Cyclic pressure and shear stress regulate matrix metalloproteinases and cathepsin activity in porcine aortic valves.
OBJECTIVE
It has been shown previously that the exposure of porcine aortic valve leaflets (PAVL) to elevated pressure or steady shear stress increases extracellular matrix (ECM) synthesis. It was hypothesized that exposure of the aortic valves to pressure or shear stress would regulate valvular expression of proteases such as matrix metalloproteinases (MMPs) and cathepsins.


METHODS
Fresh PAVLs were exposed to cyclic pressure (170 mmHg at 1.167 Hz) or to a steady shear stress of 25 dyne/cm2 for 48 h, with static culture serving as controls.


RESULTS
Shear stress significantly inhibited cathepsin activity and cathepsin L protein expression, but increased MMP-2/9 activity. A cyclic hypertensive pressure condition also slightly decreased MMP-2/9 and cathepsin L activities.


CONCLUSIONS
For the first time, valvular cathepsin and MMP activity were seen to be directly regulated by mechanical forces such as pressure and shear stress. The down-regulation of cathepsin L activity correlates with an up-regulation of ECM synthesis; MMP-2 and -9 activities increased with ECM synthesis under shear stress, showing that these proteinases may serve different roles in valvular remodeling. This observation may have implications for understanding valve biology, as well as for valve tissue engineering.
Platt
Manu O
MO
The Wallace H. Coulter School of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Xing
Yun
Y
Jo
Hanjoong
H
Yoganathan
Ajit P
AP
D000818:Animals; D001021:Aortic Valve / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015536:Down-Regulation; D015151:Immunoblotting; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D023421:Models, Animal; D011312:Pressure; D033081:Shear Strength; D013552:Swine; D015854:Up-Regulation
D002403:Cathepsins; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9