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

被引：63

作者：

Arita, Yoh ^{[1
,2
]}

Nakaoka, Yoshikazu ^{[1
]}

Matsunaga, Taichi ^{[3
]}

Kidoya, Hiroyasu ^{[4
]}

Yamamizu, Kohei ^{[3
]}

Arima, Yuichiro ^{[5
]}

Kataoka-Hashimoto, Takahiro ^{[1
]}

Ikeoka, Kuniyasu ^{[1
]}

Yasui, Taku ^{[1
]}

Masaki, Takeshi ^{[1
]}

Yamamoto, Kaori ^{[1
]}

Higuchi, Kaori ^{[1
]}

Park, Jin-Sung ^{[6
]}

Shirai, Manabu ^{[7
]}

Nishiyama, Koichi ^{[5
]}

Yamagishi, Hiroyuki ^{[8
]}

Otsu, Kinya ^{[9
]}

Kurihara, Hiroki ^{[5
]}

Minami, Takashi ^{[10
]}

Yamauchi-Takihara, Keiko ^{[1
]}

Koh, Gou Y. ^{[6
]}

Mochizuki, Naoki ^{[11
]}

Takakura, Nobuyuki ^{[4
]}

Sakata, Yasushi ^{[1
]}

Yamashita, Jun K. ^{[3
,12
]}

Komuro, Issei ^{[13
,14
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Cardiovasc Med, Suita, Osaka 5650871, Japan

[2] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol PRESTO, Kawaguchi, Saitama 3320012, Japan

[3] Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Inst Frontier Med Sci Dept Cell Growth Differenti, Lab Stem Cell Differentiat,Sakyo Ku, Kyoto 6068507, Japan

[4] Osaka Univ, Microbial Dis Res Inst, Dept Signal Transduct, Suita, Osaka 31, Japan

[5] Univ Tokyo, Grad Sch Med, Dept Physiol Chem & Metab, Bunkyo Ku, Tokyo 1130033, Japan

[6] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Natl Res Lab Vasc Biol & Stem Cells, Taejon 305701, South Korea

[7] Natl Cerebral & Cardiovasc Ctr Res Inst, Dept Biosci, Suita, Osaka 5658565, Japan

[8] Keio Univ, Sch Med, Dept Pediat, Shinjuku Ku, Tokyo 1608582, Japan

[9] Kings Coll London, Div Cardiovasc, London SE5 9NU, England

[10] Univ Tokyo, Res Ctr Adv Sci & Technol, Lab Vasc Biol, Meguro Ku, Tokyo, Japan

[11] JST CREST, Natl Cerebral & Cardiovasc Ctr, Res Inst, Dept Cell Biol, Suita, Osaka 5658565, Japan

[12] Kyoto Univ, Inst Frontier Med Sci, Dept Stem Cell Differentiat, Sakyo Ku, Kyoto 6068507, Japan

[13] Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Bunkyo Ku, Tokyo 1130033, Japan

[14] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

VASCULAR PROGENITORS; RETINAL VASCULATURE; ENDOTHELIAL-CELLS; EPICARDIAL CELLS; TIE2; RECEPTOR; COUP-TFII; ANGIOGENESIS; EXPRESSION; MORPHOGENESIS; ARTERIES;

D O I：

10.1038/ncomms5552

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：14

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