Vessel Maturation as a Regulator of Tissue Remodeling

血管成熟作为组织重塑的调节器

基本信息

批准号：
7122070
负责人：
MARIA A RUPNICK
金额：
$ 10.07万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-30 至 2008-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): My long-term career goal is to contribute to the advancement of angiogenesis research. As an investigator and cardiologist, my principle commitment is to research. My earlier studies showed adipose tissue growth was angiogenesis dependent. Current efforts are directed at examining vascular maturation as a regulator of this tissue remodeling. These findings have implications for endothelial regulation of tissue growth. A K02 award would enable me to devote greater than 75% effort to the laboratory protected from non-research obligations. This would not only further the studies but also greatly advance my development as an investigator. Vessel remodeling and maturation are critical events following angiogenesis. Vascular density is fine-tuned while the nascent tubes are still immature. In most tissues this vascular plasticity is transient. Pericytes then stabilize the structure and a mature, quiescent vasculature results. In contrast, tumor vessels stay immature. This enables continued remodeling but also renders the tumor vasculature susceptible to anti-angiogenic drugs. We propose that adipose tissue, like tumors, maintains a chronically immature vasculature. Unlike most adult organs, adipose tissue can undergo rapid, substantial shifts in mass. Our prior work shows that adipose vasculature is also plastic and is susceptible to angiogenesis inhibitors. Our hypothesis is that adipose tissue vasculature is chronically immature, thereby preserving its plasticity after development. We will examine markers of vessel maturity during adipose tissue remodeling in wildtype and genetically obese mice under a variety of weight modifying conditions. We will characterize and examine the functional significance of the angiopoietin/tie system and pericytes content. Lipomas and normal human adipose tissue will be compared in terms of vascular maturation was greater in the more stable pathology. These studies are expected to further our understanding of the mechanisms of vascular remodeling and identify potential strategies for regulating tissue growth via the vasculature.

描述（由申请人提供）：我的长期职业目标是为血管生成研究的进步做出贡献。作为一名研究者和心脏病专家，我的主要承诺是研究。我早期的研究表明脂肪组织的生长依赖于血管生成。目前的努力旨在检查血管成熟度作为这种组织重塑的调节剂。这些发现对组织生长的内皮调节具有影响。 K02 奖项将使我能够将超过 75% 的精力投入到实验室，从而免受非研究义务的影响。这不仅会进一步推进研究，而且会极大地促进我作为一名研究者的发展。血管重塑和成熟是血管生成后的关键事件。当新生管尚未成熟时，血管密度已得到微调。在大多数组织中，这种血管可塑性是短暂的。然后周细胞稳定结构并形成成熟、静止的脉管系统。相反，肿瘤血管仍不成熟。这使得持续重塑成为可能，但也使肿瘤脉管系统对抗血管生成药物敏感。我们认为，脂肪组织像肿瘤一样，维持着长期不成熟的脉管系统。与大多数成人器官不同，脂肪组织的质量会发生快速、实质性的变化。我们之前的工作表明，脂肪脉管系统也是可塑的，并且容易受到血管生成抑制剂的影响。我们的假设是脂肪组织脉管系统长期不成熟，从而在发育后保持其可塑性。我们将检查野生型和遗传性肥胖小鼠在各种体重改变条件下脂肪组织重塑过程中血管成熟的标志物。我们将表征并检查血管生成素/连接系统和周细胞含量的功能意义。脂肪瘤与正常人体脂肪组织相比，在血管成熟度方面会更大，病理学更稳定。这些研究有望进一步加深我们对血管重塑机制的理解，并确定通过脉管系统调节组织生长的潜在策略。