Effect of Matrix Metalloproteinase-9 (MMP9) Overexpression in Restenosis: An assay of Collagen Gel Contraction by Smooth Muscle Cells in vitro
Occlusive vascular disease leads to 50% of death in the developed world. Such disease has been frequently treated by balloon angioplasty for years. The procedure of angioplasty is initially effective in clearing out plaques, but it injures the vessel, which triggers a repair response that results in restenosis in about 30-50% of cases. Restenosis was believed to be caused by the decrease in lumen size; however, recent findings have indicated that the decrease in lumen size is caused by a decrease in cross sectional area instead. The exact mechanism of the re-narrowing of the vessel during restenosis is not completely understood, but efforts have been made to inhibit the negative modeling during the process. One of the hypotheses of preventing restenosis involves the overexpression of matrix metalloproteinase-9 (MMP9) by smooth muscle cells. It is hypothesized that MMP9 can prevent the negative remodeling by competing with hyaluronic acid in binding to the cell receptor CD44. To study the effect of overexpression of MMP9 on negative remodeling, a collagen gel contraction model was used. Fisher Rat SMC's that expresses MMP9 were cultured and suspended in collagen gels and the contraction was measured. The extent of such was measured and compared with control cells that do not express MMP9. In our study, a protease inhibitor BB94 and anti-CD44 antibodies were used to study the mechanism of the inhibitory effect of MMP9. We have shown with our results that overexpression of MMP9 inhibits SMC mediated collagen gel contraction and that the effect is not due to the enzymatic activity of the proteinase molecule itself. The mechanism of the interaction of MMP9 with the cell receptor CD44 is still under investigation and its correlation with humans is still questionable.
