To study the effect of inhibition of
MAPKK on smooth muscle cell (SMC) proliferation in vivo after
vascular injury, we performed experimental balloon angioplasty using the standard Clowes technique in male Wistar rats 14-weeks old. The animals did not receive any treatment after
vascular injury (N = 6) or were randomly assigned to receive, after balloon injury, a 30% (w/v)
pluronic gel
solution applied to the injured carotid artery, containing respectively: 1) no plasmid
DNA (n = 10); 2) RSV-lacZ (encoding the
beta-galactosidase gene) as control gene without effects on SMC proliferation (n = 10); 3) Tg-CAT (encoding cloramphenicol acetyl-
transferase gene under the control of thyreoglobulin promoter) as an additional control gene without effects on SMC proliferation (n = 7): 4) a negative mutant of
Mitogen-Activated Protein Kinase Kinase (
MAPKK-) (n = 13). Fourteen days after
vascular injury, carotid arteries were removed and cross sections were cut and stained with
hematoxylin/
eosin. Morphometric analysis demonstrated, in the
MAPKK- treated rats, a significant reduction of both
neointima (0.096+/-.018 mm2 vs. 0.184+/-0.019 mm2, p < 0.01) and
neointima/media ratio (0.603+/-0.103 vs. 1.471+/-0.161, p < 0.01) compared to control
DNA.
CONCLUSIONS: