| Project/Area Number |
11670695
|
|---|
| 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 | Miyazaki Medical College |
|---|
Principal Investigator |
KATO Johji Miyazaki Medical College, 1st Dept. Intern Med, Research Associate, 医学部, 助手 (20274780)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
|---|
| Keywords | adrenomedullin / locally-acting hormone / cardiac hypertrophy / cardiac remodeling / vascular remodeling / CRLR / RAMP / 心血管リモデリング / 細胞内Ca伝達系 / 心筋肥大 / PAMP / 心筋リモデリング / 左室肥大 / cAMP |
|---|
| Research Abstract |
Aim of this study : This research project was planned to examine the pathophysiological role of adrenomedullin (AM) in the cardiovascular tissues and to test the possibility of this peptide being used for the cardiovascular diseases. Results : (1) AM secretion from the cultured cardiomyocytes and cardiac fibroblasts was augmented by angiotensin II (Ang II), endothelin-1 (ET-1) and mechanical stretching. These stimuli, causing the cardiac hypertrophy and remodeling, were found to increase the AM production via the Ca^<2+> -dependent signaling in the myocytes. (2) AM secreted from the cardiac myocytes and fibroblasts was found to inhibit the growth of these cells in an autocrine or paracrine manner. (3) 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. (4) AM gene expressions in the cardiac ventricles increased in relation to the magnitude of cardiac hypertrophy in rats with renovascular hypertension and those with aortocaval shunt. Ang II was found to be involved in the increased AM expression in the ventricles. (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.
Conclusion : The present findings suggest that AM participates in mechanism counteracting the cardiac hypertrophy and cardiovascular remodeling as an autocrine or paracrine factor. Our research focus is going to be shifted onto the therapeutic application of adrenomedullin to the cardiovascular diseases.
|
