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Signalling Networks

The endothelium is a highly organized interconnected network of cells 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 make a decision on a physiological response lie beyond current understanding.

Flow-mediated endothelial Ca2+ Signalling

Flow-mediated endothelial Ca2+ Signalling

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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 chemical mediators acting in an auto- or paracrine manner.

In our lab, we examine mechanically- and chemically-evoked calcium signals from every endothelial cell, from a large field of view (~1000 cells), in native and diseased tissue. In doing so, we are beginning to tease apart the complex nature by which calcium is able to relay messages within the vessel wall. Individual cells do not respond in unison to an activator but instead, endothelial cells are highly heterogenous across the endothelium.

ACh Histamine Responses

ACh Histamine Responses

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Our recent studies have revealed that clusters of cells are primed the detect specific activators and these cells can communicate with one another on a small-world scale-free network. This network arrangement confers particularly dynamic endothelial properties including high signal-propagation speed, stability, and a high degree of synchronization. All which are of vital importance in maintaining cardiovascular homeostasis. Indeed, we have recently shown that these properties are compromised in disease.

Lab members working on signal networks:

Press interest arising from the work:

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