Interferon γ neutralization reduces blood pressure, uterine artery resistance index, and placental oxidative stress in placental ischemic rats

Autor: Madison T. Crosby, Olivia K. Travis, Jan M. Williams, Alex N Smith, Henry T. Nguyen, Geilda A. Tardo, Denise C. Cornelius, Tyler Johnson, George W. Booz, Chelsea Giachelli, Andrea K Brown, Shani Siddiq
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
medicine.medical_specialty
Physiology
Placenta
Intrauterine growth restriction
030204 cardiovascular system & hematology
medicine.disease_cause
Preeclampsia
Rats
Sprague-Dawley
03 medical and health sciences
Interferon-gamma
0302 clinical medicine
Pre-Eclampsia
Ischemia
Pregnancy
Physiology (medical)
medicine.artery
Internal medicine
medicine
Maternal hypertension
Animals
Arterial Pressure
Placental Circulation
Angiogenic Proteins
Uterine artery
chemistry.chemical_classification
Reactive oxygen species
Fetal Growth Retardation
business.industry
Antibodies
Monoclonal
medicine.disease
Killer Cells
Natural
Disease Models
Animal
Oxidative Stress
Uterine Artery
030104 developmental biology
Blood pressure
Endocrinology
chemistry
Female
Vascular Resistance
business
Reactive Oxygen Species
Soluble fms-like tyrosine kinase-1
Oxidative stress
Research Article
Zdroj: Am J Physiol Regul Integr Comp Physiol
Popis: Preeclampsia (PE) is characterized by maternal hypertension, intrauterine growth restriction, and increased cytolytic natural killer cells (cNKs), which secrete interferon γ (IFNγ). However, the precise role of IFNγ in contributing to PE pathophysiology remains unclear. Using the reduced uterine perfusion pressure (RUPP) rat model of placental ischemia, we tested the hypothesis that neutralization of IFNγ in RUPPs will decrease placental reactive oxygen species (ROS) and improve vascular function resulting in decreased MAP and improved fetal growth. On gestation day ( GD) 14, the RUPP procedure was performed and on GDs 15 and 18, a subset of normal pregnant rats (NP) and RUPP rats were injected with 10 μg/kg of an anti-rat IFNγ monoclonal antibody. On GD 18, uterine artery resistance index (UARI) was measured via Doppler ultrasound and on GD 19, mean arterial pressure (MAP) was measured, animals were euthanized, and blood and tissues were collected for analysis. Increased MAP was observed in RUPP rats compared with NP and was reduced in RUPP + anti-IFNγ. Placental ROS was also increased in RUPP rats compared with NP rats and was normalized in RUPP + anti-IFNγ. Fetal and placental weights were reduced in RUPP rats, but were not improved following anti-IFNγ treatment. However, UARI was elevated in RUPP compared with NP rats and was reduced in RUPP + anti-IFNγ. In conclusion, we observed that IFNγ neutralization reduced MAP, UARI, and placental ROS in RUPP recipients. These data suggest that IFNγ is a potential mechanism by which cNKs contribute to PE pathophysiology and may represent a therapeutic target to improve maternal outcomes in PE.
Databáze: OpenAIRE
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