on May 18, 2006
Published online before print May 18, 2006, doi: 10.1161/01.ATV.0000227470.72109.2b
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 22, 2005
Accepted on May 5, 2006
Laminar Shear Stress Inhibits Cathepsin L Activity in Endothelial Cells
Manu O. Platt ;
From the Coulter Department of Biomedical Engineering (M.O.P., R.F.A., H.J.), Georgia Institute of Technology, and the Division of Cardiology (H.J.), Emory University, Atlanta, Ga.
* To whom correspondence should be addressed. E-mail: hanjoong.jo{at}bme.gatech.edu.
Objective--The cysteine proteases, cathepsins, have been implicated in vascular remodeling and atherosclerosis, processes known to be regulated by shear stress. It is not known, however, whether shear regulates cathepsins. We examined the hypothesis that shear stress regulates cathepsin activity in endothelial cells.
Methods and Results--Mouse aortic endothelial cells (MAECs) exposed to atheroprotective, unidirectional laminar shear (LS) degraded significantly less BODIPY-labeled elastin and gelatin in comparison to static and proatherogenic oscillatory shear (OS). The cathepsin inhibitor E64 also reduced this activity. Gelatin zymography showed that cathepsin activity of MAECs was blunted by LS exposure and by a cathepsin L inhibitor but not by cathepsin B and S inhibitors, whereas a cathepsin K inhibitor had a minor effect. Cathepsin L siRNA knocked down cathepsin L expression, gelatinase, and elastase activity in OS and static MAECs. A partial reduction of cathepsin B protein raised the possibility that the siRNA effect on the matrix protease activity could have been attributable to cathepsin L or B. Cathepsin B activity study using the synthetic peptide showed it was not regulated by shear.
Conclusions--These results suggest that cathepsin L is a shear-sensitive matrix protease and that it may play an important role in flow-mediated vascular remodeling and atherogenic responses.
Key words: shear stress • cathepsin • elastase • gelatinase • atherosclerosis
This article has been cited by other articles:
 |
|
 |
|
  G. P. Kwon, J. L. Schroeder, M. J. Amar, A. T. Remaley, and R. S. Balaban Contribution of Macromolecular Structure to the Retention of Low-Density Lipoprotein at Arterial Branch Points Circulation, June 3, 2008; 117(22): 2919 - 2927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. M. Lutgens, K. B. J. M. Cleutjens, M. J. A. P. Daemen, and S. Heeneman Cathepsin cysteine proteases in cardiovascular disease FASEB J, October 1, 2007; 21(12): 3029 - 3041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Tressel, R.-P. Huang, N. Tomsen, and H. Jo Laminar Shear Inhibits Tubule Formation and Migration of Endothelial Cells by an Angiopoietin-2-Dependent Mechanism Arterioscler. Thromb. Vasc. Biol., October 1, 2007; 27(10): 2150 - 2156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. S. Chatzizisis, A. U. Coskun, M. Jonas, E. R. Edelman, C. L. Feldman, and P. H. Stone Role of Endothelial Shear Stress in the Natural History of Coronary Atherosclerosis and Vascular Remodeling: Molecular, Cellular, and Vascular Behavior J. Am. Coll. Cardiol., June 26, 2007; 49(25): 2379 - 2393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. O. Platt, R. F. Ankeny, G.-P. Shi, D. Weiss, J. D. Vega, W. R. Taylor, and H. Jo Expression of cathepsin K is regulated by shear stress in cultured endothelial cells and is increased in endothelium in human atherosclerosis Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1479 - H1486. [Abstract] [Full Text] [PDF]
|
|