Vol 26, No 5 (2019)
Original articles — Basic science and experimental cardiology
Published online: 2018-03-26

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Proteomics study of serum exosomes in Kawasaki disease patients with coronary artery aneurysms

Xiao-Fei Xie1, Hong-Juan Chu2, Yu-Fen Xu1, Liang Hua1, Zhou-Ping Wang1, Ping Huang1, Hong-Ling Jia3, Li Zhang1
Pubmed: 29611167
Cardiol J 2019;26(5):584-593.


Background: To study the protein profile of the serum exosomes of patients with coronary artery aneurysms (CAA) caused by Kawasaki disease (KD).

Methods: Two-dimensional electrophoresis (2-DE) was used to identify proteins from the exosomes of serum obtained from children with CAA caused by KD, as well as healthy controls. Differentially expressed proteins were identified using matrix-assisted laser desorption/ionization time-of-flight/timeof-flight mass spectrometry (MALDI-TOF/TOF MS) analysis.

Results: Thirty two differentially expressed proteins were identified (18 up-regulated and 14 downregulated) from serum exosomes of children with CAA and were compared to healthy controls. The expression levels of 4 proteins (TN, RBP4, LRG1, and APOA4) were validated using Western blotting. Classification analysis and protein–protein network analysis showed that they are associated with multiple functional groups, including host immune response, inflammation, apoptotic process, developmental process, and biological adhesion process.

Conclusions: These findings establish a comprehensive proteomic profile of serum exosomes from children with CAA caused by KD, and provide additional insights into the mechanisms of CAA caused by KD.

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  1. Takahashi K, Oharaseki T, Yokouchi Y. Pathogenesis of Kawasaki disease. Clin Exp Immunol. 2011; 164 Suppl 1: 20–22.
  2. Uehara R, Belay ED. Epidemiology of Kawasaki disease in Asia, Europe, and the United States. J Epidemiol. 2012; 22(2): 79–85.
  3. Duarte R, Cisneros S, Fernandez G, et al. Kawasaki disease: a review with emphasis on cardiovascular complications. Insights Imaging. 2010; 1(4): 223–231.
  4. Sabharwal T, Manlhiot C, Benseler SM, et al. Comparison of factors associated with coronary artery dilation only versus coronary artery aneurysms in patients with Kawasaki disease. Am J Cardiol. 2009; 104(12): 1743–1747.
  5. McCrindle BW, Li JS, Minich LL, et al. Coronary artery involvement in children with Kawasaki disease: risk factors from analysis of serial normalized measurements. Circulation. 2007; 116(2): 174–179.
  6. Leung DYM, Meissner HC, Shulman ST, et al. Prevalence of superantigen-secreting bacteria in patients with Kawasaki disease. J Pediatr. 2002; 140(6): 742–746.
  7. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. 2005; 111(23): e394–e434.
  8. Lakkaraju A, Rodriguez-Boulan E. Itinerant exosomes: emerging roles in cell and tissue polarity. Trends Cell Biol. 2008; 18(5): 199–209.
  9. Simpson RJ, Jensen SS, Lim JWE. Proteomic profiling of exosomes: current perspectives. Proteomics. 2008; 8(19): 4083–4099.
  10. Vlassov AV, Magdaleno S, Setterquist R, et al. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta. 2012; 1820(7): 940–948.
  11. Wang W, Jia HL, Huang JM, et al. Identification of biomarkers for lymph node metastasis in early-stage cervical cancer by tissue-based proteomics. Br J Cancer. 2014; 110(7): 1748–1758.
  12. Ayusawa M, Sonobe T, Uemura S, et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int. 2005; 47(2): 232–234.
  13. Rekker K, Saare M, Roost AM, et al. Comparison of serum exosome isolation methods for microRNA profiling. Clin Biochem. 2014; 47(1-2): 135–138.
  14. Wu SC, Yang JCS, Rau CS, et al. Profiling circulating microRNA expression in experimental sepsis using cecal ligation and puncture. PLoS One. 2013; 8(10): e77936.
  15. Zhang Li, Jia HL, Huang WM, et al. Monitoring of the serum proteome in Kawasaki disease patients before and after immunoglobulin therapy. Biochem Biophys Res Commun. 2014; 447(1): 19–25.
  16. Cohen P, OʼGara P. Coronary Artery Aneurysms. Cardiology in Review. 2008; 16(6): 301–304.
  17. Takahashi K, Oharaseki T, Yokouchi Y, et al. Kawasaki disease as a systemic vasculitis in childhood. Ann Vasc Dis. 2010; 3(3): 173–181.
  18. Clemmensen I, Petersen LC, Kluft C. Purification and characterization of a novel, oligomeric, plasminogen kringle 4 binding protein from human plasma: tetranectin. Eur J Biochem. 1986; 156(2): 327–333.
  19. Wang ES, Sun Y, Guo JG, et al. Tetranectin and apolipoprotein A-I in cerebrospinal fluid as potential biomarkers for Parkinson's disease. Acta Neurol Scand. 2010; 122(5): 350–359.
  20. Obrist P, Spizzo G, Ensinger C, et al. Aberrant tetranectin expression in human breast carcinomas as a predictor of survival. J Clin Pathol. 2004; 57(4): 417–421.
  21. O'Donnell LC, Druhan LJ, Avalos BR. Molecular characterization and expression analysis of leucine-rich alpha2-glycoprotein, a novel marker of granulocytic differentiation. J Leukoc Biol. 2002; 72(3): 478–485.
  22. Kakisaka T, Kondo T, Okano T, et al. Plasma proteomics of pancreatic cancer patients by multi-dimensional liquid chromatography and two-dimensional difference gel electrophoresis (2D-DIGE): up-regulation of leucine-rich alpha-2-glycoprotein in pancreatic cancer. J Chromatogr B Analyt Technol Biomed Life Sci. 2007; 852(1-2): 257–267.
  23. Okano T, Kondo T, Kakisaka T, et al. Plasma proteomics of lung cancer by a linkage of multi-dimensional liquid chromatography and two-dimensional difference gel electrophoresis. Proteomics. 2006; 6(13): 3938–3948.
  24. Quadro L, Blaner WS, Salchow DJ, et al. Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein. EMBO J. 1999; 18(17): 4633–4644.
  25. Calò LA, Maiolino G, Pagnin E, et al. Increased RBP4 in a human model of activated anti-atherosclerotic and antiremodelling defences. Eur J Clin Invest. 2014; 44(6): 567–572.
  26. Bobbert T, Raila J, Schwarz F, et al. Relation between retinol, retinol-binding protein 4, transthyretin and carotid intima media thickness. Atherosclerosis. 2010; 213(2): 549–551.
  27. Steinmetz A, Barbaras R, Ghalim N, et al. Human apolipoprotein A-IV binds to apolipoprotein A-I/A-II receptor sites and promotes cholesterol efflux from adipose cells. J Biol Chem. 1990; 265(14): 7859–7863.
  28. Omori M, Watanabe M, Matsumoto K, et al. Impact of serum apolipoprotein A-IV as a marker of cardiovascular disease in maintenance hemodialysis patients. Ther Apher Dial. 2010; 14(3): 341–348.