PROSTACYCLIN SYNTHESIS IN PULMONARY HYPERTENSION

描述（改编自申请人摘要）：前列环素具有 有效的血管舒张、抗聚集、抗血小板聚集和 抗增殖特性。 在严重的人类肺动脉高压中， 肺缺乏PGI2合酶。 计划的总体目标 研究是收集关键信息所需的了解 肺动脉高压血管PGI2合酶受损的病因学。 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。 目前的建议将审查 通过基因治疗增加PGI2合成的策略。 这个想法 将测试在肺特异性表达PGI2合酶的小鼠， 暴露于缺氧后， 它们的野生型对应物。 肺内皮细胞和气道细胞 还将用PGI2合酶基因转染大鼠， 缺氧检查。

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.