Unfolded Protein Response supports endothelial barrier function.

Ongoing efforts are oriented towards the development of novel therapeutic agents to repress lung hyperpermeability responses due to inflammation. The endothelial barrier dysfunction triggered by such events, may eventually lead to severe cardiovascular complications, such as the Acute Respiratory Distress Syndrome. Hsp90 inhibitors are anticancer compounds, associated with strong anti-inflammatory responses in the endothelium. Our latest observations in experimental models of Acute Lung Injury suggest that P53 orchestrates, at least in part, such activities. Remarkably, both Hsp90 inhibition and P53 induction are associated with the activation of the Unfolded Protein Response element. The purpose of the current manuscript, is to introduce the hypotheses that UPR induction protects the vasculature against inflammation.