Advertisement

Pediatric Cardiology

, Volume 37, Issue 2, pp 322–329 | Cite as

Elevated Inducible Nitric Oxide Levels and Decreased Hydrogen Sulfide Levels Can Predict the Risk of Coronary Artery Ectasia in Kawasaki Disease

  • Ruixia Song
  • Guiying LiuEmail author
  • Xiaohui LiEmail author
  • Wenya Xu
  • Jia Liu
  • Hongfang Jin
Original Article

Abstract

Kawasaki disease (KD) is a vasculitis disease in children that is associated with coronary artery ectasia (CAE). We investigated whether inducible nitric oxide synthase (i-NOS) and hydrogen sulfide (H2S) could be used to predict CAE secondary to KD. We enrolled 65 children with KD (35 cases with CAE and 30 cases without CAE), 33 healthy children, and 32 children with fever but without vasculitis disease (febrile group). We measured plasma nitric oxide (NO), total nitric oxide synthase (Total-NOS), i-NOS, constructive nitric oxide synthase (c-NOS) levels, and H2S content in all patients. Plasma NO, Total-NOS, i-NOS, and H2S were higher in KD children than in healthy and febrile children (P < 0.05). The i-NOS level was higher in KD children with CAE compared to those without CAE, while the H2S was lower (both P < 0.05). Using a combination of i-NOS (higher than 10 U/mL) and H2S (lower than 3.31 μmol/L) to predict CAE had 80 % sensitivity and 81 % specificity (P < 0.05). Elevated plasma i-NOS and decreased plasma H2S levels in the acute phase of KD have good predictive value for CAE and may be used to guide appropriate clinical treatment and prevent future cardiovascular complications.

Keywords

Kawasaki disease Inducible nitric oxide synthase Hydrogen sulfide Coronary artery ectasia 

Abbreviations

AUC

Area under the curve

CAE

Coronary artery ectasia

CBS

Cystathionine-β-synthase

CSE

Cystathionine-γ-lyase

c-NOS

Constructive nitric oxide synthase

EDTA

Ethylenediamine tetraacetic acid

H2S

Hydrogen sulfide

i-NOS

Inducible nitric oxide synthase

KD

Kawasaki disease

LPS

Lipopolysaccharide

NaHS

Sodium hydrosulfide

NO

Nitric oxide

NOS

Nitric oxide synthase

O2

Superoxide anion

OH

Hydroxyl radical

ROC

Receiver operating characteristic curve

Total-NOS

Total nitric oxide synthase

Notes

Acknowledgments

This study was funded by the science foundation for Beijing Scientific Research and Technology Project (Z131100006813024), which was given to Guiying Liu.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

This research had acquired the approval from the Ethics Committee of Beijing Anzhen Hospital, China. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed Consent

Before the experiment, informed consent from each patients’ parent or guardian was obtained.

References

  1. 1.
    Adewuya O, Irie Y, Bian K et al (2003) Mechanism of vasculitis and aneurysms in Kawasaki disease: role of nitric oxide. Nitric Oxide 8:15–25CrossRefPubMedGoogle Scholar
  2. 2.
    Ayusawa M, Sonobe T, Uemura S et al (2005) Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int 47:232–234CrossRefPubMedGoogle Scholar
  3. 3.
    Azzam N, Zafrir B, Fares F et al (2015) Endothelial nitric oxide synthase polymorphism and prognosis in systolic heart failure patients. Nitric Oxide 47:91–96CrossRefPubMedGoogle Scholar
  4. 4.
    Baer Aryeh Z, Rubin Lorry G, Shapiro Craig A et al (2006) Prevalence of coronary artery lesions on the initial echocardiogram in Kawasaki syndrome. Arch Pediatr Adolesc Med 160:686–690CrossRefPubMedGoogle Scholar
  5. 5.
    Beiser AS, Takahashi M, Baker AL et al (1998) A predictive instrument for coronary artery aneurysms in Kawasaki disease. US Multicenter Kawasaki Disease Study Group. Am J Cardiol 81:1116–1120CrossRefPubMedGoogle Scholar
  6. 6.
    Belmont HM, Levartovsky D, Goel A et al (1997) Increased nitric oxide production accompanied by the up-regulation of inducible nitric oxide synthase in vascular endothelium from patients with systemic lupus erythematosus. Arthritis Rheum 40:1810–1816CrossRefPubMedGoogle Scholar
  7. 7.
    Burns JC (2007) The riddle of Kawasaki disease. N Engl J Med 356:659–661CrossRefPubMedGoogle Scholar
  8. 8.
    Cai WJ, Wang MJ, Moore PK et al (2007) The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation. Cardiovasc Res 76:29–40CrossRefPubMedGoogle Scholar
  9. 9.
    Carreras MC, Pargament GA, Catz SD et al (1994) Kinetics of nitric oxide and hydrogen peroxide production and formation of peroxynitrite during the respiratory burst of human neutrophils. FEBS Lett 341:65–68CrossRefPubMedGoogle Scholar
  10. 10.
    Desai KM, Chang T, Untereiner A et al (2011) Hydrogen sulfide and the metabolic syndrome. Expert Rev Clin Pharmacol 4:63–73CrossRefPubMedGoogle Scholar
  11. 11.
    Dinerman JL, Mehta JL (1990) Endothelial, platelet and leukocyte interactions in ischemic heart disease: insights into potential mechanisms and their clinical relevance. J Am Coll Cardiol 16:207–222CrossRefPubMedGoogle Scholar
  12. 12.
    Hongfang J, Zhenzhen L (2013) Cardiovascular regulation of the metabolic end products of endogenous sulfur-containing amino acid. J Peking Univ (Health Sci) 2:177–181 (in Chinese) Google Scholar
  13. 13.
    Iciek M, Bilska A, Ksiazek L et al (2005) Allyl disulfide as donor and cyanide as acceptor of sulfane sulfur in the mouse tissues. Pharmacol Rep 57:212–218PubMedGoogle Scholar
  14. 14.
    Ikemoto Y, Teraguchi M, Ono A et al (2003) Serial changes of plasma nitrate in the acute phase of Kawasaki disease. Pediatr Int 45:421–425CrossRefPubMedGoogle Scholar
  15. 15.
    Jin HF, Sun Y, Liang JM et al (2008) Hypotensive effects of hydrogen sulfide via attenuating vascular inflammation in spontaneously hypertensive rats. Zhonghua Xin Xue Guan Bing Za Zhi 36:541–545PubMedGoogle Scholar
  16. 16.
    Kroncke KD, Fehsel K, Kold-Bachofen V (1998) Inducible nitric oxide synthase in human diseases. Clin Exp Immunol 113:147–156PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Kubes P, Suzuki M, Granger DN (1991) Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 88:4651–4655PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Lepoivre M, Flaman JM, Bobé P et al (1994) Quenching of the tyrosyl free radical of ribonucleotide reductase by nitric oxide. Relationship to cytostasis induced in tumor cells by cytotoxic macrophages. J Biol Chem 269:21891–21897PubMedGoogle Scholar
  19. 19.
    Li L, Rossoni G, Sparatore A et al (2007) Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative. Free Radic Biol Med 42:706–719CrossRefPubMedGoogle Scholar
  20. 20.
    Li XH, Zhang CY, Wu JX et al (2011) Changes in plasma hydrogen sulfide and nitric oxide levels and their clinical significance in children with Kawasaki disease. Chin Med J (Engl) 124:3445–3449Google Scholar
  21. 21.
    Liang Y (2005) Mucocutaneous lymph node syndrome. In: Hu Y, Jiang Z (eds) Practice of pediatrics, 7th edn. People’s Medical publishing House, Beijing, pp 698–704Google Scholar
  22. 22.
    Liu YH, Lu M, Hu LF et al (2012) Hydrogen sulfide in the mammalian cardiovascular system. Antioxid Redox Signal 17:141–185CrossRefPubMedGoogle Scholar
  23. 23.
    Marsden PA, Heng HHG, Duff CL et al (1994) Localization of the human gene for inducible nitric oxide synthase(NOS2) to chromosome17q 11.2~q12. Genomics 19:l83–l85CrossRefGoogle Scholar
  24. 24.
    Skovgaard N, Gouliaev A, Aalling M et al (2011) The role of endogenous H2S in cardiovascular physiology. Curr Pharm Biotechnol 12:1385–1393CrossRefPubMedGoogle Scholar
  25. 25.
    Wang XB, Jin HF, Tang CS et al (2010) Significance of endogenous sulphur-containing gases in the cardiovascular system. Clin Exp Pharmacol Physiol 37:745–752CrossRefPubMedGoogle Scholar
  26. 26.
    Wei Lu, Jin Hongfang, Tang Changshu et al (2011) Alteration in nitric oxide/nitric oxide synthase system in aortas of spontaneously hypertensive rats. J Appl Clin Pediatr 26:530–537 (in Chinese) Google Scholar
  27. 27.
    Whiteman M, Le Trionnaire S, Chopra M et al (2011) Emerging role of hydrogen sulfide in health and disease: critical appraisal of biomarkers and pharmacological tools. Clin Sci (Lond) 121:459–488CrossRefGoogle Scholar
  28. 28.
    Yu X, Hirono KI, Ichida F et al (2004) Enhanced iNOS expression in leukocytes and circulating endothelial cells is associated with the progression of coronary artery lesions in acute kawasaki disease. Pediatr Res 55:688–694CrossRefPubMedGoogle Scholar
  29. 29.
    Yue’e H, Yuanhai Z, Rulian X et al (2008) Change and significance of NO and iNOS in coronary artery lesion of kawasaki disease. In: The fifth national pediatric young and middle-aged academic exchange conference of Chinese medical association 514-7 The fifth national pediatric young and middle-aged academic exchange conference of Chinese medical associationGoogle Scholar
  30. 30.
    Zanardo RC, Brancaleone V, Distrutti E et al (2006) Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation. FASEB J 20:2118–2120CrossRefPubMedGoogle Scholar
  31. 31.
    Zhao LL, Wang YB, Suo L (2011) Meta-analysis of the risk factors for coronary artery lesion secondary to Kawasaki disease in Chinese children. Zhonghua Er Ke Za Zhi 49:459–467PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Cardiovascular DiseasesChildren’s Hospital Affiliated to Capital Institute of PediatricsBeijingChina
  2. 2.Department of PediatricsBeijing Anzhen HospitalBeijingChina
  3. 3.Department of PediatricsPeking University First HospitalBeijingChina

Personalised recommendations