Differential effect of wall tension on matrix metalloproteinase promoter activation in the thoracic aorta.
Differential effect of wall tension on matrix metalloproteinase promoter activation in the thoracic aorta.
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DOI：
10.1016/j.jss.2008.12.033
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发表时间：
2010-05-15
期刊：
影响因子：
--
通讯作者：
Ikonomidis JS
中科院分区：
文献类型：
--
作者：
Ruddy JM;Jones JA;Stroud RE;Mukherjee R;Spinale FG;Ikonomidis JS
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. 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 mmHg for 3 hours. Relative gene expression of lacZ, directly reflecting MMP promoter activity, was then quantified by QPCR. MMP-2 promoter activity decreased to 0.42±0.11 at 0 mmHg and increased to 1.57±0.24 fold at 100 mmHg (p<0.05), whereas MMP-9 was unaffected. 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.
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