MODULATORS OF NEOVASCULARIZATION IN THE DEVELOPING LUNG

新生血管是胎儿生长和发育的关键调节过程 发育，为组织提供营养和氧气。改建 在这个过程中会导致血管的异常和受损 组织发育。尽管关于这个问题我们知道很多 促进肺脏生长发育的因素相互作用 脉管系统，对其分子机制一无所知 可以抵消这些刺激。因此，这一行动的总体目标是 提议是首次在分子水平上确定 一种可能的肺血管生长负调控因子的作用。我选择了 关注内皮单核细胞激活多肽II作为一种 候选负调制子，因为我们最近确定了一个新的角色 该细胞因子在肿瘤血管中作为抗血管生成因子 开发和我现在有初步数据表明，它可能会发挥作用 在发育过程中负向调节血管生成的关键作用 小鼠肺。我假设EMAP II是一个重要的负面因素- 调节剂在血管生理学发育和新生血管形成中的作用 阿龙。该项目的具体目标是：1)确定临时-- EMAP II在小鼠胚胎肺中的空间表达，2) 确定EMAP II抑制肺血管的机制 3)确定EMAP II的分子基础， 抗血管生成因子，通过以下途径抑制血管内皮细胞生长 分析外源性EMAP II对细胞增殖的影响 细胞周期事件。这些拟议的研究将确定EMPA是否 II是肺发育中重要的负性调节因子 新生血管的形成，并将决定废除和 过度表达。基于这些信息，新的方法来解决 肺缺血再灌注后肺再生的临床治疗 损伤、慢性肺损伤和肺移植可被识别。

Neovascularization is a key regulatory process in fetal growth and development, providing nutrients and oxygen to tissues. Alterations within this process can lead to vascular abnormalities and impaired tissue development. Although a great deal is known regarding the interaction of factors promoting growth and development of the pulmonary vasculature, nothing is known regarding the molecular mechanisms that may counteract these stimuli. Accordingly the overall goals of this proposal are to determine, at a molecular level for the first time, the role of one putative negative modulator of lung vascular growth. I chose to focus on Endothelial monocyte activating polypeptide (EMAP) II as a candidate negative modulator because we recently identified a novel role for this cytokine as an anti-angiogenic factor in tumor vascular development and I now have preliminary data indicating that it may play a key role in negatively modulating angiogenesis within the developing mouse lung. I hypothesize that EMAP II is an important negative- regulator in the physiologic development and neovascularization of the lung. The specific aims of this project are: 1) To define the temporo- spatial expression of EMAP II in the embryonic mouse lung, 2) To determine the mechanism by which EMAP II inhibits lung vascular development, and 3) To determine the molecular basis by which EMAP II, an anti-angiogenic factor, inhibits vascular endothelial cell growth by analyzing the effect of exogenous EMAP II on cell proliferation, and cell cycle events. These proposed studies will determine whether EMPA II is an important negative regulator in lung development and neovascularization and will determine the effect of abrogation and overexpression. Based on this information, novel approaches to the clinical treatment of lung regeneration after ischemia-reperfusion injury, chronic lung damage and lung transplantation may be identified.