Abstract | BACKGROUND:
Guanosine is a natural product and an endogenous nucleoside that has shown to increase during myocardial ischemia. Platelets are critically involved in ischemic coronary events. It remains unknown, however, whether guanosine may affect platelet activation and function. We sought to investigate the potential antiplatelet and antithrombotic properties of guanosine and decipher the mechanisms behind. METHODS: RESULTS:
Guanosine markedly inhibited platelet activation/aggregation-challenged by ADP and, although to a lesser extent, also reduced platelet aggregation challenged by collagen, AA and TRAP-6. Guanosine significantly reduced thrombus formation both in vitro and in vivo without significantly affects bleeding. Guanosine antiplatelet effects were associated with the activation of the cAMP/PKA signaling pathway, and a reduction in thromboxane B2 levels and PLC and PKC phosphorylation. The platelet aggregation and binding affinity assays revealed that guanosine effects on platelets were mediated by adenosine. CONCLUSION:
Guanosine effectively reduces ADP-induced platelet aggregation and limits thrombotic risk. These antithrombotic properties are associated with the activation of the cAMP/PKA signaling pathway.
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Authors | Francisco Fuentes, Marcelo Alarcón, Lina Badimon, Manuel Fuentes, Karl-Norbert Klotz, Gemma Vilahur, Sonja Kachler, Teresa Padró, Iván Palomo, Eduardo Fuentes |
Journal | International journal of cardiology
(Int J Cardiol)
Vol. 248
Pg. 294-300
(Dec 01 2017)
ISSN: 1874-1754 [Electronic] Netherlands |
PMID | 28811090
(Publication Type: Journal Article)
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Copyright | Copyright © 2017. Published by Elsevier B.V. |
Chemical References |
- Fibrinolytic Agents
- Platelet Aggregation Inhibitors
- Guanosine
- Cyclic AMP
- Cyclic AMP-Dependent Protein Kinases
- Adenosine
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Topics |
- Adenosine
(pharmacology)
- Animals
- Cyclic AMP
(metabolism)
- Cyclic AMP-Dependent Protein Kinases
(metabolism)
- Dose-Response Relationship, Drug
- Fibrinolytic Agents
(pharmacology)
- Guanosine
(pharmacology)
- Humans
- Mice
- Mice, Inbred C57BL
- Platelet Aggregation
(drug effects, physiology)
- Platelet Aggregation Inhibitors
(pharmacology)
- Signal Transduction
(drug effects, physiology)
- Swine
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