Circulating endothelial cells as a novel biomarker in cardiogenic shock

Background Cardiogenic shock (CS) is a critical medical condition characterised by inadequate cardiac output, leading to insufficient blood flow to meet the body's metabolic demands. Despite advancements in therapeutic strategies, such as device mediated therapy, the mortality rate of CS remains high at approximately 35-50%, and accurate diagnostic and prognostic biomarkers beyond lactate are still lacking. Recently, increasing attention has been given to the role of microvascular dysfunction in CS, which appears to be strongly associated with patient outcomes. A promising area of research in this context is the investigation of circulating endothelial cells (CECs) as potential real-time biomarkers of microvascular damage. CECs have already been implicated in various cardiovascular diseases and may provide valuable insights into both the pathomechanisms and the severity and prognosis of CS. Purpose This study aimed to investigate CECs as a novel biomarker in CS. Furthermore, we sought to enhance the current understanding of the pathomechanisms underlying CS, investigating the pro-thrombotic potential of CECs during microcirculatory dysfunction. Methods Using a standardised flow cytometry protocol with established surface antigens, CECs and their subtypes were detected in peripheral blood samples from patients with CS, non-ST-elevation myocardial infarction (NSTEMI), and stable heart disease. For an unbiased evaluation of the data, an artificial intelligence approach was used using the CITRUS algorithm. To validate these results, a manual gating strategy was applied. Additionally, proteome analysis was performed on immunomagnetically enriched CECs. Finally, the effects of CECs on platelets were investigated by incubating isolated platelets with CECs sorted via fluorescence activated cell sorting (FACS), followed by platelet activation assessment using flow cytometry. Results Across the three study groups, comprising a total of 51 patients, those with CS exhibited significantly increased CEC counts and activation marker expression (Fig. 1-2). Proteome analysis revealed altered levels of β-2-glycoprotein I/apolipoprotein H (Apo-H) in CECs from CS patients, whereas plasma Apo-H levels remained unchanged across groups (Fig. 3-4). Apo-H is a known mediator of platelet function, thus co-incubation of CS CECs and platelets from healthy donors were performed, demonstrating that isolated CECs induce platelet activation ex vivo (Fig. 5). Conclusion CS is associated with a marked increase in blood CEC counts and activation, reflecting microvascular damage. The observed platelet activating effects of CECs may contribute to microcirculatory dysfunction and the heightened thrombotic risk in CS. These findings suggest that CECs are promising candidates both as a prognostic biomarker and as a potential therapeutic target in CS.