City Research Online

Abstract

Maternal vascular remodelling is an essential process which takes place during the early stages of pregnancy to enable increased nutrients and respiratory gases to the developing fetus. During this process, endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are lost from maternal spiral arteries and are replaced with fetal trophoblast cells. Defects in this process are associated with severe pregnancy complications, such as pre-eclampsia. Trophoblast cells have previously been shown to stimulate both ECs and VSMCs to express stanniocalcin-1 (STC-1). This protein plays a diverse role within female reproductive tissues and is implicated in physiological and pathophysiological cardiovascular function. This study aimed to understand the regulation of STC-1 in vascular cells and elucidate its role in the vascular remodelling process. STC-1 was found to be expressed within first trimester maternal decidual tissue in the presence of trophoblast cells. Trophoblast cell secreted factors stimulated secretion of STC-1 from VSMCs and ECs but did not affect intracellular STC-1 expression. It was demonstrated that trophoblast conditioned media (TCM) contains a wide range of cytokines but the specific factor(s) which induced vascular cell STC-1 secretion was not identified. TCM stimulation of vascular cells induced activation of proteins in major cell signalling pathways including Akt, glycogen synthase kinase 3β, mitogen-activated protein kinase, and serum/glucocorticoid regulated kinase 1. Akt was found to be implicated in the regulation of TCM-induced STC-1 secretion from ECs. Activation of protein kinase C (PKC) induced secretion of STC-1 from vascular cells, but TCM-induced secretion of STC-1 is not regulated through PKC. To determine the role of STC-1 in this system, tools to overexpress and knockdown STC-1 expression in VSMCs and ECs were developed. Overexpression of STC-1 reduced the rate of EC migration but did not affect VSMC migration.

Publication Type:	Thesis (Doctoral)
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology R Medicine > RG Gynecology and obstetrics
Departments:	School of Health & Medical Sciences > Neuroscience and Cell Biology Research Institute School of Health & Medical Sciences > School of Health & Medical Sciences Doctoral Theses Doctoral Theses

Export

Downloads