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Open Access The role of heterodimerisation between VEGFR-1 and VEGFR-2 in the regulation of vasculogenesis, angiogenesis and endothelial cell homeostasis, MRC

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Blood vessels play a role in virtually every medical condition. They transport white blood cells to sites of infection and inflammation; they can become blocked leading to heart attacks and strokes and can cause cancers to progress by feeding the tumour with nutrients and oxygen. Angiogenesis is a term used to describe the growth of new blood vessels. In the adult, angiogenesis is a critical process for wound healing, menstruation and allowing the placenta to meet the nutritional demands of a growing baby. However, when angiogenesis is not properly controlled, there can be serious health implications. In some conditions, there are not enough healthy blood vessels to provide the necessary oxygen and nutrients to the tissue, this can present as the pain in angina or intermittent claudication, conditions, which if left untreated can result in a heart attack or amputation of the lower limbs. On the other hand, in diseases such as cancer and age-related macular degeneration (AMD), the growth of new blood vessels is unwanted, as it leads to the spread of the tumour or blindness. So, therapies aimed at either promoting or reducing angiogenesis have the potential to make a huge impact in medicine. Unfortunately, it has not been easy to control blood vessel growth, which is thought to be because the factors that coordinate it are much more complicated than initially thought. One of the most important proteins involved in blood vessel growth is called Vascular Endothelial Growth Factor (VEGF). This protein binds to receptors on the surface of cells that only it can bind to, similar to a key only fitting a specific lock. Once this occurs proteins inside the cell are activated and cause the cells to divide, move around and form new vessels. The system becomes complicated because there are a number of different receptors that can come together in different ways and many different proteins inside the cell. The cell will respond in different ways and different proteins inside the cell will become active depending on which receptor or combination of receptors VEGF binds to. It is also thought that in particular diseases the combination and location of these receptors will be changed compared to normal tissues and this may contribute to the diseases. This research, being undertaken at the University of Edinburgh, aims to screen healthy and abnormal human tissues for a certain receptor combination that we think may be changed in some disorders, work out what controls the receptor combinations and if the proteins activated inside the cell are altered when VEGF binds to different receptor combinations. We will then use techniques to examine how the various combinations of VEGF receptors control angiogenesis in normal and abnormal conditions. Ultimately, we will use all the information we gain from this research to help produce more precise therapies to cause or prevent angiogenesis depending on the medical conditions being targeted.
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Document Type: Research Article

Publication date: August 1, 2017

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