SP 2

The role of inflammation in cardiac regeneration in Zebrafish

Inflammation plays a crucial role in healing after myocardial infarction and influences the development of cardiac function. Monocytes and macrophages are key players of the innate immune response. While zebrafish hearts have the capability to fully recover from injury under normal conditions, we have found that removal of macrophages has a detrimental effect on the regeneration process and prevents the recovery of cardiac function.

Accumulation of neutrophils and monocyte/ macrophages after cardiac injury.
AOI: area of interest.

This subproject aims to investigate (1) what changes can be detected in injured zebrafish hearts after macrophage depletion on a time-resolved transcriptome, miRNAome and epigenome level to identify crucial pathways involved at the interplay between cardiomyocytes and immune cells during cardiac regeneration. In addition, this subproject will (2) generate dynamic multi-omics data in experimental myocardial infarction in mouse and swine to allow an in-depth differentiation of regenerating and non-regenerating hearts after injury and (3) evaluate these findings in samples from a large cohort of patients with acute coronary syndromes. With this approach, we aim to identify novel targets to improve healing after myocardial infarction and prevent the development of heart failure.

Depletion of macrophages in adult zebrafish by clondronate liposomes increases infarct size and results in impaired healing (30 days after cryo injury).

 

Keywords: myocardial injury, inflammation