Sphingolipid composition of circulating extracellular vesicles after myocardial ischemia

Abstract

Sphingolipids are structural components of cell membrane, displaying several functions in cell signalling. Extracellular vesicles (EV) are lipid bilayer membrane nanoparticle and their lipid composition may be different from parental cells, with a significant enrichment in sphingolipid species, especially in pathological conditions. We aimed at optimizing EV isolation from plasma and describing the differential lipid content of EV, as compared to whole plasma. As pilot study, we evaluated the diagnostic potential of lipidomic signature of circulating EV in patients with a diagnosis of ST-segment-elevation myocardial infarction (STEMI). STEMI patients were evaluated before reperfusion and 24-h after primary percutaneous coronary intervention. Twenty sphingolipid species were quantified by liquid-chromatography tandem-mass-spectrometry. EV-ceramides, -dihydroceramides, and -sphingomyelins increased in STEMI vs. matched controls and decreased after reperfusion. Their levels correlated to hs-troponin, leucocyte count, and ejection fraction. Plasma sphingolipids levels were 500-to-700-fold higher as compared to EV content; nevertheless, only sphingomyelins differed in STEMI vs. control patients. Different sphingolipid species were enriched in EV and their linear combination by machine learning algorithms accurately classified STEMI patients at pre-PCI evaluation. In conclusion, EV lipid signature discriminates STEMI patients. These findings may contribute to the identification of novel biomarkers and signaling mechanisms related to cardiac ischemia.

Circulating extracellular vesicles are endowed with enhanced procoagulant activity in SARS-CoV-2 infection

“…We have previously shown that the median fluorescence intensity (MFI) detected by flow cytometer for specific EV surface tetraspanins (CD9, CD63 and CD81) from bio-fluids, can be considered a reliable parameter to evaluate the concentration of circulating vesicles in individuals [ 19 , 35 , 37 , 38 ]. CD9/CD63/CD81 MFI as a measure of EV concentration was increased in serum samples from subjects with respiratory symptoms (with or without SARS-CoV-2 infection) compared to HC ( P < 0.001; Fig.…”

“…Particle concentrations were determined by dynamic light scattering using NTA technology (Nanosight, Malvern), as previously described (Fig. S1a) [35] .…”

From Prevention to Disease Perturbations: A Multi-Omic Assessment of Exercise and Myocardial Infarctions

“…We also noted opposite trends when comparing CVD onset results from the literature and our ETT cohort; carnitines have been reported to be downregulated in exercise but upregulated in CVD onset, further reflecting the importance of the shift in energy processes between PMI and exercise [ 69 , 78 ]. These findings are significant for further elucidating the mechanisms of CVD, which we and others have shown reflect drastic changes in the lipidome but are missed from polar metabolomics experiments [ 4 , 48 , 51 , 53 ]. We would, however, like to note that the limited size of our patient study fails to capture sex-based differentiation of CVD onset established previously [ 79 , 80 , 81 , 82 ].…”

“…The previous targeted metabolomic study for both the ETT and PMI cohorts provided great insight into statistically significant polar metabolites [ 26 , 27 , 45 ], but overlooked important nonpolar molecules changing due to each event. The recent annotation of lipids in both CVD and exercise has elucidated the critical roles these molecules serve in each event [ 24 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. Therefore, the inclusion of lipidomic and multi-omic assessments in this manuscript provides a more in-depth profile of ETT and PMI molecular mechanisms.…”

“… Comparison of lipidomic and metabolomic trends for exercise ( left ), cardiovascular disease (CVD) onset ( middle ) and planned myocardial infarction (PMI) model ( right ). Results include a summary of observed results from this and the referenced previous studies noted by citation number in the figure [ 4 , 24 , 51 , 52 , 61 , 69 , 78 ]. …”