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Proangiogenic actors: From the uterus to peripheral arterial disease?

  • Nirvana Sadaghianloo
    Correspondence
    Correspondence: Nirvana Sadaghianloo, MD, PhD, Chirurgie Vasculaire, Hôpital Pasteur 1, 30 Voie Romaine, 06000 Nice, France
    Affiliations
    Department of Vascular Surgery, Centre Hospitalier Universitaire Côte d’Azur, Université Côte d’Azur, Nice, France
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Open AccessPublished:October 26, 2022DOI:https://doi.org/10.1016/j.jvssci.2022.10.003
      In their study, Wolf et al

      K.Wolf, E.B. Crawford, N.M. Wartan, S.K. Schneiderman, V. E. Riehl, S.V. Dambaeva, et al. Ephrin-B2-expressing Natural Killer cells induce angiogenesis. J Vasc Surg Vasc Sci. .

      elegantly show that once again the circulatory system and the immune system are globally intertwined. By examining the function of natural killer (NK) cells in the uterus, whose potent proangiogenic role is known in the secretory phase of menstruation and during pregnancy,
      • Sojka D.K.
      • Yang L.
      • Yokoyama W.M.
      Uterine natural killer cells: to protect and to nurture.
      they were able to show their proangiogenic potential on endothelial cells through tubule formation. While in the functioning of the female body, the intercellular communication is done via proangiogenic cytokines, the present study unveils an unexpected molecular pathway via the secretion of Ephrin-B2, ligand of the Eph-B4 tyrosine kinase receptor present on the surface of endothelial cells. As the interactions of this signaling pathway are well-known in the determination of the arterial or venous phenotype of vascular cells, this discovery opens an additional exploratory field on angiogenesis.
      • Sojka D.K.
      • Yang L.
      • Yokoyama W.M.
      Uterine natural killer cells: to protect and to nurture.
      ,
      • Wolf K.
      • Hu H.
      • Isaji T.
      • Dardik A.
      Molecular identity of arteries, veins, and lymphatics.
      Furthermore, the authors were able to induce nonuterine NK cells to secrete this ligand.

      K.Wolf, E.B. Crawford, N.M. Wartan, S.K. Schneiderman, V. E. Riehl, S.V. Dambaeva, et al. Ephrin-B2-expressing Natural Killer cells induce angiogenesis. J Vasc Surg Vasc Sci. .

      This gives hope for the induction of NK or other immune cells, ex vivo or in vivo on targeted territories.
      • Radomska-Leśniewska D.M.
      • Bialoszewska A.
      • Kaminski P.
      Angiogenic properties of NK cells in cancer and other angiogenesis-dependent diseases.
      Subject to the applicability of these results in vivo, one can imagine the induction of this pathway locally to treat critical limb ischemia, but also other ischemic territories and organs such as the brain or the kidney.
      The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the JVS: Vascular Science or the Society for Vascular Surgery.

      References

      1. K.Wolf, E.B. Crawford, N.M. Wartan, S.K. Schneiderman, V. E. Riehl, S.V. Dambaeva, et al. Ephrin-B2-expressing Natural Killer cells induce angiogenesis. J Vasc Surg Vasc Sci. .

        • Sojka D.K.
        • Yang L.
        • Yokoyama W.M.
        Uterine natural killer cells: to protect and to nurture.
        Birth Defects Res. 2018; 110: 1531-1538https://doi.org/10.1002/bdr2.1419
        • Wolf K.
        • Hu H.
        • Isaji T.
        • Dardik A.
        Molecular identity of arteries, veins, and lymphatics.
        J Vasc Surg. 2019; 69: 253-262https://doi.org/10.1016/j.jvs.2018.06.195
        • Radomska-Leśniewska D.M.
        • Bialoszewska A.
        • Kaminski P.
        Angiogenic properties of NK cells in cancer and other angiogenesis-dependent diseases.
        Cells. 2021; 10: 1621https://doi.org/10.3390/cells10071621

      Linked Article

      • Ephrin-B2-expressing natural killer cells induce angiogenesis
        JVS-Vascular ScienceVol. 3
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          Therapeutic angiogenesis aims to induce new blood vessel growth in ischemic tissues; however, previous clinical trials have had limited success. Studies of uterine angiogenesis revealed a specialized subset of natural killer (NK) cells, called uterine NK (uNK) cells, which have unique proangiogenic abilities.
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