1GF AXIS IN PULMONARY VASCULAR REMODELING

胰岛素样生长因子-II和胰岛素样生长因子结合蛋白在急性肺血管病变中的作用 与新生儿肺动脉高压相关的重构将是 学习。这种疾病的纤维增生性反应是其特征 新生儿，可能代表着一种独特的发育易感性 循环生理和血管发生显著变化时的损伤 成熟。我们的初步数据表明，增加表达的作用 IGF-II在血管增殖反应中的表达。IGF-BPS由 血管壁细胞在胰岛素样生长因子的定位和调控中发挥核心作用 在细胞层面上的行动。我们假设IGF-II的增加 肺血管壁中的表达是一种重要的调节因子 新生儿缺氧性肺血管增殖反应的研究 高血压。我们认为IGF-II在新生儿中的表达增加 肺动脉高压反映了胎儿基因模式的持续性 围产期的表达与表达的改变有关 和特定的IGF-BP的积累。我们假设 IGF-II和IGF-BP的表达受体外低氧的调节 对外膜成纤维细胞和血管平滑肌细胞的不同影响。 目标是：1)评估IGF-II的正常发育变化 和IGF-BP在胎儿晚期和晚期肺循环中的表达 早期新生儿生命，以及低氧对这些生命的影响 新生儿的肺动脉高压，以及2)如何直接检查 缺氧改变胎儿、新生儿和脑组织中IGF-II和IGF-Bps的表达 体外培养高血压血管壁细胞。

The role of IGF-II and IGF-BP's in the dramatic pulmonary vascular remodeling associated with neonatal pulmonary hypertension will be studied. The fibroproliferative response in this disease characterizes the neonate, and may represent a unique developmental susceptibility to injury at a time of marked changes in circulatory physiology and vessel maturation. Our preliminary data suggest a role for increased expression of IGF-II in the vascular proliferative response. IGF-BPs produced by vascular wall cells play a central role in localizing and modulating IGF actions at the cellular level. We hypothesize that increased IGF-II expression in the pulmonary vessel wall is a critical modulator of the vascular proliferative response in neonatal hypoxic pulmonary hypertension. We propose that increased IGF-II expression in neonatal pulmonary hypertension reflects persistence of a fetal pattern of gene expression in the perinatal period, associated with altered expression and accumulation of specific IGF-BP's. We postulate that altered expression of IGF-II and IGF-BP's is regulated by hypoxia in vitro, with different effects on the adventitial fibroblast and vascular smooth cell. The goals are: 1) to evaluate the normal developmental changes in IGF-II and IGF-BP expression in the pulmonary circulation during late fetal and early neonatal life, and how these are affected by developing hypoxic pulmonary hypertension in the newborn, and 2) to examine directly how hypoxia alters expression of IGF-II and IGF-BPs in fetal, neonatal, and hypertensive vascular wall cells in vitro.