MODULATORS OF NEOVASCULARIZATION IN THE DEVELOPING LUNG

新生血管形成是胎儿生长的关键调节过程， 发育，为组织提供营养和氧气。改变 在这个过程中可能会导致血管异常和受损 组织发育 虽然很多人都知道 促进肺动脉瘤生长发育因素的相互作用 血管系统，没有什么是已知的分子机制， 可以抵消这些刺激。 因此，本项目的总体目标 第一次在分子水平上确定， 肺血管生长的一种假定的负调节剂的作用。我选择 将内皮单核细胞激活多肽（EMAP）II作为 候选负调节剂，因为我们最近发现了一种新的作用， 对于这种细胞因子作为肿瘤血管中的抗血管生成因子， 我现在有初步数据表明，它可能发挥作用， 在发育中的血管生成中起负调节作用的关键作用， 小鼠肺。 我假设EMAP II是一个重要的负面因素- 调节剂的生理发展和新血管形成的 肺。该项目的具体目标是：1）确定时间- EMAP II在小鼠胚胎肺中的空间表达，2）为了 确定EMAP II抑制肺血管的机制 发展，和3）为了确定EMAP II， 一种抗血管生成因子，通过以下方式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，和 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调节因子， 新血管形成，并将确定废除的效果， 过度表达 基于这些信息，新的方法， 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。

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.