PMID- 28501275
OWN - NLM
STAT- MEDLINE
DCOM- 20180319
LR  - 20200914
IS  - 2210-7797 (Electronic)
IS  - 2210-7789 (Print)
IS  - 2210-7789 (Linking)
VI  - 8
DP  - 2017 Apr
TI  - Dysregulation of the Fas/FasL system in an experimental animal model of HELLP 
      syndrome.
PG  - 26-30
LID - S2210-7789(16)30044-7 [pii]
LID - 10.1016/j.preghy.2017.02.004 [doi]
AB  - INTRODUCTION: Placental FasL is up-regulated in women with HELLP (hemolysis 
      elevated liver enzyme and low platelet) syndrome and has been proposed to 
      contribute to the liver damage seen in these patients. OBJECTIVE: This study 
      aimed to determine if an experimental rodent model of HELLP also had 
      dysregulation of Fas/FasL compared to normal pregnant (NP) rats. We also set out 
      to determine if blockade of the endothelin system regulated Fas/FasL expression 
      in HELLP rats. STUDY DESIGN: On gestational day (GD) 12, sEng (7ug/kg) and sFlt-1 
      (4.7ug/kg) infusion began via mini-osmotic pump into NP rats. On GD19 plasma and 
      tissue were collected and FasL and Fas were measured via enzyme linked 
      immunosorbent assay and gene expression via real-time PCR. RESULTS: HELLP rats 
      had significantly more circulating and placental FasL compared to NP rats, 
      whereas hepatic FasL was decreased and placental Fas was increased compared to NP 
      rats. Administration of an endothelin A receptor antagonist (ET(A)) beginning on 
      GD12 significantly decreased placental expression of Fas in HELLP rats. Liver 
      mRNA transcript of Fas was significantly increased in HELLP rats compared to NP 
      rats. CONCLUSION: These data suggest that rats in this experimental model of 
      HELLP syndrome have abnormal expression of the Fas/FasL system. Future studies 
      will examine the sources of Fas/FasL dysregulation in this model and if blockade 
      could reduce some of the inflammation and hypertension associated with HELLP 
      syndrome.
CI  - Copyright (c) 2017 International Society for the Study of Hypertension in 
      Pregnancy. Published by Elsevier B.V. All rights reserved.
FAU - Gibbens, Jacob
AU  - Gibbens J
AD  - Department of Obstetrics & Gynecology, University of Mississippi Medical Center, 
      2500 North State St., Jackson, MS 39216, USA. Electronic address: 
      jdgibbens@umc.edu.
FAU - Morris, Rachael
AU  - Morris R
AD  - Department of Obstetrics & Gynecology, University of Mississippi Medical Center, 
      2500 North State St., Jackson, MS 39216, USA. Electronic address: 
      rmorris@umc.edu.
FAU - Bowles, Teylor
AU  - Bowles T
AD  - Department of Obstetrics & Gynecology, University of Mississippi Medical Center, 
      2500 North State St., Jackson, MS 39216, USA. Electronic address: 
      tbowles@umc.edu.
FAU - Spencer, Shauna-Kay
AU  - Spencer SK
AD  - Department of Obstetrics & Gynecology, University of Mississippi Medical Center, 
      2500 North State St., Jackson, MS 39216, USA. Electronic address: 
      sspencer2@umc.edu.
FAU - Wallace, Kedra
AU  - Wallace K
AD  - Department of Obstetrics & Gynecology, University of Mississippi Medical Center, 
      2500 North State St., Jackson, MS 39216, USA. Electronic address: 
      kwallace2@umc.edu.
LA  - eng
GR  - P20 GM103476/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20170224
PL  - Netherlands
TA  - Pregnancy Hypertens
JT  - Pregnancy hypertension
JID - 101552483
RN  - 0 (Endoglin)
RN  - 0 (Endothelin A Receptor Antagonists)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fas protein, rat)
RN  - 0 (Faslg protein, rat)
RN  - 0 (Pyrrolidines)
RN  - 0 (RNA, Messenger)
RN  - 0 (fas Receptor)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
RN  - V6D7VK2215 (Atrasentan)
SB  - IM
MH  - Animals
MH  - Atrasentan
MH  - Disease Models, Animal
MH  - Endoglin
MH  - Endothelin A Receptor Antagonists/pharmacology
MH  - Fas Ligand Protein/blood/genetics/*metabolism
MH  - Female
MH  - Gene Expression Regulation
MH  - HELLP Syndrome/blood/chemically induced/genetics/*metabolism
MH  - Liver/drug effects/*metabolism
MH  - Placenta/drug effects/*metabolism
MH  - Pregnancy
MH  - Pyrrolidines/pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats, Sprague-Dawley
MH  - Time Factors
MH  - Vascular Endothelial Growth Factor Receptor-1
MH  - fas Receptor/blood/genetics/*metabolism
PMC - PMC5433259
MID - NIHMS858056
OTO - NOTNLM
OT  - Endothelin
OT  - Fas
OT  - Fas ligand
OT  - HELLP syndrome
OT  - Pregnancy
COIS- None of the authors have any conflicts of interest to disclose
EDAT- 2017/05/16 06:00
MHDA- 2018/03/20 06:00
PMCR- 2018/04/01
CRDT- 2017/05/15 06:00
PHST- 2016/05/02 00:00 [received]
PHST- 2017/02/06 00:00 [revised]
PHST- 2017/02/21 00:00 [accepted]
PHST- 2017/05/15 06:00 [entrez]
PHST- 2017/05/16 06:00 [pubmed]
PHST- 2018/03/20 06:00 [medline]
PHST- 2018/04/01 00:00 [pmc-release]
AID - S2210-7789(16)30044-7 [pii]
AID - 10.1016/j.preghy.2017.02.004 [doi]
PST - ppublish
SO  - Pregnancy Hypertens. 2017 Apr;8:26-30. doi: 10.1016/j.preghy.2017.02.004. Epub 
      2017 Feb 24.