Gene treatment protects against heart damage caused by chemotherapy
MHH research team uses telomerase for oxygen detoxification in heart muscle cells.
Status: 27 January 2021
According to an estimate by the Robert Koch Institute, around 510,000 people in Germany were newly diagnosed with cancer last year. Thanks to improved therapies, cancer diseases can be treated more and more successfully - but what causes lasting damage to the tumours often also has severe side effects. The highly effective therapeutics from the group of anthracyclines, for example, prevent cancer cells from dividing. At the same time, however, they promote the formation of free oxygen radicals. These molecules, also known as reactive oxygen species (ROS), are toxic to the cells and damage the heart muscle, among other things.
This also applies to the active substance doxorubicin, which successfully fights cancer cells, but at the same time can cause the death of heart muscle cells (cardiomyocytes). Possible consequences are chronic heart failure or even heart failure. So far, there are hardly any therapeutic approaches against cardiotoxicity in chemotherapy. A research group of the Institute for Molecular and Translational Therapy Strategies of the Hannover Medical School (MHH) has now found an approach to save heart function. The study, led by Institute Director Professor Dr. Dr. Thomas Thum and Dr. Christian Bär, has been funded by the German Research Foundation and published in the journal Molecular Therapy. The first author is Dr Shambhabi Chatterjee.
"Immortality enzyme" frees cells from toxic oxygen compounds
The research group has focused on telomerase. The enzyme protects the ends of the chromosomes, the telomeres, from damage and shortening during cell division. In this way, the cell retains its ability to divide and does not age. This is why telomerase is also known as the "immortality enzyme" and is the subject of anti-ageing research. "In adults, this enzyme is normally switched off," explains Dr Bär. Only in certain cell types, such as blood stem cells, is telomerase still active. In previous studies on mice, the molecular biologist had already found that switching telomerase back on helps against age-related diseases and protects the heart. Since the heart muscle cells in adult mammals do not divide, the research team suspected that telomerase relieves the cells of toxic oxygen radicals by performing an "extra-telomeric task" beyond its function. They used doxorubicin to first increase ROS levels and cause cardiotoxic effects. In the mouse model, the administration of telomerase via a gene shuttle led to the detoxification of cardiac muscle cells, better protection against cell death and thus improved cardiac function. This protective effect could be confirmed in experiments with human heart muscle cells, which had been produced from induced pluripotent stem cells.
Telomerase also protects the "power plants" of the cells
"Gene therapy with telomerase apparently prevents the cell death of the heart muscle cells," says Dr Bär. At the same time, it also protects the mitochondria from the harmful side effects caused by the chemotherapeutic drug. Mitochondria, as the "power plants of the cell", provide the necessary energy for all metabolic processes and also react sensitively to doxorubicin-promoted ROS formation. "When the cell is under stress, telomerase migrates from the cell nucleus to the mitochondria and protects them from damage," the researcher explains. In the heart muscle cells, detoxification of the cell power plants ensures that the heart's pumping function improves. Telomerase gene therapy could be a new strategy to prevent heart damage caused by chemotherapeutic drugs.
After a heart attack: Recognising healing in the image and treating specifically
Leducq Foundation funds a new research network with 5.9 million euros.
Status: 26 January 2021
Hannover Medical School (MHH) is involved in an international research network that is investigating the interplay of inflammation and fibrosis after a heart attack in greater detail and thereby aims to contribute to personalised treatment approaches. The Leducq Foundation, based in France, is funding the project for five years with 5.9 million euros. "The 'Immuno-Fib' research network aims to advance the field of immune cardiology and to investigate how the body's own immune system can contribute to improving the treatment of patients with heart disease," emphasises Professor Dr. Frank Bengel, Director of the MHH Clinic for Nuclear Medicine, whose research group is involved in the network. The project with working groups from St. Louis, Philadelphia, Bar Harbor, London, Aachen, Heidelberg and MHH started on 1 January 2021.
Better understanding of key components in the development of common heart diseases
Carefully regulated inflammatory and fibrosis processes are decisive for a good healing process after a heart attack. However, if there is an excess of inflammation in the damaged heart tissue or too much storage of connective tissue – a fibrosis - this can cause the heart to change unfavourably after the infarction and become less efficient.
The researchers have set themselves the following priorities: They want to better understand the interplay between inflammatory cells and connective tissue-producing cells (fibroblasts) and identify different groups of fibroblasts in the heart. With the help of positron emission tomography (PET), the team wants to image inflammation and fibrosis after a heart attack better and more gently for the patients. This is a long-standing focus of Professor Bengel's research group, in which he works very closely with the team from Professor Dr. Johann Bauersachs' MHH Clinic for Cardiology.
After all, the network is also supposed to be about improved treatments. The scientists are considering the use of fibrosis-dissolving immune cells, so-called CAR-T cells, as a possible treatment, which have so far been more familiar in tumour medicine. In this process, the body's own immune cells are modified in a genetic engineering procedure so that they can recognise and fight certain harmful cells - including an excess of fibroblasts.
About the Leducq Foundation
The Leducq Foundation's mission is to improve human health through international efforts to combat cardiovascular disease and stroke. Based in France, the Foundation supports Transatlantic Networks of Excellence in Cardiovascular and Neurovascular Research to strengthen internationally collaborative basic and translational research. Scientists supported in this programme work together to advance knowledge of cardiovascular and neurovascular disease and improve outcomes for patients.
Experts for big data
New Master's degree course in Biomedical Data Science to start in winter semester 2021/22 at MHH
Status: 25. January 2021
Digitalisation is advancing all the time. In research, diagnostics and therapy, it is becoming increasingly important to be able to handle large amounts of data - for example, in the planning and evaluation of clinical studies. However, there are still too few experts in this field. The new four-semester Master's degree course "Biomedical Data Science" at the MHH, which will start in the winter semester 2021/2022 with a total of 24 students, is intended to change this.
Analysis of large amounts of data is indispensable in individualised medicine
The new degree course is an excellent addition to the university's two already established master's degree courses in biochemistry and biomedicine. It was accredited in autumn 2020 and is funded by the RESIST cluster of excellence. "We are very pleased that the Master's programme can start soon. The evaluation of large amounts of data is also indispensable for individualised medicine, among other things, for people with weak immune systems, for example, for whom we conduct research in our RESIST Cluster of Excellence," says RESIST spokesperson Professor Dr Thomas Schulz, head of the MHH Institute of Virology. Together with Professor Dr. Dr. Michael Marschollek, Head of the MHH Institute for Medical Informatics, he is responsible for the degree course.
Focus of the Master's degree course is on infection biology
The focus of this interdisciplinary and multiprofessional degree course is on the acquisition, maintenance, processing, analysis and communication of data in the field of infection biology. "Students learn to generate and handle large, heterogeneous and complex data sets and to develop and apply IT solutions," explains Professor Marschollek. They can then work as scientists in research institutions or as experts in (research) companies, biotechnological or clinical laboratories as well as government agencies - at the interface of bioscience, medicine and informatics. The degree course also provides the basis for a doctorate. Graduates of a life science bachelor's degree course or a medical study course can apply. The application period runs from 30 April to 15 July 2021. The main language of instruction is German. A large part of the study programme takes place online, although there are also attendance phases of several days at the MHH. For more information, prospective students can visit the programme's homepage www.mhh.de/master-biomeddat and contact Dr. Melina Celik, programme coordinator, phone: 0511 532-5700, email: email@example.com.
RESIST Cluster of Excellence: Research for the Weakest
In the RESIST Cluster of Excellence, under the leadership of the Hannover Medical School (MHH), more than 50 teams from six institutions are researching why people are predisposed to infections in different ways. Their goal is to be able to better protect particularly predisposed people from infections. For more information please visit: www.RESIST-cluster.de.
For more information, please contact Dr. Melina Celik, coordinator of the study course, phone: 0511 532-5700, e-mail: firstname.lastname@example.org.
A symbolic photo for the new Master's programme in Biomedical Data Science at the MHH can be found here. (Copyright: "Karin Kaiser / MHH")
In 2020 almost 3.000 children were born in the MHH
Births largely took place normally despite Corona restrictions.
Status: 21 January 2021
Despite the pandemic, life goes on - probably nowhere is this more evident than in maternity clinics. In the Department of Gynaecology and Obstetrics at Hannover Medical School (MHH), a total of 2.939 children came into the world in 2020. Of these, 1.414 were girls, 1.522 boys and three of unknown sex. Of the total of 2.824 births, 111 were multiple births. With the birth figures, the clinic is roughly at the same level as in previous years. In 2019, 3.071 newborns were registered. The first baby delivered in 2021 was a baby boy, born at 0.56 am on 1st January.
Deliveries under difficult circumstances
The pandemic caused by the coronavirus is also affecting procedures in the delivery room and on the mother-child ward. Nevertheless, Professor Dr. Constantin von Kaisenberg, Head of the Department of Prenatal Medicine and Obstetrics, draws a positive balance: "We got through the past year well and were able to care for our patients around pregnancy and birth almost unchanged." And this despite the fact that midwives, nurses, doctors and physicians have been working under difficult conditions since the outbreak of the pandemic. The expectant mothers and their families also have to cope with restrictions. For example, the person accompanying the woman in labour is not allowed to join her until the final stage of delivery. Visits to the clinic are limited to one hour per day. In addition, only one permanent visitor per pregnant woman is allowed for the entire duration of the stay in the clinic.
Information evenings online
The MHH Department of Gynaecology and Obstetrics is one of the most popular maternity clinics in the region of Hannover. Professor Dr. Peter Hillemanns, Director of the Department of Gynaecology and Obstetrics, attributes this to the wide range of services offered - from care during pregnancy, childbirth and puerperium to support through the first year of the child's life. "Even in the current difficult situation, direct contact with the parents-to-be is important to us," says the clinic director. That is why the clinic has been offering web-based information evenings for future mothers and fathers since August 2020. In a weekly live broadcast, they can find out about topics relating to pregnancy and birth at the MHH.
Current visiting rules for the MHH and especially the Department of Gynaecology and Obstetrics can be found here: https://corona.mhh.de/besuch
State of Lower Saxony funds innovative MHH teaching project
University trains medical students in knowledge and technology transfer for the first time and receives 50.000 euros for a new elective subject.
Status: 15 January 2021
Success for teaching at the Hannover Medical School (MHH): In a call for proposals by the Lower Saxony Ministry of Science and Culture, the university has received 50.000 euros for an innovative teaching project. The money from the "Innovation plus" funding program of the state of Lower Saxony will be used to set up a new teaching module at the MHH. The aim is to develop didactic and digital teaching and learning methods for the new elective subject "From idea to product - knowledge and technology transfer".
For the first time, the teaching project introduces methods for the development of business ideas, transfer processes and strategies into medical studies and is intended to sharpen students' awareness of the possibilities of transferring research results and ideas for the medical care of patients to the economy and society.
"Especially in medicine, it is elementary that science and the health sector work hand in hand. Only the transfer of research results to patient care opens the door for new examination and treatment methods that can save lives," explains Björn Thümler, Lower Saxony Minister for Science and Culture. "I am very pleased that the MHH also wants to further advance this area in teaching."
Knowledge and technology transfer will become part of medical studies
The prospective medical students will gain insight into successful examples of translation and acquire the necessary tools to be able to introduce ideas for medical care and therapy into the health system after their studies. "We have already trained researchers and students in the life sciences in knowledge and technology transfer and now we would like to be one of the first universities in Germany to pass on this knowledge in medical studies," explains Professor Dr. Dr. Thomas Thum, Head of the MHH Institute for Molecular and Translational Therapy Strategies and founder of Cardior Pharmaceuticals GmbH, who is responsible for teaching.
Together with the MHH's Research Promotion, Knowledge and Technology Transfer (FWT) staff unit, on whose initiative the project came about, Professor Thum will contribute his knowledge as an expert in this field. "The earlier we start imparting knowledge, the greater the chance that good ideas will ultimately be of benefit for the patient," says Christiane Bock von Wülfingen, head of the FWT staff unit. The new teaching offer for students from the 4th academic year onwards will start in summer.
Prof. Thum has joined Fraunhofer ITEM as institute director
Status: 12 January 2021
On January 1, 2021, Prof. Thomas Thum joined the Fraunhofer Institute for Toxicology and Experimental Medicine ITEM in Hannover as new institute director. He will henceforth manage the institute together with Prof. Norbert Krug, who has been director of Fraunhofer ITEM for the past four years. In addition, Prof. Thum has accepted the call to a full professorship in “Translational validation of innovative therapeutics” at the nearby Hannover Medical School (MHH), a position that is linked to the Fraunhofer Institute directorship.
For many years, the specialist in cardiology and bioscience has been doing research on the functional characterization and translational potential of novel therapeutic RNA strategies targeting cardiovascular diseases, most recently at MHH as professor and director of the Institute of Molecular and Translational Therapeutic Strategies. With over 400 publications, he is a world-renowned expert in this subject area. At present, Prof. Thum’s research activities are focused on the diagnosis and therapy of organ dysfunction and fibrosis, gene therapy approaches as well as mechanisms of COVID-19 and appropriate therapeutic strategies with regard to the cardiovascular system and beyond. He has founded the successful biotech company Cardior Pharmaceuticals GmbH as a spin-off from MHH and has filed and licensed numerous patents in the areas of RNA diagnostics and therapy.
Broader focus: the heart complementing the lung
Prof. Thum’s research focus ideally complements the existing focuses of Fraunhofer ITEM in the field of lung and airway research. Besides chronic lung conditions, heart failure in particular is playing an important role, a worldwide increasing disease with a prevalence of currently up to 60 million patients and one of the main reasons for hospitalization. Especially due to the COVID-19 pandemic and the long-term consequences of this disease, the number of patients with heart failure is likely to increase significantly. Despite the growing importance of this medical condition, however, there has been little progress in the research on heart failure over the past 20 years.
“We are pursuing a completely novel approach,” says Prof. Thum. “Using high-throughput methods and platform technologies, we are seeking RNA-based strategies as effective therapies for heart disease. We have already made remarkable progress in this area and industry is showing strong interest. For Fraunhofer ITEM, enhancing its research focus to include also the organ system heart is both a challenge and a great opportunity. In past collaborative projects, we already identified promising synergies and potential. I am very much looking forward to further expanding these together now!”
Benefit for translational medicine
While Professor Thum's work in the context of his new professorship at MHH will have a primary focus on basic research, his Fraunhofer activities will be more of a translational and application-oriented nature, in line with the Fraunhofer model. "We are very pleased that Prof. Thum, who is an outstanding researcher, will further expand and strengthen the synergies between MHH and Fraunhofer ITEM," says MHH president Prof. Michael Manns. These further strengthened ties with MHH and the intensified translation from bench to bedside will be a benefit to Fraunhofer's innovative strength in health research and eventually also to mankind. Prof. Thum has already successfully advanced several molecules identified in his laboratories to the stage of clinical use in humans.
“Key criteria for the success of a Fraunhofer Institute include not only scientific success, but also transfer competence. This is why I am very happy to be able to shape the future of Fraunhofer ITEM together with Prof. Thum, to provide decisive scientific impetus and translate it into applications,” emphasizes Prof. Krug. “The institute’s continued development is essential in making our vision – being pioneers for sustainable health – come true.”
Both institute directors will manage Fraunhofer ITEM in tandem. Prof. Thum will be in charge of the institute’s divisions of Preclinical Pharmacology and Toxicology, Chemical Safety, and Translational Biomedical Engineering. In addition, he will set up a new research unit “Cardiovascular Research” at the institute. Prof. Krug will continue to be in charge of the division of Clinical Airway Research, the Braunschweig-based division of Pharmaceutical Biotechnology and the Regensburg-based division of Personalized Tumor Therapy.
Read more about Prof. Thomas Thum:
About Fraunhofer ITEM:
The Fraunhofer Institute for Toxicology and Experimental Medicine ITEM is one of 74 institutions of the Fraunhofer-Gesellschaft, Europe's leading organization for applied research. Protecting man from health hazards in our industrialized world and contributing to the development of novel therapeutic approaches are the aims Fraunhofer ITEM is pursuing with its contract research. The institute’s R&D portfolio comprises three business units, with a focus on airway research: Drug Development, Chemical Safety and Assessment, and Translational Biomedical Engineering. In addition, the institute’s Regensburg-based division does research on personalized tumor therapy. With a staff of approximately 380 at its locations in Hannover, Braunschweig and Regensburg, the institute cooperates in projects with industry, service providers and universities that drive economic development and serve the wider benefit of society.
Martina Saurin is the new Vice-President of the MHH
Experienced business graduate heads the Department of Business Management and Administration
Status: December 30, 2021
Hannover Medical School (MHH) has a new Vice-President: Martina Saurin, a long-standing player in the healthcare sector and in various management positions, heads the Department of Business Management and Administration in the University's Presidential Board. "Ms Saurin's vast experience in various management positions in university medicine will be of great benefit to the MHH," explains Lower Saxony's Minister of Science Björn Thümler.
"We are pleased to have gained an excellently qualified and networked Vice-President for Business Management and Administration for our Executive Board in Ms Saurin. Ms Saurin will strengthen us in the Executive Board and be able to provide decisive impetus on the path to a successful future for the MHH," emphasises MHH President Professor Dr Michael Manns. "In addition, she brings with her expertise with regard to the upcoming construction projects, which will significantly determine the further development of the MHH in the coming years."
Change from UKE to MHH
The business graduate studied in Kiel and gained professional experience in Hamburg and Rostock - not only in the hospital sector, but also in auditing and industry. In the past four years, Martina Saurin worked at the UKE as Business Unit Manager Finance and Deputy Commercial Director, and from mid-2017 to the end of 2018 as a provisional member of the Executive Board.
"Since my first experiences at the University Medical Center Rostock, I have been fascinated by the complexity of university medical facilities. The responsibility of taking on difficult cases, ensuring the education of students and at the same time driving the future of medicine through research is particularly high under today's circumstances," says the 56-year-old. "Keeping an eye on economic efficiency in the process is my challenge, which I am happy to take up here in Hannover."
Martina Saurin succeeds Andrea Aulkemeyer, who is following a professional reorientation after six years at the MHH.
MHH President is one of the most cited researchers worldwide
Status: November 24, 2020
Another success for Professor Dr. Michael Manns: As in previous years, the internist and gastroenterologist is once again on the list of the most frequently cited scientists worldwide. The list of the "Highly Cited Researchers 2020" of the U.S. company Clarivate Analytics comprises around 6200 names in 22 disciplines. This makes the MHH President one of the most influential minds in research. He was already listed as a Highly Cited Researcher in 2019, 2018 and 2017. "I am very pleased to receive this award as recognition of my research work," says the award-winning liver and hepatitis researcher.
Professor Manns is listed in the "Cross-Field" category. It covers researchers who have an interdisciplinary influence on science - i.e. beyond their actual field of work. The "Web of Science", in which all citations of scientific studies are collected, serves as the basis for the list of best researchers. For the evaluation, the scientific publications of the years 2009 to 2019 were analyzed and it was examined how often the work of the researchers was cited by colleagues from the scientific community in their publications. But not only the number of citations is an indicator of the scientific influence. The reputation of the scientific journal in which publications were made is also included in the evaluation.
The current list includes about 6200 researchers from the natural and social sciences and medicine, including 345 from Germany. The evaluation is based on data and analyses from the "Institute for Scientific Information" at Clarivate and takes into account the one percent of publications that were cited most frequently within a specific discipline within the specified period. The "Who's Who" of science also provides information on the countries and research institutions in which the scientific elite work.
Further information is available from Professor Dr. Michael P. Manns, email@example.com, telephone (0511) 532-6000.
The complete list of "Highly Cited Researchers 2020" and further information is available on the Web of Science website.
MHH starts COVID-19 therapy study with blood plasma from convalescents
Status: November 17, 2020
There is still no really promising drug against COVID-19. One option is the treatment with blood plasma of people who have already survived this disease - with so-called convalescent plasma. Antibodies against the virus contained in blood serum could support the immune defence of infected persons in their fight against SARS-CoV-2. Now a new clinical study is to clarify how well this passive immunization actually works. Under the direction of Professor Dr. Rainer Blasczyk, Head of the Institute for Transfusion Medicine and Transplant Engineering at Hannover Medical School (MHH), researchers from the MHH, the clinics in Dortmund, Krefeld, Magdeburg and Essen as well as the Siloah Hospital in Hannover are investigating whether the therapeutic transmission of antibodies against SARS-CoV-2 can prevent severe courses of COVID-19 disease. The multi-center study, entitled COMET, starts this Tuesday at the MHH and is funded by the German Federal Ministry of Health (BMG) with approximately 3.34 million Euros.
Preventing severe disease progression
Although convalescent plasma is already being used in clinics against COVID-19 - due to the special situation in times of a pandemic, an exception is provided for in the German Medicines Act. However, there is still no proof of efficacy for this form of therapy. This is now to be provided by clinical studies. Two of these are already underway, but are investigating plasma administration in critically ill patients. In contrast, 340 COVID-19 patients between the ages of 18 and 75 years, who have a rather mild course of disease, are participating in the COMET study: Although they need to be treated in a hospital, they do not yet require ventilation. Passive immunization with the donated pathogen-specific antibodies could thus prevent lighter COVID-19 patients from having to be transferred to the intensive care unit during their hospital stay. "We believe that the earlier we use adoptive immunotherapy, the better," says Professor Blasczyk. The transfusion physician is therefore convinced that prophylactic treatment - for example for non-infected high-risk patients - could even prevent the disease completely.
Donor plasma is being closely examined
The study participants are divided into two groups. One group will receive 250 milliliters of donor plasma on two consecutive days, the other group will not receive plasma as a comparison group. In order to ensure that the plasmas contain sufficient anti-SARS-CoV-2 active antibodies on the one hand and no potentially harmful substances on the other, the donor plasma is first tested in the laboratories at the MHH Institute of Virology and TWINCORE. "Plasma has two advantages: It is safe and is available within a short time", emphasises Professor Blasczyk. The COMET study runs until the end of next year. However, the transfusion physician hopes to be able to present results much earlier.
SARS-CoV-2: How many neutralizing antibodies are needed for protection?
Status: November 05, 2020
Infections with the coronavirus SARS-CoV-2 can progress in very different ways: While some people have no symptoms, others fall seriously ill. An important question that often arises after surviving an infection is the extent to which neutralizing antibodies against the virus have been produced, as only these can protect the body from re-infection.
To detect neutralizing antibodies, infectious viruses, living cells and laboratories with a high safety standard are usually required. Due to the very high requirements of this test, only very limited blood samples from convalescent patients can be tested for the presence of neutralizing antibodies in blood serum. "To change this, we have developed a very simple and rapid procedure that requires only two proteins that are important for the infection process: The spike protein of the virus and the protein ACE2 of the cell. If the binding of the spike protein to ACE2 is suppressed by serum antibodies, these antibodies are also able to prevent the infection of cells with the virus," says Dr. Berislav Bosnjak from the Institute of Immunology at the Hannover Medical School (MHH). He is first author of the study now published in the journal Cellular and Molecular Immunology.
New test can be further developed for the clinic
"With the help of the test developed by us it is now possible to examine a large number of patients over a longer period of time in clinical studies and to determine how long these so important antibodies are present in the blood", emphasizes Professor Dr. Reinhold Foerster, head of the MHH Institute of Immunology and senior author of the study. The new method is still only available for research. However, it could potentially be adapted so that it can be used for routine tests in the future.
With both the previous and the new method, the team was able to show that about ten percent of SARS-CoV-2 infected persons had no protective antibodies in their blood. This primarily affected infected persons who showed only mild symptoms and were only ill for a short time. On the other hand, the patients developed many antibodies that had stronger symptoms and were ill for longer periods of time. "It is still unclear how much neutralizing antibody is needed to protect convalescents from re-infection. But with the test now available, it will be possible to answer this important question more quickly," says Professor Förster.
Other staff members of the MHH Institute of Immunology, the Institute of Virology and the Institute of Transfusion Medicine and Transplant Engineering were involved in the study. Teams of the Clinic for Rheumatology and Immunology as well as the Clinic for Pneumology and the German Primate Center in Göttingen also participated.
The research project "Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods" was funded by the Corona Research Funding Program of Lower Saxony, the Cluster of Excellence RESIST and the Collaborative Research Center SFB 900 of the German Research Foundation.
Keyword: Neutralizing antibodies
Of the antibodies that people have in their blood after successfully surviving an infection with SARS-CoV-2, the neutralizing antibodies are particularly effective. They are a particularly important group of antibodies because they dock to the virus and prevent the virus from entering and multiplying in human cells. Neutralizing antibodies can therefore switch off the virus.
You can find the original paper here.
How the heart really beats - MHH researchers refute textbook theory
Our heart beats unceasingly and of its own accord - but not always at the same speed. MHH researchers have now investigated how the heartbeat is regulated.
Last update: November 04, 2020
Our heart is a high-performance engine. Without a break, the hollow muscle pumps blood through the body and ensures that all cells are supplied with oxygen. In a healthy adult, this happens about 60 to 80 times every minute, or about three billion heartbeats in the course of a lifetime. Even outside the body, the heart can do its work at a constant rate. This is because the heartbeat is created in the heart itself. Specialized heart muscle cells in the right atrium form the so-called sinus node as pacemaker cells.
Whether our heart beats faster during exertion or slower at rest is regulated by the autonomous, so-called autonomic nervous system. A research group led by Professor Dr. Christian Wahl-Schott, Head of the Institute of Neurophysiology at the Hannover Medical School (MHH), in cooperation with the Institute of Pharmacology for Natural Sciences at the Ludwig Maximilian University of Munich, has now investigated in more detail how this mechanism works, thereby refuting a common doctrine. The joint study has now been published in the renowned journal Nature Communications.
Ion channels stabilize the heart rhythm
Pacemaker cells are electrically active. Special ion channels guide positively charged particles through the cell membranes in the sinus node. These HCN channels (hyperpolarisation-activated cyclic nucleotid-gated cation channels) are modulated by a specific signal molecule, cAMP (cyclic adenosine monophosphate). "For decades, the hypothesis was valid that a higher cAMP concentration increases the heart rate, a lower one slows down the heartbeat," explains Professor Wahl-Schott. But contradictory observations from practice increasingly cast doubt on the theory. To test the old assumption with molecular biology methods, the research team genetically modified the binding site for cAMP in the HCN channels in the heart of mice and prevented the messenger substance from switching on the channels. "The mice have developed an irregular heartbeat as a result," says the physician. "Contrary to previous assumptions, however, the heart rhythm could still be regulated.
Since the binding site between messenger substance and ion channel is very similar in mice and humans, the results of the study can be transferred from animal models to humans: They show that especially the ion channels of the subunit HCN4 stabilize the heart rhythm and prevent excessive reactions of the autonomous nervous system. Individual pacemaker cells even pause for minutes and do not fire any electrical signals to the heart muscle cells at all, thus directly regulating the heart rate. "These findings are important in order to better understand the mechanisms of heart diseases such as rhythm disturbances or the sick sinus syndrome in the future," emphasizes Professor Wahl-Schott. However, the new observations on the heartbeat's clock could also have an impact on the treatment of heart diseases - for example, when using drugs that specifically influence the HCN channels.
- The original publication "cAMP-dependent regulation of HCN4 controls the tonic entrainment process in sinoatrial node pacemaker cells" can be found here.