Mast cell activation and degranulation in acute artery injury : A target for post-operative therapy
Published 2023. This article is a U.S. Government work and is in the public domain in the USA..
The increasing incidence of cardiovascular disease (CVD) has led to a significant ongoing need to address this surgically through coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI). From this, there continues to be a substantial burden of mortality and morbidity due to complications arising from endothelial damage, resulting in restenosis. Whilst mast cells (MC) have been shown to have a causative role in atherosclerosis and other vascular diseases, including restenosis due to vein engraftment; here, we demonstrate their rapid response to arterial wire injury, recapitulating the endothelial damage seen in PCI procedures. Using wild-type mice, we demonstrate accumulation of MC in the femoral artery post-acute wire injury, with rapid activation and degranulation, resulting in neointimal hyperplasia, which was not observed in MC-deficient KitW-sh/W-sh mice. Furthermore, neutrophils, macrophages, and T cells were abundant in the wild-type mice area of injury but reduced in the KitW-sh/W-sh mice. Following bone-marrow-derived MC (BMMC) transplantation into KitW-sh/W-sh mice, not only was the neointimal hyperplasia induced, but the neutrophil, macrophage, and T-cell populations were also present in these transplanted mice. To demonstrate the utility of MC as a target for therapy, we administered the MC stabilizing drug, disodium cromoglycate (DSCG) immediately following arterial injury and were able to show a reduction in neointimal hyperplasia in wild-type mice. These studies suggest a critical role for MC in inducing the conditions and coordinating the detrimental inflammatory response seen post-endothelial injury in arteries undergoing revascularization procedures, and by targeting the rapid MC degranulation immediately post-surgery with DSCG, this restenosis may become a preventable clinical complication.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:37 |
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| Enthalten in: |
FASEB journal : official publication of the Federation of American Societies for Experimental Biology - 37(2023), 7 vom: 13. Juli, Seite e23029 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Harper, Rebecca L [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.06.2023 Date Revised 07.07.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1096/fj.202201745RR |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM358122643 |
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| 100 | 1 | |a Harper, Rebecca L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mast cell activation and degranulation in acute artery injury |b A target for post-operative therapy |
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| 500 | |a Date Completed 15.06.2023 | ||
| 500 | |a Date Revised 07.07.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Published 2023. This article is a U.S. Government work and is in the public domain in the USA. | ||
| 520 | |a The increasing incidence of cardiovascular disease (CVD) has led to a significant ongoing need to address this surgically through coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI). From this, there continues to be a substantial burden of mortality and morbidity due to complications arising from endothelial damage, resulting in restenosis. Whilst mast cells (MC) have been shown to have a causative role in atherosclerosis and other vascular diseases, including restenosis due to vein engraftment; here, we demonstrate their rapid response to arterial wire injury, recapitulating the endothelial damage seen in PCI procedures. Using wild-type mice, we demonstrate accumulation of MC in the femoral artery post-acute wire injury, with rapid activation and degranulation, resulting in neointimal hyperplasia, which was not observed in MC-deficient KitW-sh/W-sh mice. Furthermore, neutrophils, macrophages, and T cells were abundant in the wild-type mice area of injury but reduced in the KitW-sh/W-sh mice. Following bone-marrow-derived MC (BMMC) transplantation into KitW-sh/W-sh mice, not only was the neointimal hyperplasia induced, but the neutrophil, macrophage, and T-cell populations were also present in these transplanted mice. To demonstrate the utility of MC as a target for therapy, we administered the MC stabilizing drug, disodium cromoglycate (DSCG) immediately following arterial injury and were able to show a reduction in neointimal hyperplasia in wild-type mice. These studies suggest a critical role for MC in inducing the conditions and coordinating the detrimental inflammatory response seen post-endothelial injury in arteries undergoing revascularization procedures, and by targeting the rapid MC degranulation immediately post-surgery with DSCG, this restenosis may become a preventable clinical complication | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a acute arterial injury | |
| 650 | 4 | |a blood vessel | |
| 650 | 4 | |a cardiovascular disease | |
| 650 | 4 | |a coronary arterial disease | |
| 650 | 4 | |a mast cell | |
| 650 | 4 | |a neointima hyperplasia | |
| 650 | 4 | |a percutaneous coronary intervention | |
| 650 | 4 | |a restenosis | |
| 650 | 4 | |a revascularization | |
| 700 | 1 | |a Fang, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a San, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Negro, Alejandra |e verfasserin |4 aut | |
| 700 | 1 | |a St Hilaire, Cynthia |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Guibin |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Dmitrieva, Natalia I |e verfasserin |4 aut | |
| 700 | 1 | |a Lanzer, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Davaine, Jean-Michel |e verfasserin |4 aut | |
| 700 | 1 | |a Schwartzbeck, Robin |e verfasserin |4 aut | |
| 700 | 1 | |a Walts, Avram D |e verfasserin |4 aut | |
| 700 | 1 | |a Kovacic, Jason C |e verfasserin |4 aut | |
| 700 | 1 | |a Boehm, Manfred |e verfasserin |4 aut | |
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