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.
This is a preview of subscription content, log in to check access.
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.
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.
Before the experiment, informed consent from each patients’ parent or guardian was obtained.
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
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
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
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
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
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
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
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
Desai KM, Chang T, Untereiner A et al (2011) Hydrogen sulfide and the metabolic syndrome. Expert Rev Clin Pharmacol 4:63–73CrossRefPubMedGoogle Scholar
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
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
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
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
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
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
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
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
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
Liu YH, Lu M, Hu LF et al (2012) Hydrogen sulfide in the mammalian cardiovascular system. Antioxid Redox Signal 17:141–185CrossRefPubMedGoogle Scholar
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
Skovgaard N, Gouliaev A, Aalling M et al (2011) The role of endogenous H2S in cardiovascular physiology. Curr Pharm Biotechnol 12:1385–1393CrossRefPubMedGoogle Scholar
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
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
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
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
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
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
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