| Project/Area Number |
07670515
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内科学一般
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
MURANO Shunichi Chiba University School of Medicine, Assistant, 医学部, 助手 (50231634)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MORISAKI Nobuhiro Chiba University School of Medicine, Lecturer, 医学部, 講師 (40174411)
|
|---|
| Project Period (FY) |
1995 – 1996
|
| Project Status |
Completed (Fiscal Year 1996)
|
| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | Werner syndrome / atherosclerosis / pasminogen activator inhibitor-1 / intercellular adhesion molecule-1 / vascular cell adhesion molecule-1 / Intercelular adhesion molecule-1 / scavenger receptor / fibronectin / OLETFラット / mitochondria / acetylated LDL |
|---|
| Research Abstract |
Werner syndrome is a rare premature aging syndrome accompanied by severe atherosclerosis. The etiology of atherosclerosis is suspected to be due to its complications, namely diabetes mellitus, hyperinsulinemia and hyperlipidemia. But from an autopsy case we found that some other risk factors may be involving in the mechanism of atherosclerosis in this syndrome. Previously we revealed that pasminogen activator inhibitor-1 (PAI-1) gene was being overexpressed in skin fibroblasts from a patient with this syndrome. PAI-1 is a potent inhibitor of tissue plasminogen activator and a possible risk factor of atherosclerosis. This led us to assess the plasma concentration of PAI-1. Our working hypothesis was that PAI-1 gene was upregulated or not fully suppressed in cells responsible for the production of PAI-1 in plasma as well as in fibroblasts. The result shown a high concentration of plasma PAI-1. One of well-known physiological substances that induce the PAI-1 gene is tumor necrosis factor-alpha (TNF-alpha), which also induces other possible risk factors of atherosclerosis, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1. We found the serum concentration of ICAM-1 to be elevated in patients with this syndrome. We conclude that high concentration of PAI-1 and ICAM-1 in blood may be one of the potent causes of severe atherosclerosis in Werner syndrome.
|
