Researchers at the Hubrecht Institute have mapped the recovery of the heart after a heart attack in great detail. They found that cardiac muscle cells – also called cardiomyocytes – play an important role in intracellular communication after a heart attack. The researchers documented their findings in a database that can be accessed by scientists around the world. This brings the research field a step closer to the development of therapies to improve recovery after cardiac injury. The results were published in Communication Biology on the 29th of January.
In the Netherlands, an average of 95 people end up in the hospital every day because of a heart attack. During a heart attack, the blood supply to a part of the heart is blocked, for example, due to a blood clot in a coronary artery. Attempts to restore blood supply are made as quickly as possible, also known as reperfusion. However, part of the heart has been without oxygen for some time. Depending on the size and duration of the infarction, this causes the heart muscle cells – also called cardiomyocytes – to die. This can result in the formation of scar tissue, which is more rigid than normal heart tissue and therefore makes proper contraction of the heart more difficult. This can cause deterioration of the heart’s pumping function, which can lead to heart failure.
An infarcted heart is shown where green represents cardiomyocytes (cardiac muscle cells), red shows B2M expression and blue represents cell nuclei. The private green area is the infarcted area. Credit: Louk Timmer © Hubrecht Institute
Heart recovery
In other words, knowledge about the recovery of the heart after a heart attack and how it leads to the formation of scar tissue is extremely important. However, much is still unknown. Reason enough for researchers in Eva van Rooij’s laboratory to examine this in more detail. They studied how the rats’ hearts recover at three different times after a heart attack. For that, they used the sequencing of single cells, a technique that makes it possible to examine the RNA of individual cells. The researchers generated a huge set of data with information about the role of different types of cells during the recovery process after a heart attack.
Communication network
Consequently, they used the data to map a communication network. Louk Timmer, researcher for the project, explains: “The cells communicate with each other through the secretion of molecules. These molecules then trigger the recipient cell to perform a specific action, which can be important for the recovery process. We now map in great detail how the different cells communicate with each other at different times after a heart attack. This had never been done so completely before. ”This communication network is now documented in a database and accessible to scientists around the world.
A control heart is shown in which green represents cardiomyocytes (cardiac muscle cells), red shows B2M expression and blue represents cell nuclei. Credit: Louk Timmer © Hubrecht Institute
Scar tissue formation
Especially the role of cardiomyocytes in recovery after a heart attack was still largely unknown, in part because of technical difficulties. However, another recent article by Van Rooij’s laboratory has resolved these obstacles, allowing researchers to specifically study the role of cardiomyocytes in the recovery process. “We realized that at the first point measured after the heart attack, the cardiomyocytes were secreting increased amounts of a molecule called B2M. Subsequent experiments showed that the secretion of B2M can result in the activation of so-called fibroblasts – cells responsible for the formation of scar tissue ”, says Timmer. Cardiomyocytes, therefore, seem to indirectly stimulate the production of scar tissue at the beginning of the recovery process. “Intuitively, we have already thought that cardiomyocytes play an important role in intracellular communication during cardiac recovery and it is great that we have now been able to confirm that.”
Improve the recovery process
When asked about the next steps within this field of research, Timmer emphasizes the importance of further studies. “Several scientists and specialists can use this data, which allows us to better understand the cells and molecules that are involved in the recovery of the heart and the way they communicate. Fortunately, we can improve the recovery process so that people suffer less damage after a heart attack. “
Reference: “Single cell transcriptomics after ischemic injury identifies a role for B2M in cardiac repair” by Bas Molenaar, Louk T. Timmer, Marjolein Droog, Ilaria Perini, Danielle Versteeg, Lieneke Kooijman, Jantine Monshouwer-Kloots, Hesther de Ruiter, Monika M. Gladka and Eva van Rooij, 29 January 2021, Communication Biology.
DOI: 10.1038 / s42003-020-01636-3
Eva van Rooij is a group leader at the Hubrecht Institute and professor of Molecular Cardiology at the University Medical Center Utrecht.