Immunological signatures in acute and chronic myocardial infarction

Improving the outcome of patients after a heart attack is one of the major challenges of cardiology. This includes a comprehensive understanding of the pathophysiology and early detection of those patients who have a high risk of an unfavorable outcome. Researchers have now used high-tech biomedical and bioinformatics methods to comprehensively map the immune response to myocardial infarction in humans and identify signatures that correlate with the clinical course of the disease. The results of this groundbreaking work were published in the high-ranking scientific journal Nature Medicine.

According to findings from animal studies, the inflammatory reaction plays an important role after an infarction and has a decisive influence on whether the functions of the heart muscle are restored. "A misdirected or excessive immune response can jeopardize the recovery of the heart function," says the lead author of the new study.

The team has analyzed for the first time how the immune system reacts to a heart attack in humans. The researchers examined the blood samples of heart attack patients who were treated and showed different clinical outcomes.

The immune cells in the blood were analyzed cell by cell with regard to their RNA expression profile. RNA is produced when cells translate the information of their genes into proteins - a so-called transcriptome analysis can reveal the current state and characteristics of a cell. In addition, the blood plasma was examined for various substances using protein analyses, which provide details on the inflammatory and other processes. These analyses are among the most modern possible methods, so-called multi-omics methods.

A specific bioinformatics technique (MOFA, for Multi-Omics Factor Analysis) recognized overarching patterns in the mass of data obtained. "This method is ideal for identifying and summarizing many smaller effects that are coordinated in the same direction," says the author. This made it possible to create an atlas of immune responses after a heart attack. "These patterns can explain differences between the clinical and temporal courses of the patients," says the author. This means that certain of these "immune signatures" are associated with a better recovery of heart function, others with a worse one.

MOFA reveals multicellular immune signatures characterized by distinct monocyte, natural killer and T cell substates and immune-communication pathways that explain a large proportion of inter-patient variance. The authors also identify specific factors that reflect disease state or associate with treatment outcome. 

This atlas of the immune response in myocardial infarction is highly relevant for further basic cardiovascular research and potentially indicates that multi-omics analyses of blood samples could be used to predict the clinical course of a heart attack patient. However, the concept of MOFA-based diagnostics in cardiovascular diseases must be tested in further studies - and this is what the Munich researchers intend to do in the coming years.