title: Cathepsin L stimulates autophagy and inhibits apoptosis of ox-LDL-induced endothelial cells: potential role in atherosclerosis.
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.
authors.affiliation: Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, P.R. China. weizhonghua99@126.com
authors.forename: Dang-Heng
authors.initials: DH
authors.lastname: Wei
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Jia
authors.forename: Yang-Hui
authors.initials: YH
authors.lastname: Liu
authors.forename: Feng-Xia
authors.initials: FX
authors.lastname: Guo
authors.forename: Zhi-Han
authors.initials: ZH
authors.lastname: Tang
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.forename: Zuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Lu-Shan
authors.initials: LS
authors.lastname: Liu
authors.forename: Gui-Xue
authors.initials: GX
authors.lastname: Wang
authors.forename: Zhi-Sheng
authors.initials: ZS
authors.lastname: Jian
authors.forename: Chang-Geng
authors.initials: CG
authors.lastname: Ruan
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D001343:Autophagy / Q000187:drug effects; D015820:Cadherins / Q000378:metabolism; D056668:Cathepsin L / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D056668:Cathepsin L; D008077:Lipoproteins, LDL; D011480:Protease Inhibitors; D012333:RNA, Messenger; D000099152:Cadherin 5; C099252:oxidized low density lipoprotein