Carbonic Anhydrase Inhibitors suppress platelet procoagulant responses and in vivo thrombosis
| Autor: | Christopher Williams, Xiaojuan Zhao, E.O. Agbani, Alastair W. Poole, Erik R. Swenson, Riyaad Aungraheeta, Ingeborg Hers |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
biology Chemistry Hematology General Medicine 030204 cardiovascular system & hematology Pharmacology In vitro 3. Good health 03 medical and health sciences 030104 developmental biology 0302 clinical medicine In vivo Carbonic anhydrase medicine biology.protein Platelet Platelet activation Acetazolamide Methazolamide Intracellular medicine.drug |
| Zdroj: | Platelets. 31:853-859 |
| ISSN: | 1369-1635 0953-7104 |
| DOI: | 10.1080/09537104.2019.1709632 |
| Popis: | Carbonic anhydrase (CA) inhibitors have a long history of safe clinical use as mild diuretics, in the treatment of glaucoma and for altitude sickness prevention. In this study, we aimed to determine if CA inhibition may be an alternative approach to control thrombosis. We utilized a high-resolution dynamic imaging approach to provide mechanistic evidence that CA inhibitors may be potent anti-procoagulant agents in vitro and effective anti-thrombotics in vivo. Acetazolamide and methazolamide, while sparing platelet secretion, attenuated intracellular chloride ion entry and suppressed the procoagulant response of activated platelets in vitro and thrombosis in vivo. The chemically similar N-methyl acetazolamide, which lacks CA inhibitory activity, did not affect platelet procoagulant response in vitro. Outputs from rotational thromboelastometry did not reflect changes in procoagulant activity and reveal the need for a suitable clinical test for procoagulant activity. Drugs specifically targeting procoagulant remodeling of activated platelets, by blockade of carbonic anhydrases, may provide a new way to control platelet-driven thrombosis without blocking essential platelet secretion responses. |
| Databáze: | OpenAIRE |
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