Millions of people worldwide suffer from heart failure. It is one of the most serious and deadly cardiac diseases. Researchers have now discovered a potential new treatment approach.
Researchers from the Heart Center at the University Medical Center Göttingen (UMG) have discovered a potential new treatment approach for heart muscle weakness (also called heart failure or heart failure). Their findings were published in the journal “Circulation Research”.
Half of those affected have an iron deficiency
As stated in a statement from the UMG, according to the World Health Organization (WHO), around 27 percent of the world’s population suffers from a severe iron deficiency, which often leads to anemia.
In anemia, the number of red blood cells is very low, so the blood cannot carry enough oxygen to the body. Patients with iron deficiency often suffer from exhaustion, weakness and paleness, even shortness of breath and chest pain.
In people with heart failure, iron deficiency worsens the symptoms and worsens the prognosis. About 50 percent of those affected by heart failure have an iron deficiency due to a defect in iron absorption, circulation and excretion in the intestine.
In addition to this iron absorption defect in the intestine, there are other mechanisms that ensure iron absorption into individual cells. However, these were found in heart muscle cells, also known as cardiomyocytes, but were largely not understood.
Broken transport route restored
At this point, the Göttingen research team led by Priv.-Doz. Dr. Antje Ebert, last author of the study and group leader of the “Cardiovascular Cell Biology and Systems Medicine” working group in the Heart Center of the University Medical Center Göttingen (UMG).
The scientists have discovered that patients with a pathological expansion of the heart muscle, a dilated cardiomyopathy, have an iron absorption defect.
This defect affects the absorption of iron into the heart muscle cells and its processing as well as associated metabolic processes, such as the energy supply to the cells.
At the same time, the researchers were able to show that the function of this defective transport pathway can be restored in three different ways: by administering additional iron, a special molecular compound that “repairs” the transport pathway, or using gene editing (CRISPR-Cas), a procedure for targeted modification of the genetic material.
The newly gained knowledge should now be used to research possible therapeutic approaches for those affected.
Central aspect of the new disease mechanism identified
“In order to better understand the mechanisms of iron absorption into cells, we examined cardiac muscle cells in the laboratory that were grown from stem cells. Stem cells are cells that are able to divide in a special way and thus produce copies of themselves and other cells,” explains Dr. Yuanyuan Dai, first author of the study.
These cells were previously obtained from blood samples from people suffering from a hereditary form of pathological heart muscle expansion, dilated cardiomyopathy. In addition, tissue taken during heart operations was examined.
The Göttingen team identified the defect in clathrin-mediated endocytosis in the cells as a central aspect of the new disease mechanism. This was true both in the heart muscle cells produced in the laboratory and in the heart tissue removed from the patients.
“The correction of the hereditary defect in the heart muscle cells produced in the laboratory was achieved by targeted modification of the genetic material through gene editing (CRISPR/Cas). Furthermore, treatment with a specific molecule, Rho activator II, or the administration of a larger amount of iron could rescue the transport route or restore clathrin-mediated endocytosis and the normal function of the heart muscle cells,” says Dr. Ebert.
“With the new findings about the processes involved in iron absorption into the heart muscle cells and their malfunctions in dilated cardiomyopathy, new therapeutic approaches for those affected may become possible in the future,” says Prof. Dr. Gerd Hasenfuß, Director of the Clinic for Cardiology and Pulmonology and Chairman of the UMG Heart Center. (ad)