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Reversal of stress fibre formation by Nitric Oxide mediated RhoA inhibition leads to reduction in the height of preformed thrombi

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

Authors

L. Atkinson

M. Z. Yusuf

A. Aburima

Y. Ahmed

S. G. Thomas

K. M. Naseem



Abstract

© 2018 The Author(s). Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation and inhibition. We hypothesised that Nitric oxide (NO), a platelet inhibitor, can modulate the actin cytoskeleton reversing platelet spreading, and therefore reduce the capability of thrombi to withstand a high shear environment. Our data demonstrates that GSNO, DEANONOate, and a PKG-activating cGMP analogue reversed stress fibre formation and increased actin nodule formation in adherent platelets. This effect is sGC dependent and independent of ADP and thromboxanes. Stress fibre formation is a RhoA dependent process and NO induced RhoA inhibition, however, it did not phosphorylate RhoA at ser188 in spread platelets. Interestingly NO and PGI 2 synergise to reverse stress fibre formation at physiologically relevant concentrations. Analysis of high shear conditions indicated that platelets activated on fibrinogen, induced stress fibre formation, which was reversed by GSNO treatment. Furthermore, preformed thrombi on collagen post perfused with GSNO had a 30% reduction in thrombus height in comparison to the control. This study demonstrates that NO can reverse key platelet functions after their initial activation and identifies a novel mechanism for controlling excessive thrombosis.

Citation

Atkinson, L., Yusuf, M. Z., Aburima, A., Ahmed, Y., Thomas, S. G., Naseem, K. M., & Calaminus, S. D. J. (2018). Reversal of stress fibre formation by Nitric Oxide mediated RhoA inhibition leads to reduction in the height of preformed thrombi. Scientific reports, 8(1), Article ARTN 3032. https://doi.org/10.1038/s41598-018-21167-6

Acceptance Date Jan 24, 2018
Online Publication Date Feb 14, 2018
Publication Date Feb 14, 2018
Deposit Date Feb 16, 2018
Publicly Available Date Feb 16, 2018
Print ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 8
Issue 1
Article Number ARTN 3032
DOI https://doi.org/10.1038/s41598-018-21167-6
Keywords Multidisciplinary
Public URL https://hull-repository.worktribe.com/output/562734
Publisher URL https://www.nature.com/articles/s41598-018-21167-6
Contract Date Feb 16, 2018

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