PMID- 36290297
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221030
IS  - 2079-7737 (Print)
IS  - 2079-7737 (Electronic)
IS  - 2079-7737 (Linking)
VI  - 11
IP  - 10
DP  - 2022 Sep 23
TI  - IDH1 Promotes Foam Cell Formation by Aggravating Macrophage Ferroptosis.
LID - 10.3390/biology11101392 [doi]
LID - 1392
AB  - A distinctive feature of ferroptosis is intracellular iron accumulation and the 
      impairment of antioxidant capacity, resulting in a lethal accumulation of lipid 
      peroxides leading to cell death. This study was conducted to determine whether 
      inhibiting isocitrate dehydrogenase 1 (IDH1) may help to prevent foam cell 
      formation by reducing oxidized low-density lipoprotein (ox-LDL)-induced 
      ferroptosis in macrophages and activating nuclear factor erythroid 2-related 
      factor 2 (NRF2). Gene expression profiling (GSE70126 and GSE70619) revealed 21 
      significantly different genes, and subsequent bioinformatics research revealed 
      that ferroptosis and IDH1 play essential roles in foam cell production. We also 
      confirmed that ox-LDL elevates macrophage ferroptosis and IDH1 protein levels 
      considerably as compared with controls. Ferrostatin-1 (Fer-1), a ferroptosis 
      inhibitor, reduced ox-LDL-induced elevated Fe(2+) levels, lipid peroxidation 
      (LPO) buildup, lactate dehydrogenase (LDH) buildup, glutathione (GSH) depletion, 
      glutathione peroxidase 4 (GPX4), ferritin heavy polypeptide 1 (FTH1), and solute 
      carrier family 7 member 11 (SLC7A11) protein downregulation. More crucially, 
      inhibiting IDH1 reduced Fe(2+) overload, lipid peroxidation, LDH, and glutathione 
      depletion, and elevated GPX4, FTH1, and SLC7A11 protein expression, resulting in 
      a reduction in ox-LDL-induced macrophage ferroptosis. IDH1 inhibition suppressed 
      ox-LDL-induced macrophage damage and apoptosis while raising NRF2 protein levels. 
      We have demonstrated that inhibiting IDH1 reduces ox-LDL-induced ferroptosis and 
      foam cell formation in macrophages, implying that IDH1 may be an important 
      molecule regulating foam cell formation and may be a promising molecular target 
      for the treatment of atherosclerosis.
FAU - Li, Ben
AU  - Li B
AUID- ORCID: 0000-0002-6577-1872
AD  - Department of Cardiovascular Surgery, The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing 210000, China.
FAU - Wang, Chufan
AU  - Wang C
AD  - Department of Cardiovascular Surgery, The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing 210000, China.
FAU - Lu, Peng
AU  - Lu P
AD  - Department of Cardiovascular Surgery, The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing 210000, China.
FAU - Ji, Yumeng
AU  - Ji Y
AD  - Department of Cardiovascular Surgery, The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing 210000, China.
FAU - Wang, Xufeng
AU  - Wang X
AD  - Department of Cardiovascular Surgery, The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing 210000, China.
FAU - Liu, Chaoyang
AU  - Liu C
AD  - Department of Cardiovascular Surgery, The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing 210000, China.
FAU - Lu, Xiaohu
AU  - Lu X
AD  - Department of Cardiovascular Surgery, The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing 210000, China.
FAU - Xu, Xiaohan
AU  - Xu X
AD  - Department of Cardiovascular Surgery, The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing 210000, China.
AD  - The Friendship Hospital of Ili Kazakh Autonomous Prefecture Ili, Jiangsu Joint 
      Institute of Health, Yining 835000, China.
FAU - Wang, Xiaowei
AU  - Wang X
AD  - Department of Cardiovascular Surgery, The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing 210000, China.
LA  - eng
GR  - ZDA2020004/The Jiangsu Provincial Department of Health provided funding for this 
      project/
PT  - Journal Article
DEP - 20220923
PL  - Switzerland
TA  - Biology (Basel)
JT  - Biology
JID - 101587988
PMC - PMC9598283
OTO - NOTNLM
OT  - IDH1
OT  - NRF2
OT  - ferroptosis
OT  - foam cell
OT  - macrophage
COIS- The authors declare no conflict of interest.
EDAT- 2022/10/28 06:00
MHDA- 2022/10/28 06:01
PMCR- 2022/09/23
CRDT- 2022/10/27 01:05
PHST- 2022/07/25 00:00 [received]
PHST- 2022/09/16 00:00 [revised]
PHST- 2022/09/20 00:00 [accepted]
PHST- 2022/10/27 01:05 [entrez]
PHST- 2022/10/28 06:00 [pubmed]
PHST- 2022/10/28 06:01 [medline]
PHST- 2022/09/23 00:00 [pmc-release]
AID - biology11101392 [pii]
AID - biology-11-01392 [pii]
AID - 10.3390/biology11101392 [doi]
PST - epublish
SO  - Biology (Basel). 2022 Sep 23;11(10):1392. doi: 10.3390/biology11101392.