Analysis of coronary vascular development in an animal model of congenital heart disease - in vivo and in vitro studies to detect a role of proepicardial organ derived cells

先天性心脏病动物模型中冠状血管发育的分析 - 体内和体外研究以检测心外膜器官衍生细胞的作用

基本信息

批准号：
16390299
负责人：
NAKAGAWA Masao
金额：
$ 7.1万
依托单位：
Shiga University of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

We examined distributional patterns of quail-derived proepicardial organ (PEO) cells in the hearts of chick-quail chimeric embryos produced following the procedure described by Manner. Quail PEO cells formed epicardium at day 5 after incubation, beneath which epithelial-mesenchymal transformation (EMT) of PEO cells were observed. Quail PEO cells also were detected in the myocardium and around the future ostia of coronary arteries at day 6 and at day 9 after incubation, respectively. In the mouse embryos at the coincident developmental stage with chick, tenascin-C was expressed in PEO but was suppressed when PEO cells moved to the cardiac surface, migrating into the myocardium. Tenascin-C expression was upregulated in EMT. Mouse PEO cells cultured on the collagen gels in the presence of fetal calf serum formed tube structures. RT-PCR analyses of RNAs extracted from cultured PEO demonstrated expression of various vascular growth factors including bFGF, HGF, VEGF, Flt-1, Flk- 1, Ang-1, Ang-2 and Tie-2, however, the expression of these growth factors were downregulated when bis-diamine was added into the culture medium. In rat embryos, vascular plexus was formed between the epicardium and myocardium at 14.5 embryonic day (ED) and vascular structure was recognized in the myocardium at ED 15.5. The vascular plexus was dispersed and vascular structures were not formed in the embryonic hearts when bis-diamine was given to mother rats at ED 10.5. Immunohistological studies showed delayed expression of the vascular growth factors in those rat embryos treated with bis-diamine.These results suggested that bis-diamine caused the abnormal development of coronary vasculature by making a direct effect on growth of PEO cells and by disturbing EMT and expression of vascular growth factors.

我们检查了按照 Manner 描述的程序产生的鸡-鹌鹑嵌合胚胎心脏中鹌鹑来源的心外膜器官 (PEO) 细胞的分布模式。鹌鹑PEO细胞在孵育后第5天形成心外膜，在其下方观察到PEO细胞的上皮间质转化(EMT)。孵化后第6天和第9天，在心肌和未来冠状动脉口周围也分别检测到鹌鹑PEO细胞。在与小鸡处于同一发育阶段的小鼠胚胎中，腱蛋白-C 在 PEO 中表达，但当 PEO 细胞移动到心脏表面并迁移到心肌中时，腱蛋白-C 被抑制。 Tenascin-C 表达在 EMT 过程中上调。在胎牛血清存在下，在胶原凝胶上培养的小鼠 PEO 细胞形成管状结构。对从培养的 PEO 中提取的 RNA 进行 RT-PCR 分析，结果显示各种血管生长因子的表达，包括 bFGF、HGF、VEGF、Flt-1、Flk-1、Ang-1、Ang-2 和 Tie-2，然而，这些因子的表达当将双二胺添加到培养基中时，生长因子被下调。在大鼠胚胎中，在 14.5 个胚胎日 (ED) 时，心外膜和心肌之间形成了血管丛，并在 ED 15.5 天时在心肌中识别出血管结构。当母鼠ED 10.5时给予双二胺时，胚胎心脏中血管丛分散，血管结构未形成。免疫组织学研究表明，用双二胺处理的大鼠胚胎中血管生长因子的表达延迟。这些结果表明，双二胺通过直接影响PEO细胞的生长以及干扰EMT和表达而导致冠状血管发育异常。血管生长因子。

项目成果

期刊论文数量（29）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

hesr1 and hesr2 are redundantly required for cardiac chamber formation and arterial formation.

hesr1 和 hesr2 对于心室形成和动脉形成来说是多余的。

DOI：
发表时间：
2005
期刊：
Dev Biol 278(2)
影响因子：
0
作者：
Kokubo H;Miyagawa-Tomita S;et al.
通讯作者：
et al.

Clinical characteristics and diagnosis of double-orifice left atrioventricular valve associated with other congenital heart disease

DOI：
10.1007/s00380-004-0818-0
发表时间：
2005-11-01
期刊：
HEART AND VESSELS
影响因子：
1.5
作者：
Ito-Akabori, S;Nakagawa, M;Kitamura, N
通讯作者：
Kitamura, N

冠動脈の発生と発達に関する最近の知見

冠状动脉发生和发展的最新发现

DOI：
发表时间：
2004
期刊：
日本冠疾患雑誌 12
影响因子：
0
作者：
宮川-富田幸子;冨澤康子;他
通讯作者：
他

Teratogenic effects of bis-diamine on the developing syocardium

双二胺对心肌发育的致畸作用

DOI：
发表时间：
2004
期刊：
Birth Defects Research (Part A) 70
影响因子：
0
作者：
Yamamoto K;Imanaka-Yoshida K;et al.;Okamoto Nobuhiko
通讯作者：
Okamoto Nobuhiko

Coronary artery obstruction due to membranous ridge of the right sinus valsalva associated with Tetralogy of Fallot : syncope mimics anovic spell.

与法洛四联症相关的右瓦萨尔瓦窦膜脊引起的冠状动脉阻塞：晕厥模仿无诺维奇发作。

DOI：
发表时间：
2004
期刊：
Ann Thorac Surg 77
影响因子：
0
作者：
Yamamoto K;Imanaka-Yoshida K;et al.;Okamoto Nobuhiko;Shiraishi Isao;Imanaka-Yoshida Kyoko;Kokubo Hiroki;Suzuki Atsuko;宮川-富田幸子;岩崎淳一;Okamoto Nobuhiko;Shiraishi Isao
通讯作者：
Shiraishi Isao