2005 Fiscal Year Final Research Report Summary
Role of cell-cycle inhibitor p21 in cardiac hypertrophy
| Project/Area Number |
15590769
|
|---|
| 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 | JICHI MEDICAL UNIVERSITY |
|---|
Principal Investigator |
YAMAMOTO Keiji Jichi Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (50245073)
|
|---|
| Project Period (FY) |
2003 – 2005
|
| Keywords | cardiac hypertrophy / cell cycle / mouse / heart failure / pressure overload |
|---|
| Research Abstract |
Pressure overload conditions such as hypertension are clinically important. Cardiomyocytes undergo terminal differentiation soon after birth, irreversibly withdrawing from the cell cycle. Previous studies from other groups have determined that cardiomyocytes expressed some of cell-cycle regulators and that cdk activity may be required for the induction of cardiomyocyte hypertrophy. Nonetheless, the exact roles and significance of these regulators in cardiomyocytes are still not precisely understood. In this study, we clarified the role of cell-cycle inhibitor p21, one of cyclin-dependent kinase inhibitors, in cardiac hypertrophy. First, we generated α-myosin heavy chain cardiac-specific p21-expreesing transgenic (p21Tg) mice. In Western blot analysis, two lines of p21Tg mice were obtained. In p21Tg mice, left ventricle was more hypertrophic compared with that of wild-type mice. Next, a model of cardiac hypertrophy was made by abdominal aortic banding as follows. A laparotomy was performed. The aortic aorta was isolated from annexed tissue, and the artery was partially ligated immediately below the celiac trunk with 7-0 silk around a 27-gauge blunted needle. Using echocardiography, cardiac ventricular dimensions and wall thicknesses were measured on 2-dimensional M-mode images at least 3 times foe each animal. In wild-type mice, wall thickness of left ventricle was increased 16 weeks after abdominal aortic banding. However, in p21Tg mice, left ventricle was dilated and its wall thickness was thin 16 weeks after abdominal aortic banding. These findings provide further evidence implicating cell-cycle factors as obligate regulators of cardiac hypertrophy and suggest that p21 may play an important role in non-compensated conditions for chronic pressure overload in heart.
|
Research Products
(8 results)
