New approaches to treating heart failure

Researchers are deciphering the molecular pathway of abnormal myocardium thickening
Many people develop morbid thickening of the heart muscle over the course of their lives, which is associated with an increased risk of heart failure, which in the worst case can have fatal consequences. Scientists at the Charité-Universitätsmedizin Berlin have now been able to decipher the molecular pathway that is responsible for the thickening of the heart walls. The scientists around Prof. Dr. Silke Rickert-Sperling hope that their current findings will make a significant contribution to the development of treatment options for heart failure.

According to the researchers, certain genes are responsible for the growth and development of the heart in early stages of development, which can be reactivated in later life and then cause a diseased thickening of the heart muscle. The research team around Prof. Dr. med. Rickert-Sperling claims to have decoded the molecular mechanism responsible for this. Their findings were published in the journal "Nucleic Acids Research". A special key protein therefore plays a crucial role in this widespread form of heart disease.

A cranial thickening of the heart muscle can lead to heart failure with a fatal consequence. (Image: psdesign1 / fotolia.com)

Thickening of the heart muscle is a significant risk factor
The pathological thickening of the heart muscle, also called hypertrophy, is the result of a continuous, increased burden on the heart, for example due to high blood pressure, explain the scientists. The heart cells increase in size, which manifests itself in a thickening of the heart walls. Also, the chambers would be smaller and the muscle becomes stiffer, which deteriorates the pumping power of the heart, report Prof. Dr. med. Rickert-Sperling and colleagues. In addition, "hypertrophy is a key risk factor for developing heart failure, a serious condition that often leads to heart failure and death."

Special protein controls the development of the heart cells
Together, researchers from the Experimental and Clinical Research Center of the Berlin Charité and the Max Delbrück Center for Molecular Medicine (MDC) have deciphered the molecular pathway with researchers from the Max Planck Institute for Molecular Genetics in Berlin and the Havard Medical School in Boston which triggers the pathological thickening of the heart muscle. According to the researchers, the protein DPF and its twin form DPF3a play a key role in this process. Thus, DPF3a is first activated by a special enzyme, a kinase, by the transfer of a phosphate moiety. Subsequently, DPF3a binds in this active form to another protein, which blocks the reading of various genes on the DNA strand, according to the Charité. Through this connection, the protein is released from its blockade position, the released genes are read and translated into proteins, explain Prof. Dr. med. Rickert-Sperling and colleagues. In this way DPF3a start increased production of proteins of early cordial development which are also markedly elevated at pathological hypertrophy. The result has been confirmed in further analyzes on cardiac samples from patients with pathological hypertrophy.

New approaches to drugs
The scientists hope that their findings will contribute to the development of treatment options for heart failure. The search for new target molecules for drugs for the treatment of heart failure is a very intensively researched field worldwide, explain Prof. Dr. med. Rickert-Sperling and colleagues. "My hope is that we were able to provide a promising new approach for this," the study director continued. (Fp)