PMID- 25171777
OWN - NLM
STAT- MEDLINE
DCOM- 20150702
LR  - 20231213
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 236
IP  - 2
DP  - 2014 Oct
TI  - Endothelial connexin 32 regulates tissue factor expression induced by 
      inflammatory stimulation and direct cell-cell interaction with activated cells.
PG  - 430-7
LID - S0021-9150(14)01301-X [pii]
LID - 10.1016/j.atherosclerosis.2014.07.025 [doi]
AB  - OBJECTIVE: Endothelial cell (EC) interacts with adjacent EC through gap junction, 
      and abnormal expression or function of Cxs is associated with cardiovascular 
      diseases. In patients with endothelial dysfunction, the up-regulation of tissue 
      factor (TF) expression promotes the pathogenic activation of blood coagulation, 
      however the relationship between gap junctions and TF expression in ECs remains 
      uncharacterized. ECs express the gap junction (GJ) proteins connexin32 (Cx32), 
      Cx37, Cx40 and Cx43. We investigated the role of endothelial gap junctions, 
      particularly Cx32, in modulating TF expression during vascular inflammation. 
      METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were 
      stimulated with tumor necrosis factor-alpha (TNF-alpha) and TF activity was assessed in 
      the presence of GJ blockers and an inhibitory anti-Cx32 monoclonal antibody. 
      Treatment with GJ blockers and anti-Cx32 monoclonal antibody enhanced the 
      TNF-alpha-induced TF activity and mRNA expression in HUVECs. TNF-alpha-activated effector 
      HUVECs or mouse MS-1 cells were co-cultured with non-stimulated acceptor HUVECs 
      and TF expression in acceptor HUVECs was detected. Effector EC induced TF 
      expression in adjacent acceptor HUVECs through direct cell-cell interaction. 
      Cell-cell interaction induced TF expression was reduced by anti-intercellular 
      adhesion molecule-1 (ICAM1) monoclonal antibody. Soluble ICAM1-Fc fusion protein 
      promotes TF expression. GJ blockers and anti-Cx32 monoclonal antibody enhanced TF 
      expression induced by cell-cell interaction and ICAM1-Fc treatment. CONCLUSION: 
      Blockade of endothelial Cx32 increased TF expression induced by TNF-alpha stimulation 
      and cell-cell interaction which was at least partly dependent upon ICAM1. These 
      results suggest that direct Cx32-mediated interaction modulates TF expression in 
      ECs during vascular inflammation.
CI  - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved.
FAU - Okamoto, Takayuki
AU  - Okamoto T
AD  - Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University 
      Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
FAU - Akita, Nobuyuki
AU  - Akita N
AD  - Faculty of Medical Engineering, Suzuka University of Medical Science, 1001-1, 
      Kishioka-cho, Suzuka, Mie 510-0293, Japan.
FAU - Hayashi, Tatsuya
AU  - Hayashi T
AD  - Department of Biochemistry, Mie Prefectural College of Nursing, 1-1-1 Yumegaoka, 
      Tsu, Mie 514-0116, Japan.
FAU - Shimaoka, Motomu
AU  - Shimaoka M
AD  - Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University 
      Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
FAU - Suzuki, Koji
AU  - Suzuki K
AD  - Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University 
      Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan; Faculty of 
      Pharmaceutical Science, Suzuka University of Medical Science, 3500-3, 
      Minamitamagaki-cho, Suzuka, Mie 513-8679, Japan. Electronic address: 
      suzukiko@suzuka-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140815
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Connexins)
RN  - 0 (Immunoconjugates)
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Oleic Acids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 7L25QK8BWO (oleylamide)
RN  - 9035-58-9 (Thromboplastin)
RN  - MM6384NG73 (Carbenoxolone)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Blood Coagulation
MH  - Carbenoxolone/pharmacology
MH  - Cell Communication
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Connexins/antagonists & inhibitors/deficiency/*physiology
MH  - Endothelial Cells/*metabolism
MH  - Gap Junctions/drug effects/physiology
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Immunoconjugates/pharmacology
MH  - Immunoglobulin Fc Fragments
MH  - Intercellular Adhesion Molecule-1/pharmacology/physiology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Oleic Acids/pharmacology
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Recombinant Fusion Proteins/pharmacology
MH  - Thromboplastin/*biosynthesis/genetics
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Vasculitis/*metabolism
MH  - Gap Junction beta-1 Protein
OTO - NOTNLM
OT  - Cell-cell interaction
OT  - Connexin
OT  - Endothelial cell
OT  - Gap junction
OT  - Inflammation
OT  - Tissue factor
EDAT- 2014/08/30 06:00
MHDA- 2015/07/03 06:00
CRDT- 2014/08/30 06:00
PHST- 2014/04/02 00:00 [received]
PHST- 2014/07/22 00:00 [revised]
PHST- 2014/07/24 00:00 [accepted]
PHST- 2014/08/30 06:00 [entrez]
PHST- 2014/08/30 06:00 [pubmed]
PHST- 2015/07/03 06:00 [medline]
AID - S0021-9150(14)01301-X [pii]
AID - 10.1016/j.atherosclerosis.2014.07.025 [doi]
PST - ppublish
SO  - Atherosclerosis. 2014 Oct;236(2):430-7. doi: 
      10.1016/j.atherosclerosis.2014.07.025. Epub 2014 Aug 15.