What we do
Cardiovascular disease kills more than one in four people in the UK (BHF, 2018) and is the leading cause of death, with heart attacks resulting in 9.5 million deaths worldwide, in 2016 alone (WHO, 2018).
We are working to develop new ways of understanding and treating cardiovascular disease.
Almost all cardiovascular disease begins with dysfunction of the endothelium, the innermost single layer of cells that lines every blood vessel. The endothelium regulates virtually every cardiovascular function including vascular tone, permeability, angiogenesis, thrombosis and smooth muscle cell proliferation, amongst others.
By understanding the endothelium in healthy people, and the dysfunction that occurs in cardiovascular disease, we hope to open new doors to the prevention and treatment of cardiovascular disease. However, because the endothelium is the innermost layer of cells in blood vessels it has been especially difficult to study. We therefore needed to develop highly innovative optical platforms that provide unparalleled light delivery and optical imaging to enable visualization of blood vessels with dramatically improved image clarity.
And so this collaboration was born...
A major focus of our research involves using these technologies to image calcium, a ubiquitous second messenger that is used by cells to relay information. To do this, we isolate intact blood vessels, expose the endothelium and load it with a calcium sensitive dye. This is a fluorescent dye that is highly sensitive to changes in calcium concentration. By measuring the change in fluorescence of the dye using the technologies that we are developing, we are able to image calcium signals with high spatial and temporal accuracy.
In this video, a field of endothelial cells is subjected to shear stress by initiating perfusion or "flow".
The red trace represents the mean fluorescence for the whole field of view whereas the blue trace represents
that from a single cell, which as you can appreciate, are quite different.
Another method we routinely use is pressure myography. By cannulating and sealing the blood vessels under specific pressures, we can measure changes in the contraction and relaxation of the vessel walls in response to various stimuli. By doing this we hope to understand the mechanisms by which blood vessels maintain and change blood pressure.
A cannulated blood vessel sealed onto the cannula at either end with fine thread.
Solutions containing various compounds under a specified pressure, can be perfused through the canulae
and into the vessel lumen. Changes in the diameter of the vessel can be measured.
The analysis methods we are developing also allow us to characterize and decode these signals, and alongside the mechanistic data, we are beginning to understand how these signals change in disease states to alter vascular function.
This work is constantly ongoing and evolving, all the while generating new insights into blood vessel function that have resulted in prizes from prestigious scientific organisations and major grant support from the Wellcome Trust and British Heart Foundation. We believe that by making these new optical platforms freely available to the entire scientific community we can accelerate progress in combating cardiovascular disease that affects so many people worldwide.