Question:

Embryonic stem (ES) cells are pluripotent cells which can differentiate into different kinds of cells, such as endothelial and haematopoietic cells. Previous studies have demonstrated that angiogenesis and inflammation are two related mechanisms. In addition, some evidence suggested that inflammation mediators such as leukotrienes, which include the 5-lipoxygenase (5-LOX) family, can regulate endothelial cell differentiation. 5-LO-activating protein (FLAP) is the key enzyme involved in leukotriene composition. Since the effects of inflammation on the capacity of ES cells to differentiate into endothelial cells and haematopoietic cells are still not clear, the contribution of leukotrienes in vasculogenesis was investigated.

Results:

To assess the role of leukotrienes, especially FLAP in mediating vasculogenesis, ES cells were treated with FLAP inhibitors as well as antagonists of the leukotriene receptors BLT2 (LY255283) or BLT1 (U75302). To further confirm the role of leukotrienes in vasculogenesis of ES cells we applied exogenous leukotrienes and arachidonic acid. Our data demonstrate that vasculogenesis of ES cells is inhibited upon downregulation of FLAP as well as upon inhibition of BLT1/2 function. In contrast exogenous addition of arachidonic acid and leukotrienes stimulated vasculogenesis of ES cells.

Conclusions:

Our data demonstrate that vasculogenesis of embryonic stem cells is critically regulated by the arachidonic acid/leukotriene signalling pathway.