Endothelial Biology
Dr Peter Clark, Head of Group
The Endothelial Group is researching how the endothelial barriers are formed, maintained and perturbed. Endothelial cells line all blood and lymph spaces, and so act as the interface between the circulation and the tissues. The barrier properties of this endothelial interface are important to normal physiology, and are perturbed during inflammation, infection and other pathologies, when, typically, the endothelial barrier-function is lost, and plasma proteins, other solutes and water leak from the blood to the interstitial tissues, leading to oedema. In addition, the endothelial cells are a barrier to circulating immune cells, and are involved in their responses to infectious agents and inflammatory stimuli. Leukocytes can, in turn, modulate the endothelial barrier. The junctions formed between endothelial cells are key to determining the barrier function.
One project is concerned with specialised vessels in the Central Nervous System. The vessels of the Blood-Brain Barrier (BBB) are considerably less leaky than in other tissues, but it is not clear what determines this distinct property. We have recently identified a novel cell adhesion molecule, Cadherin-10, which is found in the endothelial cells of the BBB, but not in vessels in the rest of the body. This molecule is of a class that is involved in determining barrier formation in epithelial and endothelial cells, and as such, is likely to be an important factor in the development and function of the BBB. Cadherin-10 is also expressed in a number of epithelial barriers, and we are currently studying why this molecule is associated with endothelial and epithelial barriers. A second project is attempting to understand how one type of leukocyte, the neutrophil, induces the breakdown of endothelial barrier properties. Neutrophils are known to promote oedema, though the mechanism is not clear. We are using in vivo and in vitro approaches to dissect the mechanisms involved. We are examining a number of signalling pathways and cellular mechanisms that have previously been implicated in vascular barrier breakdown, to determine if they are involved in neutrophil-mediated oedema. In our third project, we are studying the effects of ischaemia and reperfusion (mimicking the interruption of the blood supply in myocardial infarction) in the heart. We use light and electron microscopy and biochemical approaches, to examine changes to the endothelial cells of the cardiac capillaries, particularly how ischaemia and reperfusion affect the contractility of the endothelial cells, and how this may affect vessel diameter and blood flow in the heart muscle.
