European Journal of Biomedical and Pharmaceutical Sciences

PRELIMINARY INVESTIGATIONS ON HEART REGENERATION IN OBESE ZEBRAFISH, DANIO RERIO

C. Justin David* and G. Kumaresan

ABSTRACT

Human cardiomyocytes undergo cardiac hypertrophy after ischemic injury while zebrafish, Danio rerio, successfully regenerates ventricular cardiomyocytes. Understanding zebrafish cardiomyocyte proliferation, de-differentiation and regulation by MicroRNAs (miRNAs) may reveal novel therapeutic targets for treating myocardial infarction and other cardiac ailments in humans. Objectives: We utilized diet-induced obese zebrafish to investigate the molecular mechanisms underlying cardiac regeneration c after cardiac injury in obese patients for regenerative medicine. Myocardial injury was inflicted on control and obese zebrafish heart by ventricular resection and expression of molecular factors driving cardiomyocyte regeneration were elucidated using semi-qRT-PCR. Results: Complete recovery from ischemic injury occurred after 57 ± 6 days post injury (dpi) in controls but was significantly (P<0.05) prolonged (79 ± 7 dpi) in obese zebrafish heart. Ventricular cardiomyocytes initiated proliferation after 7 ± 2 and 15 ± 4 dpi in control and obese zebrafish, respectively. Alpha 2 macroglobulin (α2M), Gata4, miR-133a, and IGF2 were significantly (P<0.05) upregulated after 15 dpi whereas miRNA-99 and miR100 levels were completely down-regulated following injury. Interestingly, expression of Gata4 was significantly delayed during initial stages of differentiation in obese zebrafish heart compared to controls. Only ~42% of lost tissues were replaced after 38 ± 4 dpi in obese heart which may be cited as possible reasons for delayed cardiomyocyte dedifferentiation than the control. Conclusion: Obese zebrafish may serve as an excellent vertebrate model for understanding expression of genes and molecular factors involved in cardiac regeneration. Reasons for delayed proliferation, differentiation and role of transcription factors and miRNAs in zebrafish cardiac regeneration are discussed.

Keywords: Cardiac regeneration, obesity, myocardial injury, IGF2, miR133a, miR99, miR100.