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New functions of the fibrinolytic system in bone marrow cell-derived angiogenesis

  • Progress in Hematology
  • Vascular biology with relation to hematopoiesis
  • Published:
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Abstract

Angiogenesis is a process by which new blood vessels form from preexisting vasculature. This process includes differentiation of angioblasts into endothelial cells with the help of secreted angiogenic factors released from cells such as bone marrow (BM)-derived cells. The fibrinolytic factor plasmin, which is a serine protease, has been shown to promote endothelial cell migration either directly, by degrading matrix proteins such as fibrin, or indirectly, by converting matrix-bound angiogenic growth factors into a soluble form. Plasmin can also activate other pericellular proteases such as matrix metalloproteinases (MMPs). Recent studies indicate that plasmin can additionally alter cellular adhesion and migration. We showed that factors of the fibrinolytic pathway can recruit BM-derived hematopoietic cells into ischemic/hypoxic tissues by altering the activation status of MMPs. These BM-derived cells can function as accessory cells that promote angiogenesis by releasing angiogenic signals. This review will discuss recent data regarding the role of the fibrinolytic system in controlling myeloid cell-driven angiogenesis. We propose that plasmin/plasminogen may be a potential target not only for development of effective angiogenic therapeutic strategies for the treatment of cancer, but also for development of strategies to promote ischemic tissue regeneration.

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Acknowledgments

This work was supported by the following: grants from the Japan Society for the Promotion of Science and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (K.H.; B.H.); a Grant-in-Aid for Scientific Research on Priority Areas from MEXT (K.H.); Mitsubishi Pharma Research Foundation (K.H); a Grant-in-Aid for Scientific Research on Innovative Areas from MEXT (B.H.); the Program for Improvement of the Research Environment for Young Researchers (B.H.) funded by the Special Coordination Funds for Promoting Science and Technology of MEXT, Japan. The authors declare no competing financial interests.

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Authors and Affiliations

  1. Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science at the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Beate Heissig, Makiko Ohki-Koizumi, Yoshihiko Tashiro, Ismael Gritli & Koichi Hattori

  2. Frontier Research Initiative, Institute of Medical Science at the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Beate Heissig & Kaori Sato-Kusubata

  3. Atopy (Allergy) Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Beate Heissig & Koichi Hattori

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  1. Beate Heissig
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  2. Makiko Ohki-Koizumi
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  3. Yoshihiko Tashiro
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  4. Ismael Gritli
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  5. Kaori Sato-Kusubata
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  6. Koichi Hattori
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Correspondence to Beate Heissig.

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Heissig, B., Ohki-Koizumi, M., Tashiro, Y. et al. New functions of the fibrinolytic system in bone marrow cell-derived angiogenesis. Int J Hematol 95, 131–137 (2012). https://doi.org/10.1007/s12185-012-1016-y

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  • DOI: https://doi.org/10.1007/s12185-012-1016-y

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