The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Potent inhibition of human platelets by cGMP analogs independent of cGMP-dependent protein kinase
Abstract
Platelets play a key role in hemostasis through their ability to rapidly adhere to activated or injured endothelium, subendothelial matrix proteins, and other activated platelets. A strong equilibrium between activating and inhibiting processes is essential for normal platelet and vascular function, impairment of this equilibrium being associated with either thrombophilic or bleeding disorders. Both cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) have been established as crucial and synergistic intracellular messengers that mediate the effects of platelet inhibitors such as nitric oxide (NO) and prostacyclin (PG-I2). However, it was recently suggested that a rapid cGMP/cGMP-dependent protein kinase (cGK)–mediated extracellular signal-related kinase (ERK) phosphorylation promotes platelet activation. This hypothesis was examined here by evaluating established and proposed cGK activators/inhibitors with respect to their capacity to promote either platelet activation or inhibition. In particular, the regulatory role of cGK for ERK phosphorylation and thrombin-, thromboxane-, and VWF-induced platelet activation was investigated. The data obtained do not support the concept that cGK-mediated ERK phosphorylation promotes platelet activation but confirm the inhibitory role of cGK in platelet function. One explanation for these discrepancies is the novel finding that extracellular cGMP analogs potently and rapidly inhibit thrombin-, thromboxane-, and VWF-induced human platelet signaling and activation by a cGK-independent mechanism.
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“NO is a potent inhibitor of PLT aggregation, acting via activation of soluble guanylyl cyclase in PLTs (64, 65).”
From Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia (2017) · cites this paper as [64]
Citations
Cites
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The specificities of protein kinase inhibitors: an update
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Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E
Huo, Y., Schober, A., Forlow, S. B., Smith, D. F., Hyman, M. C., Jung, S., Littman, D. R., Weber, C., & Ley, K. F. (2002) · Nature Medicine · doi:10.1038/nm810 · Cited by 1,026
A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion Formation
Maßberg, S., Brand, K., Grüner, S., Page, S., Müller, E., Müller, I. I., Bergmeier, W., Richter, T., Lorenz, M. C., Konrad, I., et al. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20012044 · Cited by 885
Platelet P-selectin facilitates atherosclerotic lesion development
Burger, P. C., & Wagner, D. D. (2003) · Blood · doi:10.1182/blood-2002-07-2209 · Cited by 420
Scientific and therapeutic advances in antiplatelet therapy
Bhatt, D. L., & Topol, E. J. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd985 · Cited by 409
Distinct and specific functions of cGMP-dependent protein kinases
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Self-citationRising behind NO: cGMP-dependent protein kinases
Hofmann, F. B., Ammendola, A., & Schlossmann, J. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.10.1671 · Cited by 340
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Items 101–107 of 107
NO/cGMP/PKG pathway in platelets: inhibitory but not stimulatory
Gambaryan, S. P., Lohmann, S. M., & Walter, U. (2007) · BMC Pharmacology · doi:10.1186/1471-2210-7-s1-s50
Self-citationBilodeau, M. L., & Hamm, H. E. (2007)
Khalil, J. S. (2018) · Repository@Hull (Worktribe) (University of Hull)
Lesyk, G. M. (2019) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3-pk4m-h082
Model of trigger mechanisms of SARS CoV-2 infections
Galarza, N. C., & Condori, M. D. L. Á. M. (2020) · International Journal of Research in Medical Sciences · doi:10.18203/2320-6012.ijrms20203478
cGMP signaling: probing antagonistic cyclic nucleotide platelet signals by modeling and experimentPreprint
Breitenbach, T., Englert, N., Osmanoğlu, Ö., Rukoyatkina, N., Wangorsch, G., Friebe, A., Butt, E., Feil, R., Dittrich, M. T., Gambaryan, S. P., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.01.429103
Self-citationEffects of exercise on cAMP-mediated platelet inhibition in young women: a pilot study
O’Donoghue, L., Crognale, D., Delahunt, E., & Smolenski, A. (2024) · European Journal of Applied Physiology · doi:10.1007/s00421-024-05673-2
“It should be noted that stirring conditions lead to VASP phosphorylation at S239 (Gambaryan et al. 2004), however, all samples in this study were exposed to identical stirring conditions for the same amount of time.”
Influential
Metadata
- Authors
- Gambaryan, S., Geiger, J., Schwarz, U. R., Butt, E., Begonja, A., Obergfell, A., & Walter, U.
- Affiliations
- University of Würzburg (DE)
- From the Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Germany.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2004-04-01
- Volume
- 103
- Issue
- 7
- Pages
- 2593-2600
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2095417890
- Cited by
- 107
- References
- 27
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 8 · 2017: 5 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 5
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- platelet activation, cGMP-dependent protein kinase, ERK1/2 phosphorylation, thrombin, thromboxane, von Willebrand factor, platelet aggregation inhibition, intracellular signaling, hemostasis, thrombosis
- MeSH terms
- Blood Platelets, Calcium, Cyclic GMP, Humans, Kinetics, Platelet Aggregation, Platelet Aggregation Inhibitors, von Willebrand Factor, 8-Bromo Cyclic Adenosine Monophosphate, Cyclic GMP-Dependent Protein Kinases, Nitric Oxide Donors, S-Nitroso-N-Acetylpenicillamine
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