Carbonic Anhydrase Inhibitors suppress platelet procoagulant responses and in vivo thrombosis: Carbonic Anhydrase Inhibitors as Antithrombotics
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-10-01
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| Series: | Platelets |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/09537104.2019.1709632 |
| _version_ | 1827816804172431360 |
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| author | Ejaife O. Agbani Xiaojuan Zhao Christopher M. Williams Riyaad Aungraheeta Ingeborg Hers Erik R. Swenson Alastair W. Poole |
| author_facet | Ejaife O. Agbani Xiaojuan Zhao Christopher M. Williams Riyaad Aungraheeta Ingeborg Hers Erik R. Swenson Alastair W. Poole |
| author_sort | Ejaife O. Agbani |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T00:25:51Z |
| format | Article |
| id | doaj.art-11445fa9127a4fe7970911cc098ae65b |
| institution | Directory Open Access Journal |
| issn | 0953-7104 1369-1635 |
| language | English |
| last_indexed | 2024-03-12T00:25:51Z |
| publishDate | 2020-10-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj.art-11445fa9127a4fe7970911cc098ae65b2023-09-15T10:32:03ZengTaylor & Francis GroupPlatelets0953-71041369-16352020-10-0131785385910.1080/09537104.2019.17096321709632Carbonic Anhydrase Inhibitors suppress platelet procoagulant responses and in vivo thrombosis: Carbonic Anhydrase Inhibitors as AntithromboticsEjaife O. Agbani0Xiaojuan Zhao1Christopher M. Williams2Riyaad Aungraheeta3Ingeborg Hers4Erik R. Swenson5Alastair W. Poole6University of BristolUniversity of BristolUniversity of BristolUniversity of BristolUniversity of BristolUniversity of WashingtonUniversity of BristolCarbonic 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.http://dx.doi.org/10.1080/09537104.2019.1709632acetazolamidecarbonic anhydrasemethazolamideplatelets procoagulant membrane dynamics |
| spellingShingle | Ejaife O. Agbani Xiaojuan Zhao Christopher M. Williams Riyaad Aungraheeta Ingeborg Hers Erik R. Swenson Alastair W. Poole Carbonic Anhydrase Inhibitors suppress platelet procoagulant responses and in vivo thrombosis: Carbonic Anhydrase Inhibitors as Antithrombotics Platelets acetazolamide carbonic anhydrase methazolamide platelets procoagulant membrane dynamics |
| title | Carbonic Anhydrase Inhibitors suppress platelet procoagulant responses and in vivo thrombosis: Carbonic Anhydrase Inhibitors as Antithrombotics |
| title_full | Carbonic Anhydrase Inhibitors suppress platelet procoagulant responses and in vivo thrombosis: Carbonic Anhydrase Inhibitors as Antithrombotics |
| title_fullStr | Carbonic Anhydrase Inhibitors suppress platelet procoagulant responses and in vivo thrombosis: Carbonic Anhydrase Inhibitors as Antithrombotics |
| title_full_unstemmed | Carbonic Anhydrase Inhibitors suppress platelet procoagulant responses and in vivo thrombosis: Carbonic Anhydrase Inhibitors as Antithrombotics |
| title_short | Carbonic Anhydrase Inhibitors suppress platelet procoagulant responses and in vivo thrombosis: Carbonic Anhydrase Inhibitors as Antithrombotics |
| title_sort | carbonic anhydrase inhibitors suppress platelet procoagulant responses and in vivo thrombosis carbonic anhydrase inhibitors as antithrombotics |
| topic | acetazolamide carbonic anhydrase methazolamide platelets procoagulant membrane dynamics |
| url | http://dx.doi.org/10.1080/09537104.2019.1709632 |
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