Zebrafish Heart Failure Models

Narumanchi, Suneeta; Wang, Hong; Perttunen, Sanni; Tikkanen, Ilkka; Lakkisto, Päivi; Paavola, Jere

doi:10.3389/fcell.2021.662583

Cited by 51 publications

(37 citation statements)

References 169 publications

(216 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the prediction of a heart failure before it happens, some cardiac markers can be measured includingANP/NPPA and BNP/NPPB [ 28 , 29 , 30 ]. Natriuretic peptides are quantitative markers of cardiac hemodynamic stress and heart failure.…”

Section: Discussionmentioning

confidence: 99%

“…RT-qPCR was performed to check the expression of two critical heart failure markers; atrial natriuretic peptide (ANP/NPPA), brain natriuretic peptide (BNP/NPPB) [ 28 , 29 , 30 ]. First, RNA was extracted from zebrafish embryos, both treated and control groups (20~30 each), using IBI DNA/RNA/Protein Extraction Kit (IBI Scientific -r IB47702, Dubuque, IA, USA) according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Water-Pipe Smoking on the Normal Development of Zebrafish

Zakaria

Aladwi

Benslimane

et al. 2021

IJERPH

View full text Add to dashboard Cite

Background: Among all types of tobacco consumption, Water-Pipe Smoking (WPS) is the most widely used in the Middle East and second-most in several other countries. The effect of WPS on normal development is not yet fully understood, thus the aim of this study is to explore the acute toxicity effects of WPS extract on zebrafish larvae. Methods: In this study, we compared the effects of WPS smoke condensates at concentrations varying from 50 to 200 µg/mL on developmental, cardiac, and behavioural (neurotoxicity) functions. Gene expression patterns of cardiac biomarkers were also evaluated by RT-qPCR. Results: Exposing zebrafish embryos to 50, 100, 150 and 200 µg/mL WPS for three days did not affect the normal morphology of Zebrafish embryos, as the tail flicking, behavioural and locomotion assays did not show any change. However, WPS deregulated cardiac markers including atrial natriuretic peptide (ANP/NPPA) and brain natriuretic peptide (BNP/NPPB). Furthermore, it induced apoptosis in a dose-dependent manner. Conclusion: Our data demonstrate that WPS can significantly affect specific cardiac parameters during the normal development of zebrafish. Further investigations are necessary to elucidate the pathogenic outcome of WPS on different aspects of human life, including pregnancy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effect of Water-Pipe Smoking on the Normal Development of Zebrafish

Zakaria

Aladwi

Benslimane

et al. 2021

IJERPH

View full text Add to dashboard Cite

show abstract

“…A simple visual comparison of treated zebrafish embryos to controls at 24, 48, and 72 hpf was undertaken to explore Ponatinib’s teratogenic potential. Aristolochic acid (AA) (1 µM) was used as a positive control (PC) that induces cardiac failure per prior research [ 31 , 32 ]. Ponatinib treatment drastically reduces embryos’ survival and tail flicking in a concentration-dependent manner, as demonstrated in Figure 4 panels A and B, respectively.…”

Section: Resultsmentioning

confidence: 99%

Reduced Cardiotoxicity of Ponatinib-Loaded PLGA-PEG-PLGA Nanoparticles in Zebrafish Xenograft Model

et al. 2022

View full text Add to dashboard Cite

Tyrosine kinase inhibitors (TKIs) are the new generation of anti-cancer drugs with high potential against cancer cells’ proliferation and growth. However, TKIs are associated with severe cardiotoxicity, limiting their clinical value. One TKI that has been developed recently but not explored much is Ponatinib. The use of nanoparticles (NPs) as a better therapeutic agent to deliver anti-cancer drugs and reduce their cardiotoxicity has been recently considered. In this study, with the aim to reduce Ponatinib cardiotoxicity, Poly(D,L-lactide-co-glycolide)-b-poly(ethyleneoxide)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer was used to synthesize Ponatinib in loaded PLGA-PEG-PLGA NPs for chronic myeloid leukemia (CML) treatment. In addition to physicochemical NPs characterization (NPs shape, size, size distribution, surface charge, dissolution rate, drug content, and efficacy of encapsulation) the efficacy and safety of these drug-delivery systems were assessed in vivo using zebrafish. Zebrafish are a powerful animal model for investigating the cardiotoxicity associated with anti-cancer drugs such as TKIs, to determine the optimum concentration of smart NPs with the least side effects, and to generate a xenograft model of several cancer types. Therefore, the cardiotoxicity of unloaded and drug-loaded PLGA-PEG-PLGA NPs was studied using the zebrafish model by measuring the survival rate and cardiac function parameters, and therapeutic concentration for in vivo efficacy studies was optimized in an in vivo setting. Further, the efficacy of drug-loaded PLGA-PEG-PLGA NPs was tested on the zebrafish cancer xenograft model, in which human myelogenous leukemia cell line K562 was transplanted into zebrafish embryos. Our results demonstrated that the Ponatinib-loaded PLGA-PEG-PLGA NPs at a concentration of 0.001 mg/mL are non-toxic/non-cardio-toxic in the studied zebrafish xenograft model.

show abstract

“…In addition, zebrafish are vertebrates having organs like humans and are frequently used as model animals in various fields including genetics and developmental biology. Transparency in the early developmental stages has attracted attention in the fields of cardiovascular research, toxicology, and drug discovery because it is possible to directly observe beating hearts ( Milan et al, 2006 ; MacRae and Peterson, 2015 ; Narumanchi et al, 2021 ; Maciag et al, 2022 ). In zebrafish, ionic currents that underlie cardiac automaticity and excitability have also been studied in detail ( Nemtsas et al, 2010 ; Vornanen and Hassinen, 2016 ; Ravens, 2018 ; Stoyek and Quinn, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Two HCN4 Channels Play Functional Roles in the Zebrafish Heart

Liu

Kasuya²,

Zempo³

et al. 2022

Front. Physiol.

View full text Add to dashboard Cite

The HCN4 channel is essential for heart rate regulation in vertebrates by generating pacemaker potentials in the sinoatrial node. HCN4 channel abnormality may cause bradycardia and sick sinus syndrome, making it an important target for clinical research and drug discovery. The zebrafish is a popular animal model for cardiovascular research. They are potentially suitable for studying inherited heart diseases, including cardiac arrhythmia. However, it has not been determined how similar the ion channels that underlie cardiac automaticity are in zebrafish and humans. In the case of HCN4, humans have one gene, whereas zebrafish have two ortholog genes (DrHCN4 and DrHCN4L; ‘Dr’ referring to Danio rerio). However, it is not known whether the two HCN4 channels have different physiological functions and roles in heart rate regulation. In this study, we characterized the biophysical properties of the two zebrafish HCN4 channels in Xenopus oocytes and compared them to those of the human HCN4 channel. We found that they showed different gating properties: DrHCN4L currents showed faster activation kinetics and a more positively shifted G-V curve than did DrHCN4 and human HCN4 currents. We made chimeric channels of DrHCN4 and DrHCN4L and found that cytoplasmic domains were determinants for the faster activation and the positively shifted G-V relationship in DrHCN4L. The use of a dominant-negative HCN4 mutant confirmed that DrHCN4 and DrHCN4L can form a heteromultimeric channel in Xenopus oocytes. Next, we confirmed that both are sensitive to common HCN channel inhibitors/blockers including Cs+, ivabradine, and ZD7288. These HCN inhibitors successfully lowered zebrafish heart rate during early embryonic stages. Finally, we knocked down the HCN4 genes using antisense morpholino and found that knocking down either or both of the HCN4 channels caused a temporal decrease in heart rate and tended to cause pericardial edema. These findings suggest that both DrHCN4 and DrHCN4L play a significant role in zebrafish heart rate regulation.

show abstract

Zebrafish Heart Failure Models

Cited by 51 publications

References 169 publications

Effect of Water-Pipe Smoking on the Normal Development of Zebrafish

Effect of Water-Pipe Smoking on the Normal Development of Zebrafish

Reduced Cardiotoxicity of Ponatinib-Loaded PLGA-PEG-PLGA Nanoparticles in Zebrafish Xenograft Model

Two HCN4 Channels Play Functional Roles in the Zebrafish Heart

Contact Info

Product

Resources

About