Single-Cell Dissection of the Immune Response After Acute Myocardial Infarction

Irene V van Blokland, Roy Oelen, Hilde E Groot, Jan Walter Benjamins, Kami Pekayvaz, Corinna Losert, Viktoria Knottenberg, Matthias Heinig, Leo Nicolai, Konstantin Stark, Pim van der Harst, Lude Franke, Monique G P van der Wijst*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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BACKGROUND: The immune system's role in ST-segment-elevated myocardial infarction (STEMI) remains poorly characterized but is an important driver of recurrent cardiovascular events. While anti-inflammatory drugs show promise in reducing recurrence risk, their broad immune system impairment may induce severe side effects. To overcome these challenges, a nuanced understanding of the immune response to STEMI is needed.

METHODS: For this, we compared peripheral blood mononuclear single-cell RNA-sequencing (scRNA-seq) and plasma protein expression over time (hospital admission, 24 hours, and 6-8 weeks post-STEMI) in 38 patients and 38 controls (95 995 diseased and 33 878 control peripheral blood mononuclear cells).

RESULTS: Compared with controls, classical monocytes were increased and CD56 dim natural killer cells were decreased in patients with STEMI at admission and persisted until 24 hours post-STEMI. The largest gene expression changes were observed in monocytes, associating with changes in toll-like receptor, interferon, and interleukin signaling activity. Finally, a targeted cardiovascular biomarker panel revealed expression changes in 33/92 plasma proteins post-STEMI. Interestingly, interleukin-6R, MMP9 (matrix metalloproteinase-9), and LDLR (low-density lipoprotein receptor) were affected by coronary artery disease-associated genetic risk variation, disease status, and time post-STEMI, indicating the importance of considering these aspects when defining potential future therapies.

CONCLUSIONS: Our analyses revealed the immunologic pathways disturbed by STEMI, specifying affected cell types and disease stages. Additionally, we provide insights into patients expected to benefit most from anti-inflammatory treatments by identifying the genetic variants and disease stage at which these variants affect the outcome of these (drug-targeted) pathways. These findings advance our knowledge of the immune response post-STEMI and provide guidance for future therapeutic studies.

Original languageEnglish
Article numbere004374
Number of pages12
JournalCirculation. Genomic and precision medicine
Early online date16-May-2024
Publication statusPublished - Jun-2024


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