New opportunities for vascular protection in health and disease: manipulating the endo-thelial glycocalyx

Blood vessel dysfunction is one of the leading causes of death and illness globally. Diseases character-ised by widespread vascular dysfunction include atherosclerosis, diabetes, kidney disease, and a range of infectious diseases (this list encompasses our current projects, but is by no means exhaustive!). The aim of work in our laboratory is to understand the role of the endothelial glycocalyx, the inner lining of every blood vessel in the body, in the initiation and progression of these disease processes. Our vision is that the endothelial glycocalyx can be restored (as we have previously demonstrated), and that this will provide an entirely new treatment for protecting blood vessels in a broad range of disease states.
The endothelial glycocalyx is the primary interface between flowing blood and the vessel wall. It is a highly specialised extracellular matrix made up of components produced by endothelial cells (proteogly-cans and glycosaminoglycans) and substances circulating in blood (albumin and other proteins). The endothelial glycocalyx controls a host of critical vessel functions such as the ability of leukocytes to ad-here to the vessel wall, the ability of the vessel wall to detect mechanical forces such as shear stress, and the permeability of the vessel wall. Damage to the endothelial glycocalyx results in leukocyte adhesion, impaired vasodilation and increased permeability: all features of the above diseases.
Because the endothelial glycocalyx is a dynamic structure resulting from both flowing blood and perfused vessel walls, we use a broad range of techniques to examine the structure, function and composition of the endothelial glycocalyx in intact living vessels, including
- advanced fluorescence microscopy techniques (confocal and multiphoton microscopy) to exam-ine endothelial glycocalyx structure, composition and function alongside simultaneous assessment of intact blood vessel function;
- detailed nanostructural examination of endothelial glycocalyx architecture with standard trans-mission and advanced tomography electron microscopy techniques;
- regulation of endothelial glycocalyx turnover using immortalised human endothelial cells;
- relevance to human diseases with novel and unique tools to examine human blood vessel anat-omy and physiology in real time;
- zebrafish and transgenic rodent technologies to study the role of the endothelial glycocalyx in physiology and representative disease states.
We are at the forefront of developing these technologies and their application to physiology, transgenic systems and human disease states.
We welcome applications from motivated individuals interested in contributing to an exciting and cutting-edge programme in this highly-relevant biomedical field, with a long-term view to develop new therapies in a range of conditions affecting individuals in both the developed and developing world. Projects can be designed to advance our current programme or tailored to match the interests of the individual. More detailed information is available
- from our website (http://www.bris.ac.uk/phys-pharm/people/person/andy-h-salmon/overview.html),
- from contacting Dr Salmon directly ([Email Address Removed])
- and in recent references: