Abstract P213: Placental Ischemia-Stimulated Natural Killer Cells Contribute To Hypertension, Vascular Dysfunction, And Intrauterine Growth Restriction In Pregnant Rats

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Olivia K Travis ◽  
Cedar Baik ◽  
Geilda A Tardo ◽  
Lorena M Amaral ◽  
Carmilya Jackson ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Natural Killer ◽  
Intrauterine Growth Restriction ◽  
Vascular Dysfunction ◽  
Growth Restriction ◽  
Fetal Weight ◽  
Direct Role ◽  
Pregnant Rats ◽  
Intrauterine Growth ◽  
Placental Ischemia

The Reduced Uterine Perfusion Pressure (RUPP) rat model of placental ischemia mimics many characteristics of preeclampsia (PE) such as hypertension (HTN), intrauterine growth restriction (IUGR), and increased cytolytic natural killer cells (cNKs). We have previously shown that natural killer (NK) cell depletion in RUPP rats improves PE pathophysiology and that RUPP NKs have a 5-fold increase in cytotoxicity vs normal pregnant NKs. In this study, we tested the hypotheses that (1) RUPP stimulated NKs play a direct role in causing HTN and IUGR in pregnant rats and (2) normal pregnant control (Sham) NKs attenuate HTN and IUGR in RUPP rats. NKs were isolated from the placentas of Sham and RUPP rats on gestation day (GD) 19. On GD14, vehicle or 5x10 6 RUPP NKs were infused i.v. into a subset of Sham rats, and vehicle or 5x10 6 Sham NKs were infused i.v. into a subset of RUPP rats. On GD18, Uterine Artery Resistance Index (UARI) was measured via Doppler Ultrasound; GD19, cNKs were quantified via flow cytometry and MAP, fetal weight, and blood were acquired. Plasma VEGF and sFlt-1 were measured via ELISA. Placental cNKs (% gated) increased from 3±1% in Sham to 19±5% in RUPP and 21±4% in Sham+RUPP NK (p<0.05 vs Sham), and decreased to 3±1% in RUPP+Sham NK (p<0.05 vs RUPP). Circulating cNKs also followed this trend. MAP increased from 102±1 mmHg in Sham to 130±2 mmHg in RUPP and 121±2 mmHg in Sham+RUPP NK (p<0.05 vs Sham), and was blunted to 113±1 mmHg in RUPP+Sham NK (p<0.05 vs RUPP). Fetal weight decreased from 2.4±0.04 g in Sham to 2.1±0.07 g in RUPP and 2.1±0.03 g in Sham+RUPP NK (p<0.05 vs Sham), and this was normalized to 2.3±0.03 g in RUPP+Sham NK (p<0.05 vs RUPP). UARI increased from 0.56±0.05 in Sham to 0.75±0.06 in RUPP and 0.76±0.05 in Sham+RUPP NK (p<0.05 vs Sham), and decreased to 0.64±0.05 in RUPP+Sham NK (p<0.05 vs RUPP). Circulating sFlt-1 increased from 76±15 pg/mL in Sham to 1391±424 pg/mL in RUPP (p<0.05 vs Sham), 780±256 pg/mL in Sham+RUPP NK, and decreased to 67±8 pg/mL in RUPP+Sham NK (p<0.05 vs RUPP). Furthermore, circulating VEGF decreased in RUPP and Sham+RUPP NK compared to Sham (p<0.05), and increased in RUPP+Sham NK (p<0.05 vs RUPP). These data demonstrate a direct role for cNKs to mediate vascular dysfunction in PE and for normal NKs to promote positive maternal and fetal outcomes.

Abstract 017: Cytolytic Natural Killer Cells Play a Direct Role in Causing Hypertension and Intrauterine Growth Restriction in Pregnant Rats

Hypertension ◽  
2019 ◽  
Vol 74 (Suppl_1) ◽  
Author(s):  
Olivia K Travis ◽  
Cedar H Baik ◽  
Carmilya Jackson ◽  
Chelsea Giachelli ◽  
Jan M Williams ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Natural Killer ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Direct Role ◽  
Pregnant Rats ◽  
Killer Cells ◽  
Intrauterine Growth

Abstract 133: Depletion of Natural Killer Cell Activation in Response to Placental Ischemia Improves Hypertension and Intrauterine Growth Restriction During Pregnancy

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Denise C Cornelius ◽  
Jamil Elfarra ◽  
Lorena M Amaral ◽  
Maggie McCalmon ◽  
Mark W Cunningham ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nk Cells ◽  
Renal Dysfunction ◽  
Natural Killer ◽  
Intrauterine Growth Restriction ◽  
Cell Activation ◽  
Nk Cell ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Placental Ischemia

Women with preeclampsia (PE), newly developed hypertension and renal dysfunction during pregnancy, have small-for-gestational-age babies and demonstrate an increase in the cytolytic natural killer (NK) cell activation. The specific role of cytolytic NK cells in the pathophysiology of PE has not been clearly defined. The reduced uterine perfusion pressure (RUPP) model of placental ischemia (PI) exhibits many of the characteristics of PE including hypertension, renal dysfunction, chronic inflammation and intrauterine growth restriction (IUGR). In this study, we tested the hypothesis that PI results in cytolytic activation of NK cells, and examined a role for a reduction in NK cells in RUPP to attenuate PE-like characteristics in response to PI. In this study NK cells were depleted in RUPP rats by intraperitoneal administration of the Anti-asialo GM1 antibody on gestation days 15 and 17. PBMCs and placental lymphocytes were examined via flow cytometry to quantify cytolytic NK cells and to verify NK cell depletion, blood pressure (MAP) and pup weight were measured. While total placental NK cells numbers did not change in response to PI (NP: 14±4.5%; RUPP: 14.3±3.8%), cytolytic activation of placental NK cells significantly increased in response to PI (NP: 3.4±1.1% vs RUPP 10.0±3.4%; p<0.05). Moreover, depletion of NK cells in RUPP (total NK: RUPP: 14.3±3.8% vs RUPP+NKD: 3.5±0.9%) significantly improved blood pressure and intrauterine growth restriction (IUGR): MAP significantly increased in response to PI from 109.5±2.3 mmHg in NP (n=10) to 125.4±2.7 mmHg (n=9) in RUPP rats (p<0.001). Depletion of NK cells with the cell specific depleting antibody significantly lowered blood pressure to 114.4.±1.9 mmHg in RUPP+NKD rats (n=11, p<0.01). Additionally, NK cell depletion in RUPP significantly reduced IUGR in response to PI (1.85±0.06g in RUPP vs. 2.0±0.4g in RUPP+NKD; p<0.05). Depletion of NK cells in RUPP rats was positively associated with lowering blood pressure and blunting IUGR in response to PI. These results suggest a role for cytolytic NK in contributing to hypertension and IUGR in response to PI, potentially identifying previously unknown mechanisms of PE pathophysiology and new therapeutic targets to improve maternal and fetal outcomes of PE.

scholarly journals Natural killer cells mediate pathophysiology in response to reduced uterine perfusion pressure

2017 ◽  
Vol 131 (23) ◽  
pp. 2753-2762 ◽  
Author(s):  
Jamil Elfarra ◽  
Lorena M. Amaral ◽  
Maggie McCalmon ◽  
Jeremy D. Scott ◽  
Mark W. Cunningham ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Intrauterine Growth Restriction ◽  
Perfusion Pressure ◽  
Interferon Γ ◽  
Growth Restriction ◽  
Pregnant Rats ◽  
Intrauterine Growth ◽  
Uterine Perfusion ◽  
Factor Α

Preeclampsia is associated with hypertension, small-for-gestational-age babies, and increased cytolytic natural killer (NK) cells. The specific role of cytolytic NK cells in the pathophysiology of preeclampsia has not been clearly defined. We hypothesized that Reduced Uterine Perfusion Pressure (RUPP) stimulates proliferation and cytolytic activation of NK cells, and that reducing NK cells in RUPP would prevent hypertension, intrauterine growth restriction, and inflammation in response to placental ischemia. RUPP was induced on gestation day (GD) 14 in pregnant rats. NK cells were depleted by i.p. administration of anti-asialo GM1 antibody on GDs 15 and 17. Placental and circulating NK cells were quantified via flow cytometry, mean arterial pressure (MAP), fetal weights, and cytokines were measured on GD 19. Total placental NK cells were 7.4 ± 2% of gated cells in normal pregnant (NP; n=10) and 16.5 ± 3% of gated cells in RUPP (n=10) rats. Furthermore, cytolytic placental NK cells also increased in RUPP. Depletion of NK cells in RUPP (RUPP + anti-ASGM1) significantly improved MAP and fetal weights. MAP was 108 ± 2 mmHg in NP, 125 ± 2 mmHg in RUPP, and 112 ± 2 mmHg in RUPP + anti-ASGM1 (n=12). Fetal weight was 2.32 ± 0.05 in NP, 1.8 ± 0.04g in RUPP, and increased to 2.0 ± 0.04g in RUPP + anti-ASGM1. Placental interferon-γ (IFN-γ) was 40.4 ± 5.2 pg/mg in NP, 72.17 ± 3.2 pg/mg in RUPP, and 44.0 ± 6.5 pg/mg in RUPP + anti-ASGM1 (P<0.05). Placental tumor necrosis factor-α (TNF-α) was 17.9 ± 1.7 pg/mg in NP, 23.9 ± 2.2 pg/mg in RUPP, and 12.9 ± 2.3 pg/mg in RUPP + anti-ASGM1 (P<0.05). Depletion of NK cells significantly lowered MAP, intrauterine growth restriction, and inflammation in RUPP rats indicating that cytolytic NK cells are important in preeclampsia pathophysiology.

scholarly journals Intralipid Infusion in Pregnant Rats Induces Plasma Angiogenic Imbalance, Inflammation, and Intrauterine Growth Restriction

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Jeremy W. Duncan ◽  
Matthew Bergeron ◽  
Jessica L. Bradshaw ◽  
Frank T. Spradley ◽  
Joey P. Granger
Keyword(s):  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Pregnant Rats ◽  
Intrauterine Growth

CORRELATION BETWEEN CEREBROPLACENTAL RATIO AND ADVERSE OUTCOMES IN INTRAUTERINE GROWTH RESTRICTION

2018 ◽  
Vol 8 (3) ◽  
pp. 82-89
Author(s):  
Tran Thao Nguyen Nguyen ◽  
Van Duc Vo ◽  
Ngoc Thanh Cao
Keyword(s):  
Gestational Age ◽  
Intrauterine Growth Restriction ◽  
Adverse Outcomes ◽  
Growth Restriction ◽  
Fetal Weight ◽  
Intrauterine Growth ◽  
Cerebroplacental Ratio ◽  
Gestational Age At Delivery ◽  
The Mean ◽  
Estimated Fetal Weight

Objectives: To identify the values of CPR in intrauterine growth restriction and evaluate the correlation between cerebroplacental ratio and adverse outcomes in intrauterine growth restriction. Material and methods: A prospective study was conducted on 74 cases of intrauterine growth restriction with an estimated fetal weight less than 10th percentile, at Departement of Obstetric and Gynecology of Hue University of Medicine and Pharmacy from 05/2016 – 05/2017. CPR was calculated by PIMCA/PIUA.. The adverse outcomes included gestational age at delivery, methods used to delivery, APGAR score below 7 at 1 minutes and 5 minutes, admission at NICU, perinatal deaths, neonatals deaths. Results: The mean of CPR in group of early IUGR and late IUGR were 0.55 ± 0.14, 1.59 ± 0.69, respectively. The mean of CPR in group IUGR with an estimated fetal weight under the 3th percentile was 1.49 ± 0.76, lower than the mean of CPR in group IUGR with an estimated fetal weight from 3th percentile to 10th percentile. With cut – off at 1, CPR < 1 had the higher prevalence in group of early IUGR, in group IUGR with the estimated fetal weight below the 3th percentile, in group IUGR with hypoamniotic or oligohydramnios. The mean of gestational age at delivery of group IUGR with CPR < 1 and CPR >1 were 37.00 ± 3.18, and 38.59 ± 1.76, respectively. The rate of emergency cesarean section deliveries in the CPR < 1 and CPR > 1 group were 68.75% and 39.65%, respectively (p <0.05). Percentage of neonatal with APGAR ≤ 7 at 1 minute in the group with CPR < 1 and CPR > 1 were 56.25% and 22.41%, respectively. Rate of prenatal death was 12.5 in group IUGR with CPR < 1. Conclusion: There was a strong correlation between CPR and adverse outcomes in intrauterine growth restriction. Key words: intrauterine growth restriction, CPR ratio, middle cerebro artery, umbilical artery

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