PMID- 32457656
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 11
DP  - 2020
TI  - 2-Chlorofatty Aldehyde Elicits Endothelial Cell Activation.
PG  - 460
LID - 10.3389/fphys.2020.00460 [doi]
LID - 460
AB  - Endothelial activation and dysfunction are hallmarks of inflammation. 
      Neutrophil-vascular endothelium interactions have significant effects on vascular 
      wall physiology and pathology. Myeloperoxidase (MPO)-derived products released 
      from activated neutrophils can mediate the inflammatory response and contribute 
      to endothelial dysfunction. 2-Chlorofatty aldehyde (2-ClFALD) is the direct 
      oxidation product of MPO-derived hypochlorous acid (HOCl) targeting plasmalogen 
      phospholipids. The role of 2-ClFALD in endothelial dysfunction is poorly 
      understood and may be dependent on the vascular bed. This study compared the role 
      of 2-ClFALD in eliciting endothelial dysfunction in human coronary artery 
      endothelial cells (HCAEC), human lung microvascular endothelial cells (HLMVEC), 
      and human kidney endothelial cells (HKEC). Profound increases in selectin surface 
      expression as well as ICAM-1 and VCAM-1 surface expression were observed in HCAEC 
      and HLMVEC. The surface expression of these adherence molecules resulted in 
      robust adherence of neutrophils and platelets to 2-ClFALD treated endothelial 
      cells. In contrast to HCAEC and HLMVEC, 2-ClFALD-treated HKEC had substantially 
      reduced adherence molecule surface expression with no resulting increase in 
      platelet adherence. 2-ClFALD-treated HKEC did have an increase in neutrophil 
      adherence. All three endothelial cell lines treated with 2-ClFALD displayed a 
      time-dependent loss of barrier function. Further studies revealed 2-ClHDyA 
      localizes to ER and Golgi when using a synthetic alkyne analog of 2-ClFALD in 
      HCAEC and HLMVEC. These findings indicate 2-ClFALDs promote endothelial cell 
      dysfunction with disparate degrees of responsiveness depending on the vascular 
      bed of origin.
CI  - Copyright (c) 2020 McHowat, Shakya and Ford.
FAU - McHowat, Jane
AU  - McHowat J
AD  - Department of Pathology, Saint Louis University School of Medicine, St. Louis, 
      MO, United States.
AD  - Center for Cardiovascular Research, Saint Louis University School of Medicine, 
      St. Louis, MO, United States.
FAU - Shakya, Shubha
AU  - Shakya S
AD  - Center for Cardiovascular Research, Saint Louis University School of Medicine, 
      St. Louis, MO, United States.
AD  - Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis 
      University School of Medicine, St. Louis, MO, United States.
FAU - Ford, David A
AU  - Ford DA
AD  - Center for Cardiovascular Research, Saint Louis University School of Medicine, 
      St. Louis, MO, United States.
AD  - Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis 
      University School of Medicine, St. Louis, MO, United States.
LA  - eng
GR  - R01 GM115553/GM/NIGMS NIH HHS/United States
GR  - R01 GM129508/GM/NIGMS NIH HHS/United States
GR  - R01 HL137006/HL/NHLBI NIH HHS/United States
GR  - R01 HL137915/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20200508
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC7225355
OTO - NOTNLM
OT  - endothelial cells
OT  - fatty acids
OT  - inflammation
OT  - lipid mediators
OT  - plasmalogens
OT  - vascular biology
EDAT- 2020/05/28 06:00
MHDA- 2020/05/28 06:01
PMCR- 2020/05/08
CRDT- 2020/05/28 06:00
PHST- 2019/10/30 00:00 [received]
PHST- 2020/04/16 00:00 [accepted]
PHST- 2020/05/28 06:00 [entrez]
PHST- 2020/05/28 06:00 [pubmed]
PHST- 2020/05/28 06:01 [medline]
PHST- 2020/05/08 00:00 [pmc-release]
AID - 10.3389/fphys.2020.00460 [doi]
PST - epublish
SO  - Front Physiol. 2020 May 8;11:460. doi: 10.3389/fphys.2020.00460. eCollection 
      2020.