Journal
ADVANCED SCIENCE
Volume 6, Issue 23, Pages -Publisher
WILEY
DOI: 10.1002/advs.201900878
Keywords
angiogenesis; pericytes; placenta; pre-eclampsia; vascular dysfunction
Categories
Funding
- NSERC post-doctoral fellowship
- National Science Foundation [CBET-0939511]
- Canadian Institutes of Health Research
- MIT Ludwig Center for Molecular Oncology Graduate Fellowship
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Placental vasculopathies are associated with a number of pregnancy-related diseases, including pre-eclampsia (PE)-a leading cause of maternal-fetal morbidity and mortality worldwide. Placental presentations of PE are associated with endothelial dysfunction, reduced vessel perfusion, white blood cell infiltration, and altered production of angiogenic factors within the placenta (a candidate mechanism). Despite maintaining vascular quiescence in other tissues, how pericytes contribute to vascular growth and signaling in the placenta remains unknown. Here, pericytes are hypothesized to play a detrimental role in the pathogenesis of placental vascular growth. A perfusable triculture model is developed, consisting of human endothelial cells, fibroblasts, and pericytes, capable of recapitulating growth and remodeling in a system that mimics inflamed placental microvessels. Placental pericytes are shown to contribute to growth restriction of microvessels over time, an effect that is strongly regulated by vascular endothelial growth factor and Angiopoietin/Tie2 signaling. Furthermore, this model is capable of recapitulating essential processes including tumor necrosis factor alpha (TNF alpha)-mediated vascular leakage and leukocyte infiltration, both important aspects associated with placental PE. This placental vascular model highlights that an imbalance in endothelial-pericyte crosstalk can play a critical role in the development of vascular pathology and associated diseases.
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