Cytokine concentrations direct endothelial function in pregnancy and preeclampsia
| Autor: | Amanda K. Mauro, Daniel Adu, Dinesh Shah, Amanda C. Ampey, Nauman Khurshid, Derek S. Boeldt, Danielle M. Berdahl |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Endothelium Endocrinology Diabetes and Metabolism medicine.medical_treatment 030209 endocrinology & metabolism Article Preeclampsia 03 medical and health sciences 0302 clinical medicine Endocrinology Pre-Eclampsia Pregnancy Internal medicine Human Umbilical Vein Endothelial Cells medicine Humans Calcium Signaling Endothelial dysfunction business.industry Growth factor Endothelial Cells medicine.disease Endothelial stem cell 030104 developmental biology medicine.anatomical_structure Cytokine Cytokines Intercellular Signaling Peptides and Proteins Female Tumor necrosis factor alpha business |
| Zdroj: | J Endocrinol |
| ISSN: | 1479-6805 0022-0795 |
| DOI: | 10.1530/joe-20-0397 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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