2000 Fiscal Year Final Research Report Summary
Development of intracellular therapy to induce a regression of coronary arteriosclerotic lesions
| Project/Area Number |
10357006
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A).
|
| Allocation Type | Single-year Grants |
|---|
| Section | 展開研究 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | KYUSHU UNIVERSITY |
|---|
Principal Investigator |
TAKESHITA Akira Kyushu Univ, Dept of Cardiovasc Med, Prof, 大学院・医学研究院, 教授 (30038814)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SHIMOKAWA Hiroaki Kyushu Univ, Dept of Cardiovasc Med, Assoc Prof, 大学院・医学研究院, 助教授 (00235681)
NAGAI Ryozo Tokyo Univ, Dept of Cardiol, Prof, 大学院・医学系研究科, 教授 (60207975)
SUEISHI Katsuo Kyushu Univ, Dept of Pathol, Prof, 大学院・医学研究院, 教授 (70108710)
EGASHIRA Kensuke Kyushu Univ, Dept of Cardiovasc Med, Assis Prof, 医学部・附属病院, 講師 (60260379)
UENO Hikaru Kyushu Univ, Dept of Cardiovasc Med, Assis Prof, 医学部・附属病院, 講師 (50260378)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Keywords | arteriosclerossis / coronary artery / ischemic heart disease / Rho-kinase / signal transduction / coronary vasospasm / regression |
|---|
| Research Abstract |
1. In the porcine femoral arteries injured by balloon technique, Rho-kinase was upregulated both at the mRNA and activity levels. The in vivo gene transfer of dominant-negative Rho-kinase (DNRhoK) significantly inhibited the development of the balloon injury-induced vascular lesions.
2. The long-term treatment of the porcine coronary artery from the adventitial with MCP-1 and Ox-LDL caused a development of arteriosclerotic lesions (intimal thickening and geometric remodeling). The long-term blockade of Rho-kinase with hydroxyfasudil significantly suppressed the development of those vascular lesions.
3. The long-term treatment of the porcine coronary artery from the adventitial with IL-1β caused a development of arteriosclerotic lesions (intimal thickening and geometric remodeling). The long-term blockade of Rho-kinase with hydroxy fasudil caused a regression of those vascular lesions in vivo.
4. The in vivo gene transfer of DNRhoK induced a regression of constrictive remo deling in a porcine model with IL-1b/
These results indicate that Rho-kinase is substantially involved in the pathog enesis of coronary arteriosclerosis and that the long-term inhibition of the molecule could induce a regression of the arterioclerotic vascular lesions.
|
