Background: Gestational diabetes mellitus (GDM) is characterized by a high risk of fetal macrosomia and placenta hypervascularization. There is a need to investigate the underlying mechanism to explain these associate complications. Exosomes had been known participating in the regulation of various angiogenic processes. However, the effects of exosomes from cases of GDM on placental vascular network formation remain unclear.
Methods and Results: Capillary branching per placental villi and protein level of CD31 were identified to be increased in GDM. Exosomes derived from umbilical cord blood (UE) enhanced endothelial cell vascularization significantly, especially in GDM pregnancies. The proteome of 10 normal exosomes and 10 GDM exosomes showed different profiles and uncovered two up-regulated proteins in GDM cases, namely leucine-rich alpha-2-glycoprotein-1 (LRG1) and extracellular matrix protein 1 (ECM1). Genetically engineered exosomes that overexpressed LRG1 or ECM1 resulted in hyper vascularization, including proliferation and migration.
Conclusions: Our results demonstrate for the first time the expression of LRG1 and ECM1 in normal and GDM UE and their role in regulating pathological placental angiogenesis. These findings support the potential role of LRG1 and ECM1 in monitoring placental pathologies in this increasingly prevalent condition and novel insights into the causes.
J. Yao: None. T. Duan: None. K. Wang: None.
National Natural Science Foundation of China; National Key Research and Development Program of China