Unraveling modulators of platelet reactivity in cardiovascular patients using omics strategies: Towards a network biology paradigm

• Platelets play an important role in atherosclerosis.
• Aspirin is used in the treatment and prevention of ischemic events in cardiovascular patients.
• A substantial proportion of patients display preserved platelet function under aspirin-treatment.
• Omics strategies are relevant to platelet reactivity.
• Network biology is a new paradigm to dissect platelet reactivity.

Platelets play an important role in the pathogenesis and the ischemic complications of atherosclerosis. Platelets may be activated by several different agonists, promoting the release of their granule contents and subsequent aggregation and thrombus formation; this leads to ischemic events such as myocardial infarction or stroke. Aspirin, the most popular antiplatelet agent, is a cornerstone in the treatment and prevention of ischemic events in cardiovascular patients. It inhibits a particular amplification pathway of platelet activation, based on thromboxane A2 (TxA2) generation. However, despite a consistent inhibition of TxA2 production, a substantial proportion of patients display preserved platelet function. This phenotype is defined as “high on-treatment platelet reactivity”. It is a risk factor for the recurrence of ischemic events, particularly in acute vessel injury settings. The determinants of platelet reactivity in these patients remain unclear, but previous studies, including healthy subjects, suggested that it is genetically determined.Over the last decade, technological improvements have led to the development of highly efficient omics strategies. High-throughput genomics, transcriptomics and proteomics have the potential to dissect fine metabolic modulations. However, the bioinformatics management of these large data sets remains a challenging issue. Network biology approaches permit the integration of different omics data sets and the identification of mutual interactions between gene products and/or molecules. The inherent topology of the network can be then explored at a pathway level rather than at a gene level. Network biology constitutes an efficient tool to further explore platelet metabolism and defects, such as modulators of platelet reactivity in cardiovascular patients.

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