Key result
Secretoneurin gene therapy significantly ameliorated isoproterenol-induced cardiac hypertrophy and dysfunction in mice, increasing ejection fraction by 60.8% and upregulating apolipoprotein C-III expression.
Why the study?
Following findings that secretoneurin protects against isoproterenol-induced cardiac hypertrophy in mice, the molecular mechanisms, putative target proteins, and pathways remained to be characterized.
Does secretoneurin gene therapy improve isoproterenol-induced cardiac hypertrophy in mice?
Does secretoneurin gene therapy improve isoproterenol-induced cardiac hypertrophy in mice?
Secretoneurin gene therapy ameliorates isoproterenol-induced cardiac hypertrophy and dysfunction in mice, potentially mediated by the upregulation of apolipoprotein C-III.
May support novel gene therapy development for hypertrophy; leaves open clinical translation in human heart failure.
A previous study by our group demonstrated a protective role of the neuropeptide secretoneurin (SN) in DL‑isoproterenol hydrochloride (ISO)‑induced cardiac hypertrophy in mice. To further characterize the molecular mechanism of SN treatment, an isobaric tags for relative and absolute quantification (iTRAQ)‑based quantitative proteomic analysis was applied to identify putative target proteins and molecular pathways. An SN expression vector was injected into the myocardial tissues of mice, and the animals were then subcutaneously injected with ISO (5 mg/kg/day) for 7 days to induce cardiac hypertrophy. The results of echocardiography and hemodynamic measurements indicated that the function of the heart impaired by ISO treatment was significantly ameliorated via SN gene injection. The investigation of heart proteomics was performed by iTRAQ‑based liquid chromatography‑tandem mass spectrometry analysis. A total of 2,044 quantified proteins and 15 differentially expressed proteins were associated with SN overexpression in mice with cardiac hypertrophy. Functional enrichment analysis demonstrated that these effects were possibly associated with metabolic processes. A protein‑protein interaction network analysis was constructed and the data indicated that apolipoprotein C‑III (Apoc3) was associated with the positive effect of SN on the induction of cardiac hypertrophy in mice. The present study proposed a potential mechanism of SN action on Apoc3 upregulation that may contribute to the amelioration of cardiac hypertrophy. These findings can aid the clinical application of SN in patients with cardiac hypertrophy.
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Chen et al. (2020) studied Cardiac hypertrophy (n=40). Secretoneurin (SN) gene therapy (Ad-SN) vs. Ad-con (adenovirus expressing green fluorescent protein) was evaluated on Ejection fraction (EF) (60.8% higher, p=<0.01). Secretoneurin gene therapy significantly ameliorated isoproterenol-induced cardiac hypertrophy and dysfunction in mice, increasing ejection fraction by 60.8% and upregulating apolipoprotein C-III expression.
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