A mechanism for hypoxia-induced pulmonary arterial hypertension

为了研究低氧诱导的肺动脉高压(PAH)的机制，我们确定了人肺动脉内皮细胞(HPAEC)特有的低氧反应基因。以主动脉和脐静脉内皮细胞为对照。结果，BMPR-IA和BMP受体BMPR-II被鉴定为在缺氧性HPAEC中低表达的基因和蛋白，而在其他内皮细胞中不表达。这些发现表明，低氧通过下调HPAEC中BMP受体的表达而抑制BMP信号转导，从而导致PAH的发生。有趣的是，辛伐他汀逆转了缺氧对HPAEC的抑制作用，恢复了BMPR mRNA的表达，可能对PAH有预防作用。

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.