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Prostacyclin reverses platelet stress fibre formation causing platelet aggregate instability

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

Authors

M. Z. Yusuf

Z. Raslan

L. Atkinson

S. G. Thomas

K. M. Naseem



Abstract

Prostacyclin (PGI2) modulates platelet activation 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 actin cytoskeletal modulation, 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 platelets on fibrinogen, identified a significant reduction in platelet surface area 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 caused 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.

Citation

Yusuf, M. Z., Raslan, Z., Atkinson, L., Aburima, A., Thomas, S. G., Naseem, K. M., & Calaminus, S. D. (2017). Prostacyclin reverses platelet stress fibre formation causing platelet aggregate instability. Scientific reports, 7(1), Article ARTN 5582. https://doi.org/10.1038/s41598-017-05817-9

Journal Article Type Article
Acceptance Date Jun 2, 2017
Online Publication Date Jul 17, 2017
Publication Date Dec 1, 2017
Deposit Date Jun 28, 2017
Publicly Available Date Jul 17, 2017
Journal Scientific reports
Print ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 7
Issue 1
Article Number ARTN 5582
DOI https://doi.org/10.1038/s41598-017-05817-9
Keywords Prostacyclin; Platelets
Public URL https://hull-repository.worktribe.com/output/453080
Publisher URL https://www.nature.com/articles/s41598-017-05817-9
Additional Information This is a copy of an open access article published in Scientific reports, 2017, v.7.
Contract Date Jun 28, 2017

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Copyright Statement
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.






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