Platelet pannexin-1 channels modulate neutrophil activation and migration but not the progression of abdominal aortic aneurysm
Abdominal aortic aneurysm (AAA) is a common disease and highly lethal if untreated. The progressive dilatation of the abdominal aorta is accompanied by degradation and remodeling of the vessel wall due to chronic inflammation. Pannexins represent anion-selective channels and play a crucial role in n...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1111108/full |
| _version_ | 1811159555107717120 |
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| author | Lisa Maria Metz Tobias Feige Larissa de Biasi Agnes Ehrenberg Joscha Mulorz Laura Mara Toska Friedrich Reusswig Christine Quast Norbert Gerdes Malte Kelm Hubert Schelzig Margitta Elvers |
| author_facet | Lisa Maria Metz Tobias Feige Larissa de Biasi Agnes Ehrenberg Joscha Mulorz Laura Mara Toska Friedrich Reusswig Christine Quast Norbert Gerdes Malte Kelm Hubert Schelzig Margitta Elvers |
| author_sort | Lisa Maria Metz |
| collection | DOAJ |
| description | Abdominal aortic aneurysm (AAA) is a common disease and highly lethal if untreated. The progressive dilatation of the abdominal aorta is accompanied by degradation and remodeling of the vessel wall due to chronic inflammation. Pannexins represent anion-selective channels and play a crucial role in non-vesicular ATP release to amplify paracrine signaling in cells. Thus, pannexins are involved in many (patho-) physiological processes. Recently, Panx1 channels were identified to be significantly involved in abdominal aortic aneurysm formation through endothelial derived Panx1 regulated inflammation and aortic remodeling. In platelets, Panx1 becomes activated following activation of glycoprotein (GP) VI. Since platelets play a role in cardiovascular diseases including abdominal aortic aneurysm, we analyzed the contribution of platelet Panx1 in the progression of abdominal aortic aneurysm. We detected enhanced Panx1 plasma levels in abdominal aortic aneurysm patients. In experimental abdominal aortic aneurysm using the pancreatic porcine elastase (PPE) mouse model, a major contribution of platelet Panx1 channels in platelet activation, pro-coagulant activity of platelets and platelet-mediated inflammation has been detected. In detail, platelets are important for the migration of neutrophils into the aortic wall induced by direct cell interaction and by activation of endothelial cells. Decreased platelet activation and inflammation did not affect ECM remodeling or wall thickness in platelet-specific Panx1 knock-out mice following PPE surgery. Thus, aortic diameter expansion at different time points after elastase infusion of the aortic wall was unaltered in platelet-specific Panx1 deficient mice suggesting that the modulation of inflammation alone does not affect abdominal aortic aneurysm formation and progression. In conclusion, our data strongly supports the role of platelets in inflammatory responses in abdominal aortic aneurysm via Panx1 channels and adds important knowledge about the significance of platelets in abdominal aortic aneurysm pathology important for the establishment of an anti-platelet therapy for abdominal aortic aneurysm patients. |
| first_indexed | 2024-04-10T05:43:11Z |
| format | Article |
| id | doaj.art-715ce80f15904c5caf775f925230aee4 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-10T05:43:11Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-715ce80f15904c5caf775f925230aee42023-03-06T05:43:16ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-03-011010.3389/fmolb.2023.11111081111108Platelet pannexin-1 channels modulate neutrophil activation and migration but not the progression of abdominal aortic aneurysmLisa Maria Metz0Tobias Feige1Larissa de Biasi2Agnes Ehrenberg3Joscha Mulorz4Laura Mara Toska5Friedrich Reusswig6Christine Quast7Norbert Gerdes8Malte Kelm9Hubert Schelzig10Margitta Elvers11Department of Vascular- and Endovascular Surgery, University Hospital Duesseldorf, Heinrich-Heine University, Duesseldorf, GermanyDepartment of Vascular- and Endovascular Surgery, University Hospital Duesseldorf, Heinrich-Heine University, Duesseldorf, GermanyDepartment of Vascular- and Endovascular Surgery, University Hospital Duesseldorf, Heinrich-Heine University, Duesseldorf, GermanyDepartment of Vascular- and Endovascular Surgery, University Hospital Duesseldorf, Heinrich-Heine University, Duesseldorf, GermanyDepartment of Vascular- and Endovascular Surgery, University Hospital Duesseldorf, Heinrich-Heine University, Duesseldorf, GermanyDepartment of Vascular- and Endovascular Surgery, University Hospital Duesseldorf, Heinrich-Heine University, Duesseldorf, GermanyDepartment of Vascular- and Endovascular Surgery, University Hospital Duesseldorf, Heinrich-Heine University, Duesseldorf, GermanyDepartment of Cardiology, Pulmonology and Vascular Medicine, University Hospital Duesseldorf, Heinrich-Heine University, Duesseldorf, GermanyDepartment of Cardiology, Pulmonology and Vascular Medicine, University Hospital Duesseldorf, Heinrich-Heine University, Duesseldorf, GermanyDepartment of Cardiology, Pulmonology and Vascular Medicine, University Hospital Duesseldorf, Heinrich-Heine University, Duesseldorf, GermanyDepartment of Vascular- and Endovascular Surgery, University Hospital Duesseldorf, Heinrich-Heine University, Duesseldorf, GermanyDepartment of Vascular- and Endovascular Surgery, University Hospital Duesseldorf, Heinrich-Heine University, Duesseldorf, GermanyAbdominal aortic aneurysm (AAA) is a common disease and highly lethal if untreated. The progressive dilatation of the abdominal aorta is accompanied by degradation and remodeling of the vessel wall due to chronic inflammation. Pannexins represent anion-selective channels and play a crucial role in non-vesicular ATP release to amplify paracrine signaling in cells. Thus, pannexins are involved in many (patho-) physiological processes. Recently, Panx1 channels were identified to be significantly involved in abdominal aortic aneurysm formation through endothelial derived Panx1 regulated inflammation and aortic remodeling. In platelets, Panx1 becomes activated following activation of glycoprotein (GP) VI. Since platelets play a role in cardiovascular diseases including abdominal aortic aneurysm, we analyzed the contribution of platelet Panx1 in the progression of abdominal aortic aneurysm. We detected enhanced Panx1 plasma levels in abdominal aortic aneurysm patients. In experimental abdominal aortic aneurysm using the pancreatic porcine elastase (PPE) mouse model, a major contribution of platelet Panx1 channels in platelet activation, pro-coagulant activity of platelets and platelet-mediated inflammation has been detected. In detail, platelets are important for the migration of neutrophils into the aortic wall induced by direct cell interaction and by activation of endothelial cells. Decreased platelet activation and inflammation did not affect ECM remodeling or wall thickness in platelet-specific Panx1 knock-out mice following PPE surgery. Thus, aortic diameter expansion at different time points after elastase infusion of the aortic wall was unaltered in platelet-specific Panx1 deficient mice suggesting that the modulation of inflammation alone does not affect abdominal aortic aneurysm formation and progression. In conclusion, our data strongly supports the role of platelets in inflammatory responses in abdominal aortic aneurysm via Panx1 channels and adds important knowledge about the significance of platelets in abdominal aortic aneurysm pathology important for the establishment of an anti-platelet therapy for abdominal aortic aneurysm patients.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1111108/fullplateletspannexin-1abdominal aortic aneurysminflammationECM remodelingselectin |
| spellingShingle | Lisa Maria Metz Tobias Feige Larissa de Biasi Agnes Ehrenberg Joscha Mulorz Laura Mara Toska Friedrich Reusswig Christine Quast Norbert Gerdes Malte Kelm Hubert Schelzig Margitta Elvers Platelet pannexin-1 channels modulate neutrophil activation and migration but not the progression of abdominal aortic aneurysm Frontiers in Molecular Biosciences platelets pannexin-1 abdominal aortic aneurysm inflammation ECM remodeling selectin |
| title | Platelet pannexin-1 channels modulate neutrophil activation and migration but not the progression of abdominal aortic aneurysm |
| title_full | Platelet pannexin-1 channels modulate neutrophil activation and migration but not the progression of abdominal aortic aneurysm |
| title_fullStr | Platelet pannexin-1 channels modulate neutrophil activation and migration but not the progression of abdominal aortic aneurysm |
| title_full_unstemmed | Platelet pannexin-1 channels modulate neutrophil activation and migration but not the progression of abdominal aortic aneurysm |
| title_short | Platelet pannexin-1 channels modulate neutrophil activation and migration but not the progression of abdominal aortic aneurysm |
| title_sort | platelet pannexin 1 channels modulate neutrophil activation and migration but not the progression of abdominal aortic aneurysm |
| topic | platelets pannexin-1 abdominal aortic aneurysm inflammation ECM remodeling selectin |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1111108/full |
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