PMID- 38473995
OWN - NLM
STAT- MEDLINE
DCOM- 20240314
LR  - 20240315
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 25
IP  - 5
DP  - 2024 Feb 27
TI  - Inhibitory Effects of Eicosapentaenoic Acid on Vascular Endothelial Growth 
      Factor-Induced Monocyte Chemoattractant Protein-1, Interleukin-6, and 
      Interleukin-8 in Human Vascular Endothelial Cells.
LID - 10.3390/ijms25052749 [doi]
LID - 2749
AB  - Vascular endothelial growth factor (VEGF) induces monocyte chemoattractant 
      protein-1 (MCP-1) and plays an important role in vascular inflammation and 
      atherosclerosis. We investigated the mechanisms of VEGF-induced MCP-1 expression 
      and the effects of eicosapentaenoic acid (EPA) in human umbilical vein 
      endothelial cells (HUVECs). Real-time reverse transcription polymerase chain 
      reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) demonstrated that 
      VEGF enhanced MCP-1 gene expression and protein secretion in HUVECs. Western 
      immunoblot analysis revealed that VEGF induced the phosphorylation of p38 
      mitogen-activated protein kinase (MAPK) and inhibitor of nuclear factor (NF)-kappaB 
      (IkappaB). Treatment with pharmacological inhibitors of p38 MAPK (SB203580) or NF-kappaB 
      (BAY11-7085) significantly suppressed VEGF-induced MCP-1 in HUVECs. EPA inhibited 
      VEGF-induced MCP-1 mRNA, protein secretion, phosphorylation of p38 MAPK, and the 
      translocation of phospho-p65 to the nucleus. Additionally, VEGF also stimulated 
      gene expressions of interleukin (IL)-6 and IL-8, which were suppressed by 
      SB203580, BAY11-7085, and EPA. The present study has demonstrated that 
      VEGF-induced activation of MCP-1, IL-6, and IL-8 involves the p38 MAPK and NF-kappaB 
      signaling pathways and that EPA inhibits VEGF-induced MCP-1, IL-6, and IL-8 via 
      suppressing these signaling pathways. This study supports EPA as a beneficial 
      anti-inflammatory and anti-atherogenic drug to reduce the VEGF-induced activation 
      of proinflammatory cytokine and chemokines.
FAU - Takenoshita, Yoko
AU  - Takenoshita Y
AD  - Institute for Clinical Research, NHO Kagoshima Medical Center, Kagoshima 
      892-0853, Japan.
FAU - Tokito, Akinori
AU  - Tokito A
AD  - Institute for Clinical Research, NHO Kagoshima Medical Center, Kagoshima 
      892-0853, Japan.
FAU - Jougasaki, Michihisa
AU  - Jougasaki M
AUID- ORCID: 0000-0002-3685-453X
AD  - Institute for Clinical Research, NHO Kagoshima Medical Center, Kagoshima 
      892-0853, Japan.
LA  - eng
PT  - Journal Article
DEP - 20240227
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - AAN7QOV9EA (Eicosapentaenoic Acid)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Humans
MH  - *Chemokine CCL2/metabolism
MH  - *Interleukin-6/metabolism
MH  - Interleukin-8/metabolism
MH  - NF-kappa B/metabolism
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - Eicosapentaenoic Acid/pharmacology
MH  - Human Umbilical Vein Endothelial Cells/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC10931732
OTO - NOTNLM
OT  - eicosapentaenoic acid
OT  - mitogen-activated protein kinase
OT  - monocyte chemoattractant protein-1
OT  - nuclear factor-kappa B
OT  - vascular endothelial cells
OT  - vascular endothelial growth factor
COIS- The authors declare no conflict of interest.
EDAT- 2024/03/13 06:47
MHDA- 2024/03/14 06:46
PMCR- 2024/02/27
CRDT- 2024/03/13 01:23
PHST- 2024/01/26 00:00 [received]
PHST- 2024/02/23 00:00 [revised]
PHST- 2024/02/25 00:00 [accepted]
PHST- 2024/03/14 06:46 [medline]
PHST- 2024/03/13 06:47 [pubmed]
PHST- 2024/03/13 01:23 [entrez]
PHST- 2024/02/27 00:00 [pmc-release]
AID - ijms25052749 [pii]
AID - ijms-25-02749 [pii]
AID - 10.3390/ijms25052749 [doi]
PST - epublish
SO  - Int J Mol Sci. 2024 Feb 27;25(5):2749. doi: 10.3390/ijms25052749.