TY - JOUR
T1 - Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the developing heart
AU - Arita, Yoh
AU - Nakaoka, Yoshikazu
AU - Matsunaga, Taichi
AU - Kidoya, Hiroyasu
AU - Yamamizu, Kohei
AU - Arima, Yuichiro
AU - Kataoka-Hashimoto, Takahiro
AU - Ikeoka, Kuniyasu
AU - Yasui, Taku
AU - Masaki, Takeshi
AU - Yamamoto, Kaori
AU - Higuchi, Kaori
AU - Park, Jin Sung
AU - Shirai, Manabu
AU - Nishiyama, Koichi
AU - Yamagishi, Hiroyuki
AU - Otsu, Kinya
AU - Kurihara, Hiroki
AU - Minami, Takashi
AU - Yamauchi-Takihara, Keiko
AU - Koh, Gou Y.
AU - Mochizuki, Naoki
AU - Takakura, Nobuyuki
AU - Sakata, Yasushi
AU - Yamashita, Jun K.
AU - Komuro, Issei
N1 - Funding Information:
We thank Yuka Yoshimoto for secretarial assistance; Miki Nagase (Tokyo University) for providing the plasmid containing the mouse Ang1 in situ hybridization probe; David J. Anderson (California Institute of Technology) for providing the EphB4 tau-lacZ and EphrinB2 tau-lacZ knock-in mice; and Satoshi Somekawa (Nara Medical University) for helpful comments. This work was supported in part by grants from the Ministry of Education, Science, Sports and Culture of Japan (to I.K., Y.N.); Japan Heart Foundation Young Investigator’s Research Grant (to Y.N.); Suzuken Memorial Foundation (to Y.N.); Astellas Foundation for Research on Metabolic Disorders (to Y.N.); Senri Life Science Foundation (to Y.N.); Miyata Cardiology Research Promotion Funds (to Y.N.); Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Y.N.); Takeda Medical Research Foundation (to Y.N.); Daiichi-Sankyo Foundation of Life Science (to Y.N.); SENSHIN Medical Research Foundation (to Y.N.); Kobayashi Magobe (Mannari Hospital) Medical Research Foundation (to Y.N.); Japan Heart Foundation/Novartis Grant for Research Award on Molecular and Cellular Cardiology, 2012 (to Y.A.).
PY - 2014/7/29
Y1 - 2014/7/29
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms5552
DO - 10.1038/ncomms5552
M3 - Article
C2 - 25072663
AN - SCOPUS:84905269218
SN - 2041-1723
VL - 5
JO - Nature Communications
JF - Nature Communications
M1 - 4552
ER -