Laminar shear stress inhibits cathepsin L activity in endothelial cells
Laminar shear stress inhibits cathepsin L activity in endothelial cells
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DOI：
10.1161/01.atv.0000227470.72109.2b
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发表时间：
2006-08-01
影响因子：
8.7
通讯作者：
Jo, Hanjoong
中科院分区：
文献类型：
--
作者：
Platt, Manu O.;Ankeny, Randall F.;Jo, Hanjoong
半胱氨酸蛋白酶，组织蛋白酶，与血管重塑和动脉粥样硬化有关，已知这些过程受剪切应力调节。然而，尚不清楚剪切是否调节组织蛋白酶。我们研究的假设，剪切应力调节组织蛋白酶活性在endothelial cells.Methods和Results-Mouse aortic endothelial cells（MAECs）暴露于atheroprotective，单向层流剪切（LS）降解显着减少BODIPY标记的弹性蛋白和明胶相比，静态和proatherogenic振荡剪切（OS）。组织蛋白酶抑制剂E64也降低了这种活性。明胶酶谱分析表明，MAECs的组织蛋白酶活性钝化LS曝光和组织蛋白酶L抑制剂，但不是由组织蛋白酶B和S抑制剂，而组织蛋白酶K抑制剂有轻微的影响。组织蛋白酶L siRNA敲低OS和静态MAEC中的组织蛋白酶L表达、明胶酶和弹性蛋白酶活性。组织蛋白酶B蛋白的部分减少提高了siRNA对基质蛋白酶活性的影响可能归因于组织蛋白酶L或B的可能性。组织蛋白酶B活性的研究表明，它不受shield. Conclusions这些结果表明，组织蛋白酶L是一种剪切敏感的基质蛋白酶，它可能发挥重要作用，在流量介导的血管重塑和动脉粥样硬化反应。
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.