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Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the developing heart

Author

Listed:
  • Yoh Arita

    (Osaka University Graduate School of Medicine, 2-2, Yamadaoka)

  • Yoshikazu Nakaoka

    (Osaka University Graduate School of Medicine, 2-2, Yamadaoka
    Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science Technology Agency, 4-1-8, Honcho)

  • Taichi Matsunaga

    (Laboratory of Stem Cell Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53, Shogoin-Kawahara-cho)

  • Hiroyasu Kidoya

    (Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka)

  • Kohei Yamamizu

    (Laboratory of Stem Cell Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53, Shogoin-Kawahara-cho)

  • Yuichiro Arima

    (Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo)

  • Takahiro Kataoka-Hashimoto

    (Osaka University Graduate School of Medicine, 2-2, Yamadaoka)

  • Kuniyasu Ikeoka

    (Osaka University Graduate School of Medicine, 2-2, Yamadaoka)

  • Taku Yasui

    (Osaka University Graduate School of Medicine, 2-2, Yamadaoka)

  • Takeshi Masaki

    (Osaka University Graduate School of Medicine, 2-2, Yamadaoka)

  • Kaori Yamamoto

    (Osaka University Graduate School of Medicine, 2-2, Yamadaoka)

  • Kaori Higuchi

    (Osaka University Graduate School of Medicine, 2-2, Yamadaoka)

  • Jin-Sung Park

    (National Research Laboratory of Vascular Biology and Stem Cells, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), 373-1)

  • Manabu Shirai

    (National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai)

  • Koichi Nishiyama

    (Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo)

  • Hiroyuki Yamagishi

    (Keio University School of Medicine, 35, Shinano-machi)

  • Kinya Otsu

    (King’s College London, 25, Coldharbour Lane)

  • Hiroki Kurihara

    (Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo)

  • Takashi Minami

    (Laboratory for Vascular Biology, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-4, Komaba)

  • Keiko Yamauchi-Takihara

    (Osaka University Graduate School of Medicine, 2-2, Yamadaoka)

  • Gou Y. Koh

    (National Research Laboratory of Vascular Biology and Stem Cells, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), 373-1)

  • Naoki Mochizuki

    (JST-CREST, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai)

  • Nobuyuki Takakura

    (Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka)

  • Yasushi Sakata

    (Osaka University Graduate School of Medicine, 2-2, Yamadaoka)

  • Jun K. Yamashita

    (Laboratory of Stem Cell Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53, Shogoin-Kawahara-cho
    Institute for Frontier Medical Sciences, Kyoto University, 53, Shogoin-Kawahara-cho)

  • Issei Komuro

    (Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo
    Core Research for Evolutional Science and Technology (CREST), Japan Science Technology Agency, 4-1-8, Honcho)

Abstract

The origin and developmental mechanisms underlying coronary vessels are not fully elucidated. Here we show that myocardium-derived angiopoietin-1 (Ang1) is essential for coronary vein formation in the developing heart. Cardiomyocyte-specific Ang1 deletion results in defective formation of the subepicardial coronary veins, but had no significant effect on the formation of intramyocardial coronary arteries. The endothelial cells (ECs) of the sinus venosus (SV) are heterogeneous population, composed of APJ-positive and APJ-negative ECs. Among these, the APJ-negative ECs migrate from the SV into the atrial and ventricular myocardium in Ang1-dependent manner. In addition, Ang1 may positively regulate venous differentiation of the subepicardial APJ-negative ECs in the heart. Consistently, in vitro experiments show that Ang1 indeed promotes venous differentiation of the immature ECs. Collectively, our results indicate that myocardial Ang1 positively regulates coronary vein formation presumably by promoting the proliferation, migration and differentiation of immature ECs derived from the SV.

Suggested Citation

  • Yoh Arita & Yoshikazu Nakaoka & Taichi Matsunaga & Hiroyasu Kidoya & Kohei Yamamizu & Yuichiro Arima & Takahiro Kataoka-Hashimoto & Kuniyasu Ikeoka & Taku Yasui & Takeshi Masaki & Kaori Yamamoto & Kao, 2014. "Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the developing heart," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5552
    DOI: 10.1038/ncomms5552
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