https://doi.org/10.1007/s00392-025-02625-4
1Universitätsklinikum Leipzig Klinik und Poliklinik für Kardiologie Leipzig, Deutschland; 2Universitätsklinikum Leipzig Klinik und Poliklinik für Kardiologie, Forschungslabor Leipzig, Deutschland; 3Herzzentrum Leipzig - Universität Leipzig Klinik für Innere Medizin/Kardiologie Leipzig, Deutschland; 4Städtisches Klinikum Dessau Klinik für Innere Medizin II Dessau-Roßlau, Deutschland
Cardiogenic shock (CS) is the most common cause of in-hospital death in patients with acute myocardial infarction (AMI). A hallmark of CS is the activation of inflammatory signaling. The inflammatory response in individual immune cells is incompletely understood.
Single-cell RNA sequencing (scRNA-seq) was performed to analyze 171,962 peripheral blood mononuclear cells (PBMC) in 7 patients with CS at admission and 24, 48, and 72 hours after percutaneous coronary intervention (PCI). The main findings were validated in a second cohort of patients with CS (n=33) and compared to transcriptome data from patients with AMI without CS (n=38) and healthy controls (n=12).
The blood PBMCs of CS patients showed a rapid increase in monocyte levels, reaching 62.4% within 24 h after PCI, in comparison to 30.4% in controls. Conversely, there was a notable decrease in T-cell levels, from 46.3% in the control group to 25.0% in patients with CS, both was not observed to this extend in AMI without CS. Immune transcriptomes of patients with CS were characterized by an early increase in adrenomedullin (ADM) and thrombospondin 1 (THBS1) and a delayed increase in interleukin-1 alpha (IL1A) and beta (IL1B), which was primarily mediated by monocytes. Monocytes of patients with CS showed a marked upregulation of cardiogenic shock marker 1 (CSM1) expression.
Overexpression of CSM1 in monocytes led to an increase in IL1A- and IL1B-mediated inflammation. Upregulation of CSM1 was confirmed by ELISA in the CS validation cohort (n=33). Explorative analyses showed increased expression of CSM1 in patients with CS on admission compared to healthy controls and suggested an association of CSM1 with 30-day survival in the CS validation cohort.
Monocytes mediate most of the inflammatory response among the circulating blood cells in patients with CS and are characterized by increased expression of CSM1 that activates IL1-mediated inflammation. Better understanding of the cell-specific inflammatory response may improve individualized diagnosis and identify treatment targets in patients with CS.