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ST GEORGE’S OF LONDON

CARDIOVASCULAR DISEASE RESEARCH GROUP

INTRODUCTION

Welcome to the Reproductive and Cardiovascular Disease Research Group. We are interested in how aspects of cell biology such as cell motilty and cell death affect the events of early pregnancy, particularly the role of trophoblast cells and natural killer cells in the development of the placenta. Problems at this stage in pregnancy may lead to complications later on such as pre-eclampsia. We are also interested in how nitric oxide affects these processes.

The main focus of our research is investigating events that happen in early pregnancy when the placenta forms, and what happens when these processes lead to pregnancy disorders such as pre-eclampsia. During normal pregnancy, after implantation of the blastocyst (pictured) fetal trophoblast cells from the placenta invade into the uterus of the mother. Changes occur to the mothers blood vessels (the spiral arteries in the uterus) which ensure a sufficient blood supply is delivered to the baby as it grows and develops. In pre-eclampsia, a major cause of maternal and perinatal morbidity, trophoblast cells show poor invasion and there are insufficient changes to the uterine blood vessels.

We are investigating the regulation of trophoblast cell invasion, motility and survival and the cellular and molecular mechanisms responsible for the remodelling of maternal vessels in early pregnancy. We are also investigating the role maternal immune cells may play in this process, and to do this, we are also investigating in the vascular endothelial cells and smooth muscle cells which make up the spiral arteries. The formation of the placenta is a highly complex and tightly regulated process that is essential for the establishment of a healthy pregnancy. Despite this the factors that regulate this process are still poorly understood.

NITRIC OXIDE

Nitric oxide (NO) is an important signalling molecule that acts in many tissues to regulate a diverse range of physiological and cellular processes. It’s role was first discovered by several groups who were attempting to identify the agent responsible for promoting blood vessel relaxation and regulating vascular tone. This agent was termed endothelium-derived relaxing factor (EDRF), and was initially assumed to be a protein like most other signalling molecules. The discovery that EDRF was in fact nitric oxide – a highly reactive gase- has led to an explosion of interest in this field, resulted in over 60,000 papers published in the last ten years and won the Nobel prize in 1998. Nitric oxide has now been demonstrated to play a role in a variety of biological processes including neurotransmission, immune defence, the regulation of cell death (apoptosis) and cell motility. Nitric oxide is a short-lived, highly reactive molecule (with a half-life of a few seconds) that is produced from a group of enzymes known as nitric oxide synthases (NOS).

Since it is such a small molecule NO is able to diffuse rapidly across cell membranes and, depending on the conditions, is able to diffuse distances of more than several hundred microns. The biological effects of NO are mediated through the reaction of NO with a number of targets such as haem groups, cysteine residues and iron and zinc clusters. Such a diverse range of targets for NO helps explain the wide range of roles that it plays. Due to the importance of NO, abnormal regulation or control of NO synthesis is capable of affecting a number of important biological processes and has been implicated in a variety of diseases.