PMID- 37575057
OWN - NLM
STAT- MEDLINE
DCOM- 20230906
LR  - 20230925
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 325
IP  - 3
DP  - 2023 Sep 1
TI  - Inducible nitric oxide synthase activity mediates TNF-alpha-induced endothelial cell 
      dysfunction.
PG  - C780-C795
LID - 10.1152/ajpcell.00153.2023 [doi]
AB  - Inducible nitric oxide synthase (iNOS) and vascular endothelial dysfunction have 
      been implicated in the development and progression of atherosclerosis. This study 
      aimed to elucidate the role of iNOS in vascular endothelial dysfunction. 
      Ultrahigh performance liquid chromatography-quadrupole time-of-flight mass 
      spectrometry combined with multivariate data analysis was used to characterize 
      the metabolic changes in human umbilical vein endothelial cells (HUVECs) in 
      response to different treatment conditions. In addition, molecular biology 
      techniques were employed to explain the molecular mechanisms underlying the role 
      of iNOS in vascular endothelial dysfunction. Tumor necrosis factor-alpha (TNF-alpha) 
      enhances the expression of iNOS, TXNIP, and the level of reactive oxygen species 
      (ROS) facilitates the entry of nuclear factor-kappaB (NF-kappaB) into the nucleus and 
      promotes injury in HUVECs. iNOS deficiency reversed the TNF-alpha-mediated 
      pathological changes in HUVECs. Moreover, TNF-alpha increased the expression of tumor 
      necrosis factor receptor-2 (TNFR-2) and the levels of p-IkappaBalpha and IL-6 proteins 
      and CD31, ICAM-1, and VCAM-1 protein expression, which was significantly reduced 
      in HUVECs with iNOS deficiency. In addition, treating HUVECs in the absence or 
      presence of TNF-alpha or iNOS, respectively, enabled the identification of putative 
      endogenous biomarkers associated with endothelial dysfunction. These biomarkers 
      were involved in critical metabolic pathways, including 
      glycosylphosphatidylinositol-anchor biosynthesis, amino acid metabolism, 
      sphingolipid metabolism, and fatty acid metabolism. iNOS deficiency during 
      vascular endothelial dysfunction may affect the expression of TNFR-2, vascular 
      adhesion factors, and the level of ROS via cellular metabolic changes, thereby 
      attenuating vascular endothelial dysfunction.NEW & NOTEWORTHY Inducible nitric 
      oxide synthase (iNOS) deficiency during vascular endothelial dysfunction may 
      affect the expression of tumor necrosis factor receptor-2 and vascular adhesion 
      factors via cellular metabolic changes, thereby attenuating vascular endothelial 
      dysfunction.
FAU - Liu, Chen
AU  - Liu C
AUID- ORCID: 0000-0002-7333-8489
AD  - Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated 
      Hospital of Southwest Medical University, Luzhou, Sichuan, China.
FAU - Lei, Sujuan
AU  - Lei S
AD  - Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated 
      Hospital of Southwest Medical University, Luzhou, Sichuan, China.
FAU - Cai, Tianying
AU  - Cai T
AD  - Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated 
      Hospital of Southwest Medical University, Luzhou, Sichuan, China.
FAU - Cheng, Yonglang
AU  - Cheng Y
AD  - Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated 
      Hospital of Southwest Medical University, Luzhou, Sichuan, China.
FAU - Bai, Junjie
AU  - Bai J
AD  - Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated 
      Hospital of Southwest Medical University, Luzhou, Sichuan, China.
FAU - Fu, Wenguang
AU  - Fu W
AD  - Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated 
      Hospital of Southwest Medical University, Luzhou, Sichuan, China.
AD  - Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and 
      Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of 
      Southwest Medical University, Luzhou, Sichuan, China.
FAU - Huang, Meizhou
AU  - Huang M
AUID- ORCID: 0000-0003-2538-0217
AD  - Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated 
      Hospital of Southwest Medical University, Luzhou, Sichuan, China.
AD  - Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and 
      Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of 
      Southwest Medical University, Luzhou, Sichuan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230814
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (NF-kappa B)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Humans
MH  - *Tumor Necrosis Factor-alpha/pharmacology/metabolism
MH  - Nitric Oxide Synthase Type II/genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - *NF-kappa B/metabolism
MH  - Human Umbilical Vein Endothelial Cells/metabolism
MH  - Vascular Cell Adhesion Molecule-1/genetics/metabolism
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - Nitric Oxide/metabolism
OTO - NOTNLM
OT  - NF-kappaB signaling
OT  - cell metabolomics
OT  - iNOS
OT  - vascular endothelial dysfunction
EDAT- 2023/08/14 06:42
MHDA- 2023/09/06 06:42
CRDT- 2023/08/14 04:03
PHST- 2023/09/06 06:42 [medline]
PHST- 2023/08/14 06:42 [pubmed]
PHST- 2023/08/14 04:03 [entrez]
AID - 10.1152/ajpcell.00153.2023 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2023 Sep 1;325(3):C780-C795. doi: 
      10.1152/ajpcell.00153.2023. Epub 2023 Aug 14.