PI3KC2β inactivation stabilizes VE-cadherin junctions and preserves vascular integrity

Endothelium protection is critical, because of the impact of vascular leakage and edema on pathological conditions such as brain ischemia. Whereas deficiency of class II phosphoinositide 3-kinase alpha (PI3KC2 alpha) results in an increase in vascular permeability, we uncover a crucial role of the beta isoform (PI3KC2 beta) in the loss of endothelial barrier integrity following injury. Here, we studied the role of PI3KC2 beta in endothelial permeability and endosomal trafficking in vitro and in vivo in ischemic stroke. Mice with inactive PI3KC2 beta showed protection against vascular permeability, edema, cerebral infarction, and deleterious inflammatory response. Loss of PI3KC2 beta in human cerebral microvascular endothelial cells stabilized homotypic cell-cell junctions by increasing Rab11-dependent VE-cadherin recycling. These results identify PI3KC2 beta as a potential new therapeutic target to prevent aggravating lesions following ischemic stroke.

Automated summary

Protecting endothelial cells is critical in preventing the impact of vascular leakage and edema on pathological conditions. PI3KC2 beta could be a potential new therapeutic target for treating aggravating lesions following ischemic stroke.