Community Research and Development Information Service - CORDIS


zebraHeart Report Summary

Project ID: 337703
Funded under: FP7-IDEAS-ERC
Country: Switzerland

Mid-Term Report Summary - ZEBRAHEART (Novel insights into cardiac regeneration through studies in the zebrafish)

Myocardial infarction (MI) leads to ischemic cell death. Myofibroblasts (MFs) accumulate at the site of injury and produce large amounts of extracellular matrix, leading to the formation of a scar. While in humans cardiac fibrosis is irreversible, zebrafish transiently accumulate fibrotic tissue in response to cardiac lesions but are able to eliminate this extracellular matrix, and regenerate all cardiac cell types including the heart muscle. Using Echocardiography we have shown that it also recovers ventricular pumping efficiency.
Cardiac fibrosis and regeneration is preceded by an inflammatory response. While the regenerative capacity of a species has been directly linked to features of its immune system, surprisingly little is known on leukocyte subtypes in the zebrafish. We have identified a specific macrophage subtype in the regenerating heart, which will be molecularly and functionally characterized. The epicardium as a trophic factor and progenitor cell source, and we have established a high content screening that allows screening for molecules involved in epicardium formation. The epicardium also contributed to cardiac fibrosis, we are currently exploring the endogenous mechanisms leading to cardiac fibrosis regression.
In sum, this project is contributing to better understand the mechanisms of fibrotic tissue degradation and heart regrowth in an animal model with the natural ability for regeneration.

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