The human heart has only limited potential for regenerating after a heart attack. The opposite is true for zebrafish. How does this little fish regenerate its heart tissue and what roles do so-called miRNAs play in this process?
Background
Cardiovascular diseases are responsible for 40 percent of deaths in Switzerland, making them the main cause of mortality. The heart can be damaged either acutely as in myocardial infarction or gradually because of work overload, for instance in people suffering from hypertension. The mammalian heart adapts to damage by growing in size in order to maintain function. However, this eventually leads to heart failure. This condition has a high mortality risk.
Although the human heart has a limited capacity to regenerate spontaneously, organisms such as the zebrafish can produce a completely new heart after injury. Several recent lines of investigation suggest that regeneration in the human heart could also be possible. These investigations indicate that, provided the appropriate regulatory mechanisms can be discovered, recruitment of stem cells could be used to produce new heart muscle tissue in the mammalian heart.
The researchers will examine the role of the so-called miRNAs in the process of stem cell mobilization and heart tissue regeneration. miRNAs (micro ribonucleic acid) are small RNA molecules that can modulate the activity of distinct genes. To identify these molecules, the researchers will study the zebrafish heart during regeneration. Understanding how miRNAs act in the zebrafish heart may lead to ways to instruct miRNAs in the human heart to direct the response towards tissue regeneration instead of heart failure.
Aim
The aim of this project is to identify relevant miRNAs by comparing the zebrafish and the mouse heart.
Significance
Each year, coronary heart disease, myocardial infarction and heart failure are the cause of thousands of deaths in Switzerland. Currently, heart transplantation remains the only treatment option. However, the lack of organ donors limits the access to transplantation to a small number of patients. In this context, inducing cardiac regeneration in the damaged heart using selected miRNAs would offer a very attractive therapeutic approach.
Original title: Identification of miRNAs modulating the regenerative response of the heart in the zebrafish and the mouse
Grant: CHF 510’975.-
Duration: 36 months
Project leader
- Prof. Thierry Pedrazzini, Département de médecine, Université de Lausanne
- Prof. Daniel Schorderet, Institut de Recherche en Ophtalmologie, Sion
- Prof. Dario Diviani, Faculté de biologie et de médecine, Université de Lausanne