Functional evaluation of TIE2 activators identified in a model system using human umbilical vein endothelial cells

TIE2 (or TEK) receptor is a tyrosine kinase receptor important for maintaining vascular system function. Decreased TIE2 signalling associates with various diseases and deletion of TIE2 increases the risk of vascular diseases like atherosclerosis. Therefore, activators of TIE2 are suggested and shown to be efficient for maintaining healthy vascular systems and protect from diseases. We have previously explored several plant derived compounds as TIE2 activator using transiently expressed TIE2 in HeLa cells. In this study, we evaluated if the identified TIE2 activators, casuarinin, procyanidin tetramer (PC4), and morin, are capable to activate TIE2 signalling in human umbilical vein endothelial cells. We showed that casuarinin and PC4 activates AKT and ERK, the two kinase downstream of TIE2, and enhances tube formation in human umbilical vein endothelial cells. These results support the idea that the TIE2 activators identified in the TIE2-expressing HeLa cells are candidates for vascular protection.