2002 Fiscal Year Final Research Report Summary
NEW TREATMENT FOR DIASTOLIC DYSFUNCTION BY PREVENTING CARDIAC FIBROSIS -GENE THERAPY USING A MUTANT TGF-β, RECEPTOR-
| Project/Area Number |
13670767
|
|---|
| 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 | KURUME UNIVERSITY |
|---|
Principal Investigator |
KAI Hisashi Kurume University ・ Cardiovascular Research Institute ・ Associate Professor, 循環器病研究所, 助教授 (60281531)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NIIYAMA Hiroshi Kurume University ・ School of Medicine/ Assistant Professor, 医学部, 助手 (30309778)
KUWAHARA Fumitaka Kurume University ・ School of Medicine/ Assistant Professor, 医学部, 助手 (90279167)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Keywords | TGF-β / myocardial fibrosis / hypertension / diastolic dysfunction / gene therapy / neutralizing antibody |
|---|
| Research Abstract |
(1) By using PCR, a soluble mutant TGF-β receptor (TβRII : Fc) is being constructed by conjugating an extracellular domain of human TGF-β receptor with human IgG Fc segment.
(2) To block the in vivo activity of TGF-β, we used an anti-TGF-β monoclonal TGF-β neutralizing antibody (NAb). Chronic daily treatment with NAb did not change blood pressure elevation and LV hypertrophy induced by aortic constriction (AC) in rats, but almost abolished the AC-induced fibroblast proliferation and myocardial fibrosis. Furthermore, NAb prevented of diastolic dysfunction in AC rats.
(3) In the intramyocardial arteries of AC rats, ICAM-1 expression and MCP-1 expression were rapidly and transiently observed, associated with the perivascular macrophage accumulation. Anti-ICAM-1 monoclonal antibody not only reduced macrophage accumulation but also prevented myocardial fibrosis.
(4) Chronic NAb treatment did not significantly affected the progression of cardiac fibrosis in Dahl salt-sensitive rats of OLETF rats, probably because the activity of NAb might not remain during the too long treatment (>6 weeks).
|
Research Products
(10 results)
