Single-Cell Dissection of the Immune Response After Acute Myocardial Infarction.
Circ Genom Precis Med
; 17(3): e004374, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38752343
ABSTRACT
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 (95â 995 diseased and 33â 878 control peripheral blood mononuclear cells).RESULTS:
Compared with controls, classical monocytes were increased and CD56dim 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Single-Cell Analysis
Limits:
Aged
/
Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Circ Genom Precis Med
Year:
2024
Type:
Article
Affiliation country:
Netherlands