Abstract | OBJECTIVE: METHODS: TLR4-deficient mice (C.C3H-Tlr4(lps-d), n = 6), wild-type (WT) genetic background mice (BALB/c, n = 6), TLR4-deleted strain (C57BL/10ScCr, n = 8), and WT controls (C57BL/10ScSn, n = 8) were subjected to aortic banding for 2 weeks. Age-matched surgically operated mice served as controls. In a separate experiment, rapamycin (2 mg/kg, daily) was administered to TLR4-deficient mice and WT mice immediately following aortic banding. The ratio of heart weight/body weight (HW/BW) was calculated, and cardiac myocyte size was examined by FITC-labeled wheat germ agglutinin staining of membranes. NFkappaB binding activity and the levels of phospho-p70S6K in the myocardium were also examined. RESULTS: Aortic banding significantly increased the ratio of HW/BW by 33.9% (0.601 +/- 0.026 vs. 0.449 +/- 0.004) and cell size by 68.4% in WT mice and by 10.00% (0.543 +/- 0.011 vs. 0.495 +/- 0.005) and by 11.8% in TLR4-deficient mice, respectively, compared with respective sham controls. NFkappaB binding activity and phospho-p70S6K levels were increased by 182.6% and 115.2% in aortic-banded WT mice and by 78.0% and 162.0% in aortic-banded TLR4-deficient mice compared with respective sham controls. In rapamycin-treated aortic-banded mice, the ratio of HW/BW was increased by 18.0% in WT mice and by 3.5% in TLR4-deficient mice compared with respective sham controls. CONCLUSION: Our results demonstrate that TLR4 is a novel receptor contributing to the development of cardiac hypertrophy in vivo and that both the TLR4-mediated pathway and PI3K/Akt/mTOR signaling are involved in the development of cardiac hypertrophy in vivo.
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Authors | Tuanzhu Ha, Yuehua Li, Fang Hua, Jinag Ma, Xiang Gao, Jim Kelley, Aiqiu Zhao, Georges E Haddad, David L Williams, I William Browder, Race L Kao, Chuanfu Li |
Journal | Cardiovascular research
(Cardiovasc Res)
Vol. 68
Issue 2
Pg. 224-34
(Nov 01 2005)
ISSN: 0008-6363 [Print] England |
PMID | 15967420
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- NF-kappa B
- Tlr4 protein, mouse
- Toll-Like Receptor 4
- Ribosomal Protein S6 Kinases, 70-kDa
- Sirolimus
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Topics |
- Animals
- Cardiomegaly
(drug therapy, metabolism)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Models, Animal
- Myocardial Infarction
- Myocardium
(chemistry, metabolism)
- NF-kappa B
(metabolism)
- Ribosomal Protein S6 Kinases, 70-kDa
(analysis)
- Signal Transduction
(physiology)
- Sirolimus
(therapeutic use)
- Toll-Like Receptor 4
(deficiency)
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