Hr. Lijnen et al., Accelerated neointima formation after vascular injury in mice with stromelysin-3 (MMP-11) gene inactivation, ART THROM V, 19(12), 1999, pp. 2863-2870
The hypothesis that stromelysin-3 (MMP-11), a unique member of the matrix m
etalloproteinase (MMP) family, plays a role in neointima formation was test
ed with the use of a vascular injury model in wild-type (MMP-11(+/+)) and M
MP-11-deficient (MMP-11(-/-)) mice. Neointima formation 2 to 3 weeks after
electric injury of the femoral artery was significantly enhanced in MMP-11-
/- as compared with MMP-11(+/+) mice, in both mice of a pure 129SV genetic
background (0.014 versus 0.0010 mm(2) at 2 weeks, P<0.001) and those of a 5
0/50 mixed 129SV/BL6 background (0.030 versus 0.013 mm(2) at 3 weeks, P<0.0
5). The medial areas were comparable, resulting in intima/media ratios that
were significantly increased in MMP-11(-/-) as compared with MMP-11(+/+) a
rteries, in mice of both the 129SV (1.0 versus 0.18, P<0.001) and mixed (1.
5 versus 0.70, P<0.05) backgrounds. Nuclear cell counts in cross-sectional
areas of the intima of the injured region were higher in arteries from MMP-
11(-/-) mice than in those from MMP-11(+/+) mice (210 versus 48, P<0.001, i
n pure 129SV mice and 290 versus 150, P<0.01, in mice of the mixed genetic
background). Immunocytochemical analysis revealed that alpha-actin-positive
and CD45-positive cells were more abundant in intimal sections of MMP-11-/
- mice. Degradation of the internal elastic lamina was more extensive in ar
teries of MMP-11(-/-) mice than in those of MMP-11(+/+) mice (39% versus 6.
8% at 3 weeks, P<0.005). The mechanisms by which MMP-11 could impair elasti
n degradation and cellular migration in this model remain, however, unknown
.