A mechanism for hypoxia-induced pulmonary arterial hypertension

缺氧引起的肺动脉高压的机制

• 批准号: 21790748
• 负责人: SATOH Takashi
• 金额: $ 2.75万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790748/
• 关键词: 肺動脈性高血圧症; 低酸素; 血管内皮細胞; BMP受容体; シンバスタチン

To examine mechanisms for hypoxia-induced pulmonary arterial hypertension (PAH), we identified for hypoxia-responsive genes unique to human pulmonary artery endothelial cells (HPAEC). Aorta and umbilical vein endothelial cells were used as controls. As a result, BMPR-IA and BMPR-II, a receptor for BMP, were identified as genes and proteins down-regulated in hypoxic HPAEC, but not in other endothelial cells. These findings suggest that hypoxia suppresses BMP signaling via down-regulation of BMP receptor in HPAEC, leading to development of PAH. Interestingly, simvastatin reversed the inhibitory effects of hypoxia and restored BMPR mRNA expression in HPAEC, might prevent PAH.

为了研究缺氧诱导肺动脉高压（PAH）的机制，我们鉴定了人类肺动脉内皮细胞（HPAEC）特有的缺氧反应基因。以主动脉和脐静脉内皮细胞为对照。结果，BMP受体BMPR-IA和BMPR-II在缺氧HPAEC中被鉴定为下调的基因和蛋白，而在其他内皮细胞中则没有下调。这些发现表明，缺氧通过下调HPAEC中BMP受体抑制BMP信号，导致PAH的发生。有趣的是，辛伐他汀逆转了缺氧的抑制作用，恢复了HPAEC中BMPR mRNA的表达，可能预防PAH。