| ORIGINAL ARTICLE |
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| Year : 2017 | Volume
: 2
| Issue : 2 | Page : 81-85 |
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Rapamycin attenuates atrial fibrosis in 5/6 nephrectomized rats by inhibiting mammalian target of rapamycin and profibrotic signaling
Yajuan Yang1, Mengqi Gong1, Hongliang Li1, Xue Liang1, Zhiwei Zhang1, Meng Yuan1, Yue Zhang1, Zhanquan Jiao1, Gary Tse2, Guangping Li1, Tong Liu1
1 Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
2 Department of Medicine and Therapeutics, Chinese University of Hong Kong; Li Ka Shing Institute of Health Sciences, 30-32 Ngan Shing St, Hong Kong 999077, China
Correspondence Address:
Tong Liu
Department of Cardiology, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211
China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/IJHR.IJHR_1_17
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Background: Atrial fibrosis plays a vital role in the pathogenesis of atrial fibrillation. However, the complex interplay between inflammation and remodeling remains incompletely understood. In this study, we examined the potential beneficial effects of the immunosuppressant rapamycin on reverse atrial remodeling in a 5/6 nephrectomized (5/6Nx) rat model of chronic kidney disease (CKD). Materials and Methods: Sprague-Dawley male rats were housed under controlled conditions with constant temperature and humidity for 1 week before the operation. They were assigned randomly to the following groups: (1) sham procedure with vehicle treatment, (2) 5/6Nx group with vehicle treatment, and (3) 5/6Nx with rapamycin treatment. The 5/6Nx group underwent nephrectomy by resection of the upper and lower thirds of the left kidney, followed by right nephrectomy. The rapamycin group received daily rapamycin (1 mg/kg/day) from the 4th week to the 8th after operation. Results: A significant increase in the protein expression levels of mammalian target of rapamycin (mTOR), p38, and extracellular signal-regulated kinase was observed in the 5/6Nx + vehicle group (1.56 ± 0.12 vs. 0.72 ± 0.06; 2.64 ± 0.40 vs. 1.20 ± 0.20; and 3.02 ± 0.71 vs. 1.42 ± 0.34; all P < 0.05), which were suppressed by rapamycin treatment (0.88 ± 0.08 vs. 1.56 ± 0.12; 1.96 ± 0.21 vs. 2.64 ± 0.40; and 1.87 ± 1.87 vs. 3.02 ± 0.71; all P < 0.05). Cardiomyocyte hypertrophy and extensive interstitial fibrosis of the atrium were observed in the 5/6Nx + VEH group (P < 0.05). These changes were attenuated in the 5/6Nx + rapamycin group (P < 0.05). Conclusions: In this 5/6Nx CKD rat model, atrial fibrosis was mediated via the mTOR pathway, which was attenuated by rapamycin.
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