Role of the NO-GC/cGMP signaling pathway in platelet biomechanics.

Autor: Balmes A; Institute of Applied Physics, University of Tübingen, Tübingen, Germany., Rodríguez JG; Institute of Applied Physics, University of Tübingen, Tübingen, Germany.; National Heart and Lung Institute, Imperial College London, London, UK., Seifert J; Institute of Applied Physics, University of Tübingen, Tübingen, Germany., Pinto-Quintero D; Interfaculty Institute of Biochemistry (IFIB), University of Tübingen, Tübingen, Germany., Khawaja AA; National Heart and Lung Institute, Imperial College London, London, UK., Boffito M; Department of Infectious Disease, Imperial College London, London, UK.; St Stephen's Centre, Chelsea and Westminster NHS Foundation Trust, London, UK., Frye M; Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Friebe A; Physiological Institute, Julius Maximilian University of Würzburg, Würzburg, Germany., Emerson M; National Heart and Lung Institute, Imperial College London, London, UK., Seta F; Vascular Biology Section, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, USA., Feil R; Interfaculty Institute of Biochemistry (IFIB), University of Tübingen, Tübingen, Germany., Feil S; Interfaculty Institute of Biochemistry (IFIB), University of Tübingen, Tübingen, Germany., Schäffer TE; Institute of Applied Physics, University of Tübingen, Tübingen, Germany.
Jazyk: angličtina
Zdroj: Platelets [Platelets] 2024 Dec; Vol. 35 (1), pp. 2313359. Date of Electronic Publication: 2024 Feb 14.
DOI: 10.1080/09537104.2024.2313359
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: