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: 6942346
• 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/6942346
• 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.

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