| First Author | Yoshioka K | Year | 2012 |
| Journal | Nat Med | Volume | 18 |
| Issue | 10 | Pages | 1560-9 |
| PubMed ID | 22983395 | Mgi Jnum | J:247494 |
| Mgi Id | MGI:5927473 | Doi | 10.1038/nm.2928 |
| Citation | Yoshioka K, et al. (2012) Endothelial PI3K-C2alpha, a class II PI3K, has an essential role in angiogenesis and vascular barrier function. Nat Med 18(10):1560-9 |
| abstractText | The class II alpha-isoform of phosphatidylinositol 3-kinase (PI3K-C2alpha) is localized in endosomes, the trans-Golgi network and clathrin-coated vesicles; however, its functional role is not well understood. Global or endothelial-cell-specific deficiency of PI3K-C2alpha resulted in embryonic lethality caused by defects in sprouting angiogenesis and vascular maturation. PI3K-C2alpha knockdown in endothelial cells resulted in a decrease in the number of PI3-phosphate-enriched endosomes, impaired endosomal trafficking, defective delivery of VE-cadherin to endothelial cell junctions and defective junction assembly. PI3K-C2alpha knockdown also impaired endothelial cell signaling, including vascular endothelial growth factor receptor internalization and endosomal RhoA activation. Together, the effects of PI3K-C2alpha knockdown led to defective endothelial cell migration, proliferation, tube formation and barrier integrity. Endothelial PI3K-C2alpha deficiency in vivo suppressed postischemic and tumor angiogenesis and diminished vascular barrier function with a greatly augmented susceptibility to anaphylaxis and a higher incidence of dissecting aortic aneurysm formation in response to angiotensin II infusion. Thus, PI3K-C2alpha has a crucial role in vascular formation and barrier integrity and represents a new therapeutic target for vascular disease. |
