Induction of cardiac dysfunction in developing and adult zebrafish by chronic isoproterenol stimulation.

Zebrafish is a widely used model to evaluate genetic variants and modifiers that can cause heart muscle diseases. Surprisingly, the β-adrenergic receptor (β-AR) pathway in zebrafish is not well characterized, although abnormal β-AR signaling is a major contributor to human heart failure (HF). Chronic β-AR activation in the attempt to normalize heart function in the failing heart results in a reduction of the β-ARs expression and receptor desensitization, largely mediated through G-protein coupled receptor kinase 2 (GRK2) upregulation.

miR-19b Regulates Ventricular Action Potential Duration in Zebrafish.

Sudden cardiac death due to ventricular arrhythmias often caused by action potential duration (APD) prolongation is a common mode of death in heart failure (HF). microRNAs, noncoding RNAs that fine tune gene expression, are frequently dysregulated during HF, suggesting a potential involvement in the electrical remodeling process accompanying HF progression. Here, we identified miR-19b as an important regulator of heart function.

Essential light chain S195 phosphorylation is required for cardiac adaptation under physical stress.

Aims: Regulatory proteins of the sarcomere are pivotal for normal heart function and when affected by mutations are frequently causing cardiomyopathy. The exact function of these regulatory proteins and how mutations in these translate into distinct cardiomyopathy phenotypes remains poorly understood. Mutations in the essential myosin light chain (ELC) are linked to human cardiomyopathy characterized by a marked variability in disease phenotypes and high incidences of sudden death.

Advanced echocardiography in adult zebrafish reveals delayed recovery of heart function after myocardial cryoinjury.

Translucent zebrafish larvae represent an established model to analyze genetics of cardiac development and human cardiac disease. More recently adult zebrafish are utilized to evaluate mechanisms of cardiac regeneration and by benefiting from recent genome editing technologies, including TALEN and CRISPR, adult zebrafish are emerging as a valuable in vivo model to evaluate novel disease genes and specifically validate disease causing mutations and their underlying pathomechanisms. However, methods to sensitively and non-invasively assess cardiac morphology and performance in adult zebrafish are still limited.