Coordinate regulation of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 expression in human vascular smooth muscle cells

The expression of matrix metalloproteinases (MMPs) and their inhibitors (TI MPs) by human vascular smooth muscle cells (SMC) was monitored as a functio n of the phenotypic modulation in vitro. Cell phenotype was manipulated by varying serum concentration and cell density, Synthetic phenotype was chara cterized by a minimum expression of the contractile proteins and a maximal proliferation rate. Contractile phenotype was quiescent and expressed a max imal level of contractile proteins. Synthetic cells expressed the highest l evels of both MMP-1 and TIMP-1 and displayed maximal collagenolytic activit y. No significant change was detected in MMP-2 expression or catalytic acti vity. Enzyme immunoassays revealed that MMP-1 expression fell by 77+/-2.4-9 5+/-0.5%, and that of TIMP-1 by 34 +/- 0.5-59 +/- 1.9%, as the cells acquir ed a contractile phenotype, The level of the MMP-1/ TIMP-1 complex was simi larly reduced by 78 +/- 2.9-85 +/- 1.6%. These data demonstrate that the ex pression of MMP-1 and TIMP-1 are coordinately regulated with SMC phenotype.