Dataset Information

Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish

ABSTRACT:

Background

Cardiomyopathy is a kind of cardiovascular diseases, which makes it more difficult for the heart to pump blood to other parts of the body, eventually leading to heart failure. Naoxintong (NXT), as a traditional Chinese Medicine (TCM) preparation, is widely used in the treatment of cardiovascular diseases, including cardiomyopathy, while its underlying mechanism has not been fully elucidated. The purpose of this study is to investigate the therapeutic effect of NXT on cardiomyopathy and its molecular mechanism in zebrafish model.

Methods

The zebrafish cardiomyopathy model was established using terfenadine (TFD) and treated with NXT. The therapeutic effect of NXT on cardiomyopathy was evaluated by measuring the heart rate, the distance between the sinus venosus and bulbus arteriosus (SV-BA), the pericardial area, and the blood flow velocity of zebrafish. Then, the zebrafish hearts were isolated and collected; transcriptome analysis of NXT on cardiomyopathy was investigated. Moreover, the heg1 mutant of zebrafish congenital cardiomyopathy model was used to further validate the therapeutic effect of NXT on cardiomyopathy. Additionally, UPLC analysis combined with the zebrafish model investigation was performed to identify the bioactive components of NXT.

Results

In the TFD-induced zebrafish cardiomyopathy model, NXT treatment could significantly restore the cardiovascular malformations caused by cardiac dysfunction. Transcriptome and bioinformatics analyses of the TFD and TFD + NXT treated zebrafish developing hearts revealed that the differentially expressed genes were highly enriched in biological processes such as cardiac muscle contraction and heart development. As a cardiac development protein associated with cardiomyopathy, HEG1 had been identified as one of the important targets of NXT in the treatment of cardiomyopathy. The cardiovascular abnormalities of zebrafish heg1 mutant could be recovered significantly from NXT treatment, including the expanded atrial cavity and blood stagnation. qRT-PCR analysis further showed that NXT could restore cardiomyopathy phenotype in zebrafish through HEG1-CCM signaling. Among the seven components identified in NXT, paeoniflorin (PF) and salvianolic acid B (Sal B) were considered to be the main bioactive ones with myocardial protection.

Conclusion

NXT presented myocardial protective effect and could restore myocardial injury and cardiac dysfunction in zebrafish; the action mechanism was involved in HEG1-CCM signaling.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13020-021-00532-0.

SUBMITTER: Hu M

PROVIDER: S-EPMC8591872 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND: Cardiomyopathy syndrome (CMS) is a disease associated with severe myocarditis primarily in adult farmed Atlantic salmon (Salmo salar L.), caused by a double-stranded RNA virus named piscine myocarditis virus (PMCV) with structural similarities to the Totiviridae family. Here we present the first characterisation of host immune responses to CMS assessed by microarray transcriptome profiling. RESULTS: Unvaccinated farmed Atlantic salmon post-smolts were infected by intraperitoneal injection of PMCV and developed cardiac pathology consistent with CMS. From analysis of heart samples at several time points and different tissues at early and clinical stages by oligonucleotide microarrays (SIQ2.0 chip), six gene sets representing a broad range of immune responses were identified, showing significant temporal and spatial regulation. Histopathological examination of cardiac tissue showed myocardial lesions from 6 weeks post infection (wpi) that peaked at 8-9 wpi and was followed by a recovery. Viral RNA was detected in all organs from 4 wpi suggesting a broad tissue tropism. High correlation between viral load and cardiac histopathology score suggested that cytopathic effect of infection was a major determinant of the myocardial changes. Strong and systemic induction of antiviral and IFN-dependent genes from 2 wpi that levelled off during infection, was followed by a biphasic activation of pathways for B cells and MHC antigen presentation, both peaking at clinical pathology. This was preceded by a distinct cardiac activation of complement at 6 wpi, suggesting a complement-dependent activation of humoral Ab-responses. Peak of cardiac pathology and viral load coincided with cardiac-specific upregulation of T cell response genes and splenic induction of complement genes. Preceding the reduction in viral load and pathology, these responses were probably important for viral clearance and recovery. CONCLUSIONS: By comparative analysis of gene expression, histology and viral load, the temporal and spatial regulation of immune responses were characterised and novel immune genes identified, ultimately leading to a more complete understanding of host-virus responses and pathology and protection in Atlantic salmon during CMS.