Skip to main content

Novel insights into cardiac regeneration through studies in the zebrafish

Objective

Myocardial infarction (MI) leads to cardiomyocyte death and accumulation of myofibroblasts (MFs) at the site of injury, which produce large amounts of extracellular matrix (ECM), generating a scar. Initially, cardiac fibrosis protects from ventricular wall rupture, but subsequent myocardial remodelling causes heart failure, representing a leading cause of death in Europe. While MFs play a central role in cardiac fibrosis, there is confusion on their origin, a lack of specific markers and the existence of a unique MF type is debatable. Different MF might reveal distinct characteristics regarding ECM production, contractility, and autophagy, making them more or less pernicious. While in humans cardiac fibrosis is irreversible, other vertebrates have a remarkable capacity to regenerate damaged tissue. We recently established a zebrafish MI model and found that cardiac fibrosis is reversible and occurs as an intermediate step during regeneration. Here, the endogenous mechanisms of MFs and ECM regression will be explored. In addition, MF origin, types and fate will be characterized and manipulated to improve regeneration. As in mammals, cardiac injury elicits an inflammatory response in the zebrafish. The regenerative capacity of a species has been directly linked to features of its immune system, but surprisingly little is known on zebrafish leukocyte subtypes. We will study the role of macrophages and particularly analyse a subtype, which accumulates in the outer mesothelial layer of the heart, the epicardium. Epicardial derived cells play a key role as a trophic factor and progenitor cell source, and a first step towards regeneration includes the reestablishment of the epicardial layer. The zebrafish will offer a screening platform for small molecules triggering its activation. In sum, the project will increase the knowledge on the molecular and cellular basis of fibrosis regression, provide novel MF markers and identify new drugs to enhance cardiac regeneration.

Field of science

  • /natural sciences/biological sciences/zoology/mammalogy
  • /medical and health sciences/basic medicine/immunology

Call for proposal

ERC-2013-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

UNIVERSITAET BERN
Address
Hochschulstrasse 6
3012 Bern
Switzerland
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 022 489,02
Principal investigator
Nadia Isabel Mercader Huber (Dr.)
Administrative Contact
Maddalena Tognola (Ms.)

Beneficiaries (2)

UNIVERSITAET BERN
Switzerland
EU contribution
€ 1 022 489,02
Address
Hochschulstrasse 6
3012 Bern
Activity type
Higher or Secondary Education Establishments
Principal investigator
Nadia Isabel Mercader Huber (Dr.)
Administrative Contact
Maddalena Tognola (Ms.)
CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.)
Spain
EU contribution
€ 476 725,98
Address
Calle Melchor Fernandez Almagro 3
28029 Madrid
Activity type
Research Organisations
Administrative Contact
Luzma García Piqueres (Ms.)