PMID- 32640833
OWN - NLM
STAT- MEDLINE
DCOM- 20201005
LR  - 20210802
IS  - 1522-1490 (Electronic)
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 319
IP  - 2
DP  - 2020 Aug 1
TI  - Fas ligand neutralization attenuates hypertension, endothelin-1, and placental 
      inflammation in an animal model of HELLP syndrome.
PG  - R195-R202
LID - 10.1152/ajpregu.00272.2019 [doi]
AB  - Neutralization of FasL is linked to suppression of hypertension, placental 
      inflammation, and endothelin system activation in an animal model of hemolysis, 
      elevated liver enzymes, low platelets (HELLP) syndrome. During HELLP syndrome the 
      placenta has been reported to serve as the primary source of Fas ligand (FasL), 
      which has an impact on inflammation and hypertension during pregnancy and is 
      dysregulated in women with severe preeclampsia and HELLP syndrome. We hypothesize 
      that neutralization of FasL during pregnancy in an animal model of HELLP syndrome 
      decreases inflammation and placental apoptosis, improves endothelial damage, and 
      improves hypertension. On gestational day (GD) 12, rats were chronically infused 
      with placental antiangiogenic factors sFlt-1 and sEng to induce HELLP syndrome. 
      To neutralize FasL, MFL4 or FasL antibody was infused into a subset of HELLP or 
      normal pregnant rats on GD13. IgG infusion into another group of NP and HELLP 
      rats on GD13 was used as a control for FasL antibody, and all rats were 
      euthanized on GD19 after blood pressure measurement. Plasma and placentas were 
      collected to assess inflammation, apoptosis, and the degree of placental debris 
      activation of endothelial cells. Administration of MFL4 to HELLP rats 
      significantly decreased blood pressure compared with untreated HELLP rats and 
      HELLP rats infused with IgG and improved the biochemistry of HELLP syndrome. Both 
      circulating and placental FasL were significantly attenuated in response to MFL4 
      infusion, as were levels of placental and circulating TNFalpha when compared with 
      untreated HELLP rats and HELLP rats infused with IgG. Endothelial cells exposed 
      to placental debris and media from HP + MFL4 rats secreted significantly less 
      endothelin-1 compared with stimulated endothelial cells from HELLP placentas. 
      Neutralization of FasL is associated with decreased MAP and improvement in 
      placental inflammation and endothelial damage in an animal model of HELLP 
      syndrome.
FAU - Gibbens, Jacob
AU  - Gibbens J
AD  - Department of Obstetrics and Gynecology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Spencer, Shauna-Kay
AU  - Spencer SK
AD  - Department of Obstetrics and Gynecology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Solis, Lucia
AU  - Solis L
AD  - Department of Obstetrics and Gynecology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Bowles, Teylor
AU  - Bowles T
AD  - Department of Obstetrics and Gynecology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Kyle, Patrick B
AU  - Kyle PB
AD  - Department of Pathology, University of Mississippi Medical Center, Jackson, 
      Mississippi.
FAU - Szczepanski, Jamie L
AU  - Szczepanski JL
AD  - Department of Obstetrics and Gynecology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Dumas, John Polk
AU  - Dumas JP
AD  - Department of Obstetrics and Gynecology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Robinson, Reanna
AU  - Robinson R
AD  - Department of Obstetrics and Gynecology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Wallace, Kedra
AU  - Wallace K
AD  - Department of Obstetrics and Gynecology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
LA  - eng
GR  - P20 GM121334/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200708
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Endothelin-1)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
SB  - IM
MH  - Animals
MH  - Antibodies, Neutralizing/*therapeutic use
MH  - Disease Models, Animal
MH  - Endothelin-1/*blood
MH  - Fas Ligand Protein/blood/*immunology
MH  - Female
MH  - HELLP Syndrome/blood/*drug therapy/immunology/physiopathology
MH  - Immunoglobulin G
MH  - Placenta/immunology/*physiopathology
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha/blood
MH  - Vascular Endothelial Growth Factor Receptor-1/blood
PMC - PMC7473892
OTO - NOTNLM
OT  - Fas
OT  - HELLP syndrome
OT  - TNF
OT  - hypertension
OT  - preeclampsia
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2020/07/10 06:00
MHDA- 2020/10/06 06:00
PMCR- 2021/08/01
CRDT- 2020/07/10 06:00
PHST- 2020/07/10 06:00 [pubmed]
PHST- 2020/10/06 06:00 [medline]
PHST- 2020/07/10 06:00 [entrez]
PHST- 2021/08/01 00:00 [pmc-release]
AID - R-00272-2019 [pii]
AID - 10.1152/ajpregu.00272.2019 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2020 Aug 1;319(2):R195-R202. doi: 
      10.1152/ajpregu.00272.2019. Epub 2020 Jul 8.