Research Paper Volume 13, Issue 10 pp 14482—14498
Sirt1 improves heart failure through modulating the NF-κB p65/microRNA-155/BNDF signaling cascade
- 1 Department of Cardiovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China
Received: February 12, 2020 Accepted: June 18, 2020 Published: November 18, 2020
https://doi.org/10.18632/aging.103640How to Cite
Copyright: © 2021 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Heart failure (HF) affects over 26 million people worldwide, yet the pathologies of this complex syndrome have not been completely understood. Here, we investigated the involvement of deacetylase Sirtuin 1 (Sirt1) in HF and its downstream signaling pathways. A HF model was induced by the ligation of the left coronary artery in rats, where factors associated with left ventricular echocardiography, heart hemodynamics and ventricular mass indexes were recorded. Collagen volume fraction in heart tissues was determined by Masson’s trichrome staining. Cell models of HF were also established (H2O2, 30 min) in cardiomyocytes harvested from suckling rats. HF rats presented with downregulated expressions of Sirt1, brain-derived neurotrophic factor (BDNF) and exhibited upregulated expressions of NF-κB p65 and miR-155. Repressed Sirt1 expression increased acetylation of NF-κB p65, resulting in the elevation of NF-κB p65 expression. NF-κB p65 silencing improved heart functions, decreased ventricular mass and reduced apoptosis in cardiomyocytes. MiR-155 inhibition upregulated its target gene BDNF, thereby reducing cardiomyocyte apoptosis. Sirt1 overexpression upregulated BDNF, improved heart function, and reduced apoptosis in cardiomyocytes. In conclusion, Sirt1 alleviates HF in rats through the NF-κB p65/miR-155/BDNF signaling cascade.
Abbreviations
HF: Heart failure; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; miR: microRNA; BDNF: brain-derived neurotrophic factor; Sirt: Sirtuin; LVEF: left ventricular ejection fraction; NC: negative control; LVPWD: determine left ventricular posterior wall thickness; IVSD: interventricular septal dimension; LVEDD: left ventricular end diastolic diameter; LVESD : left ventricular end systolic diameter; FS: fractional shortening; LVSP: Left ventricular systolic pressure; LVEDP: left ventricular end diastolic pressure; HR: heart rate; HEPES: hydroxyethyl piperazine ethanesulfonic acid; RVM: right ventricular mass; LVM: left ventricular mass; LVMI: left ventricular mass index; RVMI: right ventricular mass index; CVF: Collagen volume fraction; ChIP: Chromatin immunoprecipitation; WT: Wild-type; MUT: mutated; UTR: 3'-untranslated region; RLU: relative light units; ANOVA: analysis of variance.