Sphingolipid composition of circulating extracellular vesicles after myocardial ischemia.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
30 09 2020
Historique:
received: 22 05 2020
accepted: 16 09 2020
entrez: 1 10 2020
pubmed: 2 10 2020
medline: 29 12 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 32999414
doi: 10.1038/s41598-020-73411-7
pii: 10.1038/s41598-020-73411-7
pmc: PMC7527456
doi:

Substances chimiques

Biomarkers 0
Sphingolipids 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

16182

Subventions

Organisme : Swiss National Science Foundation
ID : IZCOZ0_182948/ 1
Pays : Switzerland

Références

Lemaitre, R. N. et al. Plasma Ceramides and Sphingomyelins in Relation to Heart Failure Risk. Circ. Heart Fail. 12, e005708. https://doi.org/10.1161/CIRCHEARTFAILURE.118.005708 (2019).
doi: 10.1161/CIRCHEARTFAILURE.118.005708 pubmed: 31296099 pmcid: 6629465
Skotland, T. et al. Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers. Eur. J. Cancer 70, 122–132. https://doi.org/10.1016/j.ejca.2016.10.011 (2017).
doi: 10.1016/j.ejca.2016.10.011 pubmed: 27914242
Kurz, J., Parnham, M. J., Geisslinger, G. & Schiffmann, S. Ceramides as novel disease biomarkers. Trends Mol. Med. 25, 20–32. https://doi.org/10.1016/j.molmed.2018.10.009 (2019).
doi: 10.1016/j.molmed.2018.10.009 pubmed: 30477968
Park, J. Y., Lee, S. H., Shin, M. J. & Hwang, G. S. Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction. PLoS ONE 10, e0135228. https://doi.org/10.1371/journal.pone.0135228 (2015).
doi: 10.1371/journal.pone.0135228 pubmed: 26258408 pmcid: 4530944
Goulart, V. A. M. et al. Metabolic disturbances identified in plasma samples from ST-segment elevation myocardial infarction patients. Dis. Markers 2019, 7676189. https://doi.org/10.1155/2019/7676189 (2019).
doi: 10.1155/2019/7676189 pubmed: 31354891 pmcid: 6636502
Poss, A. M. et al. Machine learning reveals serum sphingolipids as cholesterol-independent biomarkers of coronary artery disease. J. Clin. Invest. 130, 1363–1376. https://doi.org/10.1172/JCI131838 (2020).
doi: 10.1172/JCI131838 pubmed: 31743112 pmcid: 7269567
Laaksonen, R. et al. Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol. Eur. Heart J. 37, 1967–1976. https://doi.org/10.1093/eurheartj/ehw148 (2016).
doi: 10.1093/eurheartj/ehw148 pubmed: 27125947 pmcid: 4929378
de Carvalho, L. P. et al. Plasma ceramides as prognostic biomarkers and their arterial and myocardial tissue correlates in acute myocardial infarction. JACC Basic Transl. Sci. 3, 163–175. https://doi.org/10.1016/j.jacbts.2017.12.005 (2018).
doi: 10.1016/j.jacbts.2017.12.005 pubmed: 30062203 pmcid: 6060200
Hilvo, M. et al. Development and validation of a ceramide- and phospholipid-based cardiovascular risk estimation score for coronary artery disease patients. Eur. Heart J. 41, 371–380. https://doi.org/10.1093/eurheartj/ehz387 (2020).
doi: 10.1093/eurheartj/ehz387 pubmed: 31209498
Heusch, G. & Gersh, B. J. The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge. Eur. Heart J. 38, 774–784. https://doi.org/10.1093/eurheartj/ehw224 (2017).
doi: 10.1093/eurheartj/ehw224 pubmed: 27354052
Stanley, W. C. Myocardial energy metabolism during ischemia and the mechanisms of metabolic therapies. J. Cardiovasc. Pharmacol. Ther. 9(Suppl 1), S31-45. https://doi.org/10.1177/107424840400900104 (2004).
doi: 10.1177/107424840400900104 pubmed: 15378130
Llorente, A. et al. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochim. Biophys. Acta 1302–1309, 2013. https://doi.org/10.1016/j.bbalip.2013.04.011 (1831).
doi: 10.1016/j.bbalip.2013.04.011
Verderio, C., Gabrielli, M. & Giussani, P. Role of sphingolipids in the biogenesis and biological activity of extracellular vesicles. J. Lipid Res. 59, 1325–1340. https://doi.org/10.1194/jlr.R083915 (2018).
doi: 10.1194/jlr.R083915 pubmed: 29853528 pmcid: 6071771
Record, M., Silvente-Poirot, S., Poirot, M. & Wakelam, M. J. O. Extracellular vesicles: lipids as key components of their biogenesis and functions. J. Lipid Res. 59, 1316–1324. https://doi.org/10.1194/jlr.E086173 (2018).
doi: 10.1194/jlr.E086173 pubmed: 29764923 pmcid: 6071772
Wubbolts, R. et al. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J. Biol. Chem. 278, 10963–10972. https://doi.org/10.1074/jbc.M207550200 (2003).
doi: 10.1074/jbc.M207550200 pubmed: 12519789
Laulagnier, K. et al. Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem. J. 380, 161–171. https://doi.org/10.1042/BJ20031594 (2004).
doi: 10.1042/BJ20031594 pubmed: 14965343 pmcid: 1224152
Trajkovic, K. et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319, 1244–1247. https://doi.org/10.1126/science.1153124 (2008).
doi: 10.1126/science.1153124 pubmed: 18309083 pmcid: 18309083
Kavaliauskiene, S. et al. Cell density-induced changes in lipid composition and intracellular trafficking. Cell Mol. Life Sci. 71, 1097–1116. https://doi.org/10.1007/s00018-013-1441-y (2014).
doi: 10.1007/s00018-013-1441-y pubmed: 23921715
Lai, R. C. et al. MSC secretes at least 3 EV types each with a unique permutation of membrane lipid, protein and RNA. J. Extracell. Vesicles 5, 29828. https://doi.org/10.3402/jev.v5.29828 (2016).
doi: 10.3402/jev.v5.29828 pubmed: 26928672
Yanez-Mo, M. et al. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles 4, 27066. https://doi.org/10.3402/jev.v4.27066 (2015).
doi: 10.3402/jev.v4.27066 pubmed: 25979354
Brouwers, J. F. et al. Distinct lipid compositions of two types of human prostasomes. Proteomics 13, 1660–1666. https://doi.org/10.1002/pmic.201200348 (2013).
doi: 10.1002/pmic.201200348 pubmed: 23404715
Simonsen, J. B. What are we looking at? Extracellular vesicles, lipoproteins, or both?. Circ. Res. 121, 920–922. https://doi.org/10.1161/CIRCRESAHA.117.311767 (2017).
doi: 10.1161/CIRCRESAHA.117.311767 pubmed: 28963190
Ambrosetti, E. et al. Quantification of circulating cancer biomarkers via sensitive topographic measurements on single binder nanoarrays. ACS Omega 2, 2618–2629. https://doi.org/10.1021/acsomega.7b00284 (2017).
doi: 10.1021/acsomega.7b00284 pubmed: 30023671 pmcid: 6044866
Thery, C., Amigorena, S., Raposo, G. & Clayton, A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Protoc. Cell Biol. 3, 22. https://doi.org/10.1002/0471143030.cb0322s30 (2006).
doi: 10.1002/0471143030.cb0322s30 pubmed: 18228490
Onodi, Z. et al. Isolation of high-purity extracellular vesicles by the combination of iodixanol density gradient ultracentrifugation and bind-elute chromatography from blood plasma. Front. Physiol. 9, 1479. https://doi.org/10.3389/fphys.2018.01479 (2018).
doi: 10.3389/fphys.2018.01479 pubmed: 30405435 pmcid: 6206048
Takov, K., Yellon, D. M. & Davidson, S. M. Comparison of small extracellular vesicles isolated from plasma by ultracentrifugation or size-exclusion chromatography: yield, purity and functional potential. J. Extracell. Vesicles 8, 1560809. https://doi.org/10.1080/20013078.2018.1560809 (2019).
doi: 10.1080/20013078.2018.1560809 pubmed: 30651940
Biemmi, V. et al. Inflammatory extracellular vesicles prompt heart dysfunction via TRL4-dependent NF-kappaB activation. Theranostics 10, 2773–2790. https://doi.org/10.7150/thno.39072 (2020).
doi: 10.7150/thno.39072 pubmed: 32194834 pmcid: 7052909
Cheow, E. S. et al. Plasma-derived extracellular vesicles contain predictive biomarkers and potential therapeutic targets for myocardial ischemic (MI) injury. Mol. Cell Proteomics 15, 2628–2640. https://doi.org/10.1074/mcp.M115.055731 (2016).
doi: 10.1074/mcp.M115.055731 pubmed: 27234505 pmcid: 4974341
Ibanez, B. et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur. Heart J. 39, 119–177. https://doi.org/10.1093/eurheartj/ehx393 (2018).
doi: 10.1093/eurheartj/ehx393 pubmed: 28886621
Platania, C. B. M. et al. Novel ophthalmic formulation of myriocin: implications in retinitis pigmentosa. Drug Deliv. 26, 237–243. https://doi.org/10.1080/10717544.2019.1574936 (2019).
doi: 10.1080/10717544.2019.1574936 pubmed: 30883241 pmcid: 6419690
Kowal, J. et al. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc. Natl. Acad. Sci. USA 113, E968-977. https://doi.org/10.1073/pnas.1521230113 (2016).
doi: 10.1073/pnas.1521230113 pubmed: 26858453
Thery, C. et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell Vesicles 7, 1535750. https://doi.org/10.1080/20013078.2018.1535750 (2018).
doi: 10.1080/20013078.2018.1535750 pubmed: 30637094 pmcid: 6322352
Canals, D., Perry, D. M., Jenkins, R. W. & Hannun, Y. A. Drug targeting of sphingolipid metabolism: sphingomyelinases and ceramidases. Br. J. Pharmacol. 163, 694–712. https://doi.org/10.1111/j.1476-5381.2011.01279.x (2011).
doi: 10.1111/j.1476-5381.2011.01279.x pubmed: 21615386 pmcid: 3111673
Jiang, X. C., Goldberg, I. J. & Park, T. S. Sphingolipids and cardiovascular diseases: lipoprotein metabolism, atherosclerosis and cardiomyopathy. Adv. Exp. Med. Biol. 721, 19–39. https://doi.org/10.1007/978-1-4614-0650-1_2 (2011).
doi: 10.1007/978-1-4614-0650-1_2 pubmed: 21910080
Di Pardo, A. et al. De novo synthesis of sphingolipids is defective in experimental models of huntington’s disease. Front Neurosci. 11, 698. https://doi.org/10.3389/fnins.2017.00698 (2017).
doi: 10.3389/fnins.2017.00698 pubmed: 29311779 pmcid: 5742211
Burrello, J. et al. An extracellular vesicle epitope profile is associated with acute myocardial infarction. J. Cell Mol. Med. https://doi.org/10.1111/jcmm.15594 (2020).
doi: 10.1111/jcmm.15594 pubmed: 32666618
Coumans, F. A. W. et al. Methodological guidelines to study extracellular vesicles. Circ. Res. 120, 1632–1648. https://doi.org/10.1161/CIRCRESAHA.117.309417 (2017).
doi: 10.1161/CIRCRESAHA.117.309417 pubmed: 28495994
Floegel, A. et al. Serum metabolites and risk of myocardial infarction and ischemic stroke: a targeted metabolomic approach in two German prospective cohorts. Eur. J. Epidemiol. 33, 55–66. https://doi.org/10.1007/s10654-017-0333-0 (2018).
doi: 10.1007/s10654-017-0333-0 pubmed: 29181692
Schissel, S. L. et al. Rabbit aorta and human atherosclerotic lesions hydrolyze the sphingomyelin of retained low-density lipoprotein. Proposed role for arterial-wall sphingomyelinase in subendothelial retention and aggregation of atherogenic lipoproteins. J. Clin. Invest. 98, 1455–1464. https://doi.org/10.1172/JCI118934 (1996).
doi: 10.1172/JCI118934 pubmed: 8823312 pmcid: 507573
Meeusen, J. W. et al. Plasma ceramides. Arterioscler. Thromb. Vasc. Biol 38, 1933–1939. https://doi.org/10.1161/ATVBAHA.118.311199 (2018).
doi: 10.1161/ATVBAHA.118.311199 pubmed: 29903731
Hammad, S. M. et al. Blood sphingolipidomics in healthy humans: impact of sample collection methodology. J. Lipid Res. 51, 3074–3087. https://doi.org/10.1194/jlr.D008532 (2010).
doi: 10.1194/jlr.D008532 pubmed: 20660127 pmcid: 2936747
Gardner, A. I. et al. Recombinant acid ceramidase reduces inflammation and infection in cystic fibrosis. Am. J. Respir. Crit. Care Med. https://doi.org/10.1164/rccm.202001-0180OC (2020).
doi: 10.1164/rccm.202001-0180OC pubmed: 32569477
Lydic, T. A. et al. Rapid and comprehensive “shotgun” lipidome profiling of colorectal cancer cell derived exosomes. Methods 87, 83–95. https://doi.org/10.1016/j.ymeth.2015.04.014 (2015).
doi: 10.1016/j.ymeth.2015.04.014 pubmed: 25907253 pmcid: 4615275
Lozanski, G., Berthier, F. & Kushner, I. The sphingomyelin-ceramide pathway participates in cytokine regulation of C-reactive protein and serum amyloid A, but not alpha-fibrinogen. Biochem. J. 328(Pt 1), 271–275. https://doi.org/10.1042/bj3280271 (1997).
doi: 10.1042/bj3280271 pubmed: 9359864 pmcid: 1218917
Corriden, R. et al. Tamoxifen augments the innate immune function of neutrophils through modulation of intracellular ceramide. Nat. Commun. 6, 8369. https://doi.org/10.1038/ncomms9369 (2015).
doi: 10.1038/ncomms9369 pubmed: 26458291 pmcid: 4610010
Jozefczuk, E., Guzik, T. J. & Siedlinski, M. Significance of sphingosine-1-phosphate in cardiovascular physiology and pathology. Pharmacol. Res. 156, 104793. https://doi.org/10.1016/j.phrs.2020.104793 (2020).
doi: 10.1016/j.phrs.2020.104793 pubmed: 32278039
Marchesini, N. & Hannun, Y. A. Acid and neutral sphingomyelinases: roles and mechanisms of regulation. Biochem. Cell Biol. 82, 27–44. https://doi.org/10.1139/o03-091 (2004).
doi: 10.1139/o03-091 pubmed: 15052326
Saddoughi, S. A., Song, P. & Ogretmen, B. Roles of bioactive sphingolipids in cancer biology and therapeutics. Subcell. Biochem. 49, 413–440. https://doi.org/10.1007/978-1-4020-8831-5_16 (2008).
doi: 10.1007/978-1-4020-8831-5_16 pubmed: 18751921 pmcid: 2636716
Meeusen, J. W., Donato, L. J. & Jaffe, A. S. Lipid biomarkers for risk assessment in acute coronary syndromes. Curr. Cardiol. Rep. 19, 48. https://doi.org/10.1007/s11886-017-0863-9 (2017).
doi: 10.1007/s11886-017-0863-9 pubmed: 28432661
Hadas, Y. et al. Altering sphingolipid metabolism attenuates cell death and inflammatory response after myocardial infarction. Circulation 141, 916–930. https://doi.org/10.1161/CIRCULATIONAHA.119.041882 (2020).
doi: 10.1161/CIRCULATIONAHA.119.041882 pubmed: 31992066
Haraszti, R. A. et al. High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources. J. Extracell. Vesicles 5, 32570. https://doi.org/10.3402/jev.v5.32570 (2016).
doi: 10.3402/jev.v5.32570 pubmed: 27863537
Suades, R. et al. Circulating microparticle signature in coronary and peripheral blood of ST elevation myocardial infarction patients in relation to pain-to-PCI elapsed time. Int. J. Cardiol. 202, 378–387. https://doi.org/10.1016/j.ijcard.2015.09.011 (2016).
doi: 10.1016/j.ijcard.2015.09.011 pubmed: 26432487
van der Zee, P. M. et al. P-selectin- and CD63-exposing platelet microparticles reflect platelet activation in peripheral arterial disease and myocardial infarction. Clin. Chem. 52, 657–664. https://doi.org/10.1373/clinchem.2005.057414 (2006).
doi: 10.1373/clinchem.2005.057414 pubmed: 16439610
Castellani, C. et al. Circulating extracellular vesicles as non-invasive biomarker of rejection in heart transplant. J. Heart Lung Transplant. https://doi.org/10.1016/j.healun.2020.06.011 (2020).
doi: 10.1016/j.healun.2020.06.011 pubmed: 32665078
Merrill, A. H. Jr., Sullards, M. C., Allegood, J. C., Kelly, S. & Wang, E. Sphingolipidomics: high-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. Methods 36, 207–224. https://doi.org/10.1016/j.ymeth.2005.01.009 (2005).
doi: 10.1016/j.ymeth.2005.01.009 pubmed: 15894491

Auteurs

J Burrello (J)

Laboratory for Cardiovascular Theranostics, Cardiocentro Ticino Foundation, Via Tesserete 48, 6900, Lugano, Switzerland.

V Biemmi (V)

Laboratory for Cardiovascular Theranostics, Cardiocentro Ticino Foundation, Via Tesserete 48, 6900, Lugano, Switzerland.
Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.

M Dei Cas (M)

Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.

M Amongero (M)

Department of Mathematical Sciences G. L. Lagrange, Polytechnic University of Torino, Torino, Italy.

S Bolis (S)

Laboratory for Cardiovascular Theranostics, Cardiocentro Ticino Foundation, Via Tesserete 48, 6900, Lugano, Switzerland.

E Lazzarini (E)

Laboratory for Cardiovascular Theranostics, Cardiocentro Ticino Foundation, Via Tesserete 48, 6900, Lugano, Switzerland.

S Bollini (S)

Regenerative Medicine Laboratory, Dept. of Experimental Medicine (DIMES), University of Genova, Genova, Italy.

G Vassalli (G)

Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
Laboratory of Cellular and Molecular Cardiology, Cardiocentro Ticino Foundation, Lugano, Switzerland.

R Paroni (R)

Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.

L Barile (L)

Laboratory for Cardiovascular Theranostics, Cardiocentro Ticino Foundation, Via Tesserete 48, 6900, Lugano, Switzerland. lucio.barile@cardiocentro.org.
Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland. lucio.barile@cardiocentro.org.
Institute of Life Science, Scuola Superiore Sant'Anna, Pisa, Italy. lucio.barile@cardiocentro.org.

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