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Mononuclear Cells Negatively Regulate Endothelial Ca2+ Signaling

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Abstract

Endothelial Ca2+ signaling has important roles to play in maintaining pregnancy associated vasodilation in the utero-placenta. Inflammatory cytokines, often elevated in vascular complications of pregnancy, negatively regulate ATP-stimulated endothelial Ca2+ signaling and associated nitric oxide production. However, the role of direct engagement of immune cells on endothelial Ca2+ signaling and therefore endothelial function is unclear. To model immune-endothelial interactions, herein, we evaluate the effects of peripheral blood mononuclear cells (PBMCs) in short-term interaction with human umbilical vein endothelial cells (HUVECs) on agonist-stimulated Ca2+ signaling in HUVECs. We find that mononuclear cells (10:1 and 25:1 mononuclear: HUVEC) cause decreased ATP-stimulated Ca2+ signaling; worsened by activated mononuclear cells possibly due to increased cytokine secretion. Additionally, monocytes, natural killers, and T-cells cause decrease in ATP-stimulated Ca2+ signaling using THP-1 (monocyte), NKL (natural killer cells), and Jurkat (T-cell) cell lines, respectively. PBMCs with Golgi-restricted protein transport prior to interaction with endothelial cells display rescue in Ca2+ signaling, strongly suggesting that secreted proteins from PBMCs mediate changes in HUVEC Ca2+ signaling. We propose that endothelial cells from normal pregnancy interacting with PBMCs may model preeclamptic endothelial-immune interaction and resultant endothelial dysfunction.

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All data reported in this paper will be shared by the lead contact upon request.

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Acknowledgements

This work is also a part of AR’s requirements towards her PhD at the University of Wisconsin Madison in Endocrinology and Reproductive Physiology Training program. This was funded by Wisconsin Alumni Research Foundation (WARF), School of Medicine and Public Health (SMPH), the Department of Obstetrics and Gynecology (Ob-Gyn), and Office of the Vice Chancellor for Research and Graduate Education (OVCRGE) at University of Wisconsin-Madison. MSP provided immune cell lines. Images in figures were produced and adapted from Servier Medical Art (smart.servier.com).

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Authors and Affiliations

  1. Department of Obstetrics & Gynecology, University of Wisconsin-Madison, School of Medicine and Public Health, Perinatal Research Laboratories, 7E UnityPoint Health-Meriter Hospital, 202 South Park St, Madison, WI, 53715, USA

    Aishwarya Rengarajan, Jason L. Austin, Aleksandar K. Stanic, Manish S. Patankar & Derek S. Boeldt

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  1. Aishwarya Rengarajan
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  2. Jason L. Austin
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  3. Aleksandar K. Stanic
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Contributions

Conceptualization — DSB, MSP, AR; methodology — AR, DSB, AKS, MSP; formal analysis — AR; investigation — AR, JA; resources — DSB, MSP; writing — original draft — AR, DSB; writing — review and editing — AR, DSB, MSP, AKS; supervision — DSB; project administration — DSB; funding acquisition — DSB.

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Correspondence to Derek S. Boeldt.

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Jointly approved by Institutional Review Board (IRB) at University of Wisconsin, Madison, and Meriter Hospital, Madison.

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Rengarajan, A., Austin, J.L., Stanic, A.K. et al. Mononuclear Cells Negatively Regulate Endothelial Ca2+ Signaling. Reprod. Sci. 30, 2292–2301 (2023). https://doi.org/10.1007/s43032-023-01164-5

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