Researchers from the Hubrecht Institute mapped the recovery of the heart after a heart attack in great detail. They found that heart muscle cells – also called cardiomyocytes – play an important role in intracellular communication after a heart attack. The researchers documented their findings in a database accessible to scientists around the world. This brings the research field one step closer to the development of therapies for improved recovery after heart injury. The results were published in Communication Biology on January 29th.
In the Netherlands, an average of 95 people end up in hospital every day due to 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 are made as soon as possible to restore the blood supply, also known as reperfusion. However, a part of the heart has been without oxygen for some time. Depending on the size and duration of the infarction, it causes heart muscle cells – also called cardiomyocytes – to die. This can lead to the formation of scar tissue, which is tighter than normal heart tissue and thus makes it more difficult for the heart to contract properly. This can cause the pumping function of the heart to deteriorate, which can eventually lead to heart failure.
Shown is an infarcted heart representing green cardiomyocytes (heart muscle cells), red B2M expression, and blue cell nuclei. The area deprived of green is the infarction area. Credit: Louk Timmer © Hubrecht Institute
Heart Recovery
In other words, insight into the recovery of the heart after a heart attack and how it leads to the formation of scar tissue is extremely important. However, many are still unknown. Reason enough for researchers from Eva van Rooij’s laboratory to investigate this further. They studied how the hearts of mice recover at three different times after a heart attack. For this purpose, they used single cell sequencing, a technique that investigates the RNA of individual cells. The researchers generated an enormous dataset with information on 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 communications network. Louk Timmer, researcher on the project, explains: “Cells communicate with each other by secreting molecules. These molecules then cause the recipient cell to take a specific action, which may be important for the repair process. We have now mapped in great detail how different cells communicate with each other at different times after a heart attack. This has never been done so thoroughly. 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 (heart muscle cells), shows red B2M expression and represents blue cell nuclei. Credit: Louk Timmer © Hubrecht Institute
Scar tissue formation
In particular, the role of cardiomyocytes in the recovery after a heart attack was still largely unknown, in part due to technical problems. However, another recent paper from Van Rooij’s laboratory solved these obstacles and enabled the researchers to specifically study the function of cardiomyocytes in the recovery process. ‘We noticed that at the earliest time, measured after the heart attack, cardiomyocytes secrete increasing amounts of a molecule called B2M. Subsequent experiments have shown that the secretion of B2M can lead to the activation of so-called fibroblasts – cells that are responsible for the formation of scar tissue, ”says Timmer. Thus, cardiomyocytes appear to indirectly stimulate scar tissue production early in the repair process. “Intuitively, we already thought that cardiomyocytes play an important role in intracellular communication during heart recovery, and it’s great that we were able to confirm that now.”
Improve recovery process
When asked about the next steps within this field of research, Timmer emphasizes the importance of additional studies. ‘Several scientists and experts can use this data, which enables us to gain a better understanding of the cells and molecules involved in the recovery of the heart and the way in which they communicate with each other. Hopefully we can finally improve the recovery process so that people get less damage after a heart attack. ”
Reference: “Single-cell transcriptomics after ischemic injury identifies a role for B2M in heart 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 group leader at the Hubrecht Institute and professor of molecular cardiology at the University Medical Center Utrecht.