Matrix metalloproteinase-9 overexpression enhances vascular smooth muscle cell migration and alters remodeling in the injured rat carotid artery

Matrix metalloproteinase-9 (MMP-9) has been implicated in the pathogenesis of atherosclerosis as well as intimal hyperplasia after vascular injury. We used Fischer rat smooth muscle cells (SMCs) overexpressing MMP-9 to determ ine the role of MMP-9 in migration and proliferation as well as in vessel r emodeling after balloon denudation, Fischer rat SMCs were stably transfecte d with a cDNA for rat MMP-9 under the control of a tetracycline-regulatable promoter. In this system, MMP-9 was overexpressed in the absence, but not in the presence, of tetracycline. In vitro SMC migration was determined usi ng a collagen invasion assay as well as a Boyden chamber assay. In vivo mig ration was determined by measuring the invasion into the medial and intimal layers of transduced SMCs seeded on the outside of the artery. Transduced SMCs were also seeded on the luminal surface, and the effect of local MMP-9 overexpression on vascular structure was measured morphometrically at inte rvals up to 28 days. MMP-9 overexpression enhanced SMC migration in both th e collagen invasion assay and Boyden chamber in vitro, increased SMC migrat ion into an arterial matrix in vivo, and altered vessel remodeling by incre asing the vessel circumference, thinning the vessel wall and decreasing int imal matrix content. These results demonstrate that MMP-9 enhances vascular SMC migration in vitro and in vivo and alters postinjury vascular remodeli ng.