Role of foetoplacental exosomes in foetoplacental endothelial dysfunction in gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a pregnancy disease associated with foetoplacental endothelial dysfunction and characterized by hyperglycaemia. Human umbilical vein endothelial cells (HUVECs) from GDM pregnancies show increased L-arginine/NO signalling pathway and expression of pro-inflammatory factors. However, the cellular mechanisms involved in the progression of GDM-associated foetoplacental endothelial dysfunction are still unknown. One of the proposed mechanisms involve exosomes, which form part of the extracellular vesicles and act as mediators of cell communication thereby modulating vascular function.

In this study, we evaluated the role of exosomes on changes associated with endothelial dysfunction in primary cultures of HUVECs from normal and GDM pregnancies. Exosomes were isolated from (1) HUVECs from normal or GDM pregnancies and (2) HUVECs from normal pregnancies exposed to basal or high D-glucose (HG) conditions. Subsequently, HUVECs from normal pregnancies were exposed to exosomes from each group.

Exosomes from GDM or HG impaired endothelial wound healing and molecules associated with the L-arginine/NO signalling pathway in normal HUVECs. Interestingly, exosomes from normal pregnancies restored some of these changes in cells from GDM pregnancies. We also evaluated the communication between monocytes and HUVECs by exosomes, which is important in the expression of ICAM-1 under HG.

This thesis proposes a differential role of exosomes from normal and GDM pregnancies, suggesting that exosomes released by HUVECs may act in an autocrine or paracrine manner. Thus, an altered exosome cargo or exosome release from the foetoplacental vasculature may modulate the progression of foetoplacental endothelial dysfunction in GDM pregnancies.

• Nombre: Tamara Sáez Gutierrez
• Laboratorio: Fisiología Celular y Molecular (Medicina UC)
• Mención: Ciencias Fisiológicas
• Director Tesis: Luis Sobrevía