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α-Lipoic Acid-Plus Ameliorates Endothelial Injury by Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in an In Vivo and In Vitro Endothelial Injury Model

α-Lipoic acid-plus (LAP), an amine derivative of α-lipoic acid, has been reported to protect cells from oxidative stress damage by reacting with lysosomal iron and is more powerful than desferrioxamine (DFO). However, the role of LAP in experimental carotid artery intimal injury (CAII) has not yet b...

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Autores principales: Wang, Yang, Bao, Dejun, Dong, Yongfei, Wei, Xiangpin, Yu, Jian, Niu, Chaoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018191/
https://www.ncbi.nlm.nih.gov/pubmed/35450412
http://dx.doi.org/10.1155/2022/8979904
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author Wang, Yang
Bao, Dejun
Dong, Yongfei
Wei, Xiangpin
Yu, Jian
Niu, Chaoshi
author_facet Wang, Yang
Bao, Dejun
Dong, Yongfei
Wei, Xiangpin
Yu, Jian
Niu, Chaoshi
author_sort Wang, Yang
collection PubMed
description α-Lipoic acid-plus (LAP), an amine derivative of α-lipoic acid, has been reported to protect cells from oxidative stress damage by reacting with lysosomal iron and is more powerful than desferrioxamine (DFO). However, the role of LAP in experimental carotid artery intimal injury (CAII) has not yet been well investigated. Therefore, we sought to uncover the role and potential endovascular protective mechanisms of LAP in endothelial injury. In vitro, oxyhemoglobin (OxyHb) stimulation of cultured human umbilical vein endothelial cells (HUVECs) simulated intimal injury. In vivo, balloon compression injury of the carotid artery was used to establish a rat CAII model. We found that the protein levels of cathepsin B/D, ferritin, transferrin receptor (TfR), cleaved caspase-3, and Bax increased in the injured endothelium and HUVECs but were rectified by DFO and LAP treatments, as revealed by western blotting and immunofluorescence staining. Additionally, DFO and LAP decreased oxidative stress levels and endothelial cell necrosis of the damaged endothelium. Moreover, DFO and LAP significantly ameliorated the increased oxidative stress, iron level, and lactic dehydrogenase activity of HUVECs and improved the reduced HUVEC viability induced by OxyHb. More importantly, DFO and LAP significantly reduced mitochondrial damage and were beneficial for maintaining lysosomal integrity, as indicated by acridine orange (AO), Lyso-Tracker Red, JC-1, and ATPB staining in HUVECs. Finally, LAP might offer more significant endovascular protective effects than DFO. Our data suggested that LAP exerted endovascular protective effects by inhibiting the apoptosis signaling pathway mediated by intralysosomal cathepsins by reacting with excessive iron in endothelial lysosomes after intimal injury.
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spelling pubmed-90181912022-04-20 α-Lipoic Acid-Plus Ameliorates Endothelial Injury by Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in an In Vivo and In Vitro Endothelial Injury Model Wang, Yang Bao, Dejun Dong, Yongfei Wei, Xiangpin Yu, Jian Niu, Chaoshi Oxid Med Cell Longev Research Article α-Lipoic acid-plus (LAP), an amine derivative of α-lipoic acid, has been reported to protect cells from oxidative stress damage by reacting with lysosomal iron and is more powerful than desferrioxamine (DFO). However, the role of LAP in experimental carotid artery intimal injury (CAII) has not yet been well investigated. Therefore, we sought to uncover the role and potential endovascular protective mechanisms of LAP in endothelial injury. In vitro, oxyhemoglobin (OxyHb) stimulation of cultured human umbilical vein endothelial cells (HUVECs) simulated intimal injury. In vivo, balloon compression injury of the carotid artery was used to establish a rat CAII model. We found that the protein levels of cathepsin B/D, ferritin, transferrin receptor (TfR), cleaved caspase-3, and Bax increased in the injured endothelium and HUVECs but were rectified by DFO and LAP treatments, as revealed by western blotting and immunofluorescence staining. Additionally, DFO and LAP decreased oxidative stress levels and endothelial cell necrosis of the damaged endothelium. Moreover, DFO and LAP significantly ameliorated the increased oxidative stress, iron level, and lactic dehydrogenase activity of HUVECs and improved the reduced HUVEC viability induced by OxyHb. More importantly, DFO and LAP significantly reduced mitochondrial damage and were beneficial for maintaining lysosomal integrity, as indicated by acridine orange (AO), Lyso-Tracker Red, JC-1, and ATPB staining in HUVECs. Finally, LAP might offer more significant endovascular protective effects than DFO. Our data suggested that LAP exerted endovascular protective effects by inhibiting the apoptosis signaling pathway mediated by intralysosomal cathepsins by reacting with excessive iron in endothelial lysosomes after intimal injury. Hindawi 2022-04-12 /pmc/articles/PMC9018191/ /pubmed/35450412 http://dx.doi.org/10.1155/2022/8979904 Text en Copyright © 2022 Yang Wang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Yang
Bao, Dejun
Dong, Yongfei
Wei, Xiangpin
Yu, Jian
Niu, Chaoshi
α-Lipoic Acid-Plus Ameliorates Endothelial Injury by Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in an In Vivo and In Vitro Endothelial Injury Model
title α-Lipoic Acid-Plus Ameliorates Endothelial Injury by Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in an In Vivo and In Vitro Endothelial Injury Model
title_full α-Lipoic Acid-Plus Ameliorates Endothelial Injury by Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in an In Vivo and In Vitro Endothelial Injury Model
title_fullStr α-Lipoic Acid-Plus Ameliorates Endothelial Injury by Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in an In Vivo and In Vitro Endothelial Injury Model
title_full_unstemmed α-Lipoic Acid-Plus Ameliorates Endothelial Injury by Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in an In Vivo and In Vitro Endothelial Injury Model
title_short α-Lipoic Acid-Plus Ameliorates Endothelial Injury by Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in an In Vivo and In Vitro Endothelial Injury Model
title_sort α-lipoic acid-plus ameliorates endothelial injury by inhibiting the apoptosis pathway mediated by intralysosomal cathepsins in an in vivo and in vitro endothelial injury model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018191/
https://www.ncbi.nlm.nih.gov/pubmed/35450412
http://dx.doi.org/10.1155/2022/8979904
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