Written by Miyako Rogers, Science Writer
In a new study published in Nature, researchers have used different multi-omic tools to create a first-of-its-kind map of myocardial infarction. By describing changes in the transcriptome and epigenome that are associated with injury, repair and remodelling processes, this map reveals novel insights into late-stage myocardial infarction pathology. This map will also serve as an invaluable resource for future researchers to investigate pathological processes and therapies for cardiac disease.
Creating the map
Myocardial infarction is a leading cause of death globally. Advances have been made in treating myocardial infarction at the early stages. However, little is known about the later stages, and as a result unless heart disease is detected early, mortality rates are high. In this study, researchers analysed the single-cell gene expression, chromatin accessibility and spatial transcriptomic profiles of human heart tissues from 23 individuals. Researchers then integrated and clustered the different multi-omics studies they performed to build a comprehensive map of myocardial infarction.
This study revealed knew insights into remodelling and repair processes in the late stages of myocardial infarction. This map characterised differences between healthy functioning parts of the heart to ischaemic and damaged tissue by analysing the genetic features associated with inflammatory and fibrotic remodelling events. Furthermore, they investigated how these remodelling events create changes in the vasculature and architecture of cardiac tissue.
This map also identified potential regulators and cardiac cells and fibroblasts, as well as differences in different cell states and subtypes of cardiac, endothelial, myeloid cells and fibroblasts. From this data they also revealed a border zone, which separates injured and healthy cardiac tissue. Further analysis showed that in this border zone there was marked upregulation of the specific genes such as ANKRD1, which is a known mediator of cardiac cell responses to stress. The map also showed that remodelling of tissues in the late stages of myocardial infarction is driven by fibrosis and identified upregulation of specific genes involved in this process.
The insights from this study alone further our understanding of myocardial infarction, but this map will also be a publicly available resource. Future studies could use this atlas of comprehensive information to do further analyses into the spatial gene expression and gene-regulatory processes and networks in the human heart.