TY - JOUR
T1 - Single-Cell Dissection of the Immune Response After Acute Myocardial Infarction
AU - van Blokland, Irene V
AU - Oelen, Roy
AU - Groot, Hilde E
AU - Benjamins, Jan Walter
AU - Pekayvaz, Kami
AU - Losert, Corinna
AU - Knottenberg, Viktoria
AU - Heinig, Matthias
AU - Nicolai, Leo
AU - Stark, Konstantin
AU - van der Harst, Pim
AU - Franke, Lude
AU - van der Wijst, Monique G P
PY - 2024/6
Y1 - 2024/6
N2 - 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.
AB - 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.
U2 - 10.1161/CIRCGEN.123.004374
DO - 10.1161/CIRCGEN.123.004374
M3 - Article
C2 - 38752343
SN - 2574-8300
VL - 17
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
M1 - e004374
ER -