Coordinate Regulation of Matrix Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinase-1 Expression in Human Vascular Smooth Muscle Cells

Abstract

The expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) by human vascular smooth muscle cells (SMC) was monitored as a function of the phenotypic modulation in vitro. Cell phenotype was manipulated by varying serum concentration and cell density. Synthetic phenotype was characterized by a minimum expression of the contractile proteins and a maximal proliferation rate. Contractile phenotype was quiescent and expressed a maximal level of contractile proteins. Synthetic cells expressed the highest levels of both MMP-1 and TIMP-1 and displayed maximal collagenolytic activity. No significant change was detected in MMP-2 expression or catalytic activity. Enzyme immunoassays revealed that MMP-1 expression fell by 77 ± 2.4-95 ± 0.5%, and that of TIMP-1 by 34 ± 0.5-59 ± 1.9%, as the cells acquired a contractile phenotype. The level of the MMP-1/TIMP-1 complex was similarly reduced by 78 ± 2.9-85 ± 1.6%. These data demonstrate that the expression of MMP-1 and TIMP-1 are coordinately regulated with SMC phenotype.

Key Words:

• Vascular smooth muscle cells
• phenotype
• matrix metalloproteinases (MMPs)
• tissue inhibitor of metalloproteinases (TIMPs)
• atherosclerosis