PROSTACYCLIN SYNTHESIS IN PULMONARY HYPERTENSION

描述(改编自申请人的摘要)：前列环素 有效的血管扩张、抗聚集、抗炎和 抗增殖性能。在严重的人类肺动脉高压中， 肺组织中PGI2-合成酶缺乏。规划的总体目标 研究是收集关键信息，以了解 肺动脉高压血管前列腺素I2合酶功能障碍的病因学研究 所获得的知识可能会导致新的、合理的治疗策略 严重高血压患者。目前的提案将审查 通过基因治疗增加PGI2合成的策略。这个想法 将测试在肺中过度表达PGI2合成酶的小鼠 与低氧相比，低氧后发生的肺动脉高压较少 它们的野生型同类。肺内皮细胞和呼吸道细胞 大鼠也将被导入PGI2合成酶基因和它们的反应 对低氧进行检查。

DESCRIPTION (Adapted from the applicant's abstract): Prostacyclin has potent vasodilatory, antiaggregatory, antiinflammatory, and antiproliferative properties. In severe human pulmonary hypertension, the lung is deficient in PGI2-synthase. The overall goal of the planned research is to gather critical information required to understand the etiology of the PGI2 synthase impairment of pulmonary hypertensive vessels. The knowledge gained may lead to new, rational treatment strategies for severely hypertensive patients. The current proposal will examine strategies leading to increased PGI2 synthesis via gene therapy. The idea will be tested that mice which overexpress PGI2 synthase in a lung specific manner develop less pulmonary hypertension after exposure to hypoxia than their wild-type counterparts. Lung endothelial cells and airway cells of rats also will be transfected with the PGI2 synthase gene and their response to hypoxia examined.