Journal article

Publication year: 2010

Pages: 37-44

Journal: Cardiovascular Research

Volume number: 86

Issue number: 1

ISSN: 0008-6363

DOI Link: https://doi.org/10.1093/cvr/cvp385

Publisher: Oxford University Press

Abstract: 

It is well established that leukotrienes (LTs), products of the 5-lipoxygenase (5-LO) pathway, participate in inflammatory tissue reactions and immune responses. In the present study, the impact of the 5-LO pathway on vasculogenesis of mouse embryonic stem (ES) cells was investigated.

Immunohistochemistry studies demonstrated that 5-LO(+) cells first appeared at day 6 of embryoid body (EB) formation from ES cells. 5-LO(+)/CD68(+) as well as 5-LO(+)/CD45(+) cells were prominent at day 10 of EB differentiation. Real-time PCR and western blot analysis revealed all constituents of the 5-LO pathway. High performance liquid chromatography analyses indicated the synthesis of LTB(4) and LTD(4) in conformity with induction of the 5-LO pathway. Furthermore, Flk-1(+)/CD105(+) cells displayed calcium- (Ca(2+)) transients in response to LTB(4), whereas CD11b(+) cells responded to LTD(4). Treatment of EBs with LTB(4) and LTD(4) resulted in phosphorylation of the mitogen-activated protein kinase ERK1/2. Pharmacological inhibition of the 5-LO pathway and stable shRNA targeting of 5-LO-activating protein decreased capillary cell areas positive for PECAM-1.

Our data demonstrate that the 5-LO pathway emerges early during ES cell differentiation into cells of the myeloid lineage and that LTs play an until now unrecognized role in vascular development of ES cells.

Harvard Citation style: Finkensieper, A., Kieser, S., Bekhite, M., Richter, M., Mueller, J., Graebner, R., et al. (2010) The 5-lipoxygenase pathway regulates vasculogenesis in differentiating mouse embryonic stem cells, Cardiovascular Research, 86(1), pp. 37-44. https://doi.org/10.1093/cvr/cvp385

APA Citation style: Finkensieper, A., Kieser, S., Bekhite, M., Richter, M., Mueller, J., Graebner, R., Figulla, H., Sauer, H., & Wartenberg, M. (2010). The 5-lipoxygenase pathway regulates vasculogenesis in differentiating mouse embryonic stem cells. Cardiovascular Research. 86(1), 37-44. https://doi.org/10.1093/cvr/cvp385