Signalling Networks

Although just a single layer of cells, the endothelium is a highly organized interconnected network that controls every aspect of vascular function including: arterial tone, blood clotting, vascular permeability, angiogenesis, smooth muscle proliferation and vascular remodelling in disease. However the precise mechanisms by which the endothelium receives, interprets, and responds to multiple stimuli to converge on a physiological response lie beyond current understanding. 

 

The ubiquitous second messenger calcium is central to relaying information within and between cells.

Calcium signals can be initiated in the endothelium by mechano-stimuli such as changes in blood flow, and by various agonists acting in an auto- or paracrine manner. 

By imaging calcium signals in native and diseased tissue, we are beginning to tease apart the complex nature by which calcium is able to relay messages within the vessel wall. In doing so we noticed differences between the signalling that occurs within individual cells compared to the wider endothelium. When a field of view is 'averaged' crucial information is lost, as shown in the video below. Therefore we extract calcium signals from each individual cell, which has revealed heterogeneity in intact endothelium.  

Lab members working on signal networks:

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