The Zebrafish Heart as a Model of Mammalian Cardiac Function

Author(s):  
Christine E. Genge ◽  
Eric Lin ◽  
Ling Lee ◽  
XiaoYe Sheng ◽  
Kaveh Rayani ◽  
...  
2019 ◽  
Vol 6 (2) ◽  
pp. 16 ◽  
Author(s):  
Suneeta Narumanchi ◽  
Karri Kalervo ◽  
Sanni Perttunen ◽  
Hong Wang ◽  
Katariina Immonen ◽  
...  

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.


2015 ◽  
Vol 309 (8) ◽  
pp. H1237-H1250 ◽  
Author(s):  
Marina Leone ◽  
Ajit Magadum ◽  
Felix B. Engel

The newt and the zebrafish have the ability to regenerate many of their tissues and organs including the heart. Thus, a major goal in experimental medicine is to elucidate the molecular mechanisms underlying the regenerative capacity of these species. A wide variety of experiments have demonstrated that naturally occurring heart regeneration relies on cardiomyocyte proliferation. Thus, major efforts have been invested to induce proliferation of mammalian cardiomyocytes in order to improve cardiac function after injury or to protect the heart from further functional deterioration. In this review, we describe and analyze methods currently used to evaluate cardiomyocyte proliferation. In addition, we summarize the literature on naturally occurring heart regeneration. Our analysis highlights that newt and zebrafish heart regeneration relies on factors that are also utilized in cardiomyocyte proliferation during mammalian fetal development. Most of these factors have, however, failed to induce adult mammalian cardiomyocyte proliferation. Finally, our analysis of mammalian neonatal heart regeneration indicates experiments that could resolve conflicting results in the literature, such as binucleation assays and clonal analysis. Collectively, cardiac regeneration based on cardiomyocyte proliferation is a promising approach for improving adult human cardiac function after injury, but it is important to elucidate the mechanisms arresting mammalian cardiomyocyte proliferation after birth and to utilize better assays to determine formation of new muscle mass.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Hidetaka Kioka ◽  
Hisakazu Kato ◽  
Yoshihiro Asano ◽  
Yasushi Sakata ◽  
Masafumi Kitakaze ◽  
...  

Introduction: We have recently established the method for the selective measurement of intra-mitochondrial ATP levels ([ATP]mito) and have identified the hypoxia-inducible protein G0/G1 switch gene 2 (G0s2) as a positive regulator of mitochondrial oxidative phosphorylation by cultured cardiomyocyte-based experiments. However, the energy metabolism in cultured cells may be much different from that in the living tissue. In this study, we examined the in vivo role of G0s2 under hypoxia by using a novel real-time in vivo ATP imaging technique in zebrafish heart. Methods and Results: We first established the in vivo ATP imaging technique by introducing a FRET-based ATP biosensor named Mit-ATeam into zebrafish heart (Mit-ATeam zebrafish). This system also allows us the simultaneous evaluation of cardiac function. Using Mit-ATeam zebrafish, we successfully observed a decline in [ATP]mito and cardiac function under hypoxic stress and the recovery of these parameters by sequential re-oxygenation. Cardiac specific G0s2 transgenic zebrafish had significantly stronger tolerance against hypoxic stress than wild type zebrafish, while mutant G0s2 transgenic zebrafish did not. In addition, we generated a chimeric zebrafish model in which G0s2 was regionally overexpressed to examine whether focal overexpression of G0s2 could preserve regional cardiac function under hypoxia. Only G0s2-overexpressing cardiomyocyte populations showed enhanced contractility with increased [ATP]mito in hypoxia compared to the control region (i.e. non-G0s2-overexpressing cardiomyocyte populations). Furthermore, we detected enhanced protein expression of G0s2 protein in the risk area in canine ischemic preconditioned heart, suggesting the possible involvement of G0s2 in ischemic preconditioning mediated cardioprotection. Conclusions: These results suggest that G0s2 functions as a guardian of ischemic myocardium and could become a therapeutic target for ischemic heart diseases. Additionally, this study is the first to connect cardiac energy metabolism and function in living animal in real-time.


2006 ◽  
Vol 5 (1) ◽  
pp. 122-123
Author(s):  
O FORSTER ◽  
D HILFIKERKLEINER ◽  
A YIP ◽  
A BECKER ◽  
M NEL ◽  
...  

2008 ◽  
Vol 7 ◽  
pp. 202-203
Author(s):  
A RIAD ◽  
S BIEN ◽  
F ESCHER ◽  
D WESTERMANN ◽  
U LANDMESSER ◽  
...  

1974 ◽  
Vol 134 (2) ◽  
pp. 253-258 ◽  
Author(s):  
A. I. Obeid

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