2005 Fiscal Year Final Research Report Summary
Role of Toll-like receptor in cardiovascular remodeling
| Project/Area Number |
16590657
|
|---|
| 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 | Yamagata University |
|---|
Principal Investigator |
KUBOTA Isao Yamagata University, Department of Cardiology, Pulmonology, and Nephrology, Professor, 医学部, 教授 (30161673)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKEISHI Yasuchika Yamagata University, Associate Professor, 医学部, 助教授 (40272067)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Keywords | Toll-like receptor / remodeling / doxorubicin / atherosclerosis / oxidative stress / innate immunity |
|---|
| Research Abstract |
Toll-like receptors (TLRs) are members of the interleukin-1 receptor family and regulate the innate immunity in response to pathogens. Recent studies have demonstrated that TLRs are activated by endogenous signals such as heat shock proteins and oxidative stress, which may contribute to the pathogenesis of cardiovascular diseases. Oxidative stress is one of the major factors for doxorubicin (Dox)-induced cardiac dysfunction. Thus, we hypothesized that TLRs contribute to the pathogenesis of Dox-induced cardiac dysfunction. Cardiac dysfunction was induced by a single injection of Dox intra-peritoneally in wild type (WT) mice and TLR-2 knockout (KO) mice. Five days after Dox injection, left ventricular dimension at end-diastole was smaller and fractional shortening was higher in KO mice compared with WT mice. NF-kB activation and production of pro-inflammatory cytokines after Dox were suppressed in KO mice compared to WT mice. Numbers of TUNEL positive nuclei and Dox-induced caspase-3 activation were less in KO mice than in WT mice. Survival rate was significantly higher in KO mice than in WT mice 14 days after Dox injection.
Next, vascular injury was induced by cuff-placement around the femoral artery in WT and TLR-2 KO mice. After cuff-placement, neo-intimal hyperplasia was markedly suppressed in KO mice compared with WT mice at 2 weeks and 4 weeks after cuff-placement. One week after cuff placement, gene expressions such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein-1 were significantly decreased in KO mice compared with WT mice. Superoxide production in the cuffed-artery was attenuated in KO mice compared with WT mice.
These findings suggest that Toll-like receptor-2 play a pivotal role in the regulation of cardiovascular remodeling.
|
Research Products
(46 results)
-
-
[Journal Article] Cardiac-specific overexpression of diacylglycerol kinase ζ prevents Gq protein coupled receptor agonists-induced cardiac hypertrophy in transgenic mice.2006
Author(s)
Arimoto T, Takeishi Y, Takahashi H, Shishido T, Niizeki T, Koyama Y, Shiga R, Nozaki N, Nakajima O, Nishimaru K, Abe JI, Endoh M, Walsh RA, Goto K, Kubota I
-
Journal Title
Circulation 113
Pages: 60-66
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Prognostic value of elevated circulating heart-type fatty acid binding protein in patients with congestive heart failure.2005
Author(s)
Arimoto T, Takeishi Y, Shiga R, Fukui A, Tachibana H, Nozaki N, Hirono O, Watanabe T, Nitobe J, Miyamoto T, Kubota I
-
Journal Title
J Card Fail 11
Pages: 56-60
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Adenovirus-mediated overexpression of diacylglycerol kinase inhibits endothelin-1-induced cardiomyocyte hypertrophy.2005
Author(s)
Takahashi H, Takeishi Y, Seidler T, Arimoto T, Akiyama H, Koyama Y, Shishido T, Tsunoda Y, Niizeki T, Hozumi Y, Abe J, Hasenfuss G, Goto K, Kubota I
-
Journal Title
Circulation 111
Pages: 1510-1516
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Journal Article] Serum heart-type fatty acid binding protein predicts cardiac events in the elderly chronic heart failure patients.2005
Author(s)
Niizeki T, Takeishi Y, Arimoto T, Okuyama H, Takabatake N, Fukui A, Tachibana H, Nozaki N, Hirono O, Tsunoda Y, Miyashita T, Takahashi H, Koyama Y, Shishido T, Kubota I
-
Journal Title
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] A combination of heart-type fatty acid binding protein and brain natriuretic peptide can reliably risk stratify patients hospitalized for chronic heart failure.2005
Author(s)
Niizeki T, Takeishi Y, Arimoto T, Takahashi T, Okuyama H, Takabatake N, Nozaki N, Hirono O, Tsunoda Y, Shishido T, Takahashi H, Koyama Y, Fukao A, Kubota I
-
Journal Title
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
[Journal Article] A Novel Polymorphism in Secretory Phospholipase A2-IID is Associated with Body Weight Loss in COPD.2005
Author(s)
Takabatake N, Sata M, Inoue S, Shibata Y, Abe S, Wada T, Machiya JI, Ji G, Matsuura T, Takeishi Y, Muramatsu M, Kubota I
-
Journal Title
Am J Respir Crit Care Med
Description
「研究成果報告書概要(欧文)」より
-
-
[Journal Article] Cystatin C is a novel predictor of cardiac events in patients with chronic heart failure.2005
Author(s)
Arimoto T, Takeishi Y, Niizeki T, Takabatake N, Okuyama H, Fukui A, Tachibana H, Nozaki N, Hirono H, Tsunoda Y, Miyashita T, Shishido T, Takahashi H, Koyama Y, Kubota I
-
Journal Title
J Card Fail 11
Pages: 595-601
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Ongoing myocardial damage relates to cardiac sympathetic nervous disintegrity in patients with heart failure.2005
Author(s)
Arimoto T, Takeishi Y, Niizeki T, Koyama Y, Okuyama H, Nozaki N, HironoO, Tsunoda Y, Miyashita T, Shishido T, Okada A, Takahashi K, Kubota I
-
Journal Title
Ann Nucl Med 19
Pages: 535-540
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Dynamic ^<123>I-BMIPP single photon emission computed tomography in patients with congestive heart failure : effect of angiotensin II type-I receptor blockade.2004
Author(s)
Takeishi Y, Minamihaba O, Yamauchi S, Arimoto T, Hirono O, Takahashi H, Akiyama H, Miyamoto T, Nitobe J, Nozaki N, Tachibana H, Okuyama M, Fukui A, Kubota I
-
Journal Title
Clin Cardiol 27
Pages: 204-210
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Dynamic ^<123>I-MIBG SPECT reflects sympathetic nervous integrity and predicts clinical outcome in patients with chronic heart failure.2004
Author(s)
Arimoto T, Takeishi Y, Fukui A, Tachibana H, Nozaki N, Hirono O, Yamaguchi H, Itoh M, Miyamoto T, Tsunoda Y, Takahashi H, Kubota I, Okada A, Takahashi K
-
Journal Title
Ann Nucl Med 18
Pages: 145-150
Description
「研究成果報告書概要(欧文)」より
-
-
-
