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Am J Physiol Heart Circ Physiol (January 23, 2003). doi:10.1152/ajpheart.00494.2002
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Submitted on June 13, 2002
Accepted on January 19, 2003

Uniaxial Strain Upregulates Matrix Degrading Enzymes Produced by Human Vascular Smooth Muscle Cells

Kazuhiko Asanuma1, Richard Magid2, Chad Johnson2, Robert M. Nerem3, and Zorina S. Galis4*

1 Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA
2 Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA
3 Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA
4 Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA; Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA

* To whom correspondence should be addressed. E-mail: zgalis{at}emory.edu.

Arteries remodel in response to environmental changes. We investigated whether mechanical strain modulates production of matrix metalloproteinases (MMPs)-2 and 9 by cultured vascular smooth muscle cells (SMC). MMP-2 and MMP-9 expression were tested using human saphenous vein SMC on silicone membranes at rest or subjected to physiological levels (5%) of stationary or cyclical (1Hz) uniaxial strain. Compared to control, stationary strain significantly increased MMP-2 mRNA levels at all time points, while cyclic strain decreased it after 48h. Both secreted and cell associated pro-MMP-2 levels were increased by stationary strain at all times (p<0.01), while cyclic strain decreased secreted levels after 48h (p<0.02). MMP-9 mRNA levels and pro-MMP-9 protein were increased after 48h of stationary stretch (p<0.01) compared to both no strain and cyclic strain. Our study indicates that vascular SMC show a selective response to different types of strain. We suggest that local increases in stationary mechanical strain resulting from stenting, hypertension, or atherosclerosis may lead to enhanced matrix degradation by SMC.




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