Effect of Matrix Metalloproteinase-9 (MMP9) Overexpression in Restenosis: An assay of Collagen Gel Contraction by Smooth Muscle Cells in vitro
Vascular diseases causes 50% of death in the developed world. Atherosclerosis is a progressive condition in which fibro fatty plaques form in blood vessels eventually decreases in lumen size and blood flow through the blood vessel. Balloon angioplasty is a popular treatment developed to treat atheroscierosis. However, such treatment produces injury and induces a repair process that leads to restenosis in 30-50% of patients. The mechanism of restenosis or negative remodeling; which is the loss of the lumen size after angioplasty, is not clear. However, it is known that the loss of lumen is the result of decrease in the cross sectional area of the artery, but not an increase in intimal area. It has been shown that the overexpression of matrix metalloproteinase-9 MMP9 may prevent the decrease in lumen area in the injured rat carotid artery normally observed over a 2 week period. It is hypothesize that one way MMP9 can prevent the negative remodeling is by competing with hyaluronate acid in binding to the cell receptor CD44. To study the effect of overexpression of MMP9 on negative remodeling, a collagen gel contraction model model is used. SMC cells that expresses MMP9 and cells that don't are cultured and suspended in separate collagen gels and the extent of contractions will be measured and contrasted. If the overexpression of MMP9 decreases collagen gel contraction, the mechanism of this effect will be investigated by determining the role of hyaluronate and CD44. Tetracycline (tet) is an transcription factor for MMP9 and it will be used to control the expression of MMP9 of cells by its presence. In addition, the smooth muscle cells are grown in serum and serum free environment and their corresponding collagen gel contraction will be measured to determine the affect of serum in the contraction of collagen by SMC.
