Effect of matrix metalloproteinase-9 knockout on vein graft remodelling in mice

Long-term success in vein grafting for bypassing arteries
blocked by atherosclerosis is limited by migration and proliferation
of smooth muscle cells to form a neointima. Matrix
metalloproteinases (MMPs), in particular MMP-2 and MMP-9,
are implicated in neointimal formation by freeing smooth
muscle cells from the cell-matrix contacts that normally restrict
migration. We investigated the role of MMP-9 in vein
grafts directly, using knockout mice. Vein grafts in MMP-9 –/–
and wild-type mice had similar luminal and graft areas at 1,
4 and 8 weeks after engraftment, increasing with time. There
was a relationship between the perimeter of the external
elastic lamina and graft thickness (indicating graft remodelling)
in MMP-9 –/– mice at 1 week after surgery not apparent
in control mice until later (r 2 = 0.933 for MMP-9 –/– mice, r 2 =
0.040 for wild-type mice). Grafts in MMP-9 –/– mice had 6-fold
more pro- and active MMP-2 (p = 0.013, p = 0.026) than grafts
in wild-type mice. Grafts from MMP-9 –/– mice also had more
collagen (p = 0.046 at 8 weeks), without any difference in cell
number. Thus, while a lack of MMP-9 did not alter vein graft
wall area or cellularity, grafts from MMP-9 –/– mice accumu-
lated more collagen and had earlier linear expansive remodelling,
possibly due to an early compensatory increase in
MMP-2.