ENDOTHELIAL CELL PROLIFERATION IN PPH

产品说明： 原发性肺动脉高压（PPH）是一种毁灭性的 以家族或散发形式出现的疾病。 的 研究人员发现，PPH与 丛源性继发性肺动脉高压（第二PH），因为 PPH中增殖的内皮细胞大多是单克隆的，而 它们在第二PH中是严格多克隆的。 PPH中增殖的单克隆扩张内皮细胞 具有内皮干细胞的特性。 此外，调查人员 推测a）PPH的发病机制可以通过以下方式理解： 调查被误导的血管发生/血管生成的概念; B） 芳香烃受体（AHR）-芳香烃受体 核转运蛋白（ARNT）和缺氧诱导因子1b（HIF-1b） 相互作用可能参与肺动脉内皮细胞的生长 控制 主要研究者的方法是通过显微切割从 PPH患者肺部、“高血压”内皮和血管平滑肌 细胞产生细胞特异性cDNA文库，应用该技术 基因表达系列分析（SAGE）和二维蛋白质 电泳以表征基因和蛋白质表达 单克隆和多克隆“高血压”肺动脉的模式 细胞 AHR/ARNT转录系统的功能重要性 肺动脉高压内皮细胞生长将在 使用活化剂的慢性剪切应力暴露的细胞培养系统和 AHR抑制剂和ARNT E盒的转录因子诱饵 核心序列

DESCRIPTION: Primary Pulmonary Hypertension (PPH) is a devastating disease which occurs in a familial and in a sporadic form. The investigators have found that PPH is categorically different from plexogenic secondary pulmonary hypertension (2nd PH), in that the proliferative endothelial cells in PPH are mostly monoclonal, whereas they are strictly polyclonal in 2nd PH. The investigators postulate that the proliferating monoclonally expanding endothelial cells in PPH have properties of endothelial stem cells. Further, the investigators speculate that a) The pathogenesis of PPH can be understood by investigating the concept of misguided vasculogenesis/angiogenesis; b) That an aryl hydrocarbon receptor (AHR) -aryl hydrocarbon receptor nuclear transporter (ARNT) and hypoxia-inducible factor 1b (HIF-1b) interaction may be involved in pulmonary artery endothelial cell growth control. The PI's approach will be to obtain, via microdissection from PPH patient lungs, "hypertensive" endothelial and vascular smooth muscle cells to generate cell-specific cDNA libraries, to apply the technique of serial analysis of gene expression (SAGE) and two-dimensional protein electrophoresis in order to characterize the gene and protein expression pattern of monoclonal and polyclonal "hypertensive" pulmonary artery cells. The functional importance of the AHR/ARNT transcription system for pulmonary hypertensive endothelial cell growth will be examined in chronic shear stress exposed cell culture system using activators and inhibitors of AHR and a transcription factor decoy of the ARNT E box core sequence.