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Ceramides and sphingomyelins in ischemic stroke: a preliminary study

Introduction: Stroke is one of the leading causes of death and permanent disability. Over 80% of strokes are ischemic strokes (ISs). Sphingolipids (SLs) are involved in platelet activation and function influencing key processes in blood clot formation, while serum ceramide levels are considered as biomarkers of adverse cardiovascular disease outcomes. However, the clinical roles of SLs in IS still remain unclear. The aim of this study was to analyse the ceramide (Cer) and sphingomyelin (SM) composition of a blood clot removed from the brain by mechanical thrombectomy in comparison with the serum Cer and SM composition of the same patient and healthy control serum. SL analysis of a blood clot causing IS has not been performed so far. Experimentals: Ceramide and SM extractions were performed using Absolute IDQ p400 kit for targeted metabolomics according to the manufacturer instructions and analysed via Dionex Ultimate 3000 UHPLC system coupled to a Q-Exactive Plus hybrid quadrupole- Orbitrap mass spectrometer through combined LC- MS/MS and FIA-MS/MS analysis. Results: From 9 Cer species analysed in healthy and patient serums, C16:0, C24:0 and C24:1 Cer species were detected and quantified, with C16:0 having the lowest concentrations. C24:0 Cer was detected in much higher concentration in the healthy serum than in the patient serum, while C24:1 Cer was detected in much higher concentration in the patient serum compared to healthy serum. In blood clot sample, the highest concentration of all analysed Cer species was detected compared to serum samples, with C24:1 Cer being the most abundant. From 31 analysed SM species, SM(C16:0) was detected in the highest concentration in serum samples, which was two times higher than the second most abundant SM(C24:1). Short-chain SMs were detected mainly in patient serum sample. In blood clot sample the highest concentration of SM(C16:0) was detected, followed by SM(C24:1), SM(C22:0), SM(C20:0) and SM(C18:0), while short-chain SMs were not detected. Conclusion: We believe that this study performed on larger number of samples will contribute to better understanding of SL roles in blood clot formation and potentially elucidate new candidates for diagnostic and therapeutic biomarkers of ischemic stroke.

Stroke ; Sphingolipids ; Ceramides ; Sphingomyelin ; Mass Spectrometry

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