Aims

Platelets play a key role in the pathophysiology of coronary artery disease and patients with enhanced platelet activation are at increased risk to develop adverse cardiovascular events. Beyond reliable cardiovascular risk factors such as dyslipoproteinemia, significant changes of platelet lipids occur in patients with coronary artery disease (CAD).

In this study we investigate the platelet lipidome by untargeted mass-spectrometry, highlighting significant changes between ACS and CCS patients. Additionally, we classify the platelet lipidome, spotlighting glycerophospholipids as key players in ACS patients. Furthermore, we examine the impact of significantly altered lipids in ACS on platelet-dependent thrombus formation and aggregation

Methods and results

In this consecutive study, we characterised the platelet lipidome in a large CAD cohort (n=139) and showed significant changes of lipids between patients with acute coronary (ACS) and chronic coronary syndrome (CCS). We found that among 928, seven platelet glycerophospholipids were significantly upregulated in ACS whereas 32 lipids were downregulated compared to CCS. Further, we were able to transfer the results using flow chamber and impedance aggregometry assay, showing that the glycerophospholipid PC18:0 (PC10:0-8:0), a highly upregulated lipid in ACS patients, significantly enhances ex vivo platelet-dependent thrombus formation and aggregation.

Conclusions

Our results reveal that the platelet lipidome is critically altered in acute coronary syndrome and upregulated lipids embody exclusively glycerophospholipids, indicating a crucial involvement in ACS. Upregulated short chain lipids in ACS, such as PC18:0, critically enhance thrombus formation and platelet aggregation, thus they might promote platelet hyperreactivity in ACS patients.

Translational perspective

Metabolomics, including platelet lipidomics have recently become a new perspective of ongoing research in various diseases. This study reveals a significant change of platelet lipids in ACS and discloses pro-thrombotic effects primarily of upregulated glycerophospholipids. Therefore assessment of platelet lipidome, especially of glycerophospholipids may become useful as potential biomarkers to detect patients at risk for cardiovascular events. Furthermore, understanding changes of the platelet lipidome in the pathophysiology of CAD, alterations may become target of therapeutic approaches, reducing enhanced platelet activation.