Heart repair and regeneration: Recent insights from zebrafish studies

Lien, Ching‐Ling; Harrison, Michael R.; Tuan, Tai‐Lan; Starnes, Vaughn A.

doi:10.1111/j.1524-475x.2012.00814.x

Cited by 46 publications

(50 citation statements)

References 72 publications

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“…After 20% of its ventricular apex is amputated, fibrin clots are formed to block the haemorrhage followed by regeneration of the damaged myocardium [4]. Those morphological recoveries are well identified through the histology of sacrificed fish hearts.…”

Section: Introductionmentioning

confidence: 98%

High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts

Kang

Park

Kim

et al. 2015

J. R. Soc. Interface.

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Adult zebrafish is a well-known small animal model for studying heart regeneration. Although the regeneration of scars made by resecting the ventricular apex has been visualized with histological methods, there is no adequate imaging tool for tracking the functional recovery of the damaged heart. For this reason, high-frequency Doppler echocardiography using dual mode pulsed wave Doppler, which provides both tissue Doppler (TD) and Doppler flow in a same cardiac cycle, is developed with a 30 MHz high-frequency array ultrasound imaging system. Phantom studies show that the Doppler flow mode of the dual mode is capable of measuring the flow velocity from 0.1 to 15 cm s 21 with high accuracy ( p-value ¼ 0.974 . 0.05). In the in vivo study of zebrafish, both TD and Doppler flow signals were simultaneously obtained from the zebrafish heart for the first time, and the synchronized valve motions with the blood flow signals were identified. In the longitudinal study on the zebrafish heart regeneration, the parameters for diagnosing the diastolic dysfunction, for example, E/Em , 10, E/A , 0.14 for wild-type zebrafish, were measured, and the type of diastolic dysfunction caused by the amputation was found to be similar to the restrictive filling. The diastolic function was fully recovered within four weeks post-amputation.

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Section: Introductionmentioning

confidence: 98%

High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts

Kang

Park

Kim

et al. 2015

J. R. Soc. Interface.

Self Cite

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“…The large number of embryos produced per clutch makes zebrafish a prominent model for higher-throughput screening of small molecules, 9 which is mandatory for preclinical drug development and toxicity assessment. 10 So far, zebrafish have been used to model a wide variety of human diseases, including hereditary muscle diseases, 11 neurological disorders, 12 tuberculosis, 13 cancer, 14 cardiovascular diseases, 15 and haematopoietic and infectious diseases. 16 In addition, zebrafish are a valuable vertebrate model for studying vision-related disorders.…”

Section: Zebrafish As An Animal Modelmentioning

confidence: 99%

Zebrafish—on the move towards ophthalmological research

Chhetri

Jacobson

Gueven

2014

Eye

138

114

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Millions of people are affected by visual impairment and blindness globally, and the prevalence of vision loss is likely to increase as we are living longer. However, many ocular diseases remain poorly controlled due to lack of proper understanding of the pathogenesis and the corresponding lack of effective therapies. Consequently, there is a major need for animal models that closely mirror the human eye pathology and at the same time allow higher-throughput drug screening approaches. In this context, zebrafish as an animal model organism not only address these needs but can in many respects reflect the human situation better than the current rodent models. Over the past decade, zebrafish have become an established model to study a variety of human diseases and are more recently becoming a valuable tool for the study of human ophthalmological disorders. Many human ocular diseases such as cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration have already been modelled in zebrafish. In addition, zebrafish have become an attractive model for pre-clinical drug toxicity testing and are now increasingly used by scientists worldwide for the discovery of novel treatment approaches. This review presents the advantages and uses of zebrafish for ophthalmological research.

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“…Zebrafish has become a powerful model with which to study cardiac development in recent years (Bakkers, 2011;Lien et al, 2012). We set out to study early heart development in zebrafish embryos expressing NS and LS variants of Shp2, taking advantage of the transparency of zebrafish embryos, which facilitates time-lapse analysis of the onset and nature of the cardiac defects in vivo.…”

Section: Introductionmentioning

confidence: 99%

Noonan and LEOPARD syndrome Shp2 variants induce heart displacement defects in zebrafish

et al. 2014

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Germline mutations in PTPN11, encoding Shp2, cause Noonan syndrome (NS) and LEOPARD syndrome (LS), two developmental disorders that are characterized by multiple overlapping symptoms. Interestingly, Shp2 catalytic activity is enhanced by NS mutations and reduced by LS mutations. Defective cardiac development is a prominent symptom of both NS and LS, but how the Shp2 variants affect cardiac development is unclear. Here, we have expressed the most common NS and LS Shp2-variants in zebrafish embryos to investigate their role in cardiac development in vivo. Heart function was impaired in embryos expressing NS and LS variants of Shp2. The cardiac anomalies first occurred during elongation of the heart tube and consisted of reduced cardiomyocyte migration, coupled with impaired leftward heart displacement. Expression of specific laterality markers was randomized in embryos expressing NS and LS variants of Shp2. Ciliogenesis and cilia function in Kupffer's vesicle was impaired, likely accounting for the left/right asymmetry defects. Mitogen-activated protein kinase (MAPK) signaling was activated to a similar extent in embryos expressing NS and LS Shp2 variants. Interestingly, inhibition of MAPK signaling prior to gastrulation rescued cilia length and heart laterality defects. These results suggest that NS and LS Shp2 variant-mediated hyperactivation of MAPK signaling leads to impaired cilia function in Kupffer's vesicle, causing left-right asymmetry defects and defective early cardiac development.

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Heart repair and regeneration: Recent insights from zebrafish studies

Cited by 46 publications

References 72 publications

High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts

High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts

Zebrafish—on the move towards ophthalmological research

Noonan and LEOPARD syndrome Shp2 variants induce heart displacement defects in zebrafish

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