A mechanism for hypoxia-induced pulmonary arterial hypertension

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790748
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Keio University
• Principal Investigator: SATOH Takashi Keio University, 医療衛生学部, 助教 (90407114)
• Co-Investigator(Renkei-kenkyūsha): KUWANA Masataka 慶應義塾大学, 医学部, 准教授 (50245479)
• Project Period (FY): 2009 – 2010
• Keywords: 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

Research Abstract

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.