Skip to main content
Log in

Serum sulfatides as a novel biomarker for cardiovascular disease in patients with end-stage renal failure

  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Sulfatides, normal components of serum lipoproteins, may play an important role in cardiovascular disease due to their various modulatory functions in haemostasis. The incidence of cardiovascular disease in patients with end-stage renal failure undergoing maintenance hemodialysis has been reported to be approximately 10 to 30 times higher than that in the general population. To elucidate the possible roles of serum sulfatides in this high incidence, we measured the level of sulfatides in 59 such patients, by converting them to lysosulfatides according to a recently developed quantitative, qualitative, high-throughput technique using matrix-assisted laser desorption ionization-time of flight mass spectrometry. The mean level of sulfatides in patients 3.58 ± 1.18 nmol/ml was significantly lower than that in age-matched normal subjects (8.21 ± 1.50 nmol/ml; P < 0.001). Patients receiving maintenance hemodialysis over a longer period had lower levels of sulfatides. When the mean levels of sulfatides were compared between patients with cardiovascular disease (N = 22) and those without the disease (N = 37), the level in the former group 2.85 ± 0.67 nmol/ml was found to be significantly lower than that in the latter group 4.01 ± 1.22 nmol/ml (P < 0.001). These findings reveal a close correlation between low levels of serum sulfatides and a high risk of cardiovascular disease in these patients. Determination of the level of serum sulfatides can contribute to predictions of the incidence of cardiovascular disease in patients with end-stage renal failure undergoing maintenance hemodialysis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

WHHL:

Watanabe hereditable hyperlipidemic

CVD:

cardiovascular disease

ESRF:

end-stage renal failure

VLDL:

very low-density lipoprotein

LDL:

low-density lipoprotein

HDL:

high-density lipoprotein. Sphingoids are abbreviated such as (4E)-sphingenine d18:1 and t18:0, 4D-hydroxysphinganine (or phytosphingosine) where the first number indicates the number of carbon atoms and the second indicates the number of double bonds and d and t mean di- and tri-hydroxyl groups respectively

LS:

lysosulfatide

LS-d18:1:

LS possessing d18:1 as a sphingoid

References

  1. Ishizuka, I.: Chemistry and functional distribution of sulfoglycolipids. Prog. Lipid Res. 36, 245–319 (1997)

    Article  PubMed  CAS  Google Scholar 

  2. Hara, A., Taketomi, T.: Occurrence of sulfatides as a major glycosphingolipid in WHHL rabbit serum lipoproteins. J. Biochem. (Tokyo) 102, 83–92 (1987)

    CAS  Google Scholar 

  3. Hara, A., Taketomi, T.: Characterization and changes of glycosphingolipids in the aorta of the Watanabe hereditable hyperlipidemic rabbit. J. Biochem. (Tokyo) 109, 904–908 (1991)

    CAS  Google Scholar 

  4. Zhu, X.H., Hara, A., Taketomi, T.: The existence of galactosylceramide I3-sulfatides in serums of various mammals and its anticoagulant activity. J. Biochem. (Tokyo) 110, 241–245 (1991)

    CAS  Google Scholar 

  5. Hara, A., Kutsukake, Y., Uemura, K., Taketomi, T.: Anticoagulant activity of sulfatides and its anti-thrombotic effect in rabbit. J. Biochem. (Tokyo) 113, 781–785 (1993)

    CAS  Google Scholar 

  6. Hara, A., Uemura, K., Taketomi, T.: Sulfatides prolongs blood-coagulation time and bleeding time by forming a complex with fibrinogen. Glycoconj. J. 13, 187–194 (1996)

    Article  PubMed  CAS  Google Scholar 

  7. Kyogashima, M., Sakai, T., Onaya, J., Hara, A.: Roles of galactose and sulfate residues in sulfatides for their antagonistic functions in the blood coagulation system. Glycoconj. J. 18, 245–251 (2001)

    Article  PubMed  CAS  Google Scholar 

  8. Kyogashima, M., Onaya, J., Hara, A., Taketomi, T.: Sulfatide can markedly enhance thrombogenesis in rat deep vein thrombosis model. Glycoconj. J. 15, 915–922 (1998)

    Article  PubMed  CAS  Google Scholar 

  9. Kyogashima, M., Onaya, J., Hara, A., Taketomi, T.: Contradictory functions of sulfatide in the blood coagulation system as coagulant and anticoagulant. Acta. Biochim. Pol. 45, 493–499 (1998)

    PubMed  CAS  Google Scholar 

  10. Mitropoulos, K.A., Reeves, B.E., Miller, G.J.: The activation of factor VII in citrated plasma by charged long-chain saturated fatty acids at the interface of large triglyceride-rich lipoproteins. Blood Coagul. Fibrinolysis. 4, 943–951 (1993)

    Article  PubMed  CAS  Google Scholar 

  11. Ida, M., Satoh, A., Matsumoto, I., Kojima-Aikawa, K.: Human annexin V binds to sulfatide: contribution to regulation of blood coagulation. J. Biochem. (Tokyo) 135, 583–588 (2004)

    CAS  Google Scholar 

  12. Devaiah, A.K., Raife, T.J., Barton, J.A., Olson, J.D.: Inhibition of human platelet function by sulfatides. Blood Coagul. Fibrinolysis 11, 543–550 (2000)

    Article  PubMed  CAS  Google Scholar 

  13. Merten, M., Thiagarajan, P.: Role for sulfatides in platelet aggregation. Circulation 104, 2955–2960 (2001)

    Article  PubMed  CAS  Google Scholar 

  14. Borthakur, G., Cruz, MA., Dong, JF., McIntire, L., Li, F., Lopez, J.A., Thiagarajan, P.: Sulfatides inhibit platelet adhesion to von Willebrand factor in flowing blood. J. Thromb. Haemost. 1, 1288–1295 (2003)

    Article  PubMed  CAS  Google Scholar 

  15. Merten, M., Beythien, C., Gutensohn, K., Kuhnl, P., Meinertz, T., Thiagarajan, P.: Sulfatides activate platelets through P-selectin and enhance platelet and platelet-leukocyte aggregation. Arterioscler. Thromb. Vasc. Biol. 25, 258–263 (2005)

    PubMed  CAS  Google Scholar 

  16. Shimazawa, M., Kondo, K., Hara, H., Nakashima, M., Umemura, K.: Sulfatides, L- and P-selectin ligands, exacerbate the intimal hyperplasia occurring after endothelial injury. Eur. J. Pharmacol. 520, 118–126 (2005)

    Article  PubMed  CAS  Google Scholar 

  17. Kyogashima, M.: The role of sulfatide in thrombogenesis and haemostasis. Arch. Biochem. Biophys. 426, 157–162 (2004)

    Article  PubMed  CAS  Google Scholar 

  18. Li, G., Hu, R., Kamijo, Y., Nakajima, T., Aoyama, T., Inoue, T., Node, K. Kannagi, R., Kyogashima, M., Hara, A.: Establishment of a quantitative, qualitative and high throughput analysis of sulfatides from small amounts of sera by MALDI-TOF MS. Anal. Biochem. 362, 1–7 (2007)

    Article  PubMed  CAS  Google Scholar 

  19. Attman, P.O., Samuelsson, O., Alaupovic, P.: Lipoprotein metabolism in renal failure. Am. J. Kidney Dis. 21, 573–592 (1993)

    PubMed  CAS  Google Scholar 

  20. Aoyama, T., Peters, J.M., Iritani, N., Nakajima, T., Furihata, K., Hashimoto, T., Gonzalez, F.J.: Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor alpha (PPARalpha). J. Biol. Chem. 273, 5678–5684 (1998)

    Article  PubMed  CAS  Google Scholar 

  21. Kasiske, B.L.: Hyperlipidemia in patients with chronic renal disease. Am. J. Kidney Dis. 32, 142–156 (1998)

    Google Scholar 

  22. Levey, A., Beto, J.A., Coronado, B.E., Eknoyan, G., Foley, R.N., Kasiske, B.L., Klag, M.J., Mailloux, L.U., Manske, C.L., Meyer, K.B., Parfrey, P.S., Pfeffer, M.A., Wenger, N.K., Wilson, P.W., Wright, J.T. Jr.,: Controlling the epidemic of cardiovascular disease in chronic renal disease: What do we know? What do we need to learn? Where do we go from here? Am. J. Kidney Dis. 32, 853–906 (1998)

    PubMed  CAS  Google Scholar 

  23. Sarnak, M.J., Levey, A.S., Schoolwerth, A.C., Coresh, J., Culleton, B., Hamm, L.L., McCullough, P.A., Kasiske, B.L., Kelepouris, E., Klag, M.J., Parfrey, P., Raij, M.L., D.J., Spinosa, Wilson, P.W.: Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 108, 2154–2169 (2003)

    Article  PubMed  Google Scholar 

  24. Roberts, M.A., Hare, D.L., Ratnaike, S., Ierino, F.L.: Cardiovascular biomarkers in CKD: pathophysiology and implications for clinical management of cardiac disease. Am. J. Kidney Dis. 48, 341–360 (2006)

    Article  PubMed  CAS  Google Scholar 

  25. Sugiyama, E. Hara, A., Uemura, A.: A quantitative analysis of serum sulfatides by matrix-assisted laser desorption ionization time-of-flight mass spectrometry with delayed ion extraction. Anal. Biochem. 274, 90–97 (1999)

    Article  PubMed  CAS  Google Scholar 

  26. Hara, A., Radin, N.S.: Lipid extraction of tissues with a low-toxicity solvent. Anal. Biochem. 90, 420–426 (1978)

    Article  PubMed  CAS  Google Scholar 

  27. Roberts, D.D., Williams, S.B., Gralnick, H.R., Ginsburg V.: von Willebrand factor binds specifically to sulfated glycolipids. J. Biol. Chem. 261, 3306–3309 (1986)

    PubMed  CAS  Google Scholar 

  28. Kyogashima, M., Tamiya-Koizumi, K., Ehara, T., Li, G., Hu, R., Hara, A., Aoyama, T., Kannagi, R.: Rapid demonstration of diversity of sulfatide molecular species from biological materials by MALDI-TOF MS. Glycobiology. 16, 719–728 (2006)

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by GL Science Inc. Japan and was supported in part by a grant from NIBIO (National Institute of Biomedical Innovation).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Mamoru Kyogashima or Atsushi Hara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hu, R., Li, G., Kamijo, Y. et al. Serum sulfatides as a novel biomarker for cardiovascular disease in patients with end-stage renal failure. Glycoconj J 24, 565–571 (2007). https://doi.org/10.1007/s10719-007-9053-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-007-9053-0

Keywords

Navigation