ADENOVIRAL VECTORS FOR DELIVERY OF ANGIOGENIC CYTOKINES

用于递送血管生成细胞因子的腺病毒载体

• 批准号: 6627547
• 负责人: HAROLD FISHER DVORAK
• 金额: $ 38.25万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6627547
• 关键词: Adenoviridae; angiogenesis; athymic mouse; biological models; blood vessels; cytokine; guinea pigs; human tissue; immunocytochemistry; in situ hybridization; ischemia; morphometry; mutant; protein isoforms; protein structure function; tissue /cell culture; transfection /expression vector; vascular endothelial growth factors; video microscopy

DESCRIPTION: Angiogenesis has a central role in many important disease processes, and it is widely anticipated that stimulation of angiogenesis in vascular insufficiency will provide important therapeutic benefits. Many different cytokines and growth factors express angiogenic activity but vascular permeability factor/vascular endothelial growth factor (VPFNEGF) stands out because of its potency, selectivity for vascular endothelium, and its importance in vasculogenesis and both pathological and physiological angiogenesis. Our long term goal is to use angiogenic cytokines to generate new, structurally and functionally mature blood vessels in ischemic tissues. Before this goal can be realized, much needs to be learned about the basic steps and mechanisms by which cytokines and particularly VPFNEGF induce new blood vessels in adult tissues. To investigate these mechanisms, we will use adenoviral vectors to express murine VPFNEGF164, its 122 and 188 amino acid isoforms, and certain functionally altered mutant VPFNEGFs in both normal and ischemic tissues of immunodeficient mice. We will characterize the structure, function and organization of the new vessels that form; investigate the basis for tissue specificity of the angiogenic response; elucidate the mechanisms by which VPFNEGF induces mother vessels, capillaries and muscular arteries/veins; and determine the origins, character and fate of glomeruloid bodies. Our specific aims are as follows: 1. Define the mechanisms by which VPF/VEGF164 induces different types of new blood vessels in normal adult tissues. Structure, function and organization of the new vessels. 2. Characterize the angiogenic responses induced by the 120 and 188 amino acid isoforms of VPFNEGF and by function-altered VPF/VEGF mutants. 3. Elucidate the mechanisms responsible for the tissue specificity of the angiogenic response induced by VPF/VEGF164. Define the origins, character and fate of glomeruloid bodies. 4.Compare the angiogenic response to ischemia with that induced by VPFNEGF164 and its 120 and 188 amino acid isoforms in ischemic and non-ischemic tissues.

描述：血管生成在许多重要疾病中具有核心作用 过程，人们普遍认为刺激血管生成 血管功能不全将提供重要的治疗益处。许多 不同的细胞因子和生长因子表达血管生成活性但血管 渗透性因子/血管内皮生长因子（VPFNEGF）脱颖而出 由于其效力，对血管内皮的选择性，其效力 血管生成以及病理和生理学的重要性 血管生成。我们的长期目标是使用血管生成细胞因子产生 缺血组织中的新，结构和功能成熟的血管。 在实现这一目标之前，需要了解基本的很多 细胞因子，尤其是VPFNEGF诱导新的步骤和机制 成人组织中的血管。为了调查这些机制，我们将使用 腺病毒载体表达鼠VPFNEGF164，其122和188氨基酸 同工型，某些功能上的突变体VPFNEGF在正常和 免疫缺陷小鼠的缺血组织。我们将表征结构， 形成的新船的功能和组织；调查基础 用于血管生成反应的组织特异性；通过 VPFNEGF会诱导母血管，毛细血管和肌肉动脉/静脉； 并确定肾小球体的起源，特征和命运。我们的 具体目的如下：1。定义VPF/VEGF164的机制 在正常成人组织中诱导不同类型的新血管。 新容器的结构，功能和组织。 2。表征 VPFNEGF的120和188氨基酸同工型引起的血管生成反应 并通过改变功能的VPF/VEGF突变体。 3。阐明机制 负责由 VPF/VEGF164。定义肾小球体的起源，特征和命运。 4.与VPFNEGF164诱导的血管生成反应对缺血的血管生成反应 及其在缺血性和非缺血组织中的120和188氨基酸同工型。