ArticleBritish journal of pharmacology2015
The sGC stimulator riociguat inhibits platelet function in washed platelets but not in whole blood.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis.Rheumatology (Oxford, England) · 2024Trial
- First-in-human trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of zagociguat (CY6463), a CNS-penetrant soluble guanylyl cyclase stimulator.Clinical and translational science · 2023Trial
- Inhaled nitric oxide to control platelet hyper-reactivity in patients with acute submassive pulmonary embolism.Nitric oxide : biology and chemistry · 2020Trial
- Assay variables and early clinical evaluation of low-angle light scattering for platelet function analysis.International journal of hematology · 2024Article
- Chloride Gradient Is Involved in Ammonium Influx in Human Erythrocytes.International journal of molecular sciences · 2024Article
- Current concepts and novel targets for antiplatelet therapy.Nature reviews. Cardiology · 2023Review
- Review
- The NO/cGMP/PKG pathway in platelets: The therapeutic potential of PDE5 inhibitors in platelet disorders.Journal of thrombosis and haemostasis : JTH · 2022Review
- Riociguat inhibits ultra-large VWF string formation on pulmonary artery endothelial cells from chronic thromboembolic pulmonary hypertension patients.Pulmonary circulation · 2022Article
- Platelet Hemostasis Reactions at Different Temperatures Correlate with Intracellular Calcium Concentration.International journal of molecular sciences · 2022Article
- Curcumin at Low Doses Potentiates and at High Doses Inhibits ABT-737-Induced Platelet Apoptosis.International journal of molecular sciences · 2021Article
- Article
- cAMP- and cGMP-elevating agents inhibit GPIbα-mediated aggregation but not GPIbα-stimulated Syk activation in human platelets.Cell communication and signaling : CCS · 2019Article
- Platelets in Systemic Sclerosis: the Missing Link Connecting Vasculopathy, Autoimmunity, and Fibrosis?Current rheumatology reports · 2019Review
- Ginkgolide B inhibits platelet and monocyte adhesion in TNFα-treated HUVECs under laminar shear stress.BMC complementary and alternative medicine · 2018Article
- Cyclic nucleotide-dependent inhibitory signaling interweaves with activating pathways to determine platelet responses.Research and practice in thrombosis and haemostasis · 2018Review
- Meeting report of the 8Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- The sGC stimulator riociguat inhibits platelet function in washed platelets but not in whole blood.British journal of pharmacology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeStimulation of soluble guanylyl cyclase (sGC) is a valuable therapeutic strategy for the treatment of several cardiovascular diseases. The sGC stimulator riociguat has been approved for the treatment of two forms of pulmonary hypertension. Platelets contain large amounts of sGC and play a key role in the regulation of haemostasis. Therefore, we investigated the effects of riociguat on platelet function. EXPERIMENTAL APPROACH: The effect of riociguat treatment on human platelet activation and aggregation was investigated. The sGC-specific effects of riociguat were determined by comparing wild-type and platelet-specific sGC-knockout mice. KEY
resultsRiociguat induced cGMP synthesis and subsequent PKG activation in human platelets, suggesting that the inhibitory effects are mediated by cGMP signalling. This finding was confirmed when sGC-knockout platelets were not inhibited by riociguat. In washed human platelets, 100 nM riociguat reduced ADP-induced GPIIb/IIIa activation, while a 10-fold higher concentration was required to reduce convulxin-stimulated GPIIb/IIIa activation. Riociguat inhibited ADP-induced platelet shape change and aggregation, while ATP-induced shape change remained unaffected. However, in PRP and whole blood, 50-100 μM riociguat was required to inhibit platelet activation and aggregation. Riociguat in combination with iloprost significantly inhibited platelet aggregation, even in whole blood. CONCLUSIONS AND IMPLICATIONS: Riociguat inhibits platelet activation in whole blood only at concentrations above 50 μM, while the plasma concentrations in riociguat-treated patients are 150 to 500 nM. This finding indicates that riociguat treatment does not affect platelet function in patients. Nevertheless, the possibility that riociguat acts synergistically with iloprost to inhibit platelet activation should be considered.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.