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Wu et al. Mast cells and vein graft remodelling

over 10-fold and the majority of the neointimal cells mechanisms, but mediated by heparin (as discussed
transdifferentiate into smooth muscle-like cells that above) or some unknown mechanisms.
initiate vascular matrix remodelling including elastin
deposition. [13,14,18,31] Therefore, elastin is unlikely to The mast cell-elastin-axis could potentially be
regulate the early events of neointima formation in the extrapolated to vascular development as the first
normolipidaemic vein graft. The modest reduction in appearance of mast cells around the foetal aorta
neointimal area in the Kit W-sh/W-sh vein graft is attributed is before the formation of aortic elastic laminae.
[34]
to the damped cell proliferation during the first week This suggests that mast cells may also contribute
rather than altered elastin deposition. [14] to the foetal arteriogenesis by assisting formation
of elastic fibres. In addition to the perivascular area,
Both our data and the literature demonstrated the mast cell population is clearly enriched in all the
[32]
that apoE mice, when fed on normal chow diet, do elastic tissue/organs including arteries, skin and lung,
-/-
not demonstrate any enhancement of neointimal indicating a universal link between mast cells and
hyperplasia. The low cell proliferation level in apoE elastin. Under pathological conditions, an increase
-/-
vein grafts at 4 weeks in the current study suggests of mast cell number is often associated with elastin-
that the neointima was stabilised, similar to that in related tissue fibrosis. [35,36] In a skin photodamage
C57BL/6J. These observations are in contrast with model, chronic ultraviolet light exposure increases
in vitro evidence that apoE smooth muscle cells skin mast cell number accompanied by a 3.6 fold
-/-
are predisposed to a higher rate of proliferation. elevation in elastin content, which was not observed
[17]
One clear difference between data from cell cultures in the mast cell-deficient Kit W/W-v mice. Similar
[37]
and neointima formation in vivo is the absence of correlation was also present in human skin. Non-
[38]
the rich extracellular matrix environment. ApoE vein elastic organs, such as the liver usually hosts only a
-/-
grafts at 4 weeks contained large amounts of elastin very small population of mast cells. In liver disease,
[39]
that can stabilise neointimal smooth muscle cells. an increase of hepatic elastin is one of the most
[18]
The reduction in neointimal elastin in apoE Kit W-sh/W-sh distinct features of hepatic fibrosis and cirrhosis,
-/-
[36]
grafts was correlated with a dramatic increase in cell correlated with a significant increase in hepatic mast
proliferation within the vein graft wall, suggesting that cells. In contrast to other leukocyte recruitment, the
[39]
the presence of elastin is an important protective increase of mast cell number persisted with the chronic
mechanism against chronic smooth muscle cell progress of hepatic cirrhosis, suggesting the mast
[40]
proliferation under pro-atherogenic conditions. cell-mediated pathological elastin accumulation was
beyond inflammatory mechanisms.
Mast cells, as innate immune cells, are well-
documented to have pro-inflammatory effects in many Collectively, accumulating evidence suggests that the
pre-clinical vascular studies. Induction of mast cell mast cell-elastin axis may be a universal mechanism
[6]
activation in a pro-inflammatory environment, either that regulates physiological and pathological elastin
using pharmacological activators or long term western metabolism. Our findings, in line with other literature,
diet in pro-atherosclerotic mouse models (apoE or raise the question of whether mast cells regulate
-/-
LDLr ), was a common feature of these studies. The vascular elastin metabolism via mechanisms
-/-
widely accepted paradigm is that high levels of pro- independent from their immunological function. More
inflammatory factors and proteinases released by comprehensive investigation is required to clarify the
activated mast cells promote vascular inflammation complex role of mast cells in vascular development
and development of vascular lesions. Indeed activated and remodelling.
mast cells may be the explanation for the clinical
correlation between mast cell-mediated allergic The current study used a mast cell-deficient mouse
disease and atherosclerosis. However, the role of model (Kit W-sh/W-sh ) and local mast cell reconstitution
[33]
unstimulated mast cells in normal vasculature or in to demonstrate that perivascular mast cells promoted
stable vascular disease is not fully understood. The neointimal elastin remodelling in vein grafts. Limited
current study provides the first evidence that mast cells by the experimental period, it was not clear whether
could exert a positive effect in vascular remodelling perivascular mast cells merely accelerated the elastin
via regulation of elastin deposition. Our unpublished deposition in the 4-week time window, or permanently
data suggests that the expression of inflammatory increased the elastin level in the neointima. Unlike
cytokines in vein grafts during the remodelling stage the elastic lamina in healthy arteries, the elastic fibres
(4 weeks after implantation) is negligible. We therefore in the neointima were diffuse. The presence of mast
speculate that the mast cell-dependent regulation of cells only increased the amount of elastic fibres but
elastin is independent of immunological/inflammatory did not improve the structure of the matrix. Further
142 Vessel Plus ¦ Volume 1 ¦ September 26, 2017