Arhgef1 Plays a Vital Role in Platelet Function and Thrombogenesis

Hanan Qasim, Zubair A. Karim, Keziah R. Hernandez, Dante Lozano, Fadi T. Khasawneh, Fatima Z. Alshbool

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Platelets are the cellular mediators of hemostasis and thrombosis, and their function is regulated by a number of molecular mediators, such as small GTPases. These small GTPases are themselves regulated by guanine nucleotide exchange factors such as Arhgefs, several of which are found in platelets, including the highly expressed Arhgef1. However, the role of Arhgef1 in platelets has not yet been investigated. Methods and Results: We employed mice with genetic deletion of Arhgef1 (ie, Arhgef1−/−) and investigated their platelet phenotype by employing a host of in vivo and in vitro platelet assays. Our results indicate that Arhgef1−/− mice had prolonged carotid artery occlusion and tail bleeding times. Moreover, platelets from these mice exhibited defective aggregation, dense and α granule secretion, αIIbβ3 integrin activation, clot retraction and spreading, in comparison to their wild-type littermates. Finally, we also found that the mechanism by which Arhgef1 regulates platelets is mediated in part by a defect in the activation of the RhoA–Rho-associated kinase axis, but not Rap1b. Conclusions: Our data demonstrate, for the first time, that Arhgef1 plays a critical role in platelet function, in vitro and in vivo.

Original languageEnglish (US)
Article numbere011712
JournalJournal of the American Heart Association
Volume8
Issue number9
DOIs
StatePublished - May 7 2019
Externally publishedYes

Keywords

  • Arhgef1
  • cardiovascular diseases
  • platelets
  • small GTPases
  • thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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