New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach.

Détails

ID Serval
serval:BIB_FB367E70B76F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach.
Périodique
Human Genetics
Auteur(s)
Zufferey A., Ibberson M., Reny J.L., Nolli S., Schvartz D., Docquier M., Xenarios I., Sanchez J.C., Fontana P.
ISSN
1432-1203 (Electronic)
ISSN-L
0340-6717
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
135
Numéro
4
Pages
403-414
Langue
anglais
Résumé
Platelet reactivity (PR) is variable between individuals and modulates clinical outcome in cardiovascular (CV) patients treated with antiplatelet drugs. Although several data point to a genetic control of platelet reactivity, the genes contributing to the modulation of this phenotype are not clearly identified. Integration of data derived from high-throughput technologies may yield novel insights into the molecular mechanisms that govern platelet reactivity. The aim of this study is to identify candidate genes modulating platelet reactivity in aspirin-treated CV patients using an integrative network-based approach. Patients with extreme high (n = 6) or low PR (n = 6) were selected and data derived from quantitative proteomic of platelets and platelet sub-cellular fractions, as well as from transcriptomic analysis were integrated with a network biology approach. Two modules within the network containing 123 and 182 genes were identified. We then specifically assessed the level of miRNAs in these two groups of patients. Among the 12 miRNAs differentially expressed, 2 (miR-135a-5p and miR-204-5p) correlated with PR. The predicted targets of these miRNAs were mapped onto the network, allowing the identification of seven overlapping genes (THBS1, CDC42, CORO1C, SPTBN1, TPM3, GTPBP2, and MAPRE2), suggesting a synergistic effect of these two miRNAs on these predicted targets. Integration of several omics data sets allowed the identification of 2 candidate miRNAs and 7 candidate genes regulating platelet reactivity in aspirin-treated CV patients.

Mots-clé
Aspirin/pharmacology, Blood Platelets/drug effects, Humans, MicroRNAs/genetics, Proteomics, RNA, Messenger/genetics
Pubmed
Web of science
Création de la notice
20/02/2016 16:26
Dernière modification de la notice
16/09/2019 5:26
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