| Project/Area Number |
12470159
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Miyazaki Medical College |
|---|
Principal Investigator |
ETO Tanenao Miyazaki Medical College, 1st Dept Intern Med, Professor, 医学部, 教授 (10038854)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KITA Toshihiro Miyazaki Medical College, 1st Dept Intern Med, Research Associate, 医学部, 助手 (70315365)
KATO Johji Miyazaki Medical College, 1st Dept Intern Med, Research Associate, 医学部, 助手 (20274780)
KITAMURA Kazuo Miyazaki Medical College, 1st Dept Intern Med, Lecturer, 医学部, 講師 (50204912)
|
|---|
| Project Period (FY) |
2000 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2002: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥6,300,000 (Direct Cost: ¥6,300,000)
|
|---|
| Keywords | adrenomedullin / locally-acting hormone / cardiac hypertrophy / cardiac remodeling / vascular remodeling / CRLR / RAMP / 圧容量負荷 / RAMPs / 局所調節因子 / AM-Gly / アミド化酵素 / 心筋細胞 / 血管平滑筋細胞 / 心血管リモデリング / PAMP / 細胞内Ca伝達系 / 心筋肥大 |
|---|
| Research Abstract |
Aim of this study : This research project was planned to clarify the molecular mechanisms for the actions and roles of adrenomedullin (AM) in the cardiovascular tissues. Results : (1) AM was found to act as an autocrine or paracrine factor inhibiting hypertrophy of cardiomyocytes and proliferation of cardiac fibroblasts. The inhibitory action of AM on cardiac fibroblast proliferation is mediated at least in part by cAMP. (2) Calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying proteins (RAMPs) act together to function as AM receptors. Both Ang II and ET-1 were found to modulate the gene expressions of CRLR and RAMPs altering intracellular cAMP response to AM in the cardiac myocytes. (3) Gene expressions of AM and AM receptor components in the cardiac ventricles increased in relation to the magnitude of cardiac hypertrophy in rats with aortic banding and aortocaval shunt. (4) Extracellular domains of RAMPs that is essential for receptor binding were identified, and the mutant RAMPs without these portions were found to act as dominant negative RAMPs. (5) Cultured human vascular smooth muscle cells produced AM, and the AM production was stimulated by aldosterone, a steroid hormone which causes the cardiovascular damage or remodeling. (6) The ex vivo experiments showed that the intermediate form AM-Gly dilates rat aorta following conversion to mature AM in aortic tissue. Conclusion : The present findings suggest that AM participates in cardiovascular homeostasis as a locally-acting hormone. Many of the AM actions cardiovascular tissues appear to be mediated by the CRLR-RAMP system, while other receptor system(s) and intracellular mechanisms of action remain to be elucidated.
|
