Heart recovery after heart attack mapped in detail

Researchers at the Hubrecht Institute have 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 field of research closer to developing therapies for better recovery from heart injury. The results were published in Communications biology January 29.

In the Netherlands, an average of 95 people end up in hospital every day because of a heart attack. During a heart attack, the blood supply to part of the heart is blocked, for example due to a blood clot in a coronary artery. Attempts to restore the blood supply are made as soon as possible, also called reperfusion. However, part of the heart has already been without oxygen for some time. Depending on the size and duration of the infarction, this leads to the death of heart muscle cells – also called cardiomyocytes. This can lead to the formation of scar tissue, which is more rigid than normal heart tissue and therefore makes it more difficult for the heart to contract properly. This can lead to deterioration of the pumping function of the heart, which can eventually lead to heart failure.

Cardiac recovery

In other words, it is extremely important to better understand the recovery of the heart after a heart attack and how this leads to the formation of scar tissue. However, much remains unknown. Reason enough for researchers in Eva van Rooij’s laboratory to explore this question further. They studied how the hearts of mice recover at three different times after a heart attack. To this end, they used unique cell sequencing, a technique that allows examination of the RNA of individual cells. The researchers generated a huge data set containing information on the role of different cell types during the recovery process after a heart attack.

Communication network

Therefore, they used the data to map a communication network. Louk Timmer, researcher on the project, explains: “Cells communicate with each other by secreting molecules. These molecules then prompt the recipient cell to take a specific action, which can be important for the recovery process. We have now mapped in great detail how different cells communicate with each other at different times after a heart attack. It had never been done so thoroughly before. This communication network is now documented in a database and accessible to scientists around the world.

Formation of scar tissue

In particular, the role of cardiomyocytes in recovery after a heart attack was still largely unknown, in part due to technical difficulties. However, another recent article from Van Rooij’s lab resolved these obstacles, allowing researchers to specifically study the function of cardiomyocytes in the recovery process. “We noticed that at the very first moment measured after the heart attack, cardiomyocytes secreted increased amounts of a molecule called B2M. Subsequent experiments showed that the secretion of B2M can lead to the activation of so-called fibroblasts – cells responsible for the formation of scar tissue, ”explains Timmer. Cardiomyocytes therefore appear to indirectly stimulate scar tissue production early in the recovery process. “Intuitively, we already thought that cardiomyocytes play an important role in intracellular communication during cardiac recovery and it’s great that we have now been able to confirm this.

Improve the recovery process

When asked about the next steps in this area of ​​research, Timmer stresses the importance of further studies. “Different scientists and experts can use this data, which allows us to better understand the cells and molecules involved in heart recovery and how they communicate with each other. Hopefully we can eventually improve the recovery process so that people end up with less damage after a heart attack. “

Reference: “Unicellular transcriptomics after ischemic injury identifies role of 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, January 29, 2021, Communications 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 in Utrecht.