title: Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the developing heart.
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.
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Yoh
authors: Y
authors: Arita
authors: 1] Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan [2] Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science Technology Agency, 4-1-8, Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors: Yoshikazu
authors: Y
authors: Nakaoka
authors: Laboratory of Stem Cell Differentiation, Institute for Frontier Medical Sciences/Department of Cell Growth &Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors: Taichi
authors: T
authors: Matsunaga
authors: Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Hiroyasu
authors: H
authors: Kidoya
authors: Laboratory of Stem Cell Differentiation, Institute for Frontier Medical Sciences/Department of Cell Growth &Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors: Kohei
authors: K
authors: Yamamizu
authors: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Yuichiro
authors: Y
authors: Arima
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Takahiro
authors: T
authors: Kataoka-Hashimoto
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Kuniyasu
authors: K
authors: Ikeoka
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Taku
authors: T
authors: Yasui
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Takeshi
authors: T
authors: Masaki
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Kaori
authors: K
authors: Yamamoto
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Kaori
authors: K
authors: Higuchi
authors: 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, Guseong-dong, Daejeon 305-701, Korea.
authors: Jin-Sung
authors: JS
authors: Park
authors: Department of Bioscience, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan.
authors: Manabu
authors: M
authors: Shirai
authors: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Koichi
authors: K
authors: Nishiyama
authors: Department of Pediatrics, Keio University School of Medicine, 35, Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Hiroyuki
authors: H
authors: Yamagishi
authors: Cardiovascular Division, King's College London, 25, Coldharbour Lane, London SE5 9NU, UK.
authors: Kinya
authors: K
authors: Otsu
authors: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Hiroki
authors: H
authors: Kurihara
authors: Laboratory for Vascular Biology, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-4, Komaba, Meguro-ku 153-8904, Tokyo, Japan.
authors: Takashi
authors: T
authors: Minami
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Keiko
authors: K
authors: Yamauchi-Takihara
authors: 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, Guseong-dong, Daejeon 305-701, Korea.
authors: Gou Y
authors: GY
authors: Koh
authors: Department of Cell Biology, JST-CREST, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan.
authors: Naoki
authors: N
authors: Mochizuki
authors: Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Nobuyuki
authors: N
authors: Takakura
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Yasushi
authors: Y
authors: Sakata
authors: 1] Laboratory of Stem Cell Differentiation, Institute for Frontier Medical Sciences/Department of Cell Growth &Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan [2] Department of Stem Cell Differentiation, Institute for Frontier Medical Sciences, Kyoto University, 53, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors: Jun K
authors: JK
authors: Yamashita
authors: 1] Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [2] Core Research for Evolutional Science and Technology (CREST), Japan Science Technology Agency, 4-1-8, Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors: Issei
authors: I
authors: Komuro
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002678:Chimera; D003331:Coronary Vessels / Q000196:embryology*; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000502:physiology*; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000196:embryology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D042683:Angiopoietin-1; D017931:DNA Primers; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins