Evidence of an Association between Age-Related Functional Modifications and Pathophysiological Changes in Zebrafish Heart

Background: Zebrafish have become a valuable model for the study of developmental biology and human disease, such as cardiovascular disease. It is difficult to discriminate between disease-related and age-related alterations. Objective: This study was aimed to investigate the effects and potential mechanisms of age-related cardiac modifications in an older zebrafish population. Methods: In this study, we calculated the survival rate and measured the spinal curvature through the aging process. A swimming challenge test was performed and showed that swimming capacity and endurance dramatically dropped in older fish groups. Results: To find out the effect of stress on zebrafish during the aging process, we recorded electrocardiograms on zebrafish and showed that during stress, aging not only led to a significant reduction in heart rate, but also caused other age-related impairments, such as arrhythmias and ST-T depression. Echocardiography showed a marked increase in end-diastolic ventricular dimensions and in isovolumic relaxation time and a notably slower mean and peak velocity of the bulboventricular valve in older zebrafish, but stroke volume and cardiac output were not different in young and old zebrafish. Both nppa and nppb (cardiac fetal genes for natriuretic factor) expression detected by real-time polymerase chain reaction analysis increased in older fish compared to the younger group. Histological staining revealed fibrosis within cardiomyocytes and an increase in ventricular myocardial density and a decrease in epicardial vessel dimensions in older fish hearts that may correlate with a deterioration of cardiac function and exercise capacity. Conclusion: These data suggest that cardiac functional modifications in zebrafish are comparable to those in humans and may partly be due to changes in the cardiovascular system including cardiac fetal gene reprogramming, myocardial density, and epicardial vessel dimensions.