Role of the NO-GC/cGMP signaling pathway in platelet biomechanics
Author(s)
Type
Journal Article
Abstract
Cyclic guanosine monophosphate (cGMP) is a second messenger produced by the NO-sensitive guanylyl cyclase (NO-GC). The NO-GC/cGMP pathway in platelets has been extensively studied. However, its role in regulating the biomechanical properties of platelets has not yet been addressed and remains unknown. We therefore investigated the stiffness of living platelets after treatment with the NO-GC stimulator riociguat or the NO-GC activator cinaciguat using scanning ion conductance microscopy (SICM). Stimulation of human and murine platelets with cGMP-modulating drugs decreased cellular stiffness and downregulated P-selectin, a marker for platelet activation. We also quantified changes in platelet shape using deep learning-based platelet morphometry, finding that platelets become more circular upon treatment with cGMP-modulating drugs. To test for clinical applicability of NO-GC stimulators in the context of increased thrombogenicity risk, we investigated the effect of riociguat on platelets from human immunodeficiency virus (HIV)-positive patients taking abacavir sulfate (ABC)-containing regimens. Our results corroborate a functional role of the NO-GC/cGMP pathway in platelet biomechanics, indicating that biomechanical properties such as stiffness or shape could be used as novel biomarkers in clinical research.
Date Issued
2024-12-31
Date Acceptance
2024-01-26
Citation
Platelets, 2024, 35 (1)
ISSN
0953-7104
Publisher
Taylor & Francis Group
Journal / Book Title
Platelets
Volume
35
Issue
1
Copyright Statement
© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38353233
Subjects
ARTERIAL STIFFNESS
Cell Biology
CELLS
Cellular stiffness
cyclic guanosine monophosphate (cGMP)
GUANYLATE-CYCLASE
Hematology
inhibition of platelet activation
Life Sciences & Biomedicine
NO-sensitive guanylyl cyclase (NO-GC) enzyme
platelet shape
PROTEIN-KINASE-A
Science & Technology
Publication Status
Published
Coverage Spatial
England
Article Number
2313359
Date Publish Online
2024-02-14