RWTH Team Involved in Mapping Human Myocardial Infarction

An international team of scientists from Aachen and Heidelberg has published their interdisciplinary research findings in Nature magazine

Heart attacks are not only acute medical emergencies; severe and sometimes fatal side effects can occur even after successful initial treatment. These side effects are caused by the changes in the heart’s size, shape, and function that can occur after a heart attack. How exactly this tissue reorganization – the remodeling of the heart – works is largely unknown. Scientists from Heidelberg University Hospital and Uniklinik RWTH Aachen have now compiled extensive data on the cellular processes during remodeling, turning them into a “map of human myocardial infarction.” Using artificial intelligence, they were able to identify cell states that are characteristic of cardiac remodeling processes.

The cross-disciplinary project team was led by Professor Rafael Kramann from the Institute for Experimental Internal Medicine and Systems Biology and Professor Ivan Costa from the Institute for Computational Genomics, both at Uniklinik RWTH Aachen, as well as Professor Julio Saez-Rodriguez from the Institute for Computational Biomedicine at University Hospital Heidelberg. Their work was funded by the Klaus Tschira Foundation’s Informatics4live initiative, the German Federal Ministry of Education and Research, and the German Research Foundation. The academic journal Nature recently published the research results under the title “A spatial multi-omics map of human myocardial infarction.”

High-Performance Analysis Allows for a Cellular View from All Angles

The team examined tissue samples from healthy individuals and compared them with samples from patients whose hearts had undergone remodeling. The samples – taken from different parts of the heart and at various points in time – were collected by Professor Henrik Milting’s group at the Erich & Hanna Klessmann Institute for Cardiovascular Research and Development in Bad Oeynhausen and by collaborating partner facilities in the Netherlands. The research team analyzed the so-called multi-omic data for individual cells – i.e., properties of the DNA (epigenome) and protein blueprints that are created from the genetic material (transcriptome). They measured the transcriptome at both single-cell and spatial resolution to study the tissue’s structure and damage. In which cell type in which part of the heart is which gene altered during remodeling after a heart attack? How do the cells differ from the cells of healthy individuals, and where are parts of the genes restricted in activity? The datasets of the spatial multi-omic analyses contained countless pieces of information that allowed the team to answer these questions. The result is a map of the heart, which can be used to better trace and understand the consequences of a heart attack. “Such extensive molecular analyses at a sufficient speed have only been possible for a few years now and only thanks to recent technological developments in analytical methods,” says non-tenured associate professor (Privatdozent) Dr. Christoph Kuppe, senior physician at the Institute for Experimental Internal Medicine and Systems Biology at RWTH Aachen Uniklinik.

"Such extensive molecular analyses at a sufficient speed have only been possible for a few years now and only thanks to recent technological developments in analytical methods,"

Artificial Intelligence Makes Patterns Visible in a Sea of Data

The multi-omic data of a single cell is a data set of many gigabytes. This amount of data can no longer be analyzed manually. Therefore, scientists are using artificial intelligence and machine learning methods to analyze the data. A specially developed procedure minutely compares every single value and sample. If it finds combinations of values that only occur in samples from individuals affected by heart disease, the combination is considered typical of the disease. The algorithm identified several cell states and cell types that appear to be characteristic of remodeling. “This is an important first step to helping us better understand the long-term effects of myocardial infarction,“ explains Professor Rafael Kramann from RWTH Aachen Uniklinik. Now the researchers, who have made their heart attack map and software freely available to the scientific community under an open-source license, hope it will serve as a basis for others to find approaches to help prevent and treat the long-term complications of heart attacks.

Following an acute myocardial infarction, three different regions in the heart can be distinguished: The ischaemic zone (IZ, zone with cell death), the border zone (BZ, zone with reversible cell damage), and the remote zone (RZ, healthy part of the post-infarct heart). In the study conducted by Kuppe et al., more than 31 samples from the different zones were used from a total of 23 patients.
Graphic: Kuppe et al. 2022
PD Dr. med. Christoph Kuppe, MHBA, FASN.
Photo: private
Projektleiter Univ.-Prof. Dr. med. Rafael Kramann.
Photo: Uniklinik RWTH Aachen

Kuppe, C., Ramirez Flores, R.O., Li, Z., et al., A spatial multi-omics map of human myocardial infarction. Nature 2022 DOI:10.1038/s41586-022-05060-x