| Project/Area Number |
12670688
|
|---|
| 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 | Omiya Medical Center, Jichi Medical School |
|---|
Principal Investigator |
UEBA Hiroto Omiya Medical Center, Jichi Medical School, Department of Internal Medicine, Instructor, 医学部, 助手 (80316546)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAWAKAMI Masanobu Omiya Medical Center, Jichi Medical School, Department of Internal Medicine, Professor, 医学部, 教授 (40161286)
KUROKI Masatoshi Omiya Medical Center, Jichi Medical School, Department of Internal Medicine, Associate Professor, 医学部, 助教授 (90215096)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
|---|
| Keywords | VEGF / HGF / MMP / HUVEC / THP-1 |
|---|
| Research Abstract |
Matrix metalloproteases (MMP) have been shown to play an important role in plaque rupture ; however, the mechanisms that regulate MMP production remain to be determined. In the present study we investigated the effect of monocyte-vascular endothelial cell (EC) interaction on MMP production using human monocyte derived cell line (THP-1) and human umbilical vein endolhelial cells (HUVEC), and. Tested the hypothesis that hepatocyte growth factor (HGF) may regulate MMP production. THP-1 were cocultured with HUVEC or cultured alone in serum-free medium for 16 h. Production of MMP-2, MMP-9, HGF and vascular endothelial growth factor (VEGF) in the medium was examined by ELISA. Anti-HGF neutralizing antibody (HGFAb) and anti-VEGF neutralizing antibody (VEGFAb) were used for blocking studies. MMP-9 production significantly increased in cocultured THP-1 compared to THP-1 alone (92.6 ±4.4 vs 28.4 ± 2.9 ng/ml, n=6 ; p<0.05), whereas MMP-2 production was unchanged. Production of HGF and VEGF also increased in cocultured THP-1 com pared to THP-1 alone (252.0±51.6 vs 182.9±29.5 pg/ml, 277.6±98,9 vs 29.5+4.8 pg/ml, respectively, n=6 ; p<0.05). HGFAb significantly increased MMP-9 production in cocultured THP-1 by 1.7-fold, whereas VEGFAb and control IgG had no effect. These data establish a novel function of HGF in monocyte-EC interaction that inhibits MMP-9 production, indicating a critical role of HGF for plaque stabilization.
|
