Prostacyclin reverses platelet stress fibre formation causing platelet aggregate instability

Steven Thomas, MZ Yusuf, Z Raslan, L Atkinson, A Aburima, S G Thomas, K M Naseem, S D J Calaminus

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Prostacyclin (PGI2) modulates platelet activation in order to regulate haemostasis. Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation. It was hypothesised that PGI2 could reverse platelet spreading by modulation of the actin cytoskeleton, leading to reduced capability of platelet aggregates to withstand a high shear
environment. Our data demonstrates that post-flow of PGI2 over activated and spread cells on fibrinogen, identified a significant reduction in surface area of platelets under high shear. Exploration of the molecular mechanisms underpinning this effect revealed that PGI2 reversed stress fibre formation in adherent platelets, reduced platelet spreading, whilst simultaneously
promoted actin nodule formation. The effects of PGI2 on stress fibres were mimicked by the adenylyl cyclase activator forskolin and prevented by inhibitors of protein kinase A (PKA). Stress fibre formation is a RhoA dependent process and we found that treatment of adherent platelets with PGI2 led to the inhibitory phosphorylation of RhoA, reduced RhoA GTP-loading and reversal of
myosin light chain phosphorylation. Phospho-RhoA was localised in actin nodules with PKA type II and a number of other phosphorylated PKA substrates. This study demonstrates that PGI2 can reverse key platelet functions after their initial activation and identifies a novel mechanism for controlling thrombosis.
Original languageEnglish
Article number5582
JournalScientific Reports
Publication statusPublished - 17 Jul 2017


  • platelets
  • thrombosis


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