Studies on the mechanism of polarized secretion of the hemostatic factor VWF in vascular endothelial cells.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07401
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Yamazaki Yasuo 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (30308621)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: オルガネラ形成 / 微小酸性環境

Outline of Final Research Achievements

Hemostasis is essential to maintain the functional blood circulation; blood is required to clot in response to vascular damage to stop bleeding. Vascular endothelial cells are thin-layered cells covering luminal surface of the blood vessel. von Willebrand factor, a hemostatic protein, is produced in endothelial cells. It forms large homomeric multimers that are stored in specialized organelles called Weibel-Palade bodies. In this supported project, we studied a mechanism how the maturation and storage of von Willebrand factor is regulated in vascular endothelial cells. We found that a factor producing a local acidic environment contributes for the storage of von Willebrand factor in Weibel-Palade bodies.

Free Research Field

血栓止血学

Academic Significance and Societal Importance of the Research Achievements

止血因子von Willebrand因子は止血反応に不可欠である。何らかの原因でvon Willebrand因子が機能しなくなると、von Willebrand病と呼ばれる血液凝固異常症を発症する。本研究の成果は、von Willebrand因子そのものが正常でも、その貯蔵機構に異常が生じるとvon Willebrand病になる可能性があることを示している。本研究課題により、これまで原因が不明であったvon Willebrand病の原因究明に貢献できる知見を得た。