Perivascular mast cells promote neointimal elastin deposition and suppress chronic vein graft restenosis in hyperlipidaemic mice

Wu, J., Lawrence, C., Wadsworth, R. M. and Kennedy, S. (2017) Perivascular mast cells promote neointimal elastin deposition and suppress chronic vein graft restenosis in hyperlipidaemic mice. Vessel Plus, 2017(1), pp. 137-144. (doi: 10.20517/2574-1209.2017.15)

Abstract

Aim: Mast cells are versatile innate immune cells and are reported to promote vascular inflammation and neointimal lesion formation, thereby contributing to the development of vascular stenosis and atherosclerosis. However, it is not clear whether mast cells also regulate vascular matrix remodelling in established neointima. This study addressed the hypothesis that perivascular mast cells regulate neointimal matrix remodelling using a mouse vein graft model. Methods: The impact of mast cells on neointimal remodelling was investigated using mast cell-deficient animals in both normolipidaemic (KitW-sh/W-sh) and hyperlipidaemic (apoE-/-KitW-sh/W-sh) conditions. The effect of perivascular mast cells on vascular matrix remodelling, including collagen and elastin deposition, was investigated using a local mast cell reconstitution method that selectively repopulated mast cells around the carotid artery (where the vein graft was inserted) in KitW-sh/W-sh mice. Results: In normolipidaemic vein grafts (KitW-sh/W-sh vs. the wild type control C57BL/6J), collagen synthesis was not affected by mast cell deficiency at 4 weeks. In contrast, neointimal elastin was reduced by 6.5-fold in mast cell-deficient KitW-sh/W-sh mice, which was prevented by perivascular mast cell reconstitution. Mast cell deficiency induced a similar reduction in neointimal elastin in hyperlipidaemic mice (apoE-/-KitW-sh/W-sh vs. apoE-/-), with a significant increase in cell proliferation and neointimal area at 4 weeks. Conclusion: Mast cells appear to promote elastin deposition in vein grafts and this may lead to further suppression of cell proliferation and neointimal thickening under hyperlipidaemic conditions.

• Item Type: Articles
• Additional Information: This work was supported by a British Heart Foundation project grant (PG/09/095).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Lawrence, Dr Catherine and Kennedy, Professor Simon
• Authors: Wu, J., Lawrence, C., Wadsworth, R. M., and Kennedy, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: Vessel Plus
• Publisher: OAE Publishing Inc.
• ISSN: 2574-1209
• ISSN (Online): 2574-1209
• Published Online: 11 July 2017
• Copyright Holders: Copyright © 2017 OAE Publishing Inc.
• First Published: First published in Vessel Plus 2017(1): 137-144
• Publisher Policy: Reproduced under a Creative Commons license