Differential Effect of Wall Tension on Matrix Metalloproteinase Promoter Activation in the Thoracic Aorta

Background. Vascular remodeling relies upon extracellular matrix restructuring by the matrix metalloproteinases (MMPs). Induction of MMP-2 and MMP-9 by biological signaling molecules has been defined, but whether a mechanical stimulus such as elevated wall tension may generate MMP promoter activation remains unknown. Accordingly, this study examined whether MMP promoter activation would occur as a function of wall tension. Materials and Methods. The MMP-2 or MMP-9 promoter sequences were fused to the reporter gene lacZ and inserted into the mouse genome. Thoracic aortic rings were harvested (6 preparations/construct) and maintained under physiological conditions at predetermined tension values corresponding to 0, 70, 85, and 100 mm Hg for 3 h. Relative gene expression of lacZ, directly reflecting MMP promoter activity, was then quantified by QPCR. Results. MMP-2 promoter activity decreased to 0.42 +/- 0.11 at 0 mm Hg and increased to 1.57 +/- 0.24-fold at 100 mm Hg (P < 0.05), whereas MMP-9 was unaffected. Conclusions. Using unique transgenic constructs with homology to human MMP promoters, this study demonstrated that a physiologically relevant mechanical stimulus was sufficient to differentially induce MMP promoter activation. (C) 2010 Elsevier Inc. All rights reserved.