Regulatory mechanisms of cAMP levels as a multiple target for antiplatelet activity and less bleeding risk

Fuentes E, Palomo I.

Abstract

Platelet activation is a critical component of atherothrombosis. The multiple pathways of platelet activation limit the effect of specific receptor/pathway inhibitors, resulting in limited clinical efficacy. Recent research has confirmed that combination therapy results in enhanced antithrombotic efficacy without increasing bleeding risk. In this way, the best-known inhibitor and turn off signaling in platelet activation is cAMP. In this article we discuss the mechanisms of regulation of intraplatelet cAMP levels, a) platelet-dependent pathway: Gi/Gs protein-coupled receptors, phosphodiesterase inhibition and activation of PPARs and b) platelet-independent pathway: inhibition of adenosine uptake by erythrocytes. With respect to the association between intraplatelet cAMP levels and bleeding risk it is possible to establish that compounds/drugswith pleitropic effect for increased intraplatelet cAMP level could have an antithrombotic activity with less risk of bleeding. (C) 2014 Elsevier Ltd. All rights reserved.

Más información

Título según WOS: Regulatory mechanisms of cAMP levels as a multiple target for antiplatelet activity and less bleeding risk
Título según SCOPUS: Regulatory mechanisms of cAMP levels as a multiple target for antiplatelet activity and less bleeding risk
Título de la Revista: THROMBOSIS RESEARCH
Volumen: 134
Número: 2
Editorial: PERGAMON-ELSEVIER SCIENCE LTD
Fecha de publicación: 2014
Página de inicio: 221
Página final: 226
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S0049384814002412
DOI:

10.1016/j.thromres.2014.04.027

Notas: ISI, SCOPUS