The 5-lipoxygenase/cyclooxygenase-2 cross-over metabolite, hemiketal E₂, enhances VEGFR2 activation and promotes angiogenesis.

ABSTRACT: Consecutive oxygenation of arachidonic acid by 5-lipoxygenase and cyclooxygenase-2 yields the hemiketal eicosanoids, HKE₂ and HKD₂. Hemiketals stimulate angiogenesis by inducing endothelial cell tubulogenesis in culture; however, how this process is regulated has not been determined. Here, we identify vascular endothelial growth factor receptor 2 (VEGFR2) as a mediator of HKE₂-induced angiogenesis in vitro and in vivo. We found that HKE₂ treatment of human umbilical vein endothelial cells dose-dependently increased the phosphorylation of VEGFR2 and the downstream kinases ERK and Akt that mediated endothelial cell tubulogenesis. In vivo, HKE₂ induced the growth of blood vessels into polyacetal sponges implanted in mice. HKE₂-

SUBMITTER: Nakashima F 

PROVIDER: S-EPMC10040730 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature