Low-Dose Acetylsalicylic Acid Treatment Modulates the Production of Cytokines and Improves Trophoblast Function in an in Vitro Model of Early-Onset Preeclampsia

Shanika Panagodage, Hannah Ee Juen Yong, Fabricio Da Silva Costa, Anthony J Borg, Bill Kalionis, Shaun P. Brennecke, Padma Murthi

Research output: Contribution to journalArticleResearchpeer-review

23 Citations (Scopus)

Abstract

Preeclampsia (PE), a serious hypertensive disorder of pregnancy, remains a leading cause of perinatal morbidity and mortality worldwide. Perturbed trophoblast function and impaired placental development early in pregnancy are key features. Low-dose acetylsalicylic acid (LDA) administered before 16 weeks' gestation significantly reduces the risk for PE. However, the exact mechanisms of action of LDA, particularly on trophoblast function, are unclear. We hypothesized that LDA influences placental trophoblast function and reverses PE-associated abnormalities. This study aimed to determine the effects of serum from normotensive women and from those with PE with or without LDA treatment on a model of placental syncytium. On cytokine profiling, LDA increased placental growth factor production and selectively restored PE serum–induced alterations in levels of cytokines [activated leukocyte cell adhesion molecule, CXCL-16, and ErbB3] to those in normotensive serum–treated cells. PE serum–induced increases in the apoptotic markers P53 mRNA expression, IKBKE mRNA expression, caspase 3 activity, and decreased BIRC8 mRNA expression, were attenuated by LDA treatment. LDA treatment also reduced abnormal differentiation caused by PE serum administration. Possible mechanisms by which LDA influences PE-affected trophoblast cells in vitro are by modulating cytokine secretion, reducing apoptosis to levels seen in normotensive serum–treated cells, and preventing the premature trophoblast differentiation commonly observed in PE.

Original languageEnglish
Pages (from-to)3217-3224
Number of pages8
JournalAmerican Journal of Pathology
Volume186
Issue number12
DOIs
Publication statusPublished - 1 Dec 2016

Cite this

@article{ed9d205d1be04c3fb45217f5f16e0ac5,
title = "Low-Dose Acetylsalicylic Acid Treatment Modulates the Production of Cytokines and Improves Trophoblast Function in an in Vitro Model of Early-Onset Preeclampsia",
abstract = "Preeclampsia (PE), a serious hypertensive disorder of pregnancy, remains a leading cause of perinatal morbidity and mortality worldwide. Perturbed trophoblast function and impaired placental development early in pregnancy are key features. Low-dose acetylsalicylic acid (LDA) administered before 16 weeks' gestation significantly reduces the risk for PE. However, the exact mechanisms of action of LDA, particularly on trophoblast function, are unclear. We hypothesized that LDA influences placental trophoblast function and reverses PE-associated abnormalities. This study aimed to determine the effects of serum from normotensive women and from those with PE with or without LDA treatment on a model of placental syncytium. On cytokine profiling, LDA increased placental growth factor production and selectively restored PE serum–induced alterations in levels of cytokines [activated leukocyte cell adhesion molecule, CXCL-16, and ErbB3] to those in normotensive serum–treated cells. PE serum–induced increases in the apoptotic markers P53 mRNA expression, IKBKE mRNA expression, caspase 3 activity, and decreased BIRC8 mRNA expression, were attenuated by LDA treatment. LDA treatment also reduced abnormal differentiation caused by PE serum administration. Possible mechanisms by which LDA influences PE-affected trophoblast cells in vitro are by modulating cytokine secretion, reducing apoptosis to levels seen in normotensive serum–treated cells, and preventing the premature trophoblast differentiation commonly observed in PE.",
author = "Shanika Panagodage and Yong, {Hannah Ee Juen} and {Da Silva Costa}, Fabricio and Borg, {Anthony J} and Bill Kalionis and Brennecke, {Shaun P.} and Padma Murthi",
year = "2016",
month = "12",
day = "1",
doi = "10.1016/j.ajpath.2016.08.010",
language = "English",
volume = "186",
pages = "3217--3224",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "American Society for Investigative Pathology",
number = "12",

}

Low-Dose Acetylsalicylic Acid Treatment Modulates the Production of Cytokines and Improves Trophoblast Function in an in Vitro Model of Early-Onset Preeclampsia. / Panagodage, Shanika; Yong, Hannah Ee Juen; Da Silva Costa, Fabricio; Borg, Anthony J; Kalionis, Bill; Brennecke, Shaun P.; Murthi, Padma.

In: American Journal of Pathology, Vol. 186, No. 12, 01.12.2016, p. 3217-3224.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Low-Dose Acetylsalicylic Acid Treatment Modulates the Production of Cytokines and Improves Trophoblast Function in an in Vitro Model of Early-Onset Preeclampsia

AU - Panagodage, Shanika

AU - Yong, Hannah Ee Juen

AU - Da Silva Costa, Fabricio

AU - Borg, Anthony J

AU - Kalionis, Bill

AU - Brennecke, Shaun P.

AU - Murthi, Padma

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Preeclampsia (PE), a serious hypertensive disorder of pregnancy, remains a leading cause of perinatal morbidity and mortality worldwide. Perturbed trophoblast function and impaired placental development early in pregnancy are key features. Low-dose acetylsalicylic acid (LDA) administered before 16 weeks' gestation significantly reduces the risk for PE. However, the exact mechanisms of action of LDA, particularly on trophoblast function, are unclear. We hypothesized that LDA influences placental trophoblast function and reverses PE-associated abnormalities. This study aimed to determine the effects of serum from normotensive women and from those with PE with or without LDA treatment on a model of placental syncytium. On cytokine profiling, LDA increased placental growth factor production and selectively restored PE serum–induced alterations in levels of cytokines [activated leukocyte cell adhesion molecule, CXCL-16, and ErbB3] to those in normotensive serum–treated cells. PE serum–induced increases in the apoptotic markers P53 mRNA expression, IKBKE mRNA expression, caspase 3 activity, and decreased BIRC8 mRNA expression, were attenuated by LDA treatment. LDA treatment also reduced abnormal differentiation caused by PE serum administration. Possible mechanisms by which LDA influences PE-affected trophoblast cells in vitro are by modulating cytokine secretion, reducing apoptosis to levels seen in normotensive serum–treated cells, and preventing the premature trophoblast differentiation commonly observed in PE.

AB - Preeclampsia (PE), a serious hypertensive disorder of pregnancy, remains a leading cause of perinatal morbidity and mortality worldwide. Perturbed trophoblast function and impaired placental development early in pregnancy are key features. Low-dose acetylsalicylic acid (LDA) administered before 16 weeks' gestation significantly reduces the risk for PE. However, the exact mechanisms of action of LDA, particularly on trophoblast function, are unclear. We hypothesized that LDA influences placental trophoblast function and reverses PE-associated abnormalities. This study aimed to determine the effects of serum from normotensive women and from those with PE with or without LDA treatment on a model of placental syncytium. On cytokine profiling, LDA increased placental growth factor production and selectively restored PE serum–induced alterations in levels of cytokines [activated leukocyte cell adhesion molecule, CXCL-16, and ErbB3] to those in normotensive serum–treated cells. PE serum–induced increases in the apoptotic markers P53 mRNA expression, IKBKE mRNA expression, caspase 3 activity, and decreased BIRC8 mRNA expression, were attenuated by LDA treatment. LDA treatment also reduced abnormal differentiation caused by PE serum administration. Possible mechanisms by which LDA influences PE-affected trophoblast cells in vitro are by modulating cytokine secretion, reducing apoptosis to levels seen in normotensive serum–treated cells, and preventing the premature trophoblast differentiation commonly observed in PE.

UR - http://www.scopus.com/inward/record.url?scp=84995946055&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2016.08.010

DO - 10.1016/j.ajpath.2016.08.010

M3 - Article

AN - SCOPUS:84995946055

VL - 186

SP - 3217

EP - 3224

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 12

ER -