Cathepsin L is up-expressed in atherosclerotic lesion induced by shear stress

Cathepsin L has been implicated a shear-sensitive matrix protease. However, there was no in vivo evidence available. In this study, ten rabbits were treated with gel-silica loop to develop a defined local stenosis in left carotid arteries straight segment and fed with high fat/cholesterol diet for 4 weeks. Numerical simulation showed that blood flow was disturbed significantly at the immediate proximal and distal vicinity of stenosis. The shear stress in proximal part of ringer was obviously increased (>;6Pa), while the shear stress in distal of ring was decreased (0~0.3Pa). Lesions were observed in both proximal and distal of the stenosis at the end of 4 weeks, however, the lesion from proximal had more macrophage cells and lipid deposition. In proximal lesions, cathepsin L was highly expressed, whereas less cathepsin L was detected in distal lesion. Taken together, shear stress attributed to atherosclerosis. High shear stress induces larger lesions with a vulnerable plaque phenotype, whereas low shear stress induces stable lesions. The differentia expression of cathepsin L may contribute to the feature of atherosclerotic lesion.