Molecular basis of coronary artery dilation and aneurysms in patients with Kawasaki disease based on differential protein expression

Liu,Wanting; Liu,Chaowu; Zhang,Li; Xie,Xiaofei; Gu,Xiaoqiong; Sang,Chuanlan; Xu,Mingguo; Xu,Weijun; Jia,Hongling

doi:10.3892/mmr.2017.8111

Molecular basis of coronary artery dilation and aneurysms in patients with Kawasaki disease based on differential protein expression

Authors:
- Wanting Liu
- Chaowu Liu
- Li Zhang
- Xiaofei Xie
- Xiaoqiong Gu
- Chuanlan Sang
- Mingguo Xu
- Weijun Xu
- Hongling Jia
View Affiliations

Affiliations: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, P.R. China, Institute of Mass Spectrometer and Atmospheric Environment, Jinan University, Guangzhou, Guangdong 510632, P.R. China, Department of Pediatric Cardiology, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong 510120, P.R. China, Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China, Department of Pediatric Cardiology, Shenzhen Children's Hospital, Shenzhen, Guangdong 518038, P.R. China, Information Center, Shenzhen Children's Hospital, Shenzhen, Guangdong 518038, P.R. China
Published online on: November 20, 2017 https://doi.org/10.3892/mmr.2017.8111
Pages: 2402-2414
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Kawasaki disease (KD) is an acquired cardiac disease with a high incidence that affects children. KD has various complications, including coronary artery dilation (CAD) and coronary artery aneurysms (CAA). The identification of differentially expressed proteins and the underlying mechanisms may be the key to understanding differences between these KD complications. In the present study, isobaric tags for relative and absolute quantitation were used to identify variations in serum proteins between KD patients with CAD and CAA. In total, 87 (37 upregulated and 50 downregulated) and 65 (33 upregulated and 32 downregulated) significantly differentially‑expressed proteins were identified in comparisons between control samples (healthy individuals) and those obtained from patients with KD and with CAD or CAA. Investigation into the underlying biological process revealed that variations between the two complications were associated with the wound healing response, as well as lipoprotein‑ and cholesterol‑associated processes. Important proteins involved in the formation of the wound healing signaling network were identified via enriched biological processes and pathway analysis using ClueGo and ReactomeFIViz software. In the present study, 5 significantly differentially‑expressed proteins, including mannose binding lectin 2 (MBL2), complement factor H (CFH), kininogen 1 (KNG1), serpin family C member 1 (SERPINC1) and fibronectin 1 (FN1), were selected and confirmed by western blotting. Analysis indicated that these proteins were associated to immunity, inflammation and metabolism, serving a key role within each module, which has never been reported previously. The present study proposed that MBL2, CFH, KNG1, SERPINC1 and FN1 may be a potentially excellent indicator group for distinguishing the two major KD complications, CAD and CAA.

View Figures

View References

1	Kawasaki T: Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Allergy. 16:178–222. 1967.(In Japanese). PubMed/NCBI
2	Chen KY, Curtis N, Dahdah N, Kowalski R, Cheung M and Burgner DP: Kawasaki disease and cardiovascular risk: A comprehensive review of subclinical vascular changes in the longer term. Acta Paediatric. 105:752–761. 2016. View Article : Google Scholar
3	Kato H, Koike S, Yamamoto M, Ito Y and Yano E: Coronary aneurysms in infants and young children with acute febrile mucocutaneous lymph node syndrome. J Pediatr. 86:892–898. 1975. View Article : Google Scholar : PubMed/NCBI
4	Uehara R and Belay ED: Epidemiology of Kawasaki disease in Asia, Europe, and the United States. J Epidemiol. 22:79–85. 2012. View Article : Google Scholar : PubMed/NCBI
5	Singh S, Vignesh P and Burgner D: The epidemiology of Kawasaki disease: A global update. Arch Dis Child. 100:1084–1088. 2015. View Article : Google Scholar : PubMed/NCBI
6	Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, Shulman ST, Bolger AF, Ferrieri P, Baltimore RS, et al: Diagnosis, treatment, and long-term management of Kawasaki disease: A statement for health professionals from the committee on rheumatic fever, endocarditis and Kawasaki disease, council on cardiovascular disease in the young, American heart association. Circulation. 110:2747–2771. 2004. View Article : Google Scholar : PubMed/NCBI
7	Mueller F, Knirsch W, Harpes P, Pretre R, Valsangiacomo Buechel E and Kretschmar O: Long-term follow-up of acute changes in coronary artery diameter caused by Kawasaki disease: Risk factors for development of stenotic lesions. Clin Res Cardiol. 98:501–507. 2009. View Article : Google Scholar : PubMed/NCBI
8	Aebersold R and Mann M: Mass spectrometry-based proteomics. Nature. 422:198–207. 2003. View Article : Google Scholar : PubMed/NCBI
9	Celis JE, Gromov P, Cabezón T, Moreira JM, Ambartsumian N, Sandelin K, Rank F and Gromova I: Proteomic characterization of the interstitial fluid perfusing the breast tumor microenvironment: A novel resource for biomarker and therapeutic target discovery. Mol Cell Proteomics. 3:327–344. 2004. View Article : Google Scholar : PubMed/NCBI
10	Ray S, Reddy PJ, Jain R, Gollapalli K, Moiyadi A and Srivastava S: Proteomic technologies for the identification of disease biomarkers in serum: Advances and challenges ahead. Proteomics. 11:2139–2161. 2011. View Article : Google Scholar : PubMed/NCBI
11	Ayusawa M, Sonobe T, Uemura S, Ogawa S, Nakamura Y, Kiyosawa N, Ishii M and Harada K; Kawasaki Disease Research Committee, : Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int. 47:232–234. 2005. View Article : Google Scholar : PubMed/NCBI
12	Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pagès F, Trajanoski Z and Galon J: ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 25:1091–1093. 2009. View Article : Google Scholar : PubMed/NCBI
13	Wu G, Dawson E, Duong A, Haw R and Stein L: ReactomeFIViz: A Cytoscape app for pathway and network-based data analysis. F1000Res. 3:1462014.PubMed/NCBI
14	Komatsu H and Fujisawa T: Kawasaki disease and infection. Nihon Rinsho. 66:278–282. 2008.(In Japanese). PubMed/NCBI
15	Lee KY, Lee HS, Hong JH, Han JW, Lee JS and Whang KT: High-dose intravenous immunoglobulin downregulates the activated levels of inflammatory indices except erythrocyte sedimentation rate in acute stage of Kawasaki Disease. J Trop Pediatr. 51:98–101. 2005. View Article : Google Scholar : PubMed/NCBI
16	Adler AC and Kodavatiganti R: Kawasaki disease and giant coronary artery aneurysms: The role of echocardiography from diagnosis through follow-up. Echocardiography. 33:1245–1250. 2016. View Article : Google Scholar : PubMed/NCBI
17	Greco A, De Virgilio A, Rizzo MI, Tombolini M, Gallo A, Fusconi M, Ruoppolo G, Pagliuca G, Martellucci S and de Vincentiis M: Kawasaki disease: An evolving paradigm. Autoimmun Rev. 14:703–709. 2015. View Article : Google Scholar : PubMed/NCBI
18	Burns JC, Herzog L, Fabri O, Tremoulet AH, Rodó X, Uehara R, Burgner D, Bainto E, Pierce D, Tyree M, et al: Seasonality of Kawasaki disease: A globalperspective. PLoS One. 8:e745292013. View Article : Google Scholar : PubMed/NCBI
19	Watanabe T: Kidney and urinary tract involvement in Kawasaki disease. Int J Pediatr. 2013:8318342013. View Article : Google Scholar : PubMed/NCBI
20	Blankier S, McCrindle BW, Ito S and Yeung RS: The role of atorvastatin in regulating the immune response leading to vascular damage in a model of Kawasaki disease. Clin Exp Immunol. 164:193–201. 2011. View Article : Google Scholar : PubMed/NCBI
21	Yoon KL: Update of genetic susceptibility in patients with Kawasaki disease. Korean J Pediatr. 58:84–88. 2015. View Article : Google Scholar : PubMed/NCBI
22	Perkins SJ, Fung KW and Khan S: Molecular interactions between complement factor H and its heparin and heparan sulfate ligands. Front Immunol. 5:1262014. View Article : Google Scholar : PubMed/NCBI
23	Biezeveld MH, Geissler J, Weverling GJ, Kuipers IM, Lam J, Ottenkamp J and Kuijpers TW: Polymorphisms in the mannose-binding lectin gene as determinants of age-defined risk of coronary artery lesions in Kawasaki disease. Arthritis Rheum. 54:369–376. 2006. View Article : Google Scholar : PubMed/NCBI
24	Brunel H, Massanet R, Martinez-Perez A, Ziyatdinov A, Martin-Fernandez L, Souto JC, Perera A and Soria JM: The central role of KNG1 gene as a genetic determinant of coagulation pathway-related traits: Exploring metaphenotypes. PLoS One. 11:e01671872016. View Article : Google Scholar : PubMed/NCBI
25	Weng LC, Cushman M, Pankow JS, Basu S, Boerwinkle E, Folsom AR and Tang W: A genetic association study of activated partial thromboplastin time in European Americans and African Americans: The ARIC study. Hum Mol Genet. 24:2401–2408. 2015. View Article : Google Scholar : PubMed/NCBI
26	Tang W, Schwienbacher C, Lopez LM, Ben-Shlomo Y, Oudot-Mellakh T, Johnson AD, Samani NJ, Basu S, Gögele M, Davies G, et al: Genetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease. Am J Hum Genet. 91:152–162. 2012. View Article : Google Scholar : PubMed/NCBI
27	Iba T and Thachil J: Is antithrombin III for sepsis-associated disseminated intravascular coagulation really ineffective? Intensive Care Med. 42:1193–1194. 2016. View Article : Google Scholar : PubMed/NCBI
28	Simioni P, Tormene D, Spiezia L, Tognin G, Rossetto V, Radu C and Prandoni P: Inherited thrombophilia and venous thromboembolism. Semin Thromb Hemost. 32:700–708. 2006. View Article : Google Scholar : PubMed/NCBI
29	Cooper PC, Coath F, Daly ME and Makris M: The phenotypic and genetic assessment of antithrombin deficiency. Int J Lab Hematol. 33:227–237. 2011. View Article : Google Scholar : PubMed/NCBI
30	Ohtsubo H, Okada T, Nozu K, Takaoka Y, Shono A, Asanuma K, Zhang L, Nakanishi K, Taniguchi-Ikeda M, Kaito H, et al: Identification of mutations in FN1 leading to glomerulopathy with fibronectin deposits. Pediatr Nephrol. 31:1459–1467. 2016. View Article : Google Scholar : PubMed/NCBI