Kallikrein inhibitor derived from immunoglobulin heavy chain junction region possesses anti-thromboinflammation potential.
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| Autores principales: | , , , , , , , , , |
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| Formato: | Artículo científico |
| Lenguaje: | en |
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Pharmacological research
2024
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| _version_ | 1868266292641792001 |
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| author | Yang, Juan Li, Ziyu Deng, Xinyi Li, Mengru Li, Bin Thuku, Rebecca Caroline Chen, Qian Sun, Xiang Lu, Qiumin Fang, Mingqian |
| author_facet | Yang, Juan Li, Ziyu Deng, Xinyi Li, Mengru Li, Bin Thuku, Rebecca Caroline Chen, Qian Sun, Xiang Lu, Qiumin Fang, Mingqian Yang, Juan Li, Ziyu Deng, Xinyi Li, Mengru Li, Bin Thuku, Rebecca Caroline Chen, Qian Sun, Xiang Lu, Qiumin Fang, Mingqian |
| collection | PubMed - marine biology |
| contents | Kallikrein inhibitor derived from immunoglobulin heavy chain junction region possesses anti-thromboinflammation potential. Yang, Juan Li, Ziyu Deng, Xinyi Li, Mengru Li, Bin Thuku, Rebecca Caroline Chen, Qian Sun, Xiang Lu, Qiumin Fang, Mingqian Animals Male Mice Anti-Inflammatory Agents Mice, Inbred C57BL Humans Thrombosis Inflammation Plasma Kallikrein Infarction, Middle Cerebral Artery Influenza vaccination is associated with a reduced incidence of cardiovascular events, cardiovascular death, and all-cause mortality. However, the functional role of the associated immunoglobulin remains unclear. This study identified a specific influenza-related immunoglobulin heavy chain junction region sequence (Ser-Leu-Gly-Ala-Ser-Asp, SD6) that inhibited plasma kallikrein (PKa) activity to resist thromboinflammatory responses and stroke injury. PKa is considered an attractive therapeutic target for alleviating the complications of thrombophilia-induced inflammation. In vitro, SD6 prolonged plasma recalcification and activated partial thromboplastin time, with no effects on bleeding risk-related prothrombin time, indicating selective inhibition of the intrinsic coagulation pathway. Correspondingly, at doses ranging from 0.25 to 4 mg/kg, SD6 attenuated arterial and cortical venous thrombosis in FeCl-induced and photochemically induced mice, without impacting hemorrhage risk, and further mitigated cerebral inflammatory injury in a mouse model of transient middle cerebral artery occlusion ischemic stroke. These findings suggest that SD6 may serve as a potential therapeutic agent for the treatment of thromboinflammatory conditions. |
| format | Artículo científico |
| id | pubmed_39393436 |
| institution | PubMed |
| language | en |
| publishDate | 2024 |
| publisher | Pharmacological research |
| record_format | pubmed |
| spellingShingle | Kallikrein inhibitor derived from immunoglobulin heavy chain junction region possesses anti-thromboinflammation potential. Yang, Juan Li, Ziyu Deng, Xinyi Li, Mengru Li, Bin Thuku, Rebecca Caroline Chen, Qian Sun, Xiang Lu, Qiumin Fang, Mingqian Animals Male Mice Anti-Inflammatory Agents Mice, Inbred C57BL Humans Thrombosis Inflammation Plasma Kallikrein Infarction, Middle Cerebral Artery Kallikrein inhibitor derived from immunoglobulin heavy chain junction region possesses anti-thromboinflammation potential. Yang, Juan Li, Ziyu Deng, Xinyi Li, Mengru Li, Bin Thuku, Rebecca Caroline Chen, Qian Sun, Xiang Lu, Qiumin Fang, Mingqian Animals Male Mice Anti-Inflammatory Agents Mice, Inbred C57BL Humans Thrombosis Inflammation Plasma Kallikrein Infarction, Middle Cerebral Artery Influenza vaccination is associated with a reduced incidence of cardiovascular events, cardiovascular death, and all-cause mortality. However, the functional role of the associated immunoglobulin remains unclear. This study identified a specific influenza-related immunoglobulin heavy chain junction region sequence (Ser-Leu-Gly-Ala-Ser-Asp, SD6) that inhibited plasma kallikrein (PKa) activity to resist thromboinflammatory responses and stroke injury. PKa is considered an attractive therapeutic target for alleviating the complications of thrombophilia-induced inflammation. In vitro, SD6 prolonged plasma recalcification and activated partial thromboplastin time, with no effects on bleeding risk-related prothrombin time, indicating selective inhibition of the intrinsic coagulation pathway. Correspondingly, at doses ranging from 0.25 to 4 mg/kg, SD6 attenuated arterial and cortical venous thrombosis in FeCl-induced and photochemically induced mice, without impacting hemorrhage risk, and further mitigated cerebral inflammatory injury in a mouse model of transient middle cerebral artery occlusion ischemic stroke. These findings suggest that SD6 may serve as a potential therapeutic agent for the treatment of thromboinflammatory conditions. |
| title | Kallikrein inhibitor derived from immunoglobulin heavy chain junction region possesses anti-thromboinflammation potential. |
| topic | Animals Male Mice Anti-Inflammatory Agents Mice, Inbred C57BL Humans Thrombosis Inflammation Plasma Kallikrein Infarction, Middle Cerebral Artery |
| url | https://pubmed.ncbi.nlm.nih.gov/39393436/ |