Abstract: SA-PO995
Effect of Omega-3 Fatty Acid on AKT-mTOR and FoxO in Heart of 5/6 Nephrectomy Rat Model
Session Information
- Hypertension and CVD: Mechanisms - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Lee, Su mi, Dong-A University, Busan, Korea (the Republic of)
- Oh, Yun Jung, Cheju Halla General Hospital, Jeju, Korea (the Republic of)
- Son, Young ki, Dong-A University, Busan, Korea (the Republic of)
- Kim, Seong Eun, Dong-A University Hospital, Busan, Korea (the Republic of)
- An, Won Suk, Dong-A University, Busan, Korea (the Republic of)
Background
Cardiac hypertrophy is common and results in mortality in patients with chronic kidney disease (CKD). Akt-mammalian target of rapamycin (mTOR) axis is related with cardiac hypertrophy. Forkhead box class O (FoxO) family is related with autophagy and apoptosis, but there is no report in the heart of CKD. The present study aimed to investigate whether omega-3 fatty acid (ω-3 FA) effect on Akt-mTOR axis and FoxO in heart of 5/6 subtotal nephrectomy (Nx) rat model.
Methods
Male Sprague Dawley rats were divided into three groups and treated for 6 weeks: sham control (0.9% saline), 5/6 Nx control (0.9% saline) and 5/6 Nx treated with ω-3 FA (300 mg/kg/day by gastric gavage). The expression of cardiac Akt, phosphorylated(p) Akt, mTOR, FoxO, PI3K, p-PI3k, AMPK, p-AMPK, smad2/3, NF-κB, cleaved caspase 3/7, LC3, muscle-specific ring finger protein-1 (MuRF1), and muscle atrophy F-box protein (MAFbx) were examined by western blot analysis. Hematoxylin and eosin staining of heart was performed.
Results
Serum creatinine level was significantly increased in 5/6 Nx group compared to control group and were not significantly different between 5/6 Nx group treated with ω-3 FA and 5/6 Nx group. Compared with control group, cardiac hypertrophy of 5/6 Nx group was found in gross and microscopic findings. No definite cardiac hypertrophy was found in 5/6 Nx group treated with ω-3 FA. P-Akt and mTOR were significantly up-regulated in heart of 5/6 Nx group compared to control group and were recovered by ω-3 FA. Compared with control group, 5/6 Nx group significantly up-regulated FoxO1 and FoxO3a expression of heart, which were significantly recovered by ω-3 FA. However, the expression of MuRF1 and MAFbx was not different among three groups. The expression of smad2/3, NF-κB, cleaved caspase 3/7, LC3 was up-regulated in the heart of 5/6 Nx group compared to control group and was recovered by ω-3 FA. The expression of p-AMPK was down-regulated in the heart of 5/6 Nx group compared to control group and was recovered by ω-3 FA.
Conclusion
ω-3 FA may prevent cardiac hypertrophy not only by decreasing p-Akt, mTOR and FoxO expression but also by reducing molecules of inflammation, autophagy and apoptosis.