordsPhosphodiesterase Platelet Thrombosis Anti-Platelet Agents Cilostazol Dipyridamole
- Chesebro JH, Steele PM, Fuster V et al (1985) Platelet-inhibitor therapy in cardiovascular disease. Effective defense against thromboembolism. Postgrad Med 78(48–50):57–71Google Scholar
- Faxon DP, Creager MA, Smith SC Jr et al (2004) Atherosclerotic Vascular Disease Conference: Executive summary: Atherosclerotic Vascular Disease Conference proceeding for healthcare professionals from a special writing group of the American Heart Association. Circulation 109:2595–2604PubMedCrossRefGoogle Scholar
- Suh JW, Lee SP, Park KW et al (2011) Multicenter randomized trial evaluating the efficacy of cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease: results of the CILON-T (influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation) trial. J Am Coll Cardiol 57:280–289PubMedCrossRefGoogle Scholar
- Wallis RM, Corbin JD, Francis SH et al (1999) Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol 83:3C–12CPubMedCrossRefGoogle Scholar