Agonist-induced platelet procoagulant activity requires shear and a Rac1-dependent signaling mechanism

Michael Keegan Delaney, Junling Liu, Kyungho Kim, Bo Shen, Aleksandra Stojanovic-Terpo, Yi Zheng, Jaehyung Cho, Xiaoping Du

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Activated platelets facilitate blood coagulation by exposing phosphatidylserine (PS) and releasing microvesicles (MVs). However, the potent physiological agonists thrombin and collagen poorly induce PS exposure when a single agonist is used. To obtain a greater procoagulant response, thrombin is commonly used in combination with glycoprotein VI agonists. However, even under these conditions, only a percentage of platelets express procoagulant activity. To date, it remains un clear why platelets poorly expose PS even when stimulated with multiple agonists and what the signaling pathways are of soluble agonist induced platelet procoagulant activity. Here we show that physiological levels of shear present in blood significantly enhance agonist-induced platelet PS exposure and MV release, enabling low doses of a single agonist to induce full-scale platelet procoagulant activity. PS exposed on the platelet surface was immediately released as MVs, revealing a tight coupling between the 2 processes under shear. Using platelet-specific Rac1-/-mice, we discovered that Rac1 plays a common role in mediating the low-dose agonist-induced procoagulant response independent of platelet aggregation, secretion, and the apoptosis pathway. Platelet-specificRac1 function was not only important for coagulation in vitro but also for fibrin accumulation in vivo following laser-induced arteriolar injury.

Original languageEnglish
Pages (from-to)1957-1967
Number of pages11
JournalBlood
Volume124
Issue number12
DOIs
StatePublished - Sep 18 2014

Fingerprint Dive into the research topics of 'Agonist-induced platelet procoagulant activity requires shear and a Rac1-dependent signaling mechanism'. Together they form a unique fingerprint.

Cite this