Department of Surgery , University of Washington , Seattle 98195 , USA .
Arterioscler Thromb Vasc Biol 16 : 28-33 ( 1996)
Abstract
Smooth muscle cell ( SMC ) migration and proliferation and extracellular matrix remodeling are essential aspects of the arterial response to injury , vessel development , and atherogenesis .
Matrix metalloproteinase ( MMP ) expression is associated with SMC proliferation and migration after arterial injury .
To assess the role of MMPs in SMC proliferation and migration and intimal thickening , we measured the effect of the synthetic MMP inhibitor BB94 ( Batimastat ) on DNA synthesis and migration of SMCs in vitro as well as the formation of a neointima after balloon injury to the rat carotid artery .
BB94 dose-dependently inhibited SMC migration induced by platelet-derived growth factor ( PDGF)-BB through a filter coated with a thick basement membrane matrix ( Matrigel ) layer but did not show any inhibitory effect on SMC migration through a lightly coated filter .
At concentrations up to 1 mumol/L , BB94 did not alter DNA synthesis induced by PDGF-AA or PDGF-BB .
Treatment with 30 mg BB94.kg-1.d-1 IP for 7 or 14 days after balloon injury to the rat carotid artery decreased the total number of intimal SMC nuclei and suppressed intimal thickening .
SMC proliferation ( 5-bromo-2'-deoxyuridine labeling ) was decreased in the media at 2 days , whereas it was increased in the intima at 7 but not 14 days .
These results suggest that BB94 inhibits intimal thickening after arterial injury by decreasing SMC migration and proliferation and support the conclusion that MMPs play a significant role in regulating intimal thickening in injured arteries .