Cytokine concentrations direct endothelial function in pregnancy and preeclampsia

in Journal of Endocrinology
Authors:
Amanda K Mauro Perinatal Research Laboratories, Department of Obstetrics & Gynecology, University of Wisconsin – Madison, School Medicine and Public Health, Madison, Wisconsin, USA

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Nauman Khurshid Perinatal Research Laboratories, Department of Obstetrics & Gynecology, University of Wisconsin – Madison, School Medicine and Public Health, Madison, Wisconsin, USA
Division of Maternal Fetal Medicine, Department of Obstetrics & Gynecology, University of Wisconsin – Madison, School Medicine and Public Health, Madison, Wisconsin, USA

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Danielle M Berdahl Perinatal Research Laboratories, Department of Obstetrics & Gynecology, University of Wisconsin – Madison, School Medicine and Public Health, Madison, Wisconsin, USA
Division of Maternal Fetal Medicine, Department of Obstetrics & Gynecology, University of Wisconsin – Madison, School Medicine and Public Health, Madison, Wisconsin, USA

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Amanda C Ampey Perinatal Research Laboratories, Department of Obstetrics & Gynecology, University of Wisconsin – Madison, School Medicine and Public Health, Madison, Wisconsin, USA

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Daniel Adu Perinatal Research Laboratories, Department of Obstetrics & Gynecology, University of Wisconsin – Madison, School Medicine and Public Health, Madison, Wisconsin, USA
Department of Pediatrics, University of Wisconsin – Madison, School Medicine and Public Health, Madison, Wisconsin, USA

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Dinesh M Shah Perinatal Research Laboratories, Department of Obstetrics & Gynecology, University of Wisconsin – Madison, School Medicine and Public Health, Madison, Wisconsin, USA
Division of Maternal Fetal Medicine, Department of Obstetrics & Gynecology, University of Wisconsin – Madison, School Medicine and Public Health, Madison, Wisconsin, USA

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Derek S Boeldt Perinatal Research Laboratories, Department of Obstetrics & Gynecology, University of Wisconsin – Madison, School Medicine and Public Health, Madison, Wisconsin, USA

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Correspondence should be addressed to D S Boeldt: dsboeldt@wisc.edu

†(N Khurshid is now at Promedica Toledo Hospital, Toledo, Ohio, USA)

‡(D M Berdahl is now at Parkview Health, Fort Wayne, Indiana, USA)

§(D Adu is now at Geisinger Medical Center, Danville, Pennsylvania, USA)

DOI:
https://doi.org/10.1530/JOE-20-0397
Volume/Issue:
Volume 248: Issue 2
Article Type:
Research Article
Page Range:
107–117
Online Publication Date:
Feb 2021
Copyright:
© 2021 Society for Endocrinology 2021
Restricted access
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Abstract

Endothelial dysfunction is a prominent feature of preeclampsia, a hypertensive disorder of pregnancy, and contributes to multiple symptoms characteristic of the syndrome. A myriad of growth factors and cytokines are dysregulated in preeclampsia as compared to normal pregnancy, however, a complete appreciation of the effect of changing concentrations of these factors on endothelial function is lacking. In this study, we evaluate the effect of a variety of growth factors and cytokines on Ca2+ signaling and monolayer integrity. We report that VEGF165, TNFα, EGF, and IL-1β either improve or inhibit Ca2+ signaling depending on dose, whereas TNFα and IL-1β reduce monolayer integrity and bFGF increases monolayer integrity. Additionally, to model the effects of combinations of growth factors and cytokines, we screened for Ca2+ signaling changes in response to 16 dose combinations of VEGF165 and TNFα together. This revealed an optimal combination capable of supporting pregnancy-adapted Ca2+ signaling, and that changes in either VEGF165 or TNFα dose would result in a shift toward suppressed function. This study shows in detail how growth factor or cytokine concentration effects endothelial cell function. Such data can be used to model how changing growth factor and cytokine levels in normal pregnancy may contribute to healthy endothelial function and in preeclampsia may promote endothelial dysfunction. The results of VEGF165 and TNFα combination treatments suggest that more complex growth factor and cytokine combination modeling may be important in order to more accurately understand the effects of circulating factors on the endothelial function.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2021 Society for Endocrinology 2021
Page(s):
11
Article Type:
Research Article
Received Date:
03 Nov 2020
Accepted Date:
25 Nov 2020
Print Publication Date:
01 Feb 2021
Online Publication Date:
Feb 2021
Keywords:
growth factor; cytokine; endothelium; pregnancy; preeclampsia

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