Artikel ; Online: Role of the NO-GC/cGMP signaling pathway in platelet biomechanics.
2024 Band 35, Heft 1, Seite(n) 2313359
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 ...
| 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. |
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| Mesh-Begriff(e) | Humans ; Mice ; Animals ; Biomechanical Phenomena ; Blood Platelets/metabolism ; Signal Transduction ; Guanylate Cyclase/metabolism ; Guanylate Cyclase/pharmacology ; Platelet Activation ; Cyclic GMP/metabolism ; Cyclic GMP/pharmacology ; Nitric Oxide/metabolism ; Platelet Aggregation | |||||
| Chemische Substanzen | Guanylate Cyclase (EC 4.6.1.2) ; Cyclic GMP (H2D2X058MU) ; Nitric Oxide (31C4KY9ESH) | |||||
| Sprache | Englisch | |||||
| Erscheinungsdatum | 2024-02-14 | |||||
| Erscheinungsland | England | |||||
| Dokumenttyp | Journal Article | |||||
| ZDB-ID | 1034283-7 | |||||
| ISSN | 1369-1635 ; 0953-7104 | |||||
| ISSN (online) | 1369-1635 | |||||
| ISSN | 0953-7104 | |||||
| DOI | 10.1080/09537104.2024.2313359 | |||||
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| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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