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Journal of Biomedical Science

, 21:57

First Online: 09 June 2014Received: 07 December 2013Accepted: 21 May 2014DOI: 10.1186-1423-0127-21-57

Cite this article as: Lu, TM., Tsai, JY., Chen, YC. et al. J Biomed Sci 2014 21: 57. doi:10.1186-1423-0127-21-57

Abstract

BackgroundIn congestive heart failure the balance between cell death and cell survival in cardiomyocytes is compromised. Sirtuin 1 Sirt1 activates cell survival machinery and has been shown to be protective against ischemia-reperfusion injury in murine heart. The role of Sirt1 in heart failure, especially in human hearts is not clear.

ResultsThe expression of Sirt1 and other associated downstream molecules in human cardiomyocytes from patients with advanced heart failure was examined. Sirt1 was down-regulated 54.92% ± 7.80% in advanced heart failure samples compared with healthy control cardiomyocytes. The modulation of molecules involved in cardiomyocyte survival and death in advanced heart failure were also examined. The expression of Mn-superoxide dismutase and thioredoxin1, as well as an antiapoptotic molecule, Bcl-xL, were all significantly reduced in advanced heart failure cardiomyoctes 0.71 ± 0.02-fold, 0.61 ± 0.05-fold, and 0.53 ± 0.08-fold vs. control, respectively; whereas the expression of proapoptotic molecule Bax was significantly increased 1.62 ± 0.18-fold vs. control. Increased TUNEL-positive number of cardiomyocytes and oxidative stress, confirmed by 8-hydorxydeoxyguanosine staining, were associated with advanced heart failure. The AMPK-Nampt-Sirt1 axis also showed inhibition in advanced heart failure in addition to severely impaired AMPK activation. Increased p53 acetyl form and decreased FoxO1 translocation in the nucleus may be the mechanism of down-regulation of antioxidants and up-regulation of proapoptotic molecules due to low expression of Sirt1.

ConclusionIn advanced heart failure, low Sirt1 expression, like aging change may be a significant contributing factor in the downregulation of antioxidants and upregulation of proapoptotic molecules through the p53, FoxO1, and oxidative stress pathways.

KeywordsAging Heart failure Sirt1 Electronic supplementary materialThe online version of this article doi:10.1186-1423-0127-21-57 contains supplementary material, which is available to authorized users.

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Autor: Tse-Min Lu - Jia-Yun Tsai - Yen-Chung Chen - Chun-Yang Huang - Hung-Lung Hsu - Chi-Feng Weng - Chun-Che Shih - Chiao-Po Hs

Fuente: https://link.springer.com/



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