Perivascular mast cells regulate vein graft neointimal formation and remodeling

Junxi Wu, Gianluca Grassia, Helen Cambrook, Armando Ialenti, Neil MacRitchie, Jaclyn Carberry, Roger M. Wadsworth, Catherine Lawrence, Simon Kennedy, Pasquale Maffia

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 Kit(W-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 Kit(W-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.

LanguageEnglish
Article numbere1192
Number of pages14
JournalPeerJ
Volume3
DOIs
Publication statusPublished - 18 Aug 2015

Fingerprint

mast cells
Mast Cells
Grafts
Veins
Transplants
L-Selectin
Macrophage Colony-Stimulating Factor
lesions (animal)
mice
Bone
Cells
Neointima
carotid arteries
Carotid Arteries
hyperplasia
blood vessels
bone marrow
neck
Hyperplasia
Blood Vessels

Keywords

  • vein graft
  • mast cells
  • neointima
  • cardiology

Cite this

Wu, J., Grassia, G., Cambrook, H., Ialenti, A., MacRitchie, N., Carberry, J., ... Maffia, P. (2015). Perivascular mast cells regulate vein graft neointimal formation and remodeling. PeerJ, 3, [e1192]. https://doi.org/10.7717/peerj.1192
Wu, Junxi ; Grassia, Gianluca ; Cambrook, Helen ; Ialenti, Armando ; MacRitchie, Neil ; Carberry, Jaclyn ; Wadsworth, Roger M. ; Lawrence, Catherine ; Kennedy, Simon ; Maffia, Pasquale. / Perivascular mast cells regulate vein graft neointimal formation and remodeling. In: PeerJ. 2015 ; Vol. 3.
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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 Kit(W-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 Kit(W-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.",
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Wu, J, Grassia, G, Cambrook, H, Ialenti, A, MacRitchie, N, Carberry, J, Wadsworth, RM, Lawrence, C, Kennedy, S & Maffia, P 2015, 'Perivascular mast cells regulate vein graft neointimal formation and remodeling' PeerJ, vol. 3, e1192. https://doi.org/10.7717/peerj.1192

Perivascular mast cells regulate vein graft neointimal formation and remodeling. / Wu, Junxi; Grassia, Gianluca; Cambrook, Helen; Ialenti, Armando; MacRitchie, Neil; Carberry, Jaclyn; Wadsworth, Roger M.; Lawrence, Catherine; Kennedy, Simon; Maffia, Pasquale.

In: PeerJ, Vol. 3, e1192, 18.08.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Perivascular mast cells regulate vein graft neointimal formation and remodeling

AU - Wu, Junxi

AU - Grassia, Gianluca

AU - Cambrook, Helen

AU - Ialenti, Armando

AU - MacRitchie, Neil

AU - Carberry, Jaclyn

AU - Wadsworth, Roger M.

AU - Lawrence, Catherine

AU - Kennedy, Simon

AU - Maffia, Pasquale

PY - 2015/8/18

Y1 - 2015/8/18

N2 - 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 Kit(W-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 Kit(W-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.

AB - 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 Kit(W-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 Kit(W-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.

KW - vein graft

KW - mast cells

KW - neointima

KW - cardiology

U2 - 10.7717/peerj.1192

DO - 10.7717/peerj.1192

M3 - Article

VL - 3

JO - PeerJ

T2 - PeerJ

JF - PeerJ

SN - 2167-8359

M1 - e1192

ER -

Wu J, Grassia G, Cambrook H, Ialenti A, MacRitchie N, Carberry J et al. Perivascular mast cells regulate vein graft neointimal formation and remodeling. PeerJ. 2015 Aug 18;3. e1192. https://doi.org/10.7717/peerj.1192