Analysis of molecular mechanism of FK506-induced endothelial dysfunction

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790985
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Hyogo Medical University
• Principal Investigator: EGUCHI Ryoji 兵庫医科大学, 医学部, 助教 (00461088)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 血管生物学 / 血管内皮細胞 / 血管内皮障害 / 免疫抑制剤 / 管腔崩壊 / 細胞死

Outline of Final Research Achievements

FK506 has been used in hematopoietic stem cell transplantations to suppress immune function, but is associated with severe endothelial dysfunction. We investigated whether FK506 induces endothelial dysfunction using a three-dimensional culture blood vessel model, in which human umbilical vein endothelial cells form and maintain capillary-like tube and lumen structures. We found that FK506 induced tube breakdown and endothelial cell death through attenuation of Akt and ERK1/2 independently of calcineurin inhibition and the caspase pathway and that recombinant human soluble thrombomodulin suppresses FK506-induced endothelial cell death through prevention of Akt inactivation.

Free Research Field

血管生物学