| Project/Area Number |
18590776
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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 | Yamaguchi University |
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Principal Investigator |
UMEMOTO Seiji Yamaguchi University, Hospital, Pharmaceutical Clinical Research Center, Associate Professor (90263772)
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Hiroki Yamaguchi University, School of Medicine Department of Molecular Cardiovascular Biology, Associate Professor (60322244)
YOSHIMURA Kouichi Yamaguchi University, School of Medicine Department of Molecular Cardiovascular Biology, Associate Professor (00322248)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Toll-like receptor / Hypertension / Heart / Hypertrophy |
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| Research Abstract |
We investigated the role of Toll-like receptor 4 (TLR4) in cardiac hypertrophy and function following angiotensin II (Ang II) or norepinephrine (NE) -induced pressure overload in mice in vivo.TLR4-knocked out mice, and wild-type (WT) genetic background mice (BALB/c) were randomized into two groups and implanted osmotic minipumps of Angiotensin II (AT II) or Norepinephrine (NE) for 2 weeks. Both Ang II and NE induced a significant increase in systolic blood pressures among the four groups (p<0.05), while blood pressures and heart rates were not significantly different among the four groups throughout the experiments. Compared with Ang II -induced pressure overload WT mice, Ang II-induced pressure overload TLR4-knockout mice showed a significant increase in both ejection fraction (EF) and % fractional shortening (%FS) (p<0.05), and also demonstrated a smaller left ventricular end-systolic dimension (LVESd, p<0.05). In contrast, compared with NE-induced pressure overload WT mice, NE-induced pressure overload TLR4-knockout mice showed smaller LVESd and an increase in EF and %FS; these indices, however, did not reach statistical significance. Left ventricular end-diastolic dimension, interventricular septum, left ventricular diastolic wall thickness, and heart weight did not differ among the four groups. Compared with Ang II-induced pressure overload WT mice, Ang II-induced pressure overload TLR4-knockout mice showed a significant increase in both perivascular collagen volume fraction (p<0.05), and wall-to-lumen ratio (p<0.05). These results suggest that TLR4 may be involved in the development of Ang II-induced cardiac systolic dysfunction without affecting cardiac hypertrophy.
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