Vol 53, No 6 (2019)
Research paper
Published online: 2019-12-05
Submitted: 2019-04-18
Accepted: 2019-10-04
Get Citation

Ceramides and sphingosine-1-phosphate as potential markers in diagnosis of ischaemic stroke

Anna Fiedorowicz, Anna Kozak-Sykała, Łukasz Bobak, Wojciech Kałas, Leon Strządała
DOI: 10.5603/PJNNS.a2019.0063
·
Pubmed: 31804702
·
Neurol Neurochir Pol 2019;53(6):484-491.

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Vol 53, No 6 (2019)
Research paper
Published online: 2019-12-05
Submitted: 2019-04-18
Accepted: 2019-10-04

Abstract

Background. Brain imaging in stroke diagnostics is a powerful tool, but one that can fail in more challenging cases, and one that is not particularly useful in identifying transient ischaemic attacks (TIAs). Thus, new reliable blood biomarkers of cerebral ischaemia are constantly sought. Objective. We studied the potential usefulness of sphingolipids (SFs) as biomarkers of acute ischaemic stroke and TIA. Material and methods. Levels of individual ceramide species and sphingosine-1-phosphate (Sph-1-P) in blood serum of patients with acute ischaemic stroke, TIA, and age-matched neurological patients without cerebral ischaemia, were assessed by tandem mass spectrometry liquid chromatography (LC- MS / MS). Results. We found significant increases of several sphingolipid levels, with particularly strong elevations of Cer-C20:0 in patients with acute stroke. Cer-C24:1 was the only ceramide species to decrease as a result of acute stroke. Moreover, its levels inversely correlated with the number of days after stroke onset, suggesting that Cer-C24:1 is an independent parameter related to the course of stroke. To increase the sensitivity of sphingolipid-based tests in stroke diagnostics, we calculated the values of ratios of Sph-1-P / individual ceramide species and Cer-C24:1 individual ceramide species. We found several ratios significantly changed in stroke patients. Two ratios, Sph-1-P / Cer-C24:1 and Cer-C24:0 / Cer-C24:1, presented especially strong increments in patients with acute stroke. Moreover, Sph-1-P / Cer-C24:1 values were augmented in TIA patients. Conclusion. Serum SFs could be good candidates to be ischaemic stroke biomarkers. We have identified two SF ratios, Sph-1-P / Cer-C24:1 and Cer-C24:0 / Cer-C24:1, with strong diagnostic potential in ischaemic stroke. We found Sph-1-P / Cer-C24:1 ratio to be possibly useful in TIA diagnostics, also in the long term after ischaemic incidence.

Abstract

Background. Brain imaging in stroke diagnostics is a powerful tool, but one that can fail in more challenging cases, and one that is not particularly useful in identifying transient ischaemic attacks (TIAs). Thus, new reliable blood biomarkers of cerebral ischaemia are constantly sought. Objective. We studied the potential usefulness of sphingolipids (SFs) as biomarkers of acute ischaemic stroke and TIA. Material and methods. Levels of individual ceramide species and sphingosine-1-phosphate (Sph-1-P) in blood serum of patients with acute ischaemic stroke, TIA, and age-matched neurological patients without cerebral ischaemia, were assessed by tandem mass spectrometry liquid chromatography (LC- MS / MS). Results. We found significant increases of several sphingolipid levels, with particularly strong elevations of Cer-C20:0 in patients with acute stroke. Cer-C24:1 was the only ceramide species to decrease as a result of acute stroke. Moreover, its levels inversely correlated with the number of days after stroke onset, suggesting that Cer-C24:1 is an independent parameter related to the course of stroke. To increase the sensitivity of sphingolipid-based tests in stroke diagnostics, we calculated the values of ratios of Sph-1-P / individual ceramide species and Cer-C24:1 individual ceramide species. We found several ratios significantly changed in stroke patients. Two ratios, Sph-1-P / Cer-C24:1 and Cer-C24:0 / Cer-C24:1, presented especially strong increments in patients with acute stroke. Moreover, Sph-1-P / Cer-C24:1 values were augmented in TIA patients. Conclusion. Serum SFs could be good candidates to be ischaemic stroke biomarkers. We have identified two SF ratios, Sph-1-P / Cer-C24:1 and Cer-C24:0 / Cer-C24:1, with strong diagnostic potential in ischaemic stroke. We found Sph-1-P / Cer-C24:1 ratio to be possibly useful in TIA diagnostics, also in the long term after ischaemic incidence.

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Keywords

ischaemic stroke marker, biomarker, brain, ceramide, mass spectrometry, observational clinical studies, sphingolipid, sphingosine-1-phosphate (Sph-1-P), transient ischaemic attack (TIA)

About this article
Title

Ceramides and sphingosine-1-phosphate as potential markers in diagnosis of ischaemic stroke

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 53, No 6 (2019)

Pages

484-491

Published online

2019-12-05

DOI

10.5603/PJNNS.a2019.0063

Pubmed

31804702

Bibliographic record

Neurol Neurochir Pol 2019;53(6):484-491.

Keywords

ischaemic stroke marker
biomarker
brain
ceramide
mass spectrometry
observational clinical studies
sphingolipid
sphingosine-1-phosphate (Sph-1-P)
transient ischaemic attack (TIA)

Authors

Anna Fiedorowicz
Anna Kozak-Sykała
Łukasz Bobak
Wojciech Kałas
Leon Strządała

References (34)
  1. Nentwich LM. Diagnosis of Acute Ischemic Stoke. Emerg Med Clin North Am. 2016; 34(4): 837–859.
  2. Kassner A, Mandell DM, Mikulis DJ. Measuring permeability in acute ischemic stroke. Neuroimaging Clin N Am. 2011; 21(2): 315–325.
  3. Guo Y, Li P, Guo Q, et al. Pathophysiology and Biomarkers in Acute Ischemic Stroke – A Review. Tropical Journal of Pharmaceutical Research. 2014; 12(6): 1097.
  4. Grösch S, Schiffmann S, Geisslinger G. Chain length-specific properties of ceramides. Prog Lipid Res. 2012; 51(1): 50–62.
  5. Car H, Zendzian-Piotrowska M, Fiedorowicz A, et al. [The role of ceramides in selected brain pathologies: ischemia/hypoxia, Alzheimer disease]. Postepy Hig Med Dosw (Online). 2012; 66: 295–303.
  6. Yu J, Novgorodov SA, Chudakova D, et al. JNK3 signaling pathway activates ceramide synthase leading to mitochondrial dysfunction. J Biol Chem. 2007; 282(35): 25940–25949.
  7. Gu L, Huang B, Shen W, et al. Early activation of nSMase2/ceramide pathway in astrocytes is involved in ischemia-associated neuronal damage via inflammation in rat hippocampi. J Neuroinflammation. 2013; 10: 109.
  8. Ohtani R, Tomimoto H, Kondo T, et al. Upregulation of ceramide and its regulating mechanism in a rat model of chronic cerebral ischemia. Brain Res. 2004; 1023(1): 31–40.
  9. Mullen TD, Hannun YA, Obeid LM. Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem J. 2012; 441(3): 789–802.
  10. Goñi FM, Sot J, Alonso A. Biophysical properties of sphingosine, ceramides and other simple sphingolipids. Biochem Soc Trans. 2014; 42(5): 1401–1408.
  11. Hopson KP, Truelove J, Chun J, et al. S1P activates store-operated calcium entry via receptor- and non-receptor-mediated pathways in vascular smooth muscle cells. Am J Physiol Cell Physiol. 2011; 300(4): C919–C926.
  12. Tong M, de la Monte SM. Mechanisms of ceramide-mediated neurodegeneration. J Alzheimers Dis. 2009; 16(4): 705–714.
  13. Herr I, Martin-Villalba A, Kurz E, et al. FK506 prevents stroke-induced generation of ceramide and apoptosis signaling. Brain Research. 1999; 826(2): 210–219.
  14. Nakane M, Kubota M, Nakagomi T, et al. Lethal forebrain ischemia stimulates sphingomyelin hydrolysis and ceramide generation in the gerbil hippocampus. Neuroscience Letters. 2000; 296(2-3): 89–92.
  15. Kimura A, Ohmori T, Kashiwakura Y, et al. Antagonism of sphingosine 1-phosphate receptor-2 enhances migration of neural progenitor cells toward an area of brain. Stroke. 2008; 39(12): 3411–3417.
  16. Thuy AV, Reimann CM, Hemdan NYA, et al. Sphingosine 1-phosphate in blood: function, metabolism, and fate. Cell Physiol Biochem. 2014; 34(1): 158–171.
  17. Vito CDi, Hadi LA, Navone SE, et al. Platelet-derived sphingosine-1-phosphate and inflammation: from basic mechanisms to clinical implications. Platelets. 2016; 27(5): 393–401.
  18. Iwaki S, Yamamura S, Asai M, et al. Posttranscriptional regulation of expression of plasminogen activator inhibitor type-1 by sphingosine 1-phosphate in HepG2 liver cells. Biochim Biophys Acta. 2012; 1819(11-12): 1132–1141.
  19. Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957; 226(1): 497–509.
  20. Kasumov T, Huang H, Chung YM, et al. Quantification of ceramide species in biological samples by liquid chromatography electrospray ionization tandem mass spectrometry. Anal Biochem. 2010; 401(1): 154–161.
  21. Haus JM, Kashyap SR, Kasumov T, et al. Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Diabetes. 2009; 58(2): 337–343.
  22. Borodzicz S, Czarzasta K, Kuch M, et al. Sphingolipids in cardiovascular diseases and metabolic disorders. Lipids Health Dis. 2015; 14: 55.
  23. Xing Yi, Tang Yi, Zhao L, et al. Plasma Ceramides and Neuropsychiatric Symptoms of Alzheimer's Disease. J Alzheimers Dis. 2016; 52(3): 1029–1035.
  24. Testai FD, Hillmann M, Amin-Hanjani S, et al. Changes in the cerebrospinal fluid ceramide profile after subarachnoid hemorrhage. Stroke. 2012; 43(8): 2066–2070.
  25. Edsfeldt A, Dunér P, Ståhlman M, et al. Sphingolipids Contribute to Human Atherosclerotic Plaque Inflammation. Arterioscler Thromb Vasc Biol. 2016; 36(6): 1132–1140.
  26. Laaksonen R, Ekroos K, Sysi-Aho M, et al. Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol. European Heart Journal. 2016; 37(25): 1967–1976.
  27. Tuttolomondo A. Relationship between Diabetes and Ischemic Stroke: Analysis of Diabetes- Related Risk Factors for Stroke and of Specific Patterns of Stroke Associated with Diabetes Mellitus. Journal of Diabetes & Metabolism. 2015; 06(05).
  28. Nielsen MMB, Lambertsen KL, Clausen BH, et al. Mass spectrometry imaging of biomarker lipids for phagocytosis and signalling during focal cerebral ischaemia. Sci Rep. 2016; 6: 39571.
  29. Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke. 2007; 38(3): 967–973.
  30. Lapchak P, Zhang A, John H. Translational Stroke Research. 2012.
  31. Anrather J, Iadecola C. Inflammation and Stroke: An Overview. Neurotherapeutics. 2016; 13(4): 661–670.
  32. Brunkhorst R, Friedlaender F, Ferreirós N, et al. Alterations of the Ceramide Metabolism in the Peri-Infarct Cortex Are Independent of the Sphingomyelinase Pathway and Not Influenced by the Acid Sphingomyelinase Inhibitor Fluoxetine. Neural Plast. 2015.
  33. Hirokawa M, Kitabayashi A, Kuroki J, et al. Induction of tissue factor production but not the upregulation of adhesion molecule expression by ceramide in human vascular endothelial cells. Tohoku J Exp Med. 2000; 191(3): 167–176.
  34. Ng TW, Ooi EM, E M, et al. Dose-dependent effects of rosuvastatin on the plasma sphingolipidome and phospholipidome in the metabolic syndrome. J Clin Endocrinol Metab. 2014; 99(11): E2335–E2340.

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