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Updated: Jul 26, 2025
Isolation of Peritoneum-derived Mast Cells and Their Functional Characterization with Ca2+-imaging and Degranulation Assays
Published on: July 4, 2018
Mast cell activation and degranulation in acute artery injury: A target for post-operative therapy
Rebecca L Harper1, Fang Fang1, Hong San1
1Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Insights
Mast cells rapidly respond to arterial injury, causing inflammation and neointimal hyperplasia. Targeting mast cells with disodium cromoglycate may prevent restenosis after procedures like PCI.
Area of Science:
- Cardiovascular Research
- Immunology
- Vascular Biology
Background:
- Cardiovascular disease (CVD) necessitates surgical interventions like coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI).
- Endothelial damage following these procedures leads to restenosis, contributing significantly to mortality and morbidity.
- Mast cells (MC) are implicated in vascular diseases, but their acute role in arterial injury response is not fully understood.
Purpose of the Study:
- To investigate the role of mast cells (MC) in the acute response to arterial wire injury, mimicking percutaneous coronary interventions (PCI).
- To assess the impact of MC on neointimal hyperplasia and associated inflammatory cell infiltration.
- To evaluate the therapeutic potential of targeting MC degranulation for preventing post-injury restenosis.
Main Methods:
- Utilized wild-type and mast cell-deficient (KitW-sh/W-sh) mice subjected to femoral artery wire injury.
- Analyzed mast cell accumulation, activation, and degranulation post-injury.
- Quantified neointimal hyperplasia and inflammatory cell (neutrophils, macrophages, T cells) presence.
- Investigated the effect of bone-marrow-derived mast cell (BMMC) transplantation.
- Administered disodium cromoglycate (DSCG), a mast cell stabilizer, post-injury.
Main Results:
- Mast cells rapidly accumulated, activated, and degranulated in the femoral artery of wild-type mice following wire injury.
- Significant neointimal hyperplasia was observed in wild-type mice but not in mast cell-deficient mice.
- Neutrophils, macrophages, and T cells were abundant at the injury site in wild-type mice, with reduced presence in deficient mice.
- BMMC transplantation into deficient mice restored neointimal hyperplasia and inflammatory cell infiltration.
- Administration of disodium cromoglycate (DSCG) significantly reduced neointimal hyperplasia in wild-type mice.
Conclusions:
- Mast cells play a critical role in the inflammatory response and neointimal hyperplasia following acute arterial injury.
- MC degranulation is a key driver of the detrimental cellular response post-endothelial injury.
- Targeting mast cell degranulation with drugs like disodium cromoglycate (DSCG) immediately post-surgery offers a potential strategy to prevent restenosis in revascularization procedures.
Abstract:
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.
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