TY - JOUR
T1 - 17-Hydroxyprogesterone caproate improves T cells and NK cells in response to placental ischemia; new mechanisms of action for an old drug
AU - Elfarra, Jamil T.
AU - Cottrell, Jesse N.
AU - Cornelius, Denise C.
AU - Cunningham, Mark W.
AU - Faulkner, Jessica L.
AU - Ibrahim, Tarek
AU - Lamarca, Babbette
AU - Amaral, Lorena M.
N1 - Funding Information:
This work was also supported by National Institutes of Health grants R01HD067541, R00HL130456, and P20GM121334, American Heart Association 19CDA34670055 and 18CDA34110264. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
This work was also supported by National Institutes of Health grants R01HD067541 , R00HL130456 , and P20GM121334 , American Heart Association 19CDA34670055 and 18CDA34110264. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2019 International Society for the Study of Hypertension in Pregnancy
PY - 2020/1
Y1 - 2020/1
N2 - Preeclampsia (PE) is new onset hypertension during pregnancy associated with increased uterine artery resistance (UARI) and an imbalance among CD4 + T lymphocytes and natural killer (NK) cells. We have shown an important role for 17-hydroxyprogesterone caproate (17-OHPC) to improve hypertension and fetal demise in the RUPP rat model of PE. However we have not examined a role for 17-OHPC to improve NK cells and CD4+TH2 cells as possible mechanisms for improved fetal weight and hypertension. Therefore, we hypothesized that 17-OHPC lowers NK cells while improving the T cell ratio in the RUPP rat. RUPP was surgically induced on gestational day 14 in pregnant rats. 17-OHPC (3.32 mg/kg) was administered intraperitoneal on day 15, UARI was measured on day 18. Blood pressure (MAP), blood and tissues were collected on GD 19. MAP in NP rats (n = 9) was 100 ± 2, 104 ± 6 in Sham rats (n = 8), 128 ± 2 in RUPP (n = 11) and 115 ± 3 mmHg in RUPP + 17-OHPC (n = 10), p < 0.05. Pup weight and UARI were improved after 17-OHPC. Total and cytolytic placental NK cells were 38 ± 5, and 12 ± 2% gate in RUPP rats which decreased to 1.6 ± 0.5 and 0.4 ± 0.2% gate in RUPP + 17OHPC rats. CD4+ T cells were 40 ± 3 in RUPP rats, which significantly decreased to 7 ± 1 RUPP + 17-OHPC rats. Circulating and placental TH2 cells were 6.0 ± 1, 0.3 ± 0.1% gate in RUPP rats and 12 ± 1%, 2 ± 0.5% gate in RUPP + 17-OHPC rats, p < 0.05 This study identifies new mechanisms whereby 17-OHPC improves outcomes in response to placental ischemia.
AB - Preeclampsia (PE) is new onset hypertension during pregnancy associated with increased uterine artery resistance (UARI) and an imbalance among CD4 + T lymphocytes and natural killer (NK) cells. We have shown an important role for 17-hydroxyprogesterone caproate (17-OHPC) to improve hypertension and fetal demise in the RUPP rat model of PE. However we have not examined a role for 17-OHPC to improve NK cells and CD4+TH2 cells as possible mechanisms for improved fetal weight and hypertension. Therefore, we hypothesized that 17-OHPC lowers NK cells while improving the T cell ratio in the RUPP rat. RUPP was surgically induced on gestational day 14 in pregnant rats. 17-OHPC (3.32 mg/kg) was administered intraperitoneal on day 15, UARI was measured on day 18. Blood pressure (MAP), blood and tissues were collected on GD 19. MAP in NP rats (n = 9) was 100 ± 2, 104 ± 6 in Sham rats (n = 8), 128 ± 2 in RUPP (n = 11) and 115 ± 3 mmHg in RUPP + 17-OHPC (n = 10), p < 0.05. Pup weight and UARI were improved after 17-OHPC. Total and cytolytic placental NK cells were 38 ± 5, and 12 ± 2% gate in RUPP rats which decreased to 1.6 ± 0.5 and 0.4 ± 0.2% gate in RUPP + 17OHPC rats. CD4+ T cells were 40 ± 3 in RUPP rats, which significantly decreased to 7 ± 1 RUPP + 17-OHPC rats. Circulating and placental TH2 cells were 6.0 ± 1, 0.3 ± 0.1% gate in RUPP rats and 12 ± 1%, 2 ± 0.5% gate in RUPP + 17-OHPC rats, p < 0.05 This study identifies new mechanisms whereby 17-OHPC improves outcomes in response to placental ischemia.
KW - 17-Hydroxyprogesterone caproate
KW - Natural killer cells
KW - Preeclampsia
KW - Progesterone
UR - https://www.scopus.com/pages/publications/85076531982
UR - https://www.scopus.com/pages/publications/85076531982#tab=citedBy
U2 - 10.1016/j.preghy.2019.11.005
DO - 10.1016/j.preghy.2019.11.005
M3 - Article
C2 - 31806502
AN - SCOPUS:85076531982
SN - 2210-7789
VL - 19
SP - 226
EP - 232
JO - Pregnancy Hypertension
JF - Pregnancy Hypertension
ER -