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Sphingolipids as Biomarkers of Disease

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Bioactive Ceramides in Health and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1159))

Abstract

Despite the advancements in modern medicine, there are still difficulties in diagnosing common illnesses. The invasiveness and price of the tests used to follow up certain diseases can be a barrier to proper patient follow-up. Sphingolipids are a diverse category of lipids. They are structural molecules in cell membranes and signaling molecules involved in the regulation of crucial cell functions, including cell growth, differentiation, proliferation and apoptosis. Recent research has shown that abnormal sphingolipid metabolism is associated with genetic and metabolic disease processes. Given their crucial role to maintain homeostasis within the body, sphingolipids have been investigated as potential biomarkers to predict disease in the population. Here we discuss how sphingolipids levels are altered in different diseases, thus illustrating their possible use as diagnostic and prognostic biomarkers for disease.

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Abbreviations

ABCA1:

ATP binding cassette family A protein 1

ACS:

acute coronary syndrome

AD:

Alzheimer disease

ASMase:

sphingomyelinase

BMI:

body mass index

BNP:

B-type natriuretic peptide

C1P:

ceramide 1-phosphate

CAD:

coronary artery disease

CKD:

chronic kidney disease

COPD:

Chronic obstructive pulmonary disease

CSF:

cerebrospinal fluid

DAG:

diacylglycerols

DHC:

dihydroceramides

DHSM:

dihydrosphingomyelin

FA:

fluorescent angioscopy

FFA:

free fatty acids

Gb3:

globotriaosylceramide

HbA1c:

hemoglobin A1c

HCC:

hepatocellular carcinoma

HDL:

high-density lipoprotein

HF:

heart failure

HOMA-IR:

homeostatic model assessment for assessing β-cell function and insulin resistance from fasting glucose and insulin concentrations

HSAN1:

hereditary sensory and autonomic neuropathy type 1

HxCer:

hexosylceramide

IDL:

intermediate-density lipoprotein

IMT:

intima media thickness

LacCer:

lactosylceramide

LDL:

low-density lipoprotein

LVEF:

left ventricular ejection fraction

LysoGb3:

globotriaosylsphingosine

MACE:

major adverse cardiovascular event

MCI:

Mild Cognitive Impairment

MELD:

Model for End-Stage Liver Disease

MI:

myocardial infarction

MMSE:

Mini-Mental State examination

NT-proBNP:

N-terminal-prohormone BNP

NYHA:

New York Heart Association

PTSD:

post-traumatic stress disorder

S1P:

sphingosine 1-phosphate

SA1Ps:

sphinganine 1-phosphate

SLE:

systemic lupus erythematous

SM:

Sphingomyelin

SPT:

serine palmitoyltransferase

TG:

triglycerides

TNF-α:

tumor necrosis factor-α

TNM:

TNM Classification of Malignant Tumors

VAD:

ventricular assist device

VLDL:

very low-density lipoprotein

References

  • Aerts JM, Groener JE, Kuiper S, Donker-Koopman WE, Strijland A, Ottenhoff R, van Roomen C, Mirzaian M, Wijburg FA, Linthorst GE, Vedder AC, Rombach SM, Cox-Brinkman J, Somerharju P, Boot RG, Hollak CE, Brady RO, Poorthuis BJ (2008) Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci 105(8):2812–2817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahmed FS, Jiang XC, Schwartz JE, Hoffman EA, Yeboah J, Shea S, Burkart KM, Barr RG (2014) Plasma sphingomyelin and longitudinal change in percent emphysema on CT. The MESA lung study. Biomarkers 19(3):207–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahrnsbrak R, Bose J, Hedden SL, Lipari RN, Lee EP (2016) Key substance use and mental health indicators in the United States: results from the 2016 national survey on drug use and health. Substance Abuse and Mental Health Services Administration (SAMHSA) under Contract No. HHSS283201300001C with SAMHSA, U.S. Department of Health and Human Services (HHS). Retrieved from https://www.samhsa.gov/data/sites/default/files/NSDUH-FFR1-2016/NSDUH-FFR1-2016.htm

  • Al Gadban MM, German J, Truman JP, Soodavar F, Riemer EC, Twal WO, Smith KJ, Heller D, Hofbauer AF, Oates JC, Hammad SM (2012) Lack of nitric oxide synthases increases lipoprotein immune complex deposition in the aorta and elevates plasma sphingolipid levels in lupus. Cell Immunol 276(1–2):42–51

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Alberg AJ, Armeson K, Pierce JS, Bielawski J, Bielawska A, Visvanathan K, Hill EG, Ogretmen B (2013) Plasma sphingolipids and lung cancer: a population-based, nested case-control study. Cancer Epidemiol Biomark Prev 22(8):1374–1382

    Article  CAS  Google Scholar 

  • Ammit AJ, Hastie AT, Edsall LC, Hoffman RK, Amrani Y, Krymskaya VP, Kane SA, Peters SP, Penn RB, Spiegel S, Panettieri RA Jr (2001) Sphingosine 1-phosphate modulates human airway smooth muscle cell functions that promote inflammation and airway remodeling in asthma. FASEB J 15(7):1212–1214

    Article  CAS  PubMed  Google Scholar 

  • Arana L, Gangoiti P, Ouro A, Trueba M, Gómez-Muñoz A (2010) Ceramide and ceramide 1-phosphate in health and disease. Lipids Health Dis 9:15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Auray-Blais C, Ntwari A, Clarke JT, Warnock DG, Oliveira JP, Young SP, Millington DS, Bichet DG, Sirrs S, West ML, Casey R, Hwu WL, Keutzer JM, Zhang XK, Gagnon R (2010) How well does urinary lyso-Gb3 function as a biomarker in Fabry disease? Clin Chim Acta 411(23–24):1906–1914

    Article  CAS  PubMed  Google Scholar 

  • Auray-Blais C, Boutin M, Gagnon R, Dupont FO, Lavoie P, Clarke JT (2012) Urinary globotriaosylsphingosine-related biomarkers for Fabry disease targeted by metabolomics. Anal Chem 84(6):2745–2753

    Article  CAS  PubMed  Google Scholar 

  • Becker S, Kinny-Köster B, Bartels M, Scholz M, Seehofer D, Berg T, Engelmann C, Thiery J, Ceglarek U, Kaiser T (2017) Low sphingosine-1-phosphate plasma levels are predictive for increased mortality in patients with liver cirrhosis. PLoS One 12(3):e0174424

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bejaoui K, Wu C, Scheffler MD, Haan G, Ashby P, Wu L, de Jong P, Brown RH Jr (2001) SPTLC1 is mutated in hereditary sensory neuropathy, type 1. Nat Genet 27(3):261–262

    Article  CAS  PubMed  Google Scholar 

  • Bergman BC, Brozinick JT, Strauss A, Bacon S, Kerege A, Bui HH, Sanders P, Siddall P, Kuo MS, Perreault L (2015) Serum sphingolipids: relationships to insulin sensitivity and changes with exercise in humans. A J Physiol Endocrinol Metab 309(4):E398–E408

    Article  CAS  Google Scholar 

  • Bertea M, Rütti MF, Othman A, Marti-Jaun J, Hersberger M, von Eckardstein A, Hornemann T (2010) Deoxysphingoid bases as plasma markers in diabetes mellitus. Lipids Health Dis 9:84

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bowler RP, Jacobson S, Cruickshank C, Hughes GJ, Siska C, Ory DS, Petrache I, Schaffer JE, Reisdorph N, Kechris K (2015) Plasma sphingolipids associated with chronic obstructive pulmonary disease phenotypes. Am J Respir Crit Care Med 191(3):275–284

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Buie JNJ, Hammad SM, Nietert PJ, Magwood G, Adams RJ, Bonilha L, Sims-Robinson C (2019 May 8) Differences in plasma levels of long chain and very long chain ceramides between African Americans and whites: an observational study. PLoS One 14(5):e0216213

    Article  PubMed  PubMed Central  Google Scholar 

  • Burla B, Arita M, Arita M, Bendt AK, Cazenave-Gassiot A, Dennis EA, Ekroos K, Han X, Ikeda K, Liebisch G, Lin MK, Loh TP, Meikle PJ, Orešič M, Quehenberger O, Shevchenko A, Torta F, Wakelam MJO, Wheelock CE, Wenk MR (2018) MS-based lipidomics of human blood plasma: a community-initiated position paper to develop accepted guidelines. J Lipid Res 59(10):2001–2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buys SS, Partridge E, Black A, Johnson CC, Lamerato L, Isaacs C, Reding DJ, Greenlee RT, Yokochi LA, Kessel B, Crawford ED, Church TR, Andriole GL, Weissfeld JL, Fouad MN, Chia D, O’Brien B, Ragard LR, Clapp JD, Rathmell JM, Riley TL, Hartge P, Pinsky PF, Zhu CS, Izmirlian G, Kramer BS, Miller AB, Xu JL, Prorok PC, Gohagan JK, Berg CD, PLCO Project Team (2011) Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA 305(22):2295–2303

    Article  CAS  PubMed  Google Scholar 

  • Candrilli SD, Davis KL, Kan HJ, Lucero MA, Rousculp MD (2007) Prevalence and the associated burden of illness of symptoms of diabetic peripheral neuropathy and diabetic retinopathy. J Diabetes Complicat 21(5):306–314

    Article  Google Scholar 

  • Chaurasia B, Summers SA (2015) Ceramides – lipotoxic inducers of metabolic disorders. Trends Endocrinol Metab 26(10):538–550

    Article  CAS  PubMed  Google Scholar 

  • Checa A, Idborg H, Zandian A, Sar DG, Surowiec I, Trygg J, Svenungsson E, Jakobsson PJ, Nilsson P, Gunnarsson I, Wheelock CE (2017) Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study. Lupus 26(10):1023–1033

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Zhou L, Zhang X, Lu X, Cao R, Xu C, Xu G (2012) Urinary hydrophilic and hydrophobic metabolic profiling based on liquid chromatography-mass spectrometry methods: differential metabolite discovery specific to ovarian cancer. Electrophoresis 33(22):3361–3369

    Article  CAS  PubMed  Google Scholar 

  • Chronic Kidney Disease Prognosis Consortium, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT (2010) Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 375(9731):2073–2081

    Article  Google Scholar 

  • Colas RA, Shinohara M, Dalli J, Chiang N, Serhan CN (2014) Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue. Am J Phys Cell Phys 307(1):C39–C54

    Article  CAS  Google Scholar 

  • Crepaldi G, Fedele D, Tiengo A, Battistin L, Negrin P, Pozza G, Canal N, Comi GC, Lenti G, Pagano G, Bergamini L, Troni W, Frigato F, Ravenna C, Mezzina C, Gallato R, Massari D, Massarotti M, Matano R, Grigoletto F, Davis H, Klein M (1983) Ganglioside treatment in diabetic peripheral neuropathy: a multicenter trial. Acta Diabetol Lat 20(3):265–276

    Article  CAS  PubMed  Google Scholar 

  • Da Costa L, Galimand J, Fenneteau O, Mohandas N (2013) Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders. Blood Rev 27(4):167–178

    Article  PubMed  CAS  Google Scholar 

  • Dawkins JL, Hulme DJ, Brahmbhatt SB, Auer-Grumbach M, Nicholson GA (2001) Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat Genet 27(3):309–312

    Article  CAS  PubMed  Google Scholar 

  • Dekker N, van Dussen L, Hollak CE, Overkleeft H, Scheij S, Ghauharali K, van Breemen MJ, Ferraz MJ, Groener JE, Maas M, Wijburg FA, Speijer D, Tylki-Szymanska A, Mistry PK, Boot RG, Aerts JM (2011) Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype, storage cell markers, and therapeutic response. Blood 118(16):e118–e127

    Article  PubMed  PubMed Central  Google Scholar 

  • Demirkan A, Isaacs A, Ugocsai P, Liebisch G, Struchalin M, Rudan I, Wilson JF, Pramstaller PP, Gyllensten U, Campbell H, Schmitz G, Oostra BA, van Duijn CM (2013) Plasma phosphatidylcholine and sphingomyelin concentrations are associated with depression and anxiety symptoms in a Dutch family-based lipidomics study. J Psychiatr Res 47(3):357–362

    Article  PubMed  Google Scholar 

  • Desnick RJ, Brady R, Barranger J, Collins AJ, Germain DP, Goldman M, Grabowski G, Packman S, Wilcox WR (2003) Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 138(4):338–346

    Article  PubMed  Google Scholar 

  • Dohrn MF, Othman A, Hirshman SK, Bode H, Alecu I, Fähndrich E, Karges W, Weis J, Schulz JB, Hornemann T, Claeys KG (2015) Elevation of plasma 1-deoxy-sphingolipids in type 2 diabetes mellitus: a susceptibility to neuropathy? Eur J Neurol 22(5):806–814, e55

    Article  CAS  PubMed  Google Scholar 

  • Dorow J, Becker S, Kortz L, Thiery J, Hauschildt S, Ceglarek U (2016) Preanalytical investigation of polyunsaturated fatty acids and eicosanoids in human plasma by liquid chromatography-tandem mass spectrometry. Biopreserv Biobank 14(2):107–113

    Article  CAS  PubMed  Google Scholar 

  • Drazba MA, Holásková I, Sahyoun NR, Ventura Marra M (2019 Apr 17) Associations of adiposity and diet quality with serum ceramides in middle-aged adults with cardiovascular risk factors. J Clin Med 8(4). pii: E527). https://doi.org/10.3390/jcm8040527. (in press)

    Article  PubMed Central  Google Scholar 

  • Duan J, Merrill AH Jr (2015) 1-Deoxysphingolipids encountered exogenously and made de novo: dangerous mysteries inside an enigma. J Biol Chem 290(25):15380–15389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan L, Zhang W, Yin M, Zhang T, Wu X, Zhang H, Sun M, Li Z, Hou Y, Zhou X, Lou G, Li K (2012) Identification of metabolic biomarkers to diagnose epithelial ovarian cancer using a UPLC/QTOF/MS platform. Acta Oncol 51(4):473–479

    Article  CAS  PubMed  Google Scholar 

  • Ferraz MJ, Kallemeijn WW, Mirzaian M, Herrera Moro D, Marques A, Wisse P, Boot RG, Willems LI, Overkleeft HS, Aerts JM (2014) Gaucher disease and Fabry disease: new markers and insights in pathophysiology for two distinct glycosphingolipidoses. Biochim Biophys Acta 1841(5):811–825

    Article  CAS  PubMed  Google Scholar 

  • Fish RG (1996) Role of gangliosides in tumour progression: a molecular target for cancer therapy? Med Hypotheses 46(2):140–144

    Article  CAS  PubMed  Google Scholar 

  • Floegel A, Stefan N, Yu Z, Mühlenbruch K, Drogan D, Joost HG, Fritsche A, Häring HU, Hrabě de Angelis M, Peters A, Roden M, Prehn C, Wang-Sattler R, Illig T, Schulze MB, Adamski J, Boeing H, Pischon T (2013) Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach. Diabetes 62(2):639–648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Friedlander AL, Lynch D, Dyar LA, Bowler RP (2007) Phenotypes of chronic obstructive pulmonary disease. COPD: J Chron Obstruct Pulmon Dis 4(4):355–384

    Article  Google Scholar 

  • Ghauharali-van der Vlugt K, Langeveld M, Poppema A, Kuiper S, Hollak CE, Aerts JM, Groener JE (2008) Prominent increase in plasma ganglioside GM3 is associated with clinical manifestations of type I Gaucher disease. Clin Chim Acta 389(1–2):109–113

    Article  CAS  PubMed  Google Scholar 

  • Gold H, Mirzaian M, Dekker N, Joao Ferraz M, Lugtenburg J, Codée JD, van der Marel GA, Overkleeft HS, Linthorst GE, Groener JE, Aerts JM, Poorthuis BJ (2013) Quantification of globotriaosylsphingosine in plasma and urine of fabry patients by stable isotope ultraperformance liquid chromatography-tandem mass spectrometry. Clin Chem 59(3):547–556

    Article  CAS  PubMed  Google Scholar 

  • Górska M, Dobrzyń A, Baranowski M (2005) Concentrations of sphingosine and sphinganine in plasma of patients with type 2 diabetes. Med Sci Monit 11(1):CR35–CR38

    PubMed  Google Scholar 

  • Gracia-Garcia P, Rao V, Haughey NJ, Bandaru VV, Smith G, Rosenberg PB, Lobo A, Lyketsos CG, Mielke MM (2011) Elevated plasma ceramides in depression. J Neuropsychiatry Clin Neurosci 23(2):215–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grammatikos G, Schoell N, Ferreirós N, Bon D, Herrmann E, Farnik H, Köberle V, Piiper A, Zeuzem S, Kronenberger B, Waidmann O, Pfeilschifter J (2016) Serum sphingolipidomic analyses reveal an upregulation of C16-ceramide and sphingosine-1-phosphate in hepatocellular carcinoma. Oncotarget 7(14):18095–18105

    Article  PubMed  PubMed Central  Google Scholar 

  • Hammad SM (2011) Blood sphingolipids in homeostasis and pathobiology. Adv Exp Med Biol 721:57–66

    Article  CAS  PubMed  Google Scholar 

  • Hammad SM, Taha TA, Nareika A, Johnson KR, Lopes-Virella MF, Obeid LM (2006) Oxidized LDL immune complexes induce release of sphingosine kinase in human U937 monocytic cells. Prostaglandins Other Lipid Mediat 79(1–2):126–140

    Article  CAS  PubMed  Google Scholar 

  • Hammad SM, Crellin HG, Wu BX, Melton J, Anelli V, Obeid LM (2008) Dual and distinct roles for sphingosine kinase 1 and sphingosine 1 phosphate in the response to inflammatory stimuli in RAW macrophages. Prostaglandins Other Lipid Mediat 85(3–4):107–114

    Article  CAS  PubMed  Google Scholar 

  • Hammad SM, Pierce JS, Soodavar F, Smith KJ, Al Gadban MM, Rembiesa B, Klein RL, Hannun YA, Bielawski J, Bielawska A (2010) Blood sphingolipidomics in healthy humans: impact of sample collection methodology. J Lipid Res 51(10):3074–3087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hammad SM, Truman JP, Al Gadban MM, Smith KJ, Twal WO, Hamner MB (2012a) Altered blood sphingolipidomics and elevated plasma inflammatory cytokines in combat veterans with post-traumatic stress disorder. Neurobiol Lipid 10:2

    Google Scholar 

  • Hammad SM, Al Gadban MM, Semler AJ, Klein RL (2012b) Sphingosine 1-phosphate distribution in human plasma: associations with lipid profiles. J Lipid 2012:180705

    Article  CAS  Google Scholar 

  • Hammad SM, Baker NL, El Abiad JM, Spassieva SD, Pierce JS, Rembiesa B, Bielawski J, Lopes-Virella MF, Klein RL, DCCT/EDIC Group of Investigators (2017) Increased plasma levels of select deoxy-ceramide and ceramide species are associated with increased odds of diabetic neuropathy in type 1 diabetes: a pilot study. NeuroMolecular Med 19(1):46–56

    Article  CAS  PubMed  Google Scholar 

  • Han X, Rozen S, Boyle SH, Hellegers C, Cheng H, Burke JR, Welsh-Bohmer KA, Doraiswamy PM, Kaddurah-Daouk R (2011) Metabolomics in early Alzheimer’s disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS One 6(7):e21643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanamatsu H, Ohnishi S, Sakai S, Yuyama K, Mitsutake S, Takeda H, Hashino S, Igarashi Y (2014) Altered levels of serum sphingomyelin and ceramide containing distinct acyl chains in young obese adults. Nutr Diabetes 4:e141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hannun YA, Obeid LM (2018) Sphingolipids and their metabolism in physiology and disease. Nat Rev Mol Cell Biol 19(3):175–191

    Article  CAS  PubMed  Google Scholar 

  • Hartwell KJ, Moran-Santa Maria MM, Twal WO, Shaftman S, DeSantis SM, McRae-Clark AL, Brady KT (2013) Association of elevated cytokines with childhood adversity in a sample of healthy adults. J Psychiatr Res 47(5):604–610

    Article  PubMed  PubMed Central  Google Scholar 

  • Haus JM, Kashyap SR, Kasumov T, Zhang R, Kelly KR, Defronzo RA, Kirwan JP (2009) Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Diabetes 58(2):337–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Havulinna AS, Sysi-Aho M, Hilvo M, Kauhanen D, Hurme R, Ekroos K, Salomaa V, Laaksonen R (2016) Circulating Ceramides Predict Cardiovascular Outcomes in the Population-Based FINRISK 2002 Cohort. Arterioscler Thromb Vasc Biol 36(12):2424–2430

    Article  CAS  PubMed  Google Scholar 

  • Intengan HD, Schiffrin EL (2001) Vascular remodeling in hypertension: roles of apoptosis, inflammation, and fibrosis. Hypertension 38(3 Pt 2):581–587

    Article  CAS  PubMed  Google Scholar 

  • Iqbal J, Walsh MT, Hammad SM, Cuchel M, Tarugi P, Hegele RA, Davidson NO, Rader DJ, Klein RL, Hussain MM (2015) Microsomal triglyceride transfer protein transfers and determines plasma concentrations of ceramide and sphingomyelin but not glycosylceramide. J Biol Chem 290(43):25863–25875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iqbal J, Walsh MT, Hammad SM, Hussain MM (2017) Sphingolipids and lipoproteins in health and metabolic disorders. Trends Endocrinol Metab 28(7):506–518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iqbal J, Walsh MT, Hammad SM, Cuchel M, Rader DJ, Hussain MM (2018) ATP binding cassette family A protein 1 determines hexosylceramide and sphingomyelin levels in human and mouse plasma. J Lipid Res 59(11):2084–2097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jensen PN, Fretts AM, Yu C, Hoofnagle AN, Umans JG, Howard BV, Sitlani CM, Siscovick DS, King IB, Sotoodehnia N, McKnight B, Lemaitre RN (2019 Mar) Circulating sphingolipids, fasting glucose, and impaired fasting glucose: the strong heart family study. EBioMedicine 41:44–49

    Article  PubMed  Google Scholar 

  • Ji R, Akashi H, Drosatos K, Liao X, Jiang H, Kennel PJ, Brunjes DL, Castillero E, Zhang X, Deng LY, Homma S, George IJ, Takayama H, Naka Y, Goldberg IJ, Schulze PC (2017) Increased de novo ceramide synthesis and accumulation in failing myocardium. JCI Insight 2(9):e82922

    Article  PubMed Central  Google Scholar 

  • Jiang XC, Paultre F, Pearson TA, Reed RG, Francis CK, Lin M, Berglund L, Tall AR (2000) Plasma sphingomyelin level as a risk factor for coronary artery disease. Arterioscler Thromb Vasc Biol 20(12):2614–2618

    Article  CAS  PubMed  Google Scholar 

  • Kamath PS, Kim WR, Advanced Liver Disease Study Group (2007) The model for end-stage liver disease (MELD). Hepatology 45(3):797–805

    Article  PubMed  Google Scholar 

  • Kamlage B, Maldonado SG, Bethan B, Peter E, Schmitz O, Liebenberg V, Schatz P (2014) Quality markers addressing preanalytical variations of blood and plasma processing identified by broad and targeted metabolite profiling. Clin Chem 60(2):399–412

    Article  CAS  PubMed  Google Scholar 

  • Karliner JS (2013) Sphingosine kinase and sphingosine 1-phosphate in the heart: a decade of progress. Biochim Biophys Acta 1831(1):203–212

    Article  CAS  PubMed  Google Scholar 

  • Kasumov T, Solomon TP, Hwang C, Huang H, Haus JM, Zhang R, Kirwan JP (2015) Improved insulin sensitivity after exercise training is linked to reduced plasma C14:0 ceramide in obesity and type 2 diabetes. Obesity (Silver Spring) 23(7):1414–1421

    Article  CAS  Google Scholar 

  • Ke C, Hou Y, Zhang H, Fan L, Ge T, Guo B, Zhang F, Yang K, Wang J, Lou G, Li K (2015) Large-scale profiling of metabolic dysregulation in ovarian cancer. Int J Cancer 136(3):516–526

    CAS  PubMed  Google Scholar 

  • Keul P, Sattler K, Levkau B (2007) HDL and its sphingosine-1-phosphate content in cardioprotection. Heart Fail Rev 12(3–4):301–306

    Article  CAS  PubMed  Google Scholar 

  • Keul P, van Borren MM, Ghanem A, Müller FU, Baartscheer A, Verkerk AO, Stümpel F, Schulte JS, Hamdani N, Linke WA, van Loenen P, Matus M, Schmitz W, Stypmann J, Tiemann K, Ravesloot JH, Alewijnse AE, Hermann S, Spijkers LJ, Hiller KH, Herr D, Heusch G, Schäfers M, Peters SL, Chun J, Levkau B (2016) Sphingosine-1-Phosphate Receptor 1 Regulates Cardiac Function by Modulating Ca2+ Sensitivity and Na+/H+ Exchange and Mediates Protection by Ischemic Preconditioning. J Am Heart Assoc 5(5):e003393

    Article  PubMed  PubMed Central  Google Scholar 

  • Klein RL, Hammad SM, Baker NL, Hunt KJ, Al Gadban MM, Cleary PA, Virella G, Lopes-Virella MF, DCCT/EDIC Research Group (2014) Decreased plasma levels of select very long chain ceramide species are associated with the development of nephropathy in type 1 diabetes. Metabolism 63(10):1287–1295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kosicek M, Kirsch S, Bene R, Trkanjec Z, Titlic M, Bindila L, Peter-Katalinic J, Hecimovic S (2010) Nano-HPLC-MS analysis of phospholipids in cerebrospinal fluid of Alzheimer's disease patients – a pilot study. Anal Bioanal Chem 398(7–8):2929–2937

    Article  CAS  PubMed  Google Scholar 

  • Kosicek M, Zetterberg H, Andreasen N, Peter-Katalinic J, Hecimovic S (2012) Elevated cerebrospinal fluid sphingomyelin levels in prodromal Alzheimer’s disease. Neurosci Lett 516(2):302–305

    Article  CAS  PubMed  Google Scholar 

  • Kowalski GM, Carey AL, Selathurai A, Kingwell BA, Bruce CR (2013) Plasma sphingosine-1-phosphate is elevated in obesity. PLoS One 8(9):e72449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kremer GJ, Atzpodien W, Schnellbacher E (1975) Plasma glycosphingolipids in diabetics and normals. Klin Wochenschr 53(13):637–638

    Article  CAS  PubMed  Google Scholar 

  • Kroll MH (2004) Evaluating interference caused by lipemia. Clin Chem 50(11):1968–1969

    Article  CAS  PubMed  Google Scholar 

  • Laaksonen R, Ekroos K, Sysi-Aho M, Hilvo M, Vihervaara T, Kauhanen D, Suoniemi M, Hurme R, März W, Scharnagl H, Stojakovic T, Vlachopoulou E, Lokki ML, Nieminen MS, Klingenberg R, Matter CM, Hornemann T, Jüni P, Rodondi N, Räber L, Windecker S, Gencer B, Pedersen ER, Tell GS, Nygård O, Mach F, Sinisalo J, Lüscher TF (2016) Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol. Eur Heart J 37(25):1967–1976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lam CW, Law CY (2014) Untargeted mass spectrometry-based metabolomic profiling of pleural effusions: fatty acids as novel cancer biomarkers for malignant pleural effusions. J Proteome Res 13(9):4040–4046

    Article  CAS  PubMed  Google Scholar 

  • Langeveld M, Aerts JM (2009) Glycosphingolipids and insulin resistance. Prog Lipid Res 48(3–4):196–205

    Article  CAS  PubMed  Google Scholar 

  • Lankinen M, Schwab U, Kolehmainen M, Paananen J, Nygren H, Seppänen-Laakso T, Poutanen K, Hyötyläinen T, Risérus U, Savolainen MJ, Hukkanen J, Brader L, Marklund M, Rosqvist F, Hermansen K, Cloetens L, Önning G, Thorsdottir I, Gunnarsdottir I, Åkesson B, Dragsted LO, Uusitupa M, Orešič M (2016) A healthy nordic diet alters the plasma lipidomic profile in adults with features of metabolic syndrome in a multicenter randomized dietary intervention. J Nutr 146(4):662–672

    Article  CAS  Google Scholar 

  • Lavoie P, Boutin M, Auray-Blais C (2013) Multiplex analysis of novel urinary lyso-Gb3-related biomarkers for Fabry disease by tandem mass spectrometry. Anal Chem 85(3):1743–1752

    Article  CAS  PubMed  Google Scholar 

  • Lippi G, Mercadanti M, Aloe R, Targher G (2012) Erythrocyte mechanical fragility is increased in patients with type 2 diabetes. Eur J Intern Med 23(2):150–153

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Hoene M, Wang X, Yin P, Häring HU, Xu G, Lehmann R (2018) Serum or plasma, what is the difference? Investigations to facilitate the sample material selection decision making process for metabolomics studies and beyond. Anal Chim Acta 1037:293–300

    Article  CAS  PubMed  Google Scholar 

  • Lopes-Virella MF, Baker NL, Hunt KJ, Hammad SM, Arthur J, Virella G, Klein RL, DCCT/EDIC Research Group (2019 Apr 3) Glycosylated sphingolipids and progression to kidney dysfunction in type 1 diabetes. J Clin Lipidolpii: S1933–2874 (19):30047–30049. https://doi.org/10.1016/j.jacl.2019.03.005. [Epub ahead of print] (in press)

    Article  PubMed  PubMed Central  Google Scholar 

  • Mäkinen VP, Tynkkynen T, Soininen P, Peltola T, Kanga AJ, Forsblom C, Thorn LM, Kaski K, Laatikainen R, Ala-Korpela M, Groop PH (2012a) Metabolic diversity of progressive kidney disease in 325 patients with type 1 diabetes (the FinnDiane Study). J Proteome Res 11(3):1782–1790

    Article  PubMed  CAS  Google Scholar 

  • Mäkinen VP, Tynkkynen T, Soininen P, Forsblom C, Peltola T, Kangas AJ, Groop PH, Ala-Korpela M (2012b) Sphingomyelin is associated with kidney disease in type 1 diabetes (The FinnDiane Study). Metabolomics 8(3):369–375

    Article  PubMed  CAS  Google Scholar 

  • Mamtani M, Kulkarni H, Wong G, Weir JM, Barlow CK, Dyer TD, Almasy L, Mahaney MC, Comuzzie AG, Glahn DC, Magliano DJ, Zimmet P, Shaw J, Williams-Blangero S, Duggirala R, Blangero J, Meikle PJ, Curran JE (2016) Lipidomic risk score independently and cost-effectively predicts risk of future type 2 diabetes: results from diverse cohorts. Lipids Health Dis 15:67

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mather AR, Siskind LJ (2011) Glycosphingolipids and kidney disease. Adv Exp Med Biol 721:121–138

    Article  CAS  PubMed  Google Scholar 

  • Mayo Clinic Laboratories (2016) Ceramide plasma [A test in focus]. Retrieved from https://news.mayocliniclabs.com/2016/07/28/ceramides-plasma-a-test-in-focus/

  • Mazaleuskaya LL, Lawson JA, Li X, Grant G, Mesaros C, Grosser T, Blair IA, Ricciotti E, FitzGerald GA (2016) A broad-spectrum lipidomics screen of antiinflammatory drug combinations in human blood. JCI Insight 1(12):e87031

    Article  PubMed  PubMed Central  Google Scholar 

  • Meeusen JW, Donato LJ, Bryant SC, Baudhuin LM, Berger PB, Jaffe AS (2018) Plasma ceramides. Arterioscler Thromb Vasc Biol 38(8):1933–1939

    Article  CAS  PubMed  Google Scholar 

  • Meikle PJ, Wong G, Barlow CK, Weir JM, Greeve MA, MacIntosh GL, Almasy L, Comuzzie AG, Mahaney MC, Kowalczyk A, Haviv I, Grantham N, Magliano DJ, Jowett JB, Zimmet P, Curran JE, Blangero J, Shaw J (2013) Plasma lipid profiling shows similar associations with prediabetes and type 2 diabetes. PLoS One 8(9):e74341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meikle PJ, Wong G, Tan R, Giral P, Robillard P, Orsoni A, Hounslow N, Magliano DJ, Shaw JE, Curran JE, Blangero J, Kingwell BA, Chapman MJ (2015) Statin action favors normalization of the plasma lipidome in the atherogenic mixed dyslipidemia of MetS: potential relevance to statin-associated dysglycemia. J Lipid Res 56(12):2381–2392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mielke MM, Haughey NJ, Bandaru VV, Schech S, Carrick R, Carlson MC, Mori S, Miller MI, Ceritoglu C, Brown T, Albert M, Lyketsos CG (2010a) Plasma ceramides are altered in mild cognitive impairment and predict cognitive decline and hippocampal volume loss. Alzheimers Dement 6(5):378–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mielke MM, Bandaru VV, Haughey NJ, Rabins PV, Lyketsos CG, Carlson MC (2010b) Serum sphingomyelins and ceramides are early predictors of memory impairment. Neurobiol Aging 31(1):17–24

    Article  CAS  PubMed  Google Scholar 

  • Mielke MM, Haughey NJ, Bandaru VV, Weinberg DD, Darby E, Zaidi N, Pavlik V, Doody RS, Lyketsos CG (2011) Plasma sphingomyelins are associated with cognitive progression in Alzheimer’s disease. J Alzheimers Dis 27(2):259–269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mielke MM, Bandaru VV, Haughey NJ, Xia J, Fried LP, Yasar S, Albert M, Varma V, Harris G, Schneider EB, Rabins PV, Bandeen-Roche K, Lyketsos CG, Carlson MC (2012) Serum ceramides increase the risk of Alzheimer disease: the Women’s Health and Aging Study. Neurology 79(7):633–641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mielke MM, Bandaru VV, Han D, An Y, Resnick SM, Ferrucci L, Haughey NJ (2015a) Demographic and clinical variables affecting mid- to late-life trajectories of plasma ceramide and dihydroceramide species. Aging Cell 14(6):1014–1023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mielke MM, Bandaru VV, Han D, An Y, Resnick SM, Ferrucci L, Haughey NJ (2015b) Factors affecting longitudinal trajectories of plasma sphingomyelins: the Baltimore Longitudinal Study of Aging. Aging Cell 14(1):112–121

    Article  CAS  PubMed  Google Scholar 

  • Mitsnefes M, Scherer PE, Friedman LA, Gordillo R, Furth S, Warady BA, CKiD Study Group (2014) Ceramides and cardiac function in children with chronic kidney disease. Pediatr Nephrol 29(3):415–422

    Article  PubMed  PubMed Central  Google Scholar 

  • Mühle C, Reichel M, Gulbins E, Kornhuber J (2013) Sphingolipids in psychiatric disorders and pain syndromes. Handb Exp Pharmacol 216:431–456

    Article  CAS  Google Scholar 

  • Mühle C, Wagner CJ, Färber K, Richter-Schmidinger T, Gulbins E, Lenz B, Kornhuber J (2019 Jun 13) Secretory acid sphingomyelinase in the serum of medicated patients predicts the prospective course of depression. J Clin Med 8(6). pii: E846. https://doi.org/10.3390/jcm8060846. (in press)

    Article  PubMed Central  Google Scholar 

  • Murata N, Sato K, Kon J, Tomura H, Yanagita M, Kuwabara A, Ui M, Okajima F (2000) Interaction of sphingosine 1-phosphate with plasma components, including lipoproteins, regulates the lipid receptor-mediated actions. Biochem J 352(Pt 3):809–315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nikolac N (2014) Lipemia: causes, interference mechanisms, detection and management. Biochemia Medica (Zagreb) 24(1):57–67

    Article  Google Scholar 

  • Nowak A, Mechtler TP, Desnick RJ, Kasper DC (2017) Plasma LysoGb3: a useful biomarker for the diagnosis and treatment of Fabry disease heterozygotes. Mol Genet Metab 120(1–2):57–61

    Article  CAS  PubMed  Google Scholar 

  • Nowling TK, Mather AR, Thiyagarajan T, Hernández-Corbacho MJ, Powers TW, Jones EE, Snider AJ, Oates JC, Drake RR, Siskind LJ (2015) Renal glycosphingolipid metabolism is dysfunctional in lupus nephritis. J Am Soc Nephrol 26(6):1402–1413

    Article  CAS  PubMed  Google Scholar 

  • Ono Y, Kurano M, Ohkawa R, Yokota H, Igarashi K, Aoki J, Tozuka M, Yatomi Y (2013) Sphingosine 1-phosphate release from platelets during clot formation: close correlation between platelet count and serum sphingosine 1-phosphate concentration. Lipids Health Dis 12:20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Othman A, Rütti MF, Ernst D, Saely CH, Rein P, Drexel H, Porretta-Serapiglia C, Lauria G, Bianchi R, von Eckardstein A, Hornemann T (2012) Plasma deoxysphingolipids: a novel class of biomarkers for the metabolic syndrome? Diabetologia 55(2):421–431

    Article  CAS  PubMed  Google Scholar 

  • Pan DA, Lillioja S, Kriketos AD, Milner MR, Baur LA, Bogardus C, Jenkins AB, Storlien LH (1997) Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes 46(6):983–988

    Article  CAS  PubMed  Google Scholar 

  • Park TS, Hu Y, Noh HL, Drosatos K, Okajima K, Buchanan J, Tuinei J, Homma S, Jiang XC, Abel ED, Goldberg IJ (2008) Ceramide is a cardiotoxin in lipotoxic cardiomyopathy. J Lipid Res 49(10):2101–2112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park JY, Lee SH, Shin MJ, Hwang GS (2015) Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction. PLoS One 10(8):e0135228

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Penno A, Reilly MM, Houlden H, Laurá M, Rentsch K, Niederkofler V, Stoeckli ET, Nicholson G, Eichler F, Brown RH Jr, von Eckardstein A, Hornemann T (2010) Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids. J Biol Chem 285(15):11178–11187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perreault L, Starling AP, Glueck D, Brozinick JT, Sanders P, Siddall P, Kuo MS, Dabelea D, Bergman BC (2016) Biomarkers of ectopic fat deposition: the next frontier in serum lipidomics. J Clin Endocrinol Metabol 101(1):176–182

    Article  CAS  Google Scholar 

  • Perzanowski MS, Ono JG, Acosta LM, Kim BI, Divjan A, Miller R, Rundle A, Worgall S, Worgall TS (2017) Distinct serum sphingolipid profiles among school-aged children with exercise-induced wheeze and asthma persistence. Am J Respir Crit Care Med 195(8):1068–1070

    Article  PubMed  PubMed Central  Google Scholar 

  • Petrusca DN, Gu Y, Adamowicz JJ, Rush NI, Hubbard WC, Smith PA, Berdyshev EV, Birukov KG, Lee CH, Tuder RM, Twigg HL 3rd, Vandivier RW, Petrache I (2010) Sphingolipid-mediated inhibition of apoptotic cell clearance by alveolar macrophages. J Biol Chem 285(51):40322–40332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pettus BJ, Bielawska A, Spiegel S, Roddy P, Hannun YA, Chalfant CE (2003) Ceramide kinase mediates cytokine- and calcium ionophore-induced arachidonic acid release. J Biol Chem 278(40):38206–28213

    Article  CAS  PubMed  Google Scholar 

  • Polzin A, Piayda K, Keul P, Dannenberg L, Mohring A, Gräler M, Zeus T, Kelm M, Levkau B (2017) Plasma sphingosine-1-phosphate concentrations are associated with systolic heart failure in patients with ischemic heart disease. J Mol Cell Cardiol 110:35–37

    Article  CAS  PubMed  Google Scholar 

  • Rawlins ML, Owen WE, Roberts WL (2005) Performance characteristics of four automated natriuretic peptide assays. Am J Clin Pathol 123(3):439–445

    Article  CAS  PubMed  Google Scholar 

  • Reichel M, Greiner E, Richter-Schmidinger T, Yedibela O, Tripal P, Jacobi A, Bleich S, Gulbins E, Kornhuber J (2010) Increased acid sphingomyelinase activity in peripheral blood cells of acutely intoxicated patients with alcohol dependence. Alcohol Clin Exp Res 34(1):46–50

    Article  CAS  PubMed  Google Scholar 

  • Reichel M, Beck J, Mühle C, Rotter A, Bleich S, Gulbins E, Kornhuber J (2011) Activity of secretory sphingomyelinase is increased in plasma of alcohol-dependent patients. Alcohol Clin Exp Res 35(10):1852–1859

    Article  CAS  PubMed  Google Scholar 

  • Rombach SM, Dekker N, Bouwman MG, Linthorst GE, Zwinderman AH, Wijburg FA, Kuiper S, Vd Bergh Weerman MA, Groener JE, Poorthuis BJ, Hollak CE, Aerts JM (2010) Plasma globotriaosylsphingosine: diagnostic value and relation to clinical manifestations of Fabry disease. Biochim Biophys Acta 1802(9):741–748

    Article  CAS  PubMed  Google Scholar 

  • Rombach SM, Aerts JM, Poorthuis BJ, Groener JE, Donker-Koopman W, Hendriks E, Mirzaian M, Kuiper S, Wijburg FA, Hollak CE, Linthorst GE (2012a) Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome. PLoS One 7(10):e47805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rombach SM, van den Bogaard B, de Groot E, Groener JE, Poorthuis BJ, Linthorst GE, van den Born BJ, Hollak CE, Aerts JM (2012b) Vascular aspects of Fabry disease in relation to clinical manifestations and elevations in plasma globotriaosylsphingosine. Hypertension 60(4):998–1005

    Article  CAS  PubMed  Google Scholar 

  • Rotthier A, Auer-Grumbach M, Janssens K, Baets J, Penno A, Almeida-Souza L, Van Hoof K, Jacobs A, De Vriendt E, Schlotter-Weigel B, Löscher W, Vondráček P, Seeman P, De Jonghe P, Van Dijck P, Jordanova A, Hornemann T, Timmerman V (2010) Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause hereditary sensory and autonomic neuropathy type I. Am J Hum Genet 87(4):513–522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Russo SB, Ross JS, Cowart LA (2013) Sphingolipids in obesity, type 2 diabetes, and metabolic disease. Handb Exp Pharmacol 216:373–401

    Article  CAS  Google Scholar 

  • Saleem M, Herrmann N, Dinoff A, Marzolini S, Mielke MM, Andreazza A, Oh PI, Vattem Venkata SL, Haughey NJ, Lanctôt KL (2018) Association between sphingolipids and cardiopulmonary fitness in coronary artery disease patients undertaking cardiac rehabilitation. J Gerontol Ser A Biol Sci Med Sci

    Google Scholar 

  • Sales S, Graessler J, Ciucci S, Al-Atrib R, Vihervaara T, Schuhmann K, Kauhanen D, Sysi-Aho M, Bornstein SR, Bickle M, Cannistraci CV, Ekroos K, Shevchenko A (2016) Gender, contraceptives and individual metabolic predisposition shape a healthy plasma lipidome. Sci Rep 6:27710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sattler K, Gräler M, Keul P, Weske S, Reimann CM, Jindrová H, Kleinbongard P, Sabbadini R, Bröcker-Preuss M, Erbel R, Heusch G, Levkau B (2015) Defects of high-density lipoproteins in coronary artery disease caused by low sphingosine-1-phosphate content: correction by sphingosine-1-phosphate-loading. J Am Coll Cardiol 66(13):1470–1485

    Article  CAS  PubMed  Google Scholar 

  • Scherer M, Leuthäuser-Jaschinski K, Ecker J, Schmitz G, Liebisch G (2010) A rapid and quantitative LC-MS/MS method to profile sphingolipids. J Lipid Res 51(7):2001–2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwarz E, Prabakaran S, Whitfield P, Major H, Leweke FM, Koethe D, McKenna P, Bahn S (2008) High throughput lipidomic profiling of schizophrenia and bipolar disorder brain tissue reveals alterations of free fatty acids, phosphatidylcholines, and ceramides. J Proteome Res 7(10):4266–4277

    Article  CAS  PubMed  Google Scholar 

  • Separovic D, Shields AF, Philip PA, Bielawski J, Bielawska A, Pierce JS, Tarca AL (2017) Altered levels of serum ceramide, sphingosine and sphingomyelin are associated with colorectal cancer: a retrospective pilot study. Anticancer Res 37(3):1213–1218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shayman JA (2016) Targeting glycosphingolipid metabolism to treat kidney disease. Nephron 134(1):37–42

    Article  CAS  PubMed  Google Scholar 

  • Shender VO, Pavlyukov MS, Ziganshin RH, Arapidi GP, Kovalchuk SI, Anikanov NA, Altukhov IA, Alexeev DG, Butenko IO, Shavarda AL, Khomyakova EB, Evtushenko E, Ashrafyan LA, Antonova IB, Kuznetcov IN, Gorbachev AY, Shakhparonov MI, Govorun VM (2014) Proteome-metabolome profiling of ovarian cancer ascites reveals novel components involved in intercellular communication. Mol Cell Proteomics 13(12):3558–3571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smesny S, Schmelzer CE, Hinder A, Köhler A, Schneider C, Rudzok M, Schmidt U, Milleit B, Milleit C, Nenadic I, Sauer H, Neubert RH, Fluhr JW (2013) Skin ceramide alterations in first-episode schizophrenia indicate abnormal sphingolipid metabolism. Schizophr Bull 39(4):933–941

    Article  PubMed  Google Scholar 

  • Spijkers LJ, van den Akker RF, Janssen BJ, Debets JJ, De Mey JG, Stroes ES, van den Born BJ, Wijesinghe DS, Chalfant CE, MacAleese L, Eijkel GB, Heeren RM, Alewijnse AE, Peters SL (2011) Hypertension is associated with marked alterations in sphingolipid biology: a potential role for ceramide. PLoS One 6(7):e21817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ståhlman M, Fagerberg B, Adiels M, Ekroos K, Chapman JM, Kontush A, Borén J (2013) Dyslipidemia, but not hyperglycemia and insulin resistance, is associated with marked alterations in the HDL lipidome in type 2 diabetic subjects in the DIWA cohort: impact on small HDL particles. Biochim Biophys Acta 1831(11):1609–1617

    Article  PubMed  CAS  Google Scholar 

  • Summers SA (2018) Could ceramides become the new cholesterol? Cell Metab 27(2):276–280

    Article  CAS  PubMed  Google Scholar 

  • Telenga ED, Hoffmann RF, t’Kindt R, Hoonhorst SJ, Willemse BW, van Oosterhout AJ, Heijink IH, van den Berge M, Jorge L, Sandra P, Postma DS, Sandra K, ten Hacken NH (2014) Untargeted lipidomic analysis in chronic obstructive pulmonary disease. Uncovering sphingolipids. Am J Respir Crit Care Med 190(2):155–164

    Article  CAS  PubMed  Google Scholar 

  • Tonks KT, Coster AC, Christopher MJ, Chaudhuri R, Xu A, Gagnon-Bartsch J, Chisholm DJ, James DE, Meikle PJ, Greenfield JR, Samocha-Bonet D (2016) Skeletal muscle and plasma lipidomic signatures of insulin resistance and overweight/obesity in humans. Obesity (Silver Spring) 24(4):908–916

    Article  CAS  Google Scholar 

  • Uchida Y, Uchida Y, Kawai S, Kanamaru R, Sugiyama Y, Tomaru T, Maezawa Y, Kameda N (2010) Detection of vulnerable coronary plaques by color fluorescent angioscopy. JACC Cardiovasc Imaging 3(4):398–408

    Article  PubMed  Google Scholar 

  • Uchida Y, Uchida Y, Kobayashi T, Shirai S, Hiruta N, Shimoyama E, Tabata T (2017) Detection of ceramide, a risk factor for coronary artery disease, in human coronary plaques by fluorescent angioscopy. Circ J 81(12):1886–1893

    Article  PubMed  Google Scholar 

  • United States Renal Data System (2014) 2014 USRDS annual data report: epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda

    Google Scholar 

  • Valentino L, Moss T, Olson E, Wang HJ, Elashoff R, Ladisch S (1990) Shed tumor gangliosides and progression of human neuroblastoma. Blood 75(7):1564–1567

    CAS  PubMed  Google Scholar 

  • van Breemen MJ, Rombach SM, Dekker N, Poorthuis BJ, Linthorst GE, Zwinderman AH, Breunig F, Wanner C, Aerts JM, Hollak CE (2011) Reduction of elevated plasma globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement therapy. Biochim Biophys Acta 1812(1):70–76

    Article  PubMed  CAS  Google Scholar 

  • Varma VR, Oommen AM, Varma S, Casanova R, An Y, Andrews RM, O'Brien R, Pletnikova O, Troncoso JC, Toledo J, Baillie R, Arnold M, Kastenmueller G, Nho K, Doraiswamy PM, Saykin AJ, Kaddurah-Daouk R, Legido-Quigley C, Thambisetty M (2018) Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: a targeted metabolomics study. PLoS Med 15(1):e1002482

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vukovic I, Bozic J, Markotic A, Ljubicic S, Ticinovic Kurir T (2015) The missing link – likely pathogenetic role of GM3 and other gangliosides in the development of diabetic nephropathy. Kidney Blood Press Res 40(3):306–314

    Article  CAS  PubMed  Google Scholar 

  • Wang DD, Toledo E, Hruby A, Rosner BA, Willett WC, Sun Q, Razquin C, Zheng Y, Ruiz-Canela M, Guasch-Ferré M, Corella D, Gómez-Gracia E, Fiol M, Estruch R, Ros E, Lapetra J, Fito M, Aros F, Serra-Majem L, Lee CH, Clish CB, Liang L, Salas-Salvadó J, Martínez-González MA, Hu FB (2017) Plasma ceramides, Mediterranean diet, and incident cardiovascular disease in the PREDIMED Trial (Prevención con Dieta Mediterránea). Circulation 135(21):2028–2040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wattenberg BW (2019) Intra- and intercellular trafficking in sphingolipid metabolism in myelination. Adv Biol Regul 71:97–103

    Article  CAS  PubMed  Google Scholar 

  • Wennekes T, van den Berg RJ, Boot RG, van der Marel GA, Overkleeft HS, Aerts JM (2009) Glycosphingolipids--nature, function, and pharmacological modulation. Angew Chem Int Ed Engl 48(47):8848–8869

    Article  CAS  PubMed  Google Scholar 

  • Wiesner P, Leidl K, Boettcher A, Schmitz G, Liebisch G (2009) Lipid profiling of FPLC-separated lipoprotein fractions by electrospray ionization tandem mass spectrometry. J Lipid Res 50(3):574–585

    Article  CAS  PubMed  Google Scholar 

  • Yamashita T, Hashiramoto A, Haluzik M, Mizukami H, Beck S, Norton A, Kono M, Tsuji S, Daniotti JL, Werth N, Sandhoff R, Sandhoff K, Proia RL (2003) Enhanced insulin sensitivity in mice lacking ganglioside GM3. Proc Natl Acad Sci 100(6):3445–3449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu Z, Kastenmüller G, He Y, Belcredi P, Möller G, Prehn C, Mendes J, Wahl S, Roemisch-Margl W, Ceglarek U, Polonikov A, Dahmen N, Prokisch H, Xie L, Li Y, Wichmann HE, Peters A, Kronenberg F, Suhre K, Adamski J, Illig T, Wang-Sattler R (2011) Differences between human plasma and serum metabolite profiles. PLoS One 6(7):e21230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu J, Pan W, Shi R, Yang T, Li Y, Yu G, Bai Y, Schuchman EH, He X, Zhang G (2015) Ceramide is upregulated and associated with mortality in patients with chronic heart failure. Can J Cardiol 31(3):357–363

    Article  PubMed  Google Scholar 

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  1. Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA

    Faris Matanes, Waleed O. Twal & Samar M. Hammad

  2. Department of Vascular Biology and Hypertension, University of Alabama at Birmingham, Birmingham, AL, USA

    Faris Matanes

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Matanes, F., Twal, W.O., Hammad, S.M. (2019). Sphingolipids as Biomarkers of Disease. In: Stiban, J. (eds) Bioactive Ceramides in Health and Disease. Advances in Experimental Medicine and Biology, vol 1159. Springer, Cham. https://doi.org/10.1007/978-3-030-21162-2_7

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