A mechanism for hypoxia-induced pulmonary arterial hypertension

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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.