2006 Fiscal Year Final Research Report Summary
Development of Chronic Heart Failure with Bacterial Infection ; Participation in Toll-like Receptor
| Project/Area Number |
17590703
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Yamagata University |
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Principal Investigator |
NOZAKI Naoki Yamagata University, Cardiology, Internal Medicine, MD, PhD, 医学部, 助手 (50333951)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Toll like receptor / Chronic heart failure / Chronic bacterial infection |
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| Research Abstract |
Background : Toll-like receptors (TLRs) are members of the interleukin-1 receptor (IL-1R) family and transduce similar signals as IL-1R in response to exogenous pathogen. Recently studies have been demonstrated that TLR-4 are activated by endogenous signals such as heat shock proteins and oxidative stress, which contributed to ventricular hypertrophy and cardiac myocyte apoptosis in pressure-overloading models in vivo. In this study, we estimated whether TLR-2 was involved in cardiac hypertrophy and fibrosis same as TLR-4.
Methods and Results : Pressure overloading was induced by transverse aortic constriction (TAC) on wild type (WT) mice, TLR-2 knockout (KO) mice and TLR-4 KO mice. The rate of increase of HW/BW ratio in TLR-4 KO mice was significantly inhibited, but not in TLR-2 KO mice. Degrees of myocardial hypertrophy and fibrosis were much less in TLR-4 KO mice than in WT and TLR-2 KO mice. Reduced transforming growth factor-βl and collagen type 1 mRNA expressions were confirmed in TLR-4 KO mice after TAC.
Conclusions : These data suggest that TLR-4 plays an important role in ventricular hypertrophy and fibrosis in pressure overloading but not TLR-2.
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