@Article {hu1900378，作者= {胡，程军和汤，金米和张，惠和弗洛克顿，阿曼达和莱克斯，绫座和柯克尼，布列塔尼和莫迪安，加里和李，分钟和瑞克，Suzette和Pugliese，Steven C.和Brown，R. Dale和Wallace，Eli M.和Graham，Brian B.和Frid，Maria G.和Stenmark，Kurt R.}，标题= {抑制HIF2信号传导的启动缺氧诱导的肺动脉高压}，体积= {54}，Number = {6}，Elocation-Id = {1900378}，年= {2019}，DOI = {10.1183 / 13993003.00378-13993003.00378-13993003.00378-13993003.00378-13993003.00378-188bet官网地址13993003.00378-13993003.00378-13993003.00378-13993003.00378-13993003.00378-13993003.00378-13993003.00378-2019}，出版商= {欧洲呼吸社会}，摘要= {大多数公布的研究解决了缺氧诱导的肺动脉高压发育中的缺氧诱导因子（HIF）的作用，采用可能不会重新承载临床环境的模型，包括使用与胚胎中的预先存在的肺/血管缺损的动物HIF消融或激活。此外，包括如何以及当HIF信号传导促成缺氧诱导的肺动脉高血压的关键问题仍然是未答复的。通过诱导基因缺失或药理学抑制（反义寡核苷酸（ASO）和小分子抑制剂）抑制全局HIF1或HIF2的通知成年啮齿动物暴露于短期（4天）或慢性（4 {\ Textendash} 5周）缺氧。进行了血液动力学研究，使动物安乐死，肺和心脏的病理和转录组分析。用于肺动脉高压起始的细胞型特异性HIF信号在体外和小鼠的正常肺血管细胞中测定（使用细胞型特异性HIF缺失）.Global HIF1A在小鼠中缺失在5周内没有防止缺氧诱导的肺动脉高压。全球HIF2A缺失的小鼠没有生存长期缺氧。 Partial Hif2a deletion or Hif2-ASO (but not Hif1-ASO) reduced vessel muscularisation, increases in pulmonary arterial pressures and right ventricular hypertrophy in mice exposed to 4{\textendash}5 weeks of hypoxia. A small molecule HIF2 inhibitor (PT2567) significantly attenuated early events (monocyte recruitment and vascular cell proliferation) in rats exposed to 4 days of hypoxia, as well as vessel muscularisation, tenascin C accumulation and pulmonary hypertension development in rats exposed to 5 weeks of hypoxia. In vitro, HIF2 induced a distinct set of genes in normal human pulmonary vascular endothelial cells, mediating inflammation and proliferation of endothelial cells and smooth muscle cells. Endothelial Hif2a knockout prevented hypoxia-induced pulmonary hypertension in mice.Inhibition of HIF2 (but not HIF1) can provide a therapeutic approach to prevent the development of hypoxia-induced pulmonary hypertension. Future studies are needed to investigate the role of HIFs in pulmonary hypertension progression and reversal.Activation of HIF2 by hypoxia initiates vascular cell proliferation and recruitment of inflammatory cells at early stages of PH development through HIF2-dependent transcription of genes involved in these pathways in pulmonary vascular cells http://bit.ly/2lFwTGM}, issn = {0903-1936}, URL = {//www.qdcxjkg.com/content/54/6/1900378}, eprint = {//www.qdcxjkg.com/content/54/6/1900378.full.pdf}, journal = {European Respiratory Journal} }