INOS AND COX2 CEREBRAL BLOOD VESSELS

INOS 和 COX2 脑血管

• 批准号: 6452792
• 负责人: Frank M Faraci
• 金额: $ 11.11万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6452792
• 关键词: Adenoviridae; blood brain barrier; blood vessels; brain circulation; cell transformation; gene expression; genetic regulation; genetically modified animals; interleukin 10; laboratory mouse; nitric oxide synthase; prostaglandin endoperoxide synthase; transfection; transfection /expression vector; vascular endothelium; vascular resistance

Endothelial and neuronal isoforms of nitric oxide synthase (NOS) appear to play a major role in regulation of cerebral circulation. The overall objectives of this project is to examine the influence of inducible NOS II and inducible cyclooxygenase (COX-2) on cerebral blood vessels. Both NOS II and COX-2 may be expressed in blood vessels in response to proinflammatory stimuli and under some pathophysiologi-cal conditions. The investigators propose to examine the influence of NOS II and COX-2 on vascular tone and permeability of the blood-brain barrier, and to examine mechanisms which regulate expression of these genes. To define the role of NOS iI in cerebral vessels, studies will now be performed using two state-of-the-art molecular approaches - NOS II knockoutmice and local overexpression using adenoviral- mediated gene transfer of NOS II. The functional importance of nuclear factor-Kappa Beta in mediating these responses will be examined. There may be interactions between the NOS and COX systems. Studies in NOS II knockout mice will allow examination of the functional importance of COX-2 in the presence and absence of NOS II. Interleukin-10 (IL-10) is an anti-inflammatory cytokine which protects against endotoxin shock. The role of IL- 10 in blood vessels is not known. Using IL-10 knockout mice, we plan to examine the hypothesis that interleukin 10 is a major endogenous regulator of expression of NOS II and COX-2 in cerebral vessels. Preliminary data support this hypothesis. Thus, state-of-the-art approaches will be used to study the role of NOS II, COX-2, and IL-10 in cerebral blood vessels. The studies should provide new insight into regulation of the cerebral circulation. Expression of these genes may be important in brain under several pathophysiological conditions including meningitis, ischemia, and in response to inflammatory stimuli.

一氧化氮合酶 (NOS) 的内皮和神经元亚型 似乎在调节脑循环方面发挥着重要作用。 该项目的总体目标是考察影响 诱导型 NOS II 和诱导型环氧合酶 (COX-2) 脑血管。 NOS II 和 COX-2 都可能是 在血管中表达以响应促炎刺激 以及在某些病理生理条件下。 调查人员 建议检查 NOS II 和 COX-2 对 血管张力和血脑屏障的通透性，以及 检查调节这些基因表达的机制。 为了确定 NOS iI 在脑血管中的作用，现在的研究将 使用两种最先进的分子方法进行 - NOS II 敲除小鼠和使用腺病毒的局部过度表达 NOS II 介导的基因转移。 功能重要性 核因子-Kappa Beta 介导这些反应将是 检查了。 NOS 和 COX 之间可能存在相互作用 系统。 NOS II 敲除小鼠的研究将允许检查 COX-2 存在时的功能重要性 NOS II 缺失。 白细胞介素 10 (IL-10) 是一种抗炎药 防止内毒素休克的细胞因子。 IL-的作用 10 在血管中的含量尚不清楚。 使用 IL-10 基因敲除小鼠，我们 计划检验白细胞介素 10 是主要的假设 NOS II 和 COX-2 表达的内源调节因子 脑血管。 初步数据支持这一假设。 因此， 最先进的方法将用于研究 NOS 的作用 脑血管中的II、COX-2和IL-10。 研究 应该为大脑调节提供新的见解 循环。 这些基因的表达可能对大脑很重要 在包括脑膜炎在内的多种病理生理条件下， 缺血以及对炎症刺激的反应。