Breakthrough Activated cell division prevents heart failure

New findings for the prevention of heart failure

Cardiac insufficiency (heart failure) is one of the most common fatal diseases. Researchers have now gained new insights into the prevention of the disease. They hope that this will soon provide an effective method for the treatment of heart failure.

One of the most common fatal diseases

Cardiac insufficiency (heart failure) affects more than 20 million people worldwide and is one of the most common fatalities. In recent years, new approaches to the treatment of heart failure have been reported repeatedly. For example, scientists at the Hannover Medical School (MHH) found that some patients could help with more iron because it makes the heart more resilient. Researchers from Göttingen have now gained new insights into the prevention of cardiac muscle weakness due to high blood pressure and heart valve diseases. They hope that this will soon provide an effective method for the treatment of cardiac hypertrophy.

Researchers have succeeded in re-activating cell division in adult heart muscle cells. They now hope that an effective treatment for heart failure will be available soon. (Image: psdesign1 / fotolia.com)

Heart muscle cells die

Hypertrophy, the thickening of the heart muscle by cell enlargement, is known in professional athletes as "athlete's heart", it says in a statement of the University Medical Center Göttingen (UMG).

It refers to a natural and reversible adaptation reaction of the heart to the permanent and enhanced training stimulus.

This is to be distinguished from a pathological thickening of the heart wall as a result of sustained pressure, which is triggered, for example, by hypertension or a heart valve disease, the aortic stenosis.

It is a serious condition that can lead to worsening of heart function, heart failure and heart failure.

Cardiac insufficiency is caused, inter alia, by the death of cardiomyocytes (cardiomyocytes).

Since the heart muscle cells can no longer divide in adulthood and thus no replacement of the dead heart muscle cells is possible, the loss leads to a sinking heart function and the formation of scarring.

Significantly prolonged survival

Researchers from the University Medical Center Göttingen (UMG) and the Indiana University School of Medicine, USA, have now jointly succeeded in reactivating cell division in adult cardiomyocytes in a mouse model.

This ability was able to prevent cardiac insufficiency and prolong the survival rate when the heart was under pressure.

The compensation of the load is carried out by a heart wall thickening, which is caused by the proliferation of the heart muscle cells rather than by increasing the volume of the individual heart muscle cells and prevents scarring.

"Interestingly, some of the existing scar tissue could even be reduced by increasing the number of cells. This represents an exciting approach to existing heart failure, "said Priv-Doz. Dr. Karl Toischer, senior physician of the Department of Cardiology and Pulmonology of the UMG and first author of the study.

In the work of the Göttingen scientists, molecular mechanisms that are necessary for the ability of the heart muscle to divide were analyzed in detail and identified.

The study provides new insights to prevent the development of heart failure in high blood pressure and heart valve disease. The results were published in the journal "Journal of Clinical Investigation".

"We are now working on therapy methods in animal models that enable the heart muscle cell to divide," says Prof. Dr. med. Gerd Hasenfuß, last author of the study, director of the Department of Cardiology and Pulmonology of the UMG and chairman of the Herzzentrum Göttingen.

"Since increased cell division ability generally involves an increased risk of tumor development, it is important to ensure that the ability of the heart muscle to divide is controllable."

Hope for new procedure for the treatment of heart failure

Previous studies have shown that targeting the cyclin D2 protein is sufficient to activate the production of cardiac DNA in genetically modified mice after a heart attack.

The resulting cell division activity of the heart cells was already sufficient to improve the constitution and function of the heart in adult mice after a heart attack.

However, it was unclear whether this therapeutic approach is also possible for other types of heart failure. Heart valve disease is either subject to a pressure load when the heart has to work against the narrowed valve (aortic stenosis) or to a volume load when too much blood flows back into the heart in the case of a leaky valve (aortic insufficiency).

In a previous Göttingen study it could be shown that the mouse models could better compensate for an increased blood volume in the heart than an increased pressure load.

The recently published study was performed to determine whether activation of cardiac cell division by the cyclin D2 protein in mice with similar volume and pressure exposures produces similar results.

The data show that the level of cardiomyocyte cell division activity in the mouse model increases with intensified pressure, which in turn leads to an increased cardiomyocyte count and increased wall thickness despite attenuated cell enlargement.

This in turn prevents heart failure and improves the survival of the mice. In contrast, with increased volume loading, neither the level of cardiac cell regeneration increased, nor did the prognosis of the test mice improve.

"The results of this study raise hopes that we will have a new, effective treatment for heart failure from hypertrophy in the foreseeable future. We are pursuing this project at full speed and want to bring it to clinical application as quickly as possible, "said Prof. Gerd Hasenfuß. (Ad)