Journalartikel

Jahr der Veröffentlichung: 2010

Seiten: 37-44

Zeitschrift: Cardiovascular Research

Bandnummer: 86

Heftnummer: 1

ISSN: 0008-6363

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

Verlag: 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-Zitierstil: 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-Zitierstil: 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