Perivascular mast cells regulate vein graft neointimal formation and remodeling

Wu, J., Grassia, G., Cambrook, H., Ialenti, A., MacRitchie, N., Carberry, J., Wadsworth, R. M., Lawrence, C., Kennedy, S. and Maffia, P. (2015) Perivascular mast cells regulate vein graft neointimal formation and remodeling. PeerJ, 3, e1192. (doi:10.7717/peerj.1192) (PMID:26312183) (PMCID:PMC4548472)

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Abstract

Objective. Emerging evidence suggests an important role for mast cells in vein graft failure. This study addressed the hypothesis that perivascular mast cells regulate in situ vascular inflammatory and proliferative responses and subsequent vein graft neointimal lesion formation, using an optimized local mast cell reconstitution method. Methods and Results. Neointimal hyperplasia was induced by insertion of a vein graft into the right carotid artery in wild type and mast cell deficient KitW−sh/W−sh mice. In some experiments, mast cells were reconstituted systemically (tail vein injection of bone marrow-derived mast cells) or locally (directly into the right neck area) prior to vein grafting. Vein graft neointimal lesion formation was significantly (P < 0.05) reduced in KitW−sh/W−sh mice. Mast cell deficiency reduced the number of proliferating cells, and inhibited L-selectin, CCL2, M-CSF and MIP-3α expression in the vein grafts. Local but not systemic mast cell reconstitution restored a perivascular mast cell population that subsequently promoted neointimal formation in mast cell deficient mice. Conclusion. Our data demonstrate that perivascular mast cells play a key role in promoting neointima formation by inducing local acute inflammatory and proliferative responses. These results suggest that ex vivo intraoperative targeting of mast cells may have therapeutic potential for the prevention of pathological vein graft remodeling.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maffia, Dr Pasquale and Lawrence, Dr Catherine and Cambrook, Dr Helen and Grassia, Dr Gianluca and Kennedy, Dr Simon and MacRitchie, Dr Neil
Authors: Wu, J., Grassia, G., Cambrook, H., Ialenti, A., MacRitchie, N., Carberry, J., Wadsworth, R. M., Lawrence, C., Kennedy, S., and Maffia, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PeerJ
Publisher:PeerJ
ISSN:2167-8359
ISSN (Online):2167-8359
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in PeerJ 3:e1192
Publisher Policy:Reproduced under a Creative Commons License

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