Growth differentiation factor 11 is involved in isoproterenol‑induced heart failure

Zhang,Xiu‑Jing; Tan,Hua; Shi,Zhi‑Fang; Li,Na; Jia,Ying; Hao,Zhe

doi:10.3892/mmr.2019.10077

Growth differentiation factor 11 is involved in isoproterenol‑induced heart failure

Authors:
- Xiu‑Jing Zhang
- Hua Tan
- Zhi‑Fang Shi
- Na Li
- Ying Jia
- Zhe Hao
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Affiliations: The First Department of Cadres Health Care, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, P.R. China, The Second Department of Cadres Health Care, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, P.R. China
Published online on: March 22, 2019 https://doi.org/10.3892/mmr.2019.10077
Pages: 4109-4118
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

The present study aimed to investigate the potential effects of growth differentiation factor 11 (GDF11) on isoproterenol (ISO)‑induced heart failure (HF) and identify the underlying molecular mechanisms. A rat model of HF was induced in vivo by intraperitoneally administering ISO (5 mg/kg/day) for 7 days. After 4 weeks following establishment of the HF model, hemodynamic analysis demonstrated that ISO induced a significant increase in the left ventricular end‑diastolic pressure and a decrease in the left ventricular systolic pressure and maximum contraction velocity. The plasma levels of myocardial injury markers, including lactate dehydrogenase (LDH), creatine kinase (CK), CK‑muscle/brain which were determined using the corresponding assay kits and plasma brain natriuretic peptide which was detected by an ELISA kit, an important biomarker of HF, increased following ISO treatment. Furthermore, levels of GDF11 expression and protein, which were estimated using reverse transcription‑quantitative polymerase chain reaction and an ELISA kit in plasma and western blotting in the heart tissue, respectively, significantly increased following ISO treatment. To demonstrate the effects of ISO on GDF11 production in cardiomyocytes, H9C2 cells (a cardiomyoblast cell line derived from embryonic rat heart tissue) were treated with ISO (50 nM) for 24 h in vitro; it was revealed that GDF11 protein and mRNA expression levels significantly increased following ISO treatment. In addition, recombinant GDF11 (rGDF11) administered to ISO‑treated H9C2 cells resulted in decreased proliferation, which was detected via a CCK‑8 assay, and increased LDH levels and cell apoptosis of cells, which was determined using Caspase‑3 activity and Hoechst 33258 staining. Additionally, rGDF11 increased the levels of reactive oxygen species and malondialdehyde due to the upregulation of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) following rGDF11 treatment. Conversely, GDF11 knockdown reduced ISO‑induced apoptosis by inhibiting oxidative stress injury. The results suggested that GDF11 production was upregulated in ISO‑induced rats with HF and in ISO‑treated H9C2 cells, and that rGDF11 treatment increased ISO‑induced oxidative stress injury by upregulating Nox4 in H9C2 cells.

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