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

Yoh Arita, Yoshikazu Nakaoka, Taichi Matsunaga, Hiroyasu Kidoya, Kohei Yamamizu, Yuichiro Arima, Takahiro Kataoka-Hashimoto, Kuniyasu Ikeoka, Taku Yasui, Takeshi Masaki, Kaori Yamamoto, Kaori Higuchi, Jin Sung Park, Manabu Shirai, Koichi Nishiyama, Hiroyuki Yamagishi, Kinya Otsu, Hiroki Kurihara, Takashi Minami, Keiko Yamauchi-TakiharaGou Y. Koh, Naoki Mochizuki, Nobuyuki Takakura, Yasushi Sakata, Jun K. Yamashita, Issei Komuro

研究成果: Article査読

49 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号4552
ジャーナルNature communications
5
DOI
出版ステータスPublished - 2014 7 29

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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