Can we eradicate and cure heart disease?

This is why the heart muscle cannot regenerate

ERLANGEN / NUREMBERG. Damage to the human heart causes cardiac muscle cells to die. It is different with zebrafish and amphibians. If their hearts are damaged and cardiac muscle cells die, the cardiac muscle cells that are still present can multiply again - with the result that the hearts regenerate.

The researchers at the Friedrich-Alexander University (FAU) Erlangen-N├╝rnberg Dr. David Zebrowski and Professor Felix B. Engel from the Nephropathological Department of the Pathological Institute of the University Hospital Erlangen have now found a possible explanation with colleagues why this does not work in human heart cells.

It's the centrosome

"In our study, we discovered that the centrosome in myocardial cells disintegrates in a creeping process that is completed shortly after birth," Engel is quoted as saying in a statement from FAU.

"Some of the proteins leave the centrosome and attach themselves to the membrane of the cell nucleus in which the DNA is stored. This process causes the centrosome to break down into its two so-called centrioles. As a result, the cell loses its ability to close multiply. "

The centrosome is an organ-like structure in a cell, the communication recalls. If the centrosome is not intact, a cell can no longer multiply.

Experiments in recent years have shown this and raised a key question: To what extent can the integrity of the centrosome be manipulated - for example in diseases such as cancer, in which cells multiply in an uncontrolled manner?

The FAU researchers have now investigated whether the state of the centrosome integrity in the animal kingdom is naturally regulated in order to control the proliferation of certain cells (eLife 2015; online August 6).

"We were very surprised to find that the centrosome in the heart muscle cells of zebrafish and amphibians remains intact into adulthood," says Zebrowski.

"This is the first time we have discovered a significant difference between the heart muscle cells of mammals and zebrafish and amphibians that can explain why humans cannot regenerate their hearts."

Diverse options for research

The fact that there is a natural process for regulating the centrosome integrity in mammalian cardiac muscle cells opens up a wide range of possibilities for future research. On the one hand, the observation offers a new starting point for possibly stimulating the reproduction of cardiac muscle cells in humans and thus cardiac regeneration.

On the other hand, centrosome integrity can be used to search for heart muscle cells that may have retained their ability to multiply - which opens up a new therapeutic goal. Finally, elucidating the mechanism in detail could also help to inhibit the uncontrolled growth of cancer cells.

The basis of research on heart regeneration is the cell cycle initiative CYDER (Cell Cycle in Disease and Regeneration), which Engel, an expert in heart regeneration, launched. CYDER has been supported by FAU since 2014 as part of its Emerging Fields Initiative (EFI), according to the FAU announcement.

EFI supports outstanding, preferably interdisciplinary projects at an early stage, flexibly and unbureaucratically. A strict selection process guarantees the quality of the funded scientists, ideas and research approaches. (eb)