Mast cell activation and degranulation in acute artery injury: A target for post-operative therapy

Rebecca L. Harper, Fang Fang, Hong San, Alejandra Negro, Cynthia St. Hilaire, Dan Yang, Guibin Chen, Zhen Yu, Natalia I. Dmitrieva, Jan Lanzer, Jean Michel Davaine, Robin Schwartzbeck, Avram D. Walts, Jason C. Kovacic, Manfred Boehm

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Article numbere23029
JournalFASEB Journal
Volume37
Issue number7
DOIs
StatePublished - Jul 2023

Keywords

  • acute arterial injury
  • blood vessel
  • cardiovascular disease
  • coronary arterial disease
  • mast cell
  • neointima hyperplasia
  • percutaneous coronary intervention
  • restenosis
  • revascularization

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