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Updated: Jul 12, 2025
12:55
A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
Published on: December 9, 2021
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Src kinase partially mediates cytokine-induced endothelial dysfunction.
Amanda K Mauro1, Luca Clemente1, Nauman Khurshid2
1Perinatal Research Laboratories, Department of Obstetrics & Gynecology, University of Wisconsin - Madison, School Medicine and Public Health, Madison, WI 53715, USA.
Pregnancy Hypertension
|October 21, 2023
Summary
Src kinase partially mediates endothelial dysfunction in preeclampsia by affecting calcium signaling and monolayer integrity. Inhibiting Src kinase protected against insults, suggesting a therapeutic target for endothelial-based treatments.
Area of Science:
- Vascular Biology
- Cell Signaling
- Preeclampsia Pathophysiology
Background:
- Endothelial dysfunction is central to preeclampsia (PE), contributing to organ damage.
- Growth factors and cytokines dysregulate endothelial function in PE, impacting calcium (Ca2+) signaling and barrier integrity.
- Delivery is the only PE treatment, necessitating novel endothelial-based therapeutic strategies.
Purpose of the Study:
- To investigate the role of Src kinase in mediating endothelial dysfunction induced by growth factors and cytokines in preeclampsia.
- To determine if Src kinase inhibition can reverse endothelial dysfunction in a cellular model of PE.
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) were exposed to growth factors or cytokines.
- Calcium (Ca2+) imaging and Electrical Cell Impedance Sensing (ECIS) were used to assess endothelial function.
- Kinase inhibitors (Src inhibitor PP2, MEK/ERK inhibitor U0126) were employed to elucidate signaling pathways.
Main Results:
- Src kinase inhibition protected HUVECs from Ca2+ signaling disruptions caused by VEGF165, bFGF, PlGF, TNFα, and IL-1β.
- Src inhibition also preserved endothelial monolayer resistance against TNFα-induced insult.
- MEK/ERK inhibition did not protect against growth factor-mediated endothelial dysfunction.
Conclusions:
- Cytokine and growth factor-stimulated Src kinase partially promotes endothelial dysfunction in HUVECs.
- Targeting Src kinase represents a potential therapeutic strategy for preeclampsia-related endothelial dysfunction.
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