Growth differentiation factor 11 is involved in isoproterenolinduced heart failure.
Mol Med Rep
; 19(5): 4109-4118, 2019 May.
Article
em En
| MEDLINE
| ID: mdl-30942402
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 enddiastolic 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), CKmuscle/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 transcriptionquantitative 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 ISOtreated H9C2 cells resulted in decreased proliferation, which was detected via a CCK8 assay, and increased LDH levels and cell apoptosis of cells, which was determined using Caspase3 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 ISOinduced apoptosis by inhibiting oxidative stress injury. The results suggested that GDF11 production was upregulated in ISOinduced rats with HF and in ISOtreated H9C2 cells, and that rGDF11 treatment increased ISOinduced oxidative stress injury by upregulating Nox4 in H9C2 cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Diferenciação de Crescimento
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Insuficiência Cardíaca
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Isoproterenol
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article