Wnt5A signaling in human coronary artery endothelial cells

Inflammatory Wnt5A signalling in human macrophages was found to be critically involved in severe systemic inflammatory response. However, the targets of Wnt5A in endothelial cells and downstream mechanisms by which Wnt5A might induce endothelial inflammation still remain unclear. We show that Wnt5A principally regulate genes involved endothelial cytoskeleton rearrangements and impairs the barrier function of cultured endothelial monolayer causing hyper permeability. We further prove that Wnt5A neither affects the expression of adhesion molecules nor induces cytokine storm in endothelial cells. These findings suggest that Wnt5A, secreted by activated macrophages during septic inflammation, paracrinically act on the endothelial wall, causing endothelial barrier breakdown and subsequent vascular leakage in sepsis. A two color competitive hybridization design was chosen. Samples from respective treatments are labelled with Cy5 and hybridized against a Cy3 labelled non-treated reference sample from the same experiment.