2006 Fiscal Year Final Research Report Summary
Intracellular signaling for the genesis of cardiac ion channel remodeling in pathological heart
| Project/Area Number |
17590720
|
|---|
| 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 | Nagoya University |
|---|
Principal Investigator |
YASUI Kenji Nagoya University, Institute of Environmental Medicine, Professor, 環境医学研究所, 教授 (70283471)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KODAMA Itsuo Nagoya University, Institute of Environmental Medicine, Professor, 環境医学研究所, 教授 (30124720)
LEE Jong-kook Nagoya University, Institute of Environmental Medicine, Associate Professor, 環境医学研究所, 助教授 (60303608)
HORIBA Mitsuru Nagoya University, Institute of Environmental Medicine, Assistant Professor, 環境医学研究所, 助手 (40345913)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Keywords | Cardiac ion channel / remodeling / signaling cascade / heart |
|---|
| Research Abstract |
Cardiac ion channel remodeling underlies the genesis of the arrhythmias in pathological hearts. Recently, fetal gene re-expression is highlighted as the cause of ion channel remodeling of diseased heart. However, intracellular signaling cascades which mediate the alternation of cardiac gene expression remain to be clarified. The purpose of this study is to examine the transcription factor of cardiac fetal gene re-expression and obtain the clue for the up-stream treatment of lethal arrhythmias in pathological hearts.
We got several results, as follows.
1) The blockers of T-type Ca^<2+> channels inhibited the cardiac hypertrophy by the inhibition of Ca^<2+>/Calmodulin/Calcineurin/NFAT3/GATA4 cascades through decreased Ca^<2+> influx.
2) Renin/angiotensin/aldosterone cascade play an important role in the pathology of heart failure. We revealed that aldosterone mediates cardiac ion channel remodeling in this study. We investigated the effect of aldosterone on If channel expression in cultured cardiac cells using electrophysiological and molecular experimental approach.
3) NRSE/NRSF cascade has been reported to regulate T-type Ca^<2+> channel gene expression, which is cardiac fetal gene. In this study, We examined the expression T-type Ca^<2+> channel, BNP and NRSF in hypertrophied cardiac muscle of aortic banding mouse model and failure hearts of myocardial infarction mouse model. The findings suggested that NRSF regulates T-type Ca^<2+> channel and BNP gene expression.
|
