CORONARY ANGIOGENESIS/VASCULOGENESIS REGULATION

冠状动脉血管生成/血管生成调节

• 批准号: 6030647
• 负责人: ROBERT J TOMANEK
• 金额: $ 14.61万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-25 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6030647
• 关键词: angiogenesis; cardiovascular function; chick embryo; coronary artery; coronary vessels; fibroblast growth factor; growth factor; heart ventricle; hemodynamics; histogenesis; immunocytochemistry; in situ hybridization; laboratory rat; microcirculation; neutralizing antibody; oxygen tension; thyroxine; vascular endothelial growth factors; vascular endothelium; vertebrate embryology

DESCRIPTION (adapted from the applicant's abstract): The overall goal of this project is to determine the role of key growth factors, ventricular loading and growth on coronary vasculogenesis and angiogenesis. The proposed experiments will utilize hearts from both avian (chicken) and mammalian (rat) species. Aim 1 is to determine the role of vascular endothelial growth factor (VEGF) in the regulation of specific events comprising coronary vascularization. The applicant will test the hypothesis that VEGF stimulates coronary vascularization during prenatal heart development by treating embryonic hearts with exogenous VEGF and it neutralizing antibodies. To test the hypothesis that hypoxia serves as a trigger for VEGF expression in the ventricle during prenatal heart development, the applicant will expose chicken embryos and embryonic rat hearts grafted in oculo to lowered O2. Aim 2 is to determine the role of fibroblast growth factor (bFGF) in the regulation of specific events comprising coronary vascularization. To test the hypothesis that bFGF modulates vascularization at key time points during prenatal and postnatal heart development, embryonic and fetal hearts will be treated with bFGF and its neutralizing antibodies commencing at different stages of development. A second hypothesis is that unlike prenatal vascularization, late postnatal vascular growth can be stimulated in the absence of bFGF. In these studies thyroxine, which has been shown to stimulate coronary angiogenesis, will be administered to rats in combination with neutralizing antibodies for bFGF. Aim 3 is to establish the influence of ventricular loading conditions and mass on specific events comprising coronary vascularization and will be explored in a chicken model of differential loading (left ventricular hypoplastic syndrome with hyperplastic right ventricle). The hypotheses that the onset and magnitude of vascular growth is regulated by the thickness of the ventricular wall and that the timing of the ingrowth of the coronary arteries is related to the acceleration or deceleration of ventricular microvascular growth will be tested. The final hypothesis is that VEGF expression is modulated by the extent of ventricular growth. These aims are based on studies which will employ a variety of approaches including immunohistochemistry, histochemistry, in situ hybridization, image analysis, and Northern and Western analyses.

描述（根据申请人的摘要改编）： 该项目是确定关键增长因素，心室的作用 冠状动脉发生和血管生成的负载和生长。 这 拟议的实验将利用禽（鸡）和 哺乳动物（大鼠）物种。 目标1是确定血管的作用 在调节特定事件的内皮生长因子（VEGF） 包括冠状动脉血管。 申请人将检验假设 VEGF刺激产前心脏期间的冠状动脉血管化 通过用外源性VEGF处理胚胎心脏的发展， 中和抗体。 检验低氧作为一种假设 触发产前心脏中VEGF表达的VEGF表达 开发，申请人将暴露鸡胚和胚胎老鼠 心脏在Oculo中移植以降低O2。 目标2是确定 在特定事件的调节中，成纤维细胞生长因子（BFGF） 包括冠状动脉血管。 测试BFGF的假设 在产前和产后调节关键时间点的血管化 心脏发育，胚胎和胎儿心脏将用BFGF治疗 它的中和抗体从不同的开发阶段开始。 第二个假设是与产前血管不同，后期后期 在没有BFGF的情况下，可以刺激血管生长。 在这些研究中 甲状腺素已被证明会刺激冠状动脉生成，将是 与中和BFGF的中和抗体结合使用。 目标3是建立心室负荷条件的影响和 质量包括包括冠状动脉血管形成的特定事件，将是 在差分负荷的鸡模型中探索（左心室 与右心室增生的综合征综合征）。 假设 血管生长的开始和大小由 心室壁的厚度和向内生长的时机 冠状动脉与加速度或减速有关 心室微血管生长将进行测试。 最后的假设是 VEGF表达受心室生长的程度调节。 这些目标是基于将采用多种方法的研究 包括免疫组织化学，组织化学，原位杂交，图像 分析以及北部和西方分析。

项目成果

Relationship of the extracellular matrix to coronary neovascularization during development.

发育过程中细胞外基质与冠状动脉新生血管的关系。

• DOI: 10.1006/jmcc.1996.0212
• 发表时间: 1996
• 期刊: Journal of molecular and cellular cardiology
• 影响因子: 5
• 作者: Rongish,BJ;Hinchman,G;Doty,MK;Baldwin,HS;Tomanek,RJ
• 通讯作者: Tomanek,RJ

Influence of graft innervation on neovascularization of embryonic heart tissue grafted in oculo.

移植物神经支配对眼移植胚胎心脏组织新血管形成的影响。

• DOI: 10.1152/ajpheart.1996.270.1.h33
• 发表时间: 1996
• 期刊: The American journal of physiology.
• 作者: Torry,RJ;Rongish,BJ;Tucker,DC;Kostreva,DR;Tomanek,RJ
• 通讯作者: Tomanek,RJ

Modulation of cell migration and vessel formation by vascular endothelial growth factor and basic fibroblast growth factor in cultured embryonic heart.

培养胚胎心脏中血管内皮生长因子和碱性成纤维细胞生长因子对细胞迁移和血管形成的调节。

• DOI: 10.1002/aja.1002030403
• 发表时间: 1995
• 期刊: Developmental dynamics : an official publication of the American Association of Anatomists.
• 作者: Ratajska,A;Torry,RJ;Kitten,GT;Kolker,SJ;Tomanek,RJ
• 通讯作者: Tomanek,RJ

VEGF and bFGF stimulate myocardial vascularization in embryonic chick.

VEGF 和 bFGF 刺激胚胎鸡的心肌血管化。

• DOI: 10.1152/ajpheart.1998.274.5.h1620
• 发表时间: 1998
• 期刊: The American journal of physiology
• 作者: Tomanek,RJ;Lotun,K;Clark,EB;Suvarna,PR;Hu,N
• 通讯作者: Hu,N

Coronary neovascularization of embryonic rat hearts cultured in oculo is independent of thyroid hormones.

眼内培养的胚胎大鼠心脏的冠状动脉新生血管形成不依赖于甲状腺激素。

• DOI: 10.1152/ajpheart.1995.268.2.h811
• 发表时间: 1995
• 期刊: The American journal of physiology.
• 作者: Rongish,BJ;Torry,RJ;Tomanek,RJ
• 通讯作者: Tomanek,RJ