Current concepts of platelet activation: possibilities for therapeutic modulation of heterotypic vs. homotypic aggregation

Gabriella Passacquale, Albert Ferro*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Thrombogenic and inflammatory activity are two distinct aspects of platelet biology, which are sustained by the ability of activated platelets to interact with each other (homotypic aggregation) and to adhere to circulating leucocytes (heterotypic aggregation). These two events are regulated by distinct biomolecular mechanisms that are selectively activated in different pathophysiological settings. They can occur simultaneously, for example, as part of a pro-thrombotic/pro-inflammatory response induced by vascular damage, or independently, as in certain clinical conditions in which abnormal heterotypic aggregation has been observed in the absence of intravascular thrombosis. Current antiplatelet drugs have been developed to target specific molecular signalling pathways mainly implicated in thrombus formation, and their ever increasing clinical use has resulted in clear benefits in the treatment and prevention of arterial thrombotic events. However, the efficacy of currently available antiplatelet drugs remains suboptimal, most likely because their therapeutic action is limited to only few of the signalling pathways involved in platelet homotypic aggregation. In this context, modulation of heterotypic aggregation, which is believed to contribute importantly to acute thrombotic events, as well to the pathophysiology of atherosclerosis itself, may offer benefits over and above the classical antiplatelet approach. This review will focus on the distinct biomolecular pathways that, following platelet activation, underlie homotypic and heterotypic aggregation, aiming potentially to identify novel therapeutic targets.

Original languageEnglish
Pages (from-to)604-618
Number of pages15
JournalBritish Journal of Clinical Pharmacology
Volume72
Issue number4
DOIs
Publication statusPublished - Oct 2011

Keywords

  • aspirin
  • heterotypic aggregation
  • homotypic aggregation
  • platelet activation
  • thienopyridines
  • VON-WILLEBRAND-FACTOR
  • PROTEIN-KINASE-C
  • ACUTE CORONARY SYNDROMES
  • SELECTIN GLYCOPROTEIN LIGAND-1
  • VASODILATOR-STIMULATED PHOSPHOPROTEIN
  • DENSE-GRANULE SECRETION
  • P-SELECTIN
  • THROMBUS FORMATION
  • IN-VIVO
  • MYOCARDIAL-INFARCTION

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