How does Myocardial Tissue Repair itself?
NEOMY: The Secret of MicroRNAs
Scientific name of the study
Examination of the myocardial regenerative capacity after cardiac surgery in newborns and children with congenital heart disease.
Our somatic cells have an exceptional ability. They continuously repair themselves. Not all of them, though. As soon as we reach adulthood, neural cells and myocardial cells lose this ability to regenerate. As we know from research, for instance in zebrafish and mice, the myocardial tissue of embryos and fetuses has a strong capacity to recover. This seems to be equally true for the myocardial tissue of unborn children and even newborns.
We will investigate this assumption more closely now. If it turned out to be true, new therapy approaches could be followed, which might benefit heart patients up to late adulthood.
Timely Intervention Improves Prognosis
The majority of cases of complex congenital heart disease requires corrective surgery. Today we know: if it takes place in time, many people are able to live a long life with their heart defect. Here, “in time” means: as early as possible. This is due to the fact that the life-saving intervention, which requires using a heart-lung machine, inevitably interferes with the myocardial tissue. This implies the risk of post-surgical myocardial failure. Accordingly, the myocardial tissue’s capacity to recover has a crucial effect on the post-operative course.
Identifying and Assessing Risks
However, existing risks always have to be balanced against each other. Particularly during the transition from the unborn stage to the newborn stage, the maturing cardiac muscle has to master a complex adjustment. For an exact and optimal timing of corrective surgery, we therefore need to know if, in addition to newborns’ myocardial capacity to recover, there is an equally increased myocardial vulnerability. Furthermore, we need to know how the level of recovery and the level of tissue damage behave in relation to each other.
Pilot Study Yields New Starting Points
In contrast to adults with acquired cardiovascular disease, the causes of myocardial failure in newborns and infants with congenital heart disease are largely uninvestigated. However, clinical practice has shown already today that especially newborns with congenital heart disease are able to recover well from corrective open heart surgery. The myocardial capacity to recover can, therefore, be assumed to be even stronger during the neonatal stage than it is in older infants. Our pilot study yielded important scientific starting points for a more thorough investigation.
Results and Publications of the Pilot Study
Change in the activity of the signaling molecules
Within the NEOMY study, the myocardium of newborns and children with congenital heart disease was examined before and after open heart surgery. The study was conducted by a research team led by Prof. Dr. Hashim Abdul-Khaliq and Dr. Martin Poryo at the Saarland University Hospital.
The scientists associated with the Competence Network for Congenital Heart Defects detected significant changes in the activity of the signaling molecules within the cells before and after patients were put on the heart-lung machine. They were able to identify microRNAs that were built increasingly or decreasingly after heart surgery involving a heart-lung machine. The researchers came across hitherto unknown microRNAs in addition to regulatory proteins that are already known to be involved in the development of heart disease.
The new data thus obtained are able to, for the very first time, shed light on the myocardial tissue’s capacity to recover and on corresponding adjustment processes taking place in the myocardial cells during surgery. According to the researchers, new treatment options for myocardial failure are able to be derived from this.
The results of the pilot study are now planned to be tested in a large multicenter study. The National Register for Congenital Heart Defects supports the researchers with collecting donated data and samples in accordance with the highest scientific standards and conforming to data privacy and ethical principles.
Learn more about the study design, material and methods, as well as the background of the study:
Differential expression of microRNAs following cardiopulmonary bypass in children with congenital heart diseases.
Abu-Halima M, Poryo M, Ludwig N, Mark J, Marsollek I, Giebels C, Petersen J, Schäfers HJ, Grundmann U, Pickardt T, Keller A, Meese E, Abdul-Khaliq H
Journal of translational medicine 15, 1, 117, (2017). Show this publication on PubMed.
Barely Pea-sized Tissue from the Cardiac Auricles
For this purpose, we examined the myocardial tissue of newborns and infants with congenital heart disease before and after the life-saving surgery. In doing so, we investigated what happens in the myocardial cells before and after patients are put on the heart-lung machine. The required samples were taken from the tissue of the right auricle of the heart. This does not imply an additional risk to the little patients. The barely pea-sized material gives way to the tube when a patient is put on the heart-lung machine and is usually disposed of in the surgical trash. The procedure is similar with respect to the comparison sample that is taken when the tube is removed. These samples greatly serve basic research. They allow for observing cell damage, cell division and the settlement of stem cells. The patients’ blood samples yield additional information regarding the mechanisms within a cell that lead to cell damage, as well as to the settlement of stem cells, and thus to the myocardial tissue’s recovery.
In a Nutshell
For the Heart to Pump
What are the myocardial cells capable of?
The myocardial cells are the essential part of the myocardium, that is, our heart muscle tissue. The heart muscle, in turn, is the vital motor for our circulation. It provides for our heart’s pump function, involving the myocardial tissue’s continuous contraction and relaxation.
At the same time, an electric conduit system makes the myocardial cells work together according to a mutual rhythm. The impulse for that is emitted by the sinus node, that is, a group of cells within the wall of the right atrium of our heart. Specific neural pathways guide the electric signals to the muscle cells in the atria and heart chambers, thus setting the rhythm of the heartbeat.
Damage to the heart causes the loss of heart muscle cells. This leads to myocardial failure, which is life-threatening. This is due to the heart not pumping properly anymore. The circulation is no longer sufficiently oxygenated.collapse
Reducing Residual Risks, Enabling Therapy Approaches
During the analysis of DNA extracted from the blood, the microRNA comes in. These signal molecules within the DNA are responsible for turning on and off, that is, for starting and stopping important processes within the cell. Analyzing their activity before and after putting a patient on the heart-lung machine reveals the effect that this process has on the myocardial cells and shows how the myocardial cells of newborns and infants with different complex congenital heart disease each recover from that. It can be assumed that, on the one hand, the residual risk of such an intervention is able to be reduced on this basis. At the same time, the findings obtained might even enable us to find out how repair mechanisms can be stimulated by using, for instance, the body’s own stem cells. The initial results of our research in this area point in that direction.
The Next Step
Accordingly, the evidence found in our pilot study has to be investigated on the basis of a larger data and sample collection in the next step. The intended multicenter study involves the collaboration of several pediatric heart centers in Germany. Should such a multicenter study confirm the findings of the pilot study, then this would be an important step forward for the future of many heart patients.
Our patients might be little, but they make a great contribution to all those affected. We would particularly like to thank all patients and their parents who have been supporting the pediatric heart centers’ research by willingly participating in the National Register and by voluntarily donating bio samples and medical data. Only a large number of participants ensures a suitable data basis. It is the essential prerequisite for being able to investigate the causes of myocardial failure and to thus find potential counter-measures.
In charge of the project:
Martin Poryo is a pediatrician at the Klinik für Pädiatrische Kardiologie at the Saarland University Hospital. More
Martin Poryo was born in 1986 and did his residency at the Klinik für Pädiatrische Kardiologie at the Saarland University Hospital. The pediatrician studied medicine at the Saarland University. His research focuses on the somatic development of children with congenital heart disease. For his doctorate, he conducted research on the physical development of children with congenital heart disease using data from the PAN study conducted by the Competence Network for Congenital Heart Defects.
Hashim Abdul-Khaliq is the Director of the Klinik für Kinderkardiologie at the Saarland University Hospital. More
After graduating and earning his doctorate at the Hannover Medical School, Hashim Abdul-Khaliq was initially based at the department of neonatology of the pediatric clinic at Auguste-Viktoria-Klinikum Berlin for three years. After that, he worked with the Department of Congenital Heart Disease – Pediatric Cardiology at Deutsches Herzzentrum Berlin for twelve years. For the past six years, he has been a senior physician there. After qualifying as a professor at the Humboldt-Universität (Berlin), he accepted a call to the Klinik für Kinderkardiologie at the Saarland University Hospital. Hashim Abdul-Khaliq is a member of the German Society of Paediatric Cardiology (DGPK), the German Cardiac Society (DGK) and the Association for European Paediatric and Congenital Cardiology (AEPC). The pediatric cardiologist additionally advises the patient associations as a member of the medical-scientific board of Marfan Hilfe (Deutschland) e. V., as well as of the advisory board of the Bundesverband Herzkranke Kinder e. V. Hashim Abdul-Khaliq is a member and the Chair of the Competence Network for Congenital Heart Defects Executive Board. He also acts as a member of the research network’s Steering Committee.