Medizinische Universität Graz - Research portal

Go directly to the nagivation.
Go directly to the content.

Navigation/Search

Selected Publication:

Gomes, LL.
Effects of the diabetic environment on the feto-placental vasculature
[ Dissertation ] Medical University of Graz; 2012. pp. 126 [OPEN ACCESS]
FullText

Authors Med Uni Graz:: Gomes Luciana Lassance
Advisor:: Desoye Gernot; Hiden Ursula
Altmetrics:
Abstract:: In a pregnancy complicated by maternal diabetes, insulin and IGF2 levels are elevated in the fetal circulation. As the insulin/IGF system regulates fetal and placental growth and development, dysregulation of insulin and IGF2 may have profound effects on the placenta. At term of gestation placental receptors for insulin and IGF2 are mainly located on the feto-placental vasculature, but insulin and IGF2 effects on placental endothelium have not yet been understood. Placentas of diabetic pregnancies show several alterations including increased weight and size and hypervascularization. Here I hypothesized that insulin and IGF2 can regulate placental endothelial cell (EC) processes such as gene expression and intracellular signaling, that may contribute to the alterations observed in placentas from diabetic pregnancies. As thickening of the placental basement membrane is also a feature of placentas from diabetic pregnancies, I investigated the effects of different basement membrane proteins on placental EC proliferation, survival and behavior. Global gene expression profiling of arterial (AEC) and venous (VEC) EC revealed that insulin and IGF2 mainly regulate genes involved in lipid metabolism and cell adhesion/junction, and AEC are more susceptible than VEC herein. Results also showed that insulin increases in vitro angiogenesis and mediates actin assembly in AEC via the Akt/eNOS/Rac1 signaling pathway. By using different basement membrane (ECM) proteins to investigate their role in EC proliferation, survival and behavior, VEC were more susceptible to changes in matrix composition than AEC. These effects were mediated by focal adhesion kinase (Fak) and modulated by oxygen. Collectively, these data suggest that altered insulin/IGF2 levels and basement membrane constitution may alter placental vascular morphology and function in diabetic pregnancies.