| Autor: |
Ha, Tuanzhu, Li, Yuehua, Hua, Fang, Ma, Jinag, Gao, Xiang, Kelley, Jim, Zhao, Aiqiu, Haddad, Georges E., Williams, David L., William Browder, I., Kao, Race L., Li, Chuanfu |
| Předmět: |
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| Zdroj: |
Cardiovascular Research; Nov2005, Vol. 68 Issue 2, p224-234, 11p |
| Abstrakt: |
Abstract: Objective: We have previously demonstrated that nuclear factor kappa B (NFκB) activation is needed for the development of cardiac hypertrophy in vivo. NFκB is a downstream transcription factor in the Toll-like receptor (TLR)-mediated signaling pathway; therefore, we investigated a role of TLR4 in cardiac hypertrophy in vivo. 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. NFκB 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. NFκB 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. [Copyright &y& Elsevier] |
| Databáze: |
Complementary Index |
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