Fas ligand neutralization attenuates hypertension, endothelin-1, and placental inflammation in an animal model of HELLP syndrome
| Autor: | Patrick B. Kyle, Reanna Robinson, Kedra Wallace, Jacob Gibbens, John Polk Dumas, Jamie Szczepanski, Teylor Bowles, Lucia Solis, Shauna-Kay Spencer |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
HELLP Syndrome medicine.medical_specialty Fas Ligand Protein Physiology HELLP syndrome Placenta Inflammation Fas ligand Preeclampsia Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Pregnancy Physiology (medical) Internal medicine medicine Animals Vascular Endothelial Growth Factor Receptor-1 030219 obstetrics & reproductive medicine Endothelin-1 Tumor Necrosis Factor-alpha business.industry medicine.disease Antibodies Neutralizing Endothelin 1 Hemolysis Rats Disease Models Animal Treatment Outcome 030104 developmental biology medicine.anatomical_structure Endocrinology Immunoglobulin G Female Tumor necrosis factor alpha medicine.symptom business Research Article |
| Zdroj: | Am J Physiol Regul Integr Comp Physiol |
| ISSN: | 1522-1490 0363-6119 |
| DOI: | 10.1152/ajpregu.00272.2019 |
| Popis: | 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 TNFα 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. |
| Databáze: | OpenAIRE |
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