Roles of hypoxia inducible factor-1 (HIF-1) in progression of vascular calcification

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461376
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Osaka City University
• Principal Investigator: SHIOI ATSUSHI 大阪市立大学, 大学院医学研究科, 講師 (90260801)
• Co-Investigator(Kenkyū-buntansha): SHOJI Tetsuo 大阪市立大学, 大学院医学研究科, 准教授 (40271192)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: マクロファージ / HIF-1 / オンコスタチンM / LPS / 動脈硬化 / 血管石灰化

Outline of Final Research Achievements

We investigated the roles of hypoxia inducible factor 1 (HIF-1) in the development of atherosclerotic plaque calcification. In apoE-deficient mice, immunohistochemical staining revealed that macrophages are localized in hypoxic areas of atherosclerotic plaque lesions and that oncostatin M (OSM) is expressed in theses macrophages. Next, we investigated the stimulatory effects of OSM on osteoblastic differentiation of human vascular smooth muscle cells (HVSMC). OSM promoted osteoblastic differentiation of HVSMC through JAK3/STAT3 signaling pathway as evidenced by the experiments using specific inhibitor reagents and siRNAs. Finally, we examined the roles of HIF-1 in LPS-induced OSM expression in macrophages. The experiments utilizing inhibitors, hypoxia mimetics, and siRNA clarified that HIF-1 inhibits LPS-induced OSM expression in macrophages. These data suggest that HIF-1 in macrophages may play an inhibitory role in plaque calcification through inhibiting expression of OSM.

Free Research Field

血管病態学