Researchers from the Hubrecht Institute in the Netherlands say they have mapped the recovery of the heart after a heart attack with great detail. They found that cardiomyocytes play an important role in the intracellular communication after a heart attack.

The team documented their findings in a database that is accessible for scientists around the world. They believe this brings the research field a step closer to the development of therapies for improved recovery after heart injury, a key development in the field of cardiovascular disease.

Their study “Single-cell transcriptomics following ischemic injury identifies a role for B2M in cardiac repair” was published in Communications Biology.

“The efficiency of the repair process following ischemic cardiac injury is a crucial determinant for the progression into heart failure and is controlled by both intra- and intercellular signaling within the heart. An enhanced understanding of this complex interplay will enable better exploitation of these mechanisms for therapeutic use,” write the investigators.

“We used single-cell transcriptomics to collect gene expression data of all main cardiac cell types at different time-points after ischemic injury. These data unveiled cellular and transcriptional heterogeneity and changes in cellular function during cardiac remodeling. Furthermore, we established potential intercellular communication networks after ischemic injury.

“Follow up experiments confirmed that cardiomyocytes express and secrete elevated levels of beta-2 microglobulin in response to ischemic damage, which can activate fibroblasts in a paracrine manner. Collectively, our data indicate phase-specific changes in cellular heterogeneity during different stages of cardiac remodeling and allow for the identification of therapeutic targets relevant for cardiac repair.”

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 the blood supply (reperfusion) are made as soon as possible. However, a part of the heart has already been without oxygen for some time. Depending on the size and duration of the infarction, this causes cardiomyocytes to die, which can result in the formation of scar tissue and is stiffer than normal heart tissue. This makes it more difficult for the heart to properly contract which causes the pumping function of the heart to deteriorate and may eventually lead to heart failure.

While research into the recovery of the heart after an attack and how this leads to the formation of scar tissue is extremely important. However, much is still unknown.

Scientists in the lab of Eva van Rooij, PhD, have been studying how the hearts of mice recover at three different time points following a heart attack. To this end, they used single cell sequencing, which enables the examination of the RNA of individual cells.

The researchers generated a dataset with information about the role of different types of cells during the recovery process after a heart attack. Consequently, they used the data to map a communication network.

“Cells communicate with each other by secreting molecules. These molecules then trigger the recipient cell to take a specific action, which may be important for the recovery process,” says Louk Timmer, researcher on the project. “We have now mapped with great detail how different cells communicate with each other at different time points after a heart attack. That had never been done so thoroughly before.”

Understanding the role of cardiomyocytes in the recovery following a heart attack was still largely unknown, partly because of technical difficulties. However, work from Van Rooij’s lab focused on these obstacles, allowing the researchers to specifically study the function of cardiomyocytes in the recovery process.

“We noticed that at the earliest time point measured after the heart attack, 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 responsible for the formation of scar tissue,” explains Timmer.

Cardiomyocytes thus seem to indirectly stimulate the production of scar tissue early in the recovery process. “Intuitively, we already thought that cardiomyocytes play an important role in intracellular communication during heart recovery and it is great that we have now been able to confirm that,” adds Timmer.

When asked about the next steps within this field of research, Timmer emphasizes the importance of additional studies.

“Various scientists and experts can use this data, which enables us to gain a better understanding of the cells and molecules that are involved in the recovery of the heart and the way they communicate with each other,” he says. “Hopefully, we can eventually improve the recovery process, so that people end up with less damage after a heart attack.”

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