| Project/Area Number |
08671340
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General surgery
|
|---|
| Research Institution | University of Tokyo |
|---|
Principal Investigator |
IMANISHI Hiroaki (1997) University of Tokyo, Department of Surgery, Assistant Professor, 医学部・附属病院, 助手 (60270881)
佐藤 紀 (1996) 東京大学, 医学部・附属病院, 助手 (40170724)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MIYATA Tetsuro University of Tokyo, Department of Surgery, Assistant Professor, 医学部・附属病院, 助手 (70190791)
TAKUWA Yoh Foundation for Advancement of International Science, Research Chief, 主任研究員 (60171592)
|
|---|
| Project Period (FY) |
1996 – 1997
|
| Project Status |
Completed (Fiscal Year 1997)
|
| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
|---|
| Keywords | PDGF / PDGFXR / neointimal SMC / adenovirus / 内膜肥厚 / Angiotensinll / アデノウィルスベクタ / 遺伝子治療 |
|---|
| Research Abstract |
Vascular stenosis occurs in many patients after angioplasty because of formation of neointima due to migration and proliferation of vascular smooth muscle cells (SMC). A variety of growth factors has been implicated in neointima formation including platelet-derived growth factor (PDGF) and angiotensin II, In this study, we studied the role of endogenous PDGF-B chain in the phase of neointimal development after arterial injury. We used the soluble extracellualr region of PDGF-beta receptor (PDGFXR) as a selective antagonist of PDGF-B.In cultured SMC, we found PDGFXR abolishes function of PDGF-B i.e. stimulation of PDGF-beta receptor tyrosine phosphoroyation and DNA synthesis. In a rat carotid balloon injured model, we demonstrated that PDGF-beta receptor is activated more significantly in the phase of the neointima development, Transfection of injured rat carotid arteries with adenoviral vector containing PDGFXR gene nearly completely suppressed activation of PDGF-beta receptor and reduced neointima formation. Moreover, we found that neointimal SMC produced PDGF-B chain in response to angiotensin II.These results indicate that PDGF-B chain, produced locally by neointimal SMC, plays an essential role in neointima formation after arterial injury. They also suggest the utility of PDGFXR as a therapeutic gene for preventing vascular stenosis after arterial injury.
|
