ArticlePloS one2012
Activation of haem-oxidized soluble guanylyl cyclase with BAY 60-2770 in human platelets lead to overstimulation of the cyclic GMP signaling pathway.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Inhaled nitric oxide to control platelet hyper-reactivity in patients with acute submassive pulmonary embolism.Nitric oxide : biology and chemistry · 2020Trial
- Bisphenols-enhanced platelet aggregation via TP, P2YFrontiers in pharmacology · 2026Article
- The NO/cGMP/PKG pathway in platelets: The therapeutic potential of PDE5 inhibitors in platelet disorders.Journal of thrombosis and haemostasis : JTH · 2022Review
- Inactivation of soluble guanylyl cyclase in living cells proceeds without loss of haem and involves heterodimer dissociation as a common step.British journal of pharmacology · 2022Article
- Calcium Regulation on the Atrial Regional Difference of Collagen Production Activity in Atrial Fibrogenesis.Biomedicines · 2021Article
- NOX5-induced uncoupling of endothelial NO synthase is a causal mechanism and theragnostic target of an age-related hypertension endotype.PLoS biology · 2020Article
- Activation of PKG and Akt Is Required for Cardioprotection by Ramelteon-Induced Preconditioning and Is Located Upstream of mKCa-Channels.International journal of molecular sciences · 2020Article
- Nitroxyl: A Novel Strategy to Circumvent Diabetes Associated Impairments in Nitric Oxide Signaling.Frontiers in pharmacology · 2020Review
- Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their RegulationPhysiological reviews · 2019Review
- Comparative Studies of the Dynamics Effects of BAY60-2770 and BAY58-2667 Binding with Human and Bacterial H-NOX Domains.Molecules (Basel, Switzerland) · 2018Article
- Effect of Polyphenols FromFrontiers in pharmacology · 2018Article
- Stimulators and activators of soluble guanylate cyclase for urogenital disorders.Nature reviews. Urology · 2018Review
- Cardioprotective effects of PKG activation by soluble GC activator, BAY 60-2770, in ischemia-reperfusion-injured rat hearts.PloS one · 2017Article
- Dynamics of Calcium duringFrontiers in plant science · 2017Article
- Soluble guanylyl cyclase-activated cyclic GMP-dependent protein kinase inhibits arterial smooth muscle cell migration independent of VASP-serine 239 phosphorylation.Cellular signalling · 2016Article
- Soluble guanylate cyclase as an alternative target for bronchodilator therapy in asthma.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The soluble guanylyl cyclase activator BAY 60-2770 potently relaxes the pulmonary artery on congenital diaphragmatic hernia rabbit model.Pediatric surgery international · 2014Article
- Regulation of soluble guanylate cyclase by matricellular thrombospondins: implications for blood flow.Frontiers in physiology · 2014Review
- Article
- Direct sGC activation bypasses NO scavenging reactions of intravascular free oxy-hemoglobin and limits vasoconstriction.Antioxidants & redox signaling · 2013Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsNitric oxide-independent soluble guanylyl cyclase (sGC) activators reactivate the haem-oxidized enzyme in vascular diseases. This study was undertaken to investigate the anti-platelet mechanisms of the haem-independent sGC activator BAY 60-2770 in human washed platelets. The hypothesis that sGC oxidation potentiates the anti-platelet activities of BAY 60-2770 has been tested.
methodsHuman washed platelet aggregation and adhesion assays, as well as flow cytometry for α(IIb)β(3) integrin activation and Western blot for α1 and β1 sGC subunits were performed. Intracellular calcium levels were monitored in platelets loaded with a fluorogenic calcium-binding dye (FluoForte).
resultsBAY 60-2770 (0.001-10 µM) produced significant inhibition of collagen (2 µg/ml)- and thrombin (0.1 U/ml)-induced platelet aggregation that was markedly potentiated by the sGC inhibitor ODQ (10 µM). In fibrinogen-coated plates, BAY 60-2770 significantly inhibited platelet adhesion, an effect potentiated by ODQ. BAY 60-2770 increased the cGMP levels and reduced the intracellular Ca(2+) levels, both of which were potentiated by ODQ. The cell-permeable cGMP analogue 8-Br-cGMP (100 µM) inhibited platelet aggregation and Ca(2+) levels in an ODQ-insensitive manner. The cAMP levels remained unchanged by BAY 60-2770. Collagen- and thrombin-induced α(IIb)β(3) activation was markedly inhibited by BAY 60-2770 that was further inhibited by ODQ. The effects of sodium nitroprusside (3 µM) were all prevented by ODQ. Incubation with ODQ (10 µM) significantly reduced the protein levels of α1 and β1 sGC subunits, which were prevented by BAY 60-2770.
conclusionThe inhibitory effects of BAY 60-2770 on aggregation, adhesion, intracellular Ca(2+) levels and α(IIb)β(3) activation are all potentiated in haem-oxidizing conditions. BAY 60-2770 prevents ODQ-induced decrease in sGC protein levels. BAY 60-2770 could be of therapeutic interest in cardiovascular diseases associated with thrombotic complications.
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