Vessel Maturation as a Regulator of Tissue Remodeling

血管成熟作为组织重塑的调节器

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/7122070
• 关键词: adipocytes; adipose tissue; angiogenesis; angiogenesis inhibitors; angiopoietins; apoptosis; blood vessels; cell proliferation; clinical research; connective tissue neoplasm; gene expression; genetically modified animals; human tissue; laboratory mouse; leptin; macrophage; northern blottings; obesity; phosphorylation; polymerase chain reaction; terminal nick end labeling; vascular endothelial growth factors; western blottings

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发展做出贡献。 作为研究者和心脏病专家，我的主要承诺是研究。 我较早的研究表明，脂肪组织生长取决于血管生成。 目前的努力旨在研究血管成熟，作为该组织重塑的调节剂。 这些发现对组织生长的内皮调节有影响。 K02奖项将使我能够为受保护的非研究义务的实验室投入超过75％的努力。 这不仅将进一步研究，而且还可以大大推动我作为研究人员的发展。 血管重塑和成熟是血管生成后的关键事件。 血管密度是微调的，而新生的管仍然不成熟。 在大多数组织中，这种血管可塑性是短暂的。 然后，周细胞稳定结构和成熟，静止的脉管系统。 相反，肿瘤血管保持不成熟。 这使得继续重塑，但也使肿瘤脉管系统容易受到抗血管生成药物的影响。 我们建议脂肪组织（如肿瘤）保持长期不成熟的脉管系统。 与大多数成年器官不同，脂肪组织可以在质量中快速，实质性转移。 我们先前的工作表明，脂肪脉管系统也是塑性的，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，从而保留其在发育后的可塑性。 我们将检查在各种体重修饰条件下，在野生型和遗传肥胖小鼠中重塑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/TIE系统和周细胞含量的功能意义。 在更稳定的病理学中，将比较脂肪瘤和正常的人脂肪组织。 这些研究有望进一步了解我们对血管重塑的机制，并确定通过脉管系统调节组织生长的潜在策略。