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Heat shock proteins in children and young adults on chronic hemodialysis

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Abstract

Chronic inflammation, lipid and autoimmune disorders are hallmarks of atherogenesis, and hemodialysis per se may be an additional factor predisposing to accelerated atherosclerosis. Elevated levels of heat shock proteins (HSP) and antibodies against these HSP have been described in adults with atherosclerotic lesions and cardiovascular events, but to date there has been a scarcity of investigations on these parameters in adult and pediatric patients on hemodialysis (HD). We have investigated the HSP profile in hemodialyzed children and the impact of a single HD session on those proteins and their correlations with known risk factors for atherosclerosis. The study group consisted of 17 children and young adults undergoing HD with polysulfone membranes. The control group comprised 15 age-matched subjects with normal kidney function. The serum concentrations of Hsp60, Hsp90alpha, anti-Hsp60, anti-Hsp70, and sE-selectin were assessed by an enzyme-linked immunosorbent assay, and serum concentration of high-sensitivity-C-reactive protein was assayed by nephelometry. The serum lipid profile [total cholesterol (CHOL), high-density lipoprotein-CHOL, low-density lipoprotein-CHOL, triglycerides] was also estimated. Compared to the control values, the median values of Hsp60 before the HD session were lower, whereas those of Hsp90alpha and anti-Hsp60 were higher. A single HD session raised the median values of Hsp60 and Hsp90alpha and decreased the concentrations of anti-Hsp60 and anti-Hsp70. In addition, the concentrations of HSPs and the antibodies against them correlated with the lipid markers both before and after HD. The altered HSP and anti-HSP concentrations in HD children, which correlated with the lipid profile and the endothelial markers, suggest a dysfunctional HSP system in this population and the possibility of HSPs being classified as new markers of atherosclerosis.

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References

  1. Andreoli MC, Dalboni MA, Watanabe R, Manfredi SR, Canziani ME, Kallas EG, Serso RC, Drabie SA, Balakrishnan VS, Jaber BL, Liangos O, Cendoroglo M (2007) Impact of dialyzer membrane on apoptosis and function of polymorphonuclear cells and cytokine synthesis by peripheral blood mononuclear cells in hemodialysis patients. Artif Organs 31:887–910

    Article  CAS  Google Scholar 

  2. Meier P, Spertini F, Blanc E, Burnier M (2007) Oxidized low-density lipoproteins activate CD4+ T cell apoptosis in patients with end-stage renal disease through Fas engagement. J Am Soc Nephrol 18:331–342

    Article  CAS  Google Scholar 

  3. Westerweel PE, Hoefer IE, Blankestijn PJ, de Bree P, Groeneveld D, van Oostrom O, Braam B, Koomans HA, Verhaar MC (2007) End-stage renal disease causes an imbalance between endothelial and smooth muscle progenitor cells. Am J Physiol Renal Physiol 292:F1132–F1140

    Article  CAS  Google Scholar 

  4. Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852–1858

    Article  CAS  Google Scholar 

  5. Gabai VL, Sherman MY (2002) Interplay between molecular chaperones as signalling pathways in survival of heat shock. J Appl Physiol 92:1743–1748

    Article  CAS  Google Scholar 

  6. Osterloh A, Breloer M (2008) Heat shock proteins: linking danger and pathogen recognition. Med Microbiol Immunol 197:1–8

    Article  CAS  Google Scholar 

  7. Calderwood SK, Mambula SS, Gray PJ Jr (2007) Extracellular heat shock proteins in cell signalling and immunity. Ann NY Acad Sci 1113:28–39

    Article  CAS  Google Scholar 

  8. van Eden W, van der Zee R, van Kooten P, Berlo SE, Cobelens PM, Kavelaars A, Heijnen CJ, Prakken B, Roord S, Albani S (2002) Balancing the immune system: Th1 and Th2. Ann Rheum Dis 61[suppl 2]:ii25–ii28

    Article  Google Scholar 

  9. Xu Q (2001) Heat shock proteins and atherosclerosis. Eur J Clin Invest 31:283–284

    Article  CAS  Google Scholar 

  10. Lamb DJ, El-Sankary W, Ferns GAA (2002) Molecular mimicry in atherosclerosis: a role for heat shock proteins in immunisation. Atherosclerosis 167:177–185

    Article  Google Scholar 

  11. Perschinka H, Mayr M, Millonig G, Ch M, Van der Zee R, Morrison SG, Morrison RP, Xu Q, Wick G (2003) Cross-reactive B-cell epitopes of microbial and human heat shock protein 60/65 in atherosclerosis. Arterioscler Thromb Vasc Biol 23:1060–1065

    Article  CAS  Google Scholar 

  12. Raj DSC, Boivin MA, Dominic EA, Boyd A, Roy PK, Rihani T, Tzamaloukas AH, Shan VO, Moseley P (2007) Haemodialysis induces mitochondrial dysfunction and apoptosis. Eur J Clin Invest 37:971–977

    Article  CAS  Google Scholar 

  13. Majewska E, Baj Z, Sułowska Z, Rysz J, Luciak M (2003) Effects of uraemia and haemodialysis on neutrophil apoptosis and expression of apoptosis-related proteins. Nephrol Dial Transplant 18:2582–2588

    Article  CAS  Google Scholar 

  14. Kirchhoff SR, Gupta S, Knowlton AA (2002) Cytosolic heat shock protein 60, apoptosis, and myocardial injury. Circulation 105:2899–2904

    Article  CAS  Google Scholar 

  15. Xu Q, Schett G, Perschinka H, Mayr M, Egger G, Oberhollenzer F, Willeit J, Kiechl S, Wick G (2000) Serum soluble heat shock protein 60 is elevated in subjects with atherosclerosis in a general population. Circulation 102:14–20

    Article  CAS  Google Scholar 

  16. Hochleitner BW, Hochleitner EO, Obrist P, Eberl T, Amberger A, Xu Q, Margreiter R, Wick G (2000) Fluid shear stress induces heat shock protein 60 expression in endothelial cells in vitro and in vivo. Arterioscler Thromb Vasc Biol 20:617–623

    Article  CAS  Google Scholar 

  17. Pockley AG (2002) Heat shock proteins, inflammation, and cardiovascular disease. Circulation 105:1012–1017

    Article  CAS  Google Scholar 

  18. Grooteman MPC, Gritters M, Wauters IM, Schalkwijk CG, Stam F, Twisk J, Ter Wee PM, Nube MJ (2005) Patient characteristics rather than the type of dialyzer predict the variability of endothelial derived surface molecules in chronic hemodialysis patients. Nephrol Dial Transplant 20:2751–2758

    Article  CAS  Google Scholar 

  19. Zwolińska D, Grzeszczak W, Szczepańska M, Kiliś-Pstrusińska K, Szprynger K (2006) Lipid peroxidation and antioxidant enzymes in children on maintenance dialysis. Pediatr Nephrol 21:705–710

    Article  Google Scholar 

  20. Zwolińska D, Medyńska A, Szprynger K, Szczepańska M (2000) Serum concentration of IL-2, IL-6, TNF-alpha and their soluble receptors in children on maintenance hemodialysis. Nephron 86:441–446

    Article  Google Scholar 

  21. Chen W, Syldath U, Bellmann K, Burkart V, Kolb H (1999) Human 60-kDa heat shock protein: a danger signal to the innate immune system. J Immunol 162:3212-3219

    CAS  PubMed  Google Scholar 

  22. Lederer SR, Kluth B, Gruber R, Bechtel U, Feucht H, Schiffl H (1998) Heat-shock protein 65 and atherosclerosis in patients on regular hemodialysis. Nephron 79:355–356

    Article  CAS  Google Scholar 

  23. van Roon JA, van Eden W, van Roy JL, Lafeber FJ, Bijlsma JW (1997) Stimulation of suppressive T cell responses by human but not bacterial 60-kDa heat shock protein in synovial fluid of patients with rheumatoid arthritis. J Clin Invest 100:459–463

    Article  Google Scholar 

  24. Wu T, Tanguay RM (2006) Antibodies against heat shock proteins in environmental stresses and diseases: friend or foe? Cell Stress Chaperones 11:1–12

    Article  CAS  Google Scholar 

  25. Zhu J, Quyyumi AA, Rott D, Csako G, Wu H, Halcox J, Epstein SE (2001) Antibodies to human heat shock protein 60 are associated with the presence and severity of coronary artery disease: Evidence for an autoimmune component of atherosclerosis. Circulation 103:1071–1075

    Article  CAS  Google Scholar 

  26. Ghayour-Mobarhan M, New SA, Lamb DJ, Starkey BJ, Livingstone C, Wang T, Vaidya N, Ferns GA (2005) Dietary antioxidants and fat are associated with plasma antibody titers to heat shock proteins 60, 65, and 70 in subjects with dyslipidemia. Am J Clin Nutr 81:998–1004

    Article  CAS  Google Scholar 

  27. Lilien MR, Koomans HA, Schroder CH (2005) Hemodialysis acutely impairs endothelial function in children. Pediatr Nephrol 20:200–204

    Article  Google Scholar 

  28. Chanard J, Lavaud S, Randoux C, Rieu P (2003) New insights in dialysis membrane biocompatibility: relevance of adsorption properties and heparin binding. Nephrol Dial Transplant 18:252–257

    Article  CAS  Google Scholar 

  29. Wang ZZ, Wang CL, Wu TC, Pan HN, Wang SK, Jiang JD (2001) Autoantibody response to heat shock protein 70 in patients with heatstroke. Am J Med 111:654–657

    Article  CAS  Google Scholar 

  30. Prohaszka Z, Duba J, Lakos G, Kiss E, Varga L, Janoskuti L (1999) Antibodies against human hsp60 and mycobacterial hsp65 differ in their antigen specificity and complement activating ability. Int Immunol 11:1363–1370

    Article  CAS  Google Scholar 

  31. Koller H, Hochegger K, Zlabinger GJ, Lhotta K, Mayer G, Rosenkranz AR (2004) Apoptosis of human polymorphonuclear neutrophils accelerated by dialysis membranes via the activation of the complement system. Nephrol Dial Transplant 19:3104–3111

    Article  CAS  Google Scholar 

  32. Liao DF, Jin ZG, Baas AS, Daum G, Gygi SP, Aebersold R, Berk BC (2000) Purification and identification of secreted oxidative stress-induced factors from vascular smooth muscle cells. J Biol Chem 275:189–196

    Article  CAS  Google Scholar 

  33. Roldan V, Marin F, Lip GY, Blann AD (2003) Soluble E-selectin in cardiovascular disease and its risk factors. A review of the literature. Thromb Haemost 90:1007–1020

    Article  CAS  Google Scholar 

  34. Musiał K, Zwolińska D, Polak-Jonkisz D, Berny U, Szprynger K, Szczepańska M (2004) Soluble adhesion molecules in children and young adults on chronic hemodialysis. Pediatr Nephrol 19:332–336

    Article  Google Scholar 

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Correspondence to Danuta Zwolińska.

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Musiał, K., Szprynger, K., Szczepańska, M. et al. Heat shock proteins in children and young adults on chronic hemodialysis. Pediatr Nephrol 24, 2029–2034 (2009). https://doi.org/10.1007/s00467-009-1197-7

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  • DOI: https://doi.org/10.1007/s00467-009-1197-7

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