肺血管收缩和结构重建是低氧性肺动脉高压(HPH)的病理生理学基础。已知的扩血管药物虽能有效降低肺动脉压，但缺乏特异性，长期服用外周血压下降使病人难以耐受。ACE2和Ang(1-7)有舒血管抗增殖特点，故促进其表达是防治HPH的有效方法。问题是如何使ACE2和Ang(1-7)根据低氧程度只在在肺血管中高表达。鉴于Tie2在肺血管内皮细胞(ECs)特异性表达，且低氧 (PaO2不低于35mmHg)时HIF-1α仅在肺血管表达增加。故本项目利用Tie2定位于肺血管ECs的特异性、HIF-1α的低氧条件性表达和ACE2与Ang(1-7)舒血管抗增殖的特点，以ACE2和Ang(1-7)为目标基因，分别构建HRE增强的Tie2启动子驱动ACE2和Ang-(1-7)表达载体，使ACE2和Ang(1-7)特异性可控性地在ECs中高表达，进而调控肺动脉平滑肌细胞，抑制低氧性肺血管收缩和结构重建。

Pulmonary vasoconstriction and pulmonary vascular structure remodeling are the pathophysiological bases of hypoxic pulmonary hypertension (HPH). ACE2 and Ang-(1-7) have characteristics of vasodilatation and anti-proliferation. Thereby increaseing the ACE2 and Ang-(1-7) may be an effective therapy for HPH. But how to make the ACE2 and Ang-(1-7) only the specific localization in the lung blood vessels and increasing only according to the degree of hypoxia are very important. Tie2 gene specifically express in pulmonary vascular endothelial cells. And HIF-1α expression are increasing only in the pulmonary vascular when are exposed in hypoxia (35mmHg <PaO2 <60mmHg). Hence, by using of the specificity of Tie2 expression located in the pulmonary vascular endothelial cells, the expression of HIF-1α only in hypoxia pulmonary vascular, and ACE2 and its main product of Ang-(1-7) have vasodilatory and anti-proliferative characteristics, we will build two vectors to increase the expression of ACE2 and Ang-(1-7) in pulmonary vascular endothelial cells, respectively. Thus PASMCs will be regulated under the high level of ACE2 and Ang-(1-7), and then pulmonary vasoconstriction and pulmonary vascular structure remodeling will be inhibited as well. At the same time, we will compare the specificity, feasibility, and effectiveness of the two vectors, and their underlying mechanisms, to provide new tools and strategies for the prevention of HPH.