ENDOTHELIAL CELL PROLIFERATION IN PPH

描述：原发性肺动脉高压(PPH)是一种毁灭性的 以家族性和零星形式发生的疾病。这个 调查人员发现，PPH与 丛源性继发性肺动脉高压(2PH) PPH中的增殖性内皮细胞多为单克隆性 在第二次PH中，它们是严格的多克隆。调查人员假设 PPH中增殖的单克隆性扩张性内皮细胞 具有内皮干细胞的特性。此外，调查人员 推测a)PPH的发病机制可通过以下方式理解 调查被误导的血管生成/血管生成的概念；b) 一种芳烃受体(AHR)-芳烃受体 核转运蛋白(ARNT)和缺氧诱导因子1b(HIF-1b) 相互作用可能参与了肺动脉内皮细胞的生长 控制力。PI的方法将是通过显微解剖从 PPH患者肺、“高血压”血管内皮细胞和血管平滑肌 细胞来生成细胞特异性的cDNA文库，以应用这项技术 基因表达序列分析(SAGE)和二维蛋白质 电泳法以鉴定基因和蛋白质的表达 单克隆性和多克隆性“高血压”型肺动脉 细胞。AHR/Arnt转录系统的功能重要性 对于肺动脉高压，内皮细胞的生长将在 慢性剪应力暴露的细胞培养系统使用激活剂和 AHR的抑制剂和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.