Faculty Opinions recommendation of Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration.

The cardiac lymphatic vascular system and its potentially critical functions in heart patients have been largely underappreciated, in part due to a lack of experimentally accessible systems. We here demonstrate that cardiac lymphatic vessels develop in young adult zebrafish, using coronary arteries to guide their expansion down the ventricle. Mechanistically, we show that in cxcr4a mutants with defective coronary artery development, cardiac lymphatic vessels fail to expand onto the ventricle. In regenerating adult zebrafish hearts the lymphatic vasculature undergoes extensive lymphangiogenesis in response to a cryoinjury. A significant defect in reducing the scar size after cryoinjury is observed in zebrafish with impaired Vegfc/Vegfr3 signaling that fail to develop intact cardiac lymphatic vessels. These results suggest that the cardiac lymphatic system can influence the regenerative potential of the myocardium.

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Decision letter: Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration

10.7554/elife.42762.sa1 ◽

2018 ◽

Author(s):

Anna Jazwinska

Keyword(s):

Heart Function ◽

Adult Zebrafish ◽

Lymphatic Vasculature ◽

Zebrafish Heart

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Author response: Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration

10.7554/elife.42762.sa2 ◽

2019 ◽

Cited By ~ 1

Author(s):

Michael RM Harrison ◽

Xidi Feng ◽

Guqin Mo ◽

Antonio Aguayo ◽

Jessi Villafuerte ◽

...

Keyword(s):

Heart Function ◽

Author Response ◽

Adult Zebrafish ◽

Lymphatic Vasculature ◽

Zebrafish Heart

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Inhibition of let-7c Regulates Cardiac Regeneration after Cryoinjury in Adult Zebrafish

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd6020016 ◽

2019 ◽

Vol 6 (2) ◽

pp. 16 ◽

Cited By ~ 1

Author(s):

Suneeta Narumanchi ◽

Karri Kalervo ◽

Sanni Perttunen ◽

Hong Wang ◽

Katariina Immonen ◽

...

Keyword(s):

Cardiac Function ◽

Cardiac Regeneration ◽

Nuclear Antigen ◽

Heart Regeneration ◽

Adult Zebrafish ◽

Tissue Samples ◽

Micro Rnas ◽

Proliferating Cell ◽

Zebrafish Heart

The let-7c family of micro-RNAs (miRNAs) is expressed during embryonic development and plays an important role in cell differentiation. We have investigated the role of let-7c in heart regeneration after injury in adult zebrafish. let-7c antagomir or scramble injections were given at one day after cryoinjury (1 dpi). Tissue samples were collected at 7 dpi, 14 dpi and 28 dpi and cardiac function was assessed before cryoinjury, 1 dpi, 7 dpi, 14 dpi and 28 dpi. Inhibition of let-7c increased the rate of fibrinolysis, increased the number of proliferating cell nuclear antigen (PCNA) positive cardiomyocytes at 7 dpi and increased the expression of the epicardial marker raldh2 at 7 dpi. Additionally, cardiac function measured with echocardiography recovered slightly more rapidly after inhibition of let-7c. These results reveal a beneficial role of let-7c inhibition in adult zebrafish heart regeneration.

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Alarm substance from adult zebrafish alters early embryonic development in offspring

Biology Letters ◽

10.1098/rsbl.2009.0944 ◽

2010 ◽

Vol 6 (4) ◽

pp. 525-528 ◽

Cited By ~ 11

Author(s):

S. Mourabit ◽

S. D. Rundle ◽

J. I. Spicer ◽

K. A. Sloman

Keyword(s):

Embryonic Development ◽

Inclusive Fitness ◽

Heart Function ◽

Physiological Responses ◽

Early Embryonic Development ◽

Alarm Substance ◽

Adult Zebrafish ◽

Skin Injury ◽

Wide Range ◽

Alarm Substances

Alarm substances elicit behavioural responses in a wide range of animals but effects on early embryonic development are virtually unknown. Here we investigated whether skin injury-induced alarm substances caused physiological responses in embryos produced by two Danio species ( Danio rerio and Danio albolineatus ). Both species showed more rapid physiological development in the presence of alarm substance, although there were subtle differences between them: D. rerio had advanced muscle contraction and heart function, whereas D. albolineatus had advanced heart function only. Hence, alarm cues from injured or dying fish may be of benefit to their offspring, inducing physiological responses and potentially increasing their inclusive fitness.

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Physiological phenotyping of the adult zebrafish heart

Marine Genomics ◽

10.1016/j.margen.2019.100701 ◽

2020 ◽

Vol 49 ◽

pp. 100701 ◽

Cited By ~ 2

Author(s):

Eric Lin ◽

Sanam Shafaattalab ◽

Jasmine Gill ◽

Bader Al-Zeer ◽

Calvin Craig ◽

...

Keyword(s):

Adult Zebrafish ◽

Zebrafish Heart

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Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart Regeneration

Biomolecules ◽

10.3390/biom9010011 ◽

2018 ◽

Vol 9 (1) ◽

pp. 11 ◽

Cited By ~ 3

Author(s):

Hagen Klett ◽

Lonny Jürgensen ◽

Patrick Most ◽

Martin Busch ◽

Fabian Günther ◽

...

Keyword(s):

Heart Function ◽

Heart Diseases ◽

Expression Profiles ◽

Temporal Organization ◽

H9c2 Cell ◽

Specific Response ◽

Heart Regeneration ◽

Cardiomyocyte Proliferation ◽

Transcriptome Response ◽

Zebrafish Heart

Heart diseases are the leading cause of death for the vast majority of people around the world, which is often due to the limited capability of human cardiac regeneration. In contrast, zebrafish have the capacity to fully regenerate their hearts after cardiac injury. Understanding and activating these mechanisms would improve health in patients suffering from long-term consequences of ischemia. Therefore, we monitored the dynamic transcriptome response of both mRNA and microRNA in zebrafish at 1–160 days post cryoinjury (dpi). Using a control model of sham-operated and healthy fish, we extracted the regeneration specific response and further delineated the spatio-temporal organization of regeneration processes such as cell cycle and heart function. In addition, we identified novel (miR-148/152, miR-218b and miR-19) and previously known microRNAs among the top regulators of heart regeneration by using theoretically predicted target sites and correlation of expression profiles from both mRNA and microRNA. In a cross-species effort, we validated our findings in the dynamic process of rat myoblasts differentiating into cardiomyocytes-like cells (H9c2 cell line). Concluding, we elucidated different phases of transcriptomic responses during zebrafish heart regeneration. Furthermore, microRNAs showed to be important regulators in cardiomyocyte proliferation over time.

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

Journal of The Royal Society Interface ◽

10.1098/rsif.2014.1154 ◽

2015 ◽

Vol 12 (103) ◽

pp. 20141154 ◽

Cited By ~ 8

Author(s):

Bong Jin Kang ◽

Jinhyoung Park ◽

Jieun Kim ◽

Hyung Ham Kim ◽

Changyang Lee ◽

...

Keyword(s):

Diastolic Dysfunction ◽

High Frequency ◽

Doppler Imaging ◽

Flow Mode ◽

Heart Regeneration ◽

Adult Zebrafish ◽

Dual Mode ◽

Doppler Flow ◽

Pulsed Wave Doppler ◽

Zebrafish Heart

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 −1 with high accuracy ( p -value = 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 / E m < 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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Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish

eLife ◽

10.7554/elife.05871 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 111

Author(s):

Matthew Gemberling ◽

Ravi Karra ◽

Amy L Dickson ◽

Kenneth D Poss

Keyword(s):

Cardiac Injury ◽

Heart Regeneration ◽

Cardiomyocyte Proliferation ◽

Adult Zebrafish ◽

Perivascular Cells ◽

Adult Heart ◽

Muscle Hyperplasia ◽

Zebrafish Heart

Heart regeneration is limited in adult mammals but occurs naturally in adult zebrafish through the activation of cardiomyocyte division. Several components of the cardiac injury microenvironment have been identified, yet no factor on its own is known to stimulate overt myocardial hyperplasia in a mature, uninjured animal. In this study, we find evidence that Neuregulin1 (Nrg1), previously shown to have mitogenic effects on mammalian cardiomyocytes, is sharply induced in perivascular cells after injury to the adult zebrafish heart. Inhibition of Erbb2, an Nrg1 co-receptor, disrupts cardiomyocyte proliferation in response to injury, whereas myocardial Nrg1 overexpression enhances this proliferation. In uninjured zebrafish, the reactivation of Nrg1 expression induces cardiomyocyte dedifferentiation, overt muscle hyperplasia, epicardial activation, increased vascularization, and causes cardiomegaly through persistent addition of wall myocardium. Our findings identify Nrg1 as a potent, induced mitogen for the endogenous adult heart regeneration program.

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