Comprehensive characterization of platelet function in dogs with hyperadrenocorticism
Hyperadrenocorticism (HAC) leads to a hypercoagulable state and contributes to the risk of thromboembolic disease. Hypercoagulation in HAC occurs in both humans and dogs. Platelets play a major role in thrombosis and hemostasis, but no study has investigated platelet function in dogs with HAC. Thus...
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| Format: | Article |
| Language: | English |
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Ferrata Storti Foundation
2025-02-01
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| Series: | Haematologica |
| Online Access: | https://haematologica.org/article/view/11932 |
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| author | Sanggu Kim Dohee Lee Preeti Kumari Chaudhary Hakhyun Kim Byeong-Teck Kang Soochong Kim |
| author_facet | Sanggu Kim Dohee Lee Preeti Kumari Chaudhary Hakhyun Kim Byeong-Teck Kang Soochong Kim |
| author_sort | Sanggu Kim |
| collection | DOAJ |
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Hyperadrenocorticism (HAC) leads to a hypercoagulable state and contributes to the risk of thromboembolic disease. Hypercoagulation in HAC occurs in both humans and dogs. Platelets play a major role in thrombosis and hemostasis, but no study has investigated platelet function in dogs with HAC. Thus, we aimed to characterize the platelet function and its molecular mechanism in dogs with HAC by using platelets isolated from normal dogs and dogs with HAC. This prospective crosssectional study included 7 dogs with HAC and 15 normal dogs. Various platelet functional responses including platelet aggregation and dense-granule secretion were evaluated. 2-MeSADP- and low concentration of thrombin-induced platelet aggregation and secretion were significantly inhibited in dogs with HAC compared to normal dogs. Furthermore, the pre-incubation of platelets with prednisolone inhibited 2-MeSADP- and thrombin-induced platelet aggregation and secretion only in normal dog platelets, whereas no additional inhibitory effect was shown in dogs with HAC confirming a role of excessive cortisol in platelet function. In addition, 2-MeSADP- and thrombininduced platelet aggregation and post-adrenocorticotropic hormone (ACTH) cortisol levels showed a negative correlation. Moreover, 2-MeSADP- and thrombin-induced thromboxane A2 (TxA2) generation was significantly inhibited in dogs with HAC compared to normal dogs, confirming the role of cortisol in TxA2 generation. Finally, thrombin-induced ERK and AKT phosphorylation were significantly inhibited in dogs with HAC. In conclusion, excessive cortisol in dogs with HAC affects platelet function by suppressing TxA2 generation through the regulation of ERK and AKT phosphorylation.
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| format | Article |
| id | doaj-art-8d4b58dd1c504b1e808401c7cb83714d |
| institution | Kabale University |
| issn | 0390-6078 1592-8721 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Ferrata Storti Foundation |
| record_format | Article |
| series | Haematologica |
| spelling | doaj-art-8d4b58dd1c504b1e808401c7cb83714d2025-02-06T19:45:05ZengFerrata Storti FoundationHaematologica0390-60781592-87212025-02-01999110.3324/haematol.2024.286496Comprehensive characterization of platelet function in dogs with hyperadrenocorticismSanggu Kim0Dohee Lee1Preeti Kumari Chaudhary2Hakhyun Kim3Byeong-Teck Kang4Soochong Kim5Laboratory of Veterinary Pathology and Platelet Signaling, College of Veterinary Medicine, Chungbuk National University, CheongjuLaboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, CheongjuLaboratory of Veterinary Pathology and Platelet Signaling, College of Veterinary Medicine, Chungbuk National University, CheongjuLaboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, CheongjuLaboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, CheongjuLaboratory of Veterinary Pathology and Platelet Signaling, College of Veterinary Medicine, Chungbuk National University, Cheongju Hyperadrenocorticism (HAC) leads to a hypercoagulable state and contributes to the risk of thromboembolic disease. Hypercoagulation in HAC occurs in both humans and dogs. Platelets play a major role in thrombosis and hemostasis, but no study has investigated platelet function in dogs with HAC. Thus, we aimed to characterize the platelet function and its molecular mechanism in dogs with HAC by using platelets isolated from normal dogs and dogs with HAC. This prospective crosssectional study included 7 dogs with HAC and 15 normal dogs. Various platelet functional responses including platelet aggregation and dense-granule secretion were evaluated. 2-MeSADP- and low concentration of thrombin-induced platelet aggregation and secretion were significantly inhibited in dogs with HAC compared to normal dogs. Furthermore, the pre-incubation of platelets with prednisolone inhibited 2-MeSADP- and thrombin-induced platelet aggregation and secretion only in normal dog platelets, whereas no additional inhibitory effect was shown in dogs with HAC confirming a role of excessive cortisol in platelet function. In addition, 2-MeSADP- and thrombininduced platelet aggregation and post-adrenocorticotropic hormone (ACTH) cortisol levels showed a negative correlation. Moreover, 2-MeSADP- and thrombin-induced thromboxane A2 (TxA2) generation was significantly inhibited in dogs with HAC compared to normal dogs, confirming the role of cortisol in TxA2 generation. Finally, thrombin-induced ERK and AKT phosphorylation were significantly inhibited in dogs with HAC. In conclusion, excessive cortisol in dogs with HAC affects platelet function by suppressing TxA2 generation through the regulation of ERK and AKT phosphorylation. https://haematologica.org/article/view/11932 |
| spellingShingle | Sanggu Kim Dohee Lee Preeti Kumari Chaudhary Hakhyun Kim Byeong-Teck Kang Soochong Kim Comprehensive characterization of platelet function in dogs with hyperadrenocorticism Haematologica |
| title | Comprehensive characterization of platelet function in dogs with hyperadrenocorticism |
| title_full | Comprehensive characterization of platelet function in dogs with hyperadrenocorticism |
| title_fullStr | Comprehensive characterization of platelet function in dogs with hyperadrenocorticism |
| title_full_unstemmed | Comprehensive characterization of platelet function in dogs with hyperadrenocorticism |
| title_short | Comprehensive characterization of platelet function in dogs with hyperadrenocorticism |
| title_sort | comprehensive characterization of platelet function in dogs with hyperadrenocorticism |
| url | https://haematologica.org/article/view/11932 |
| work_keys_str_mv | AT sanggukim comprehensivecharacterizationofplateletfunctionindogswithhyperadrenocorticism AT doheelee comprehensivecharacterizationofplateletfunctionindogswithhyperadrenocorticism AT preetikumarichaudhary comprehensivecharacterizationofplateletfunctionindogswithhyperadrenocorticism AT hakhyunkim comprehensivecharacterizationofplateletfunctionindogswithhyperadrenocorticism AT byeongteckkang comprehensivecharacterizationofplateletfunctionindogswithhyperadrenocorticism AT soochongkim comprehensivecharacterizationofplateletfunctionindogswithhyperadrenocorticism |