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Laminar shear stress inhibits cathepsin L activity in endothelial cells.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2006 Aug; Vol. 26 (8), pp. 1784-90. Date of Electronic Publication: 2006 May 18. - Publication Year :
- 2006
-
Abstract
- 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.<br />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.<br />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.
- Subjects :
- Animals
Aorta cytology
Cathepsin B metabolism
Cathepsin L
Cathepsins genetics
Cells, Cultured
Cysteine Endopeptidases genetics
Extracellular Matrix enzymology
Gelatinases metabolism
Mice
Pancreatic Elastase metabolism
Peptide Hydrolases metabolism
RNA, Small Interfering pharmacology
Stress, Mechanical
Aorta enzymology
Cathepsins metabolism
Cysteine Endopeptidases metabolism
Endothelial Cells enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 26
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 16709945
- Full Text :
- https://doi.org/10.1161/01.ATV.0000227470.72109.2b