THE ROLE OF GROWTH HORMONE IN CARDIOVASCULAR HEALTH

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们研究的具体目的将是：1.确定适当的hGH替代前后GHD人群PAI-1的昼夜节律。我们假设生长激素和纤溶酶原激活物-1的水平在正常人体内呈负相关。此外，由于GHD患者将失去其生长激素的昼夜分泌，我们假设他们的PAI-1水平将在hGH替代治疗期间长期处于高水平，而一旦被充分替代则长期处于低水平。2.评价生长激素替代治疗前后GHD患者纤溶功能的变化。我们假设GHD成人在静脉闭塞试验后会有有缺陷的纤溶反应，并且在适当的替代治疗后这种影响将被消除。3.评估生长激素替代治疗前后GHD患者的内皮功能障碍。我们假设血流介导的扩张(FMD)在GHD患者中将不那么明显，我们假设在hGH替代治疗后，血流介导的扩张将恢复到基线水平。4.利用蛋白质组学，比较生长激素替代治疗前后GHD患者中存在的蛋白质的血浆特征。缺乏或存在不同蛋白质的缺失或替换状态只会引发关于GH在炎症中的作用和动脉粥样硬化发病机制的进一步问题，这可能值得在未来进行研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The specific aims of our study will be to: 1. Determine the circadian rhythm of PAI-1 in the GHD population prior to and following appropriate replacement with hGH. We hypothesize that the levels of GH and PAI-1 will be inversely related within a normal individual. Additionally, since a GHD individual would lose their circadian secretion of GH, we hypothesize that their PAI-1 level would be chronically high while not on hGH replacement and chronically low once adequately replaced. 2. Evaluate the fibrinolytic potential of patients with GHD prior to and following replacement with hGH. We hypothesize that there will be a defective fibrinolytic response in GHD adults following the venous occlusion test, and that this effect will be abolished following adequate replacement therapy. 3. Evaluate endothelial dysfunction in patients with GHD prior to and following replacement with hGH. We hypothesize that flow-mediated dilation (FMD) will be less prominent in patients with GHD and we hypothesize that flow-mediated dilation will return to baseline following replacement therapy with hGH. 4. Compare, using proteomics, the plasma signature of proteins present in GHD individuals prior to and following replacement therapy with hGH. The absence or presence of different proteins present in the deficient versus the replaced state could only serve to raise further questions regarding the role of GH in inflammation and the pathogenesis of atherosclerosis that may warrant investigation in the future.