PMID- 35450412
OWN - NLM
STAT- MEDLINE
DCOM- 20220425
LR  - 20220716
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2022
DP  - 2022
TI  - alpha-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.
PG  - 8979904
LID - 10.1155/2022/8979904 [doi]
LID - 8979904
AB  - alpha-Lipoic acid-plus (LAP), an amine derivative of alpha-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.
CI  - Copyright (c) 2022 Yang Wang et al.
FAU - Wang, Yang
AU  - Wang Y
AD  - Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, No. 17 
      Lujiang Road, Hefei, 230001 Anhui Province, China.
FAU - Bao, Dejun
AU  - Bao D
AD  - Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, No. 17 
      Lujiang Road, Hefei, 230001 Anhui Province, China.
FAU - Dong, Yongfei
AU  - Dong Y
AD  - Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, No. 17 
      Lujiang Road, Hefei, 230001 Anhui Province, China.
FAU - Wei, Xiangpin
AU  - Wei X
AD  - Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, No. 17 
      Lujiang Road, Hefei, 230001 Anhui Province, China.
FAU - Yu, Jian
AU  - Yu J
AUID- ORCID: 0000-0003-3809-3823
AD  - Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, No. 17 
      Lujiang Road, Hefei, 230001 Anhui Province, China.
FAU - Niu, Chaoshi
AU  - Niu C
AUID- ORCID: 0000-0001-8508-567X
AD  - Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, No. 17 
      Lujiang Road, Hefei, 230001 Anhui Province, China.
AD  - Anhui Province Key Laboratory of Brain Function and Brain Disease, No. 17 Lujiang 
      Road, Hefei, 230001 Anhui Province, China.
LA  - eng
PT  - Journal Article
DEP - 20220412
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 73Y7P0K73Y (Thioctic Acid)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Endothelium/metabolism
MH  - Human Umbilical Vein Endothelial Cells/metabolism
MH  - Humans
MH  - Iron/metabolism
MH  - Oxidative Stress
MH  - Rats
MH  - *Thioctic Acid/metabolism/pharmacology
PMC - PMC9018191
COIS- The authors declare that there are no conflicts of interest.
EDAT- 2022/04/23 06:00
MHDA- 2022/04/26 06:00
PMCR- 2022/04/12
CRDT- 2022/04/22 06:42
PHST- 2021/10/10 00:00 [received]
PHST- 2022/01/27 00:00 [revised]
PHST- 2022/02/23 00:00 [accepted]
PHST- 2022/04/22 06:42 [entrez]
PHST- 2022/04/23 06:00 [pubmed]
PHST- 2022/04/26 06:00 [medline]
PHST- 2022/04/12 00:00 [pmc-release]
AID - 10.1155/2022/8979904 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2022 Apr 12;2022:8979904. doi: 10.1155/2022/8979904. 
      eCollection 2022.