Angiopoietin-1-mediated vascular development and maturation in the developing heart

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293183
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: National Cardiovascular Center Research Institute (2015); Osaka University
• Principal Investigator: NAKAOKA YOSHIKAZU 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (90393214)
• Co-Investigator(Renkei-kenkyūsha): YAMASHITA JUN 京都大学, 再生医科学研究所/iPS細胞研究所, 教授 (50335288) ; KOMURO ISSEI 東京大学医学系研究科, 循環器内科学, 教授 (30260483)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: angiopoietin-1 / 冠静脈 / 静脈洞 / 内皮細胞 / 血管形成 / 静脈分化

Outline of Final Research Achievements

The origin and developmental mechanisms underlying coronary vessels are not fully elucidated. Here we examined the role of myocardium-derived angiopoietin-1 (Ang1) for coronary vessel 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. Taken together, these data indicate that myocardial Ang1 is essential for coronary vein formation.

Free Research Field

循環器内科学