| First Author | Harper RL | Year | 2023 |
| Journal | FASEB J | Volume | 37 |
| Issue | 7 | Pages | e23029 |
| PubMed ID | 37310585 | Mgi Jnum | J:341974 |
| Mgi Id | MGI:7541631 | Doi | 10.1096/fj.202201745RR |
| Citation | Harper RL, et al. (2023) Mast cell activation and degranulation in acute artery injury: A target for post-operative therapy. FASEB J 37(7):e23029 |
| abstractText | 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 Kit(W-sh/W-sh) mice. Furthermore, neutrophils, macrophages, and T cells were abundant in the wild-type mice area of injury but reduced in the Kit(W-sh/W-sh) mice. Following bone-marrow-derived MC (BMMC) transplantation into Kit(W-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. |
