Extracellular Signal-Regulated Kinase 5 is Required for Low-Concentration H(2)O(2)-Induced Angiogenesis of Human Umbilical Vein Endothelial Cells

Background. The aim of this study was to assess the effects of low concentrations of H(2)O(2) on angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro and explore the underlying mechanisms. Methods. HUVECs were cultured and stimulated with different concentrations of H(2)O(2). Flow cytometric analysis was used to select an optimal concentration of H(2)O(2) for the following experiments. Cell proliferation, migration, and tubule formation were evaluated by Cell Counting Kit-8 (CCK-8) assays, scratch wound assays, and Matrigel tubule formation assays, respectively. For gain and loss of function studies, constitutively active MEK5 (CA-MEK5) and ERK5 shRNA lentiviruses were used to activate or knock down extracellular signal-regulated kinase 5 (ERK5). Results. We found that low concentrations of H(2)O(2) promoted HUVECs proliferation, migration, and tubule formation. ERK5 in HUVECs was significantly activated by H(2)O(2). Enhanced ERK5 activity significantly amplified the proangiogenic effects of H(2)O(2); in contrast, ERK5 knock-down abrogated the effects of H(2)O(2). Conclusions. Our results confirmed that low concentrations of H(2)O(2) promoted HUVECs angiogenesis in vitro, and ERK5 is an essential mediator of this process. Therefore, ERK5 may be a potential therapeutic target for promoting angiogenesis and improving graft survival.