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: 6560665
• 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/6560665
• 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。 目前的努力是针对检查血管成熟作为这种组织重塑的调节器。 这些发现对组织生长的内皮调节有意义。 K 02奖将使我能够将超过75%的精力投入到实验室中，免受非研究义务的影响。 这不仅会促进研究，而且会大大促进我作为一名研究人员的发展。 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，而新生管仍然不成熟。 在大多数组织中，这种血管可塑性是短暂的。 周细胞然后稳定结构和成熟的，静止的脉管系统的结果。 相反，肿瘤血管保持不成熟。 这使得能够持续重塑，但也使肿瘤血管系统对抗血管生成药物敏感。 我们认为，脂肪组织，像肿瘤，维持一个长期不成熟的脉管系统。 与大多数成人器官不同，脂肪组织可以经历快速，实质性的质量变化。 我们先前的工作表明，脂肪血管也是可塑的，对血管生成抑制剂敏感。 我们的假设是，脂肪组织血管系统是长期不成熟的，从而保持其可塑性后的发展。 我们将研究在各种体重调整条件下野生型和遗传性肥胖小鼠脂肪组织重塑过程中血管成熟的标志物。 我们将描述和检查血管生成素/领带系统和周细胞含量的功能意义。 脂肪瘤与正常人脂肪组织相比，在血管成熟方面表现得更大，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，并确定通过血管系统调节组织生长的潜在策略。