| Project/Area Number |
14570689
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Jichi Medical School |
|---|
Principal Investigator |
MIMURO Jun Jichi Medical School, Cell and molecular medicine, Assistant Professor, 医学部, 助教授 (10221607)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MURAMATSU Shin-ichi Jichi Medical School, Cell and molecular medicine, Instructor, 医学部, 助手 (10239543)
SAKATA Yoichi Jichi Medical School, Cell and molecular medicine, Professor, 医学部, 教授 (40129028)
|
|---|
| Project Period (FY) |
2001 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
|---|
| Keywords | endothelial cell / viral vector / gene therapy / PAI-1 / VEGF / 血管内皮細胞 / 血管新生 / Vascular endothelial growth factor / Angiopoietin 1 / Prostacyclin |
|---|
| Research Abstract |
We have hypothesized that there might be a kind of cross-talk between plasminogen activator-plasmin dependent fibrinolytic system and granulocyte-derived elastase dependent one, according to the following observations : 1,congenital plasminogen-deficient patients have no intravascular thrombophilic episodes. The granulocyte-derived elastase level of these patients in plasma is 10-100 times higher than that of the normal. Moreover, infusion of purified plasminogen decreases the level to a normal range. 2, plasminogen activator-plasmin dependent fibrinolytic system is supposed to be shutdown by remarkable increase of plasminogen activator inhibitor -1 in patient with disseminated intravascular coagulation associated with severe sepsis. Using ELISA system employing a monoclonal antibody specific to the granulocyte-derived elastase-fragment D species of human fibrin, we found that the elastase fibrin-digests were mostly elevated in these patients.
To support this hypothesis, we used plasminogen-deficient mice (KO mice) with synthetic elastase inhibitor. After the age of 7 weeks, 19% of KO mice develop rectal prolapse due to intravascular thrombosis in microcirculation. Unexpectedly, administration of elastase inhibitor protected KO mice from rectal prolapse. In addition, the amount of leukocyte infiltration and a fibrin deposit in the lung after lipopolysacharride loading were also decreased by concomitant elastase inhibition. These results suggest a cross-talk between two systems is more complicated and much more needs to be learned about the role of elastase in relation to alternative fibrinolytic system.
|
