Cathepsin L stimulates autophagy and inhibits apoptosis of ox-LDL-induced endothelial cells: Potential role in atherosclerosis

Wei,Dang-Heng; Jia,Xiao-Ying; Liu,Yang-Hui; Guo,Feng-Xia; Tang,Zhi-Han; Li,Xiao-Hong; Wang,Zuo; Liu,Lu-Shan; Wang,Gui-Xue; Jian,Zhi-Sheng; Ruan,Chang-Geng

doi:10.3892/ijmm.2012.1201

Cathepsin L stimulates autophagy and inhibits apoptosis of ox-LDL-induced endothelial cells: Potential role in atherosclerosis

Authors:
- Dang-Heng Wei
- Xiao-Ying Jia
- Yang-Hui Liu
- Feng-Xia Guo
- Zhi-Han Tang
- Xiao-Hong Li
- Zuo Wang
- Lu-Shan Liu
- Gui-Xue Wang
- Zhi-Sheng Jian
- Chang-Geng Ruan
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Affiliations: Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, P.R. China, Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College of Chongqing University, Chongqing 400044, P.R. China, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou 215006, P.R. China
Published online on: December 3, 2012 https://doi.org/10.3892/ijmm.2012.1201
Pages: 400-406

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Abstract

The activation of endothelial cells by oxidized low-density lipoprotein (ox-LDL) with subsequent increases in endothelial permeability occurs in the early stage of atherosclerosis. Cathepsin L (CATL) is one of the cysteine proteases and has been implicated in advanced atherosclerotic lesions and plaque instability. This study aimed to explore the role of CATL in ox-LDL-induced early atherosclerotic events and to delineate the underlying mechanism. Results showed that ox-LDL upregulated CATL protein levels and activation in human umbilical vein endothelial cells (ECs) in a concentration-dependent manner and stimulated EC autophagy and apoptosis and increased EC monolayer permeability. Concomitantly, VE-cadherin expression was decreased. When ECs were pretreated with a CATL inhibitor, ox-LDL-induced autophagy was inhibited while apoptosis was further increased. In addition, the VE-cadherin protein level was increased, and the EC monolayer permeability was reduced. Taken together, the present study showed that the upregulated expression and activation of CATL induced by ox-LDL, increased EC autophagy and antagonized EC apoptosis, which partly neutralized the effect of increased EC monolayer permeability mediated by the downregulation of VE-cadherin. Thus, the proatherogenic effect of CATL was partly neutralized by inducing autophagy and inhibiting apoptosis in early stages of atherosclerosis.

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