A multicellular endothelial signalling web coordinates vascular function and is impaired in hypertension

The endothelium is an incredible coordinator of cardiovascular function and endothelial dysfunction contributes to severe health problems including heart failure, stroke, and renal damage in hypertension. Controlling endothelial dysfunction will reduce disease progression and limit health consequences.

Here we define a novel approach to address this unmet need.

We describe an endothelial network of distinct signal detection sites and transmission pathways that are tuned to regulate different functions.

These pathways operate in parallel generating streams of interacting information that travel along a multicellular web-like network.

We show the network is compromised in hypertension with disrupted distribution of tuned cells and reduced spread of information.

Changes in network interactions, rather than individual cell activity, may underlie endothelial dysfunction in hypertension.

Using advanced approaches (abstract figure), in animal models and humans, we now seek to understand network dysfunction in intact resistance arteries at three major functional levels: (1) How is the endothelial network organized in normotension and hypertension? (2) Why does signal integration change in hypertension? (3) What is the activation-response atlas and which network components are targets to control hypertension?

Network understanding will bridge the gap between individual endothelial cell function and tissue-level responses and offer new critical targets for therapy.