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Sphingolipid composition of circulating extracellular vesicles after myocardial ischemia


Burrello, J; Biemmi, V; Dei Cas, M; Amongero, M; Bolis, S; Lazzarini, E; Bollini, S; Vassalli, G; Paroni, R; Barile, L (2020). Sphingolipid composition of circulating extracellular vesicles after myocardial ischemia. Scientific Reports, 10:16182.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Cardiocentro Ticino
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Multidisciplinary
Uncontrolled Keywords:Multidisciplinary
Language:English
Date:1 December 2020
Deposited On:18 Nov 2020 10:36
Last Modified:01 Dec 2020 14:20
Publisher:Nature Publishing Group
ISSN:2045-2322
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41598-020-73411-7
PubMed ID:32999414

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