| Project/Area Number |
17590701
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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 |
TACHIBANA Hidetada Yamagata University, Faculty of Medicine, A part-time Lecturer, 医学部, 非常勤講師 (90344796)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEISHI Yasuchika Yamagata University, Faculty of Medicine, Associate professor, 医学部, 助教授 (40272067)
NOZAKI Naoki Yamagata University, Faculty of Medicine, Assistant, 医学部, 助手 (50333951)
WATANABE Tetsu Yamagata University, Faculty of Medicine, Assistant, 医学部, 助手 (40359568)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | atrial fibrillation / atrial thrombogenesis / Atrial endothelium / toll-like receptor / 凝固因子 / 抗凝固因子 / 内皮型NO産生酵素 |
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| Research Abstract |
Atrial fibrillation (AF) is well known as one of the cardiogenic causes for thromboembolism. Although decreased flow and hypercoagulable state of the blood in the fibrillating atrium have been emphasized as the underlying mechanisms, endocardial dysfunction in maintaining the local coagulation balance was also reported to contribute to the thrombogenesis in AF (Circulation 2003 ; 108 : 2450-2452)..It has been recently reported that AF is associated with tissue inflammation (Circulation 2003 ; 108 : 3006-3010). Several reports showed that ACEIs, ARBs and statins reduce C-reactive protein (CRP) levels, and prevent AF (Cardiovasc Res 2004 ; 62 : 105-111, J Am Coll Catdiol 2005 ; 24 : 1832). Schafler reported that the expression of heat shock protein (HSP) 60 increased in patients with AF (Basic Res Cardiol 2002 ; 97 : 258-261). It is known that HSP60 is one of the endogenous ligands of toll-like receptor (TLR)-4 (N Engl J Med, 2002 ; 347 : 185-192). Therefore, we hypothesized that the local inflammation induced by innate immune. TLR signaling may play a role in development of AF and atrial thrombogensis. We examined whether TLR signaling could be related to atrial thrombogenesis in heart failure mice model induced by pressure overload. Thoracic transverse aortic constriction (TAC) was created in TLR-4 knockout (KO) mice, TLR-2 KO mice and wild-type (WT) mice. Increases in interventricular septal thickness, dilatation of the left ventricular cavity, and decreases in left ventricular systolic function in WT mice were observed with echocardiography at 4 weeks after TAC surgery. We observed less frequent occurrence of atrial thrombosis in TLR-KO mice than WT-TAC mice. Increases in vascular cell adhesion molecule (VCAM)-1 expression were significantly attenuated in TLR-4 KO mice compared with WT mice. Phosphorylations of JNK were also attenuated in TLR-4 KO mice. In conclusion, TLR signaling may accelerate atrial thrombosis in heart failure mice model.
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