Skip to main content

Advertisement

Log in

Oxidised Low-Density Lipoprotein and Its Receptor-Mediated Endothelial Dysfunction Are Associated with Coronary Artery Lesions in Kawasaki Disease

  • Original Article
  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

The study aimed to investigate the role of oxidised low-density lipoprotein (oxLDL)/lectin-like-oxLDL receptor-1 (LOX-1) in coronary artery lesions (CALs) in Kawasaki disease (KD) and of plasma oxLDL concentration in the early prediction of CALs in KD. This prospective study included 80 KD patients, 20 febrile and 20 healthy children. oxLDL, LOX-1 and other parameters were analysed in the acute phase. Plasma oxLDL concentration and LOX-1 mRNA expression in peripheral blood mononuclear cells (PBMCs) were significantly increased in KD patients compared with febrile and healthy children (P < 0.001 and P = 0.022, respectively), particularly in the group with CALs (P < 0.001 and P = 0.027, respectively). Coronary Z-score was significantly correlated with plasma oxLDL concentration and LOX-1 mRNA expression (r = 0.739 and 0.637, respectively; P < 0.01). The sensitivity and specificity of predicting CALs were 71.4% and 77.2%, respectively, at plasma oxLDL concentration ≥ 12.38 mU/L. oxLDL/LOX-1 may be involved in CAL development. The plasma oxLDL concentration in the acute phase is a potentially useful biological indicator for predicting CAL in KD patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

ALB:

albumin

ALT:

alanine aminotransferase

AST:

aspartate aminotransferase

CAL:

coronary artery lesion

CRP:

C-reactive protein

ELISA:

enzyme-linked immunosorbent assay

ESR:

erythrocyte sedimentation rate

Hb:

haemoglobin

IVIG:

intravenous immunoglobulin

LOX-1:

lectin-like-oxLDL receptor-1

Na+ :

serum sodium

NT-proBNP:

N-terminal pro brain natriuretic peptide

oxLDL:

oxidised low-density lipoprotein

N:

neutrophil ratio

Plt:

platelet count

KD:

Kawasaki disease

NCAL:

non-CAL

PCR:

polymerase chain reaction

WBC:

white blood cell count

PBMCs:

peripheral blood mononuclear cells

TG:

triglyceride

TC:

total cholesterol

LDL:

low-density lipoprotein cholesterol

HDL:

high-density lipoprotein cholesterol

References

  1. McCrindle, B. W., Rowley, A. H., Newburger, J. W., et al. (2017). Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for hearth professionals from the American Heart Association. Circulation, 135(17), e927–e999.

    Article  Google Scholar 

  2. Cheung, Y. F. (2014). Vascular health late after Kawasaki disease: Implications for accelerated atherosclerosis. Korean Journal of Pediatrics, 57, 472–478.

    Article  Google Scholar 

  3. Zhang, J., Tuokan, T., & Shi, Y. (2018). Sudden death as a sequel of ruptured giant coronary artery aneurysm in Kawasaki disease. The American Journal of Forensic Medicine and Pathology, 39(4), 375–377.

    PubMed  Google Scholar 

  4. Nomura, O., Fukuda, S., Ota, E., Ono, H., Ishiguro, A., & Kobayashi, T. (2016). Monoclonal antibody therapy for Kawasaki disease: A protocol for systematic reviews and meta-analysis. Systematic Reviews, 5(60). https://doi.org/10.1186/s13643-016-0236-2.

  5. Youn, Y., Kim, J., Hong, Y. M., & Sohn, S. (2016). Infliximab as the first retreatment in patients with Kawasaki disease resistant to initial intravenous immunoglobulin. The Pediatric Infectious Disease Journal, 35(4), 457–459. https://doi.org/10.1097/INF.0000000000001039.

    Article  PubMed  Google Scholar 

  6. Singh, S., Bhattad, S., & Gupta, A. (2016). Mortality in children with Kawasaki disease: 20 years of experience from a tertiary care Centre in North India. Clinical and Experimental Rheumatology, 34(3 Suppl 97), 129–133.

    Google Scholar 

  7. Woo, H. O. (2019). Predictive risk factors of coronary artery aneurysms in Kawasaki disease. Korean Journal of Pediatrics. https://doi.org/10.3345/kjp.2019.00073.

  8. Sun, Y., Yuan, Y., Yan, H., et al. (2015). Plasma H2S predicts coronary artery lesions in children with Kawasaki disease. Pediatrics International, 57, 840–844.

    Article  CAS  Google Scholar 

  9. Jeon, S. K., Kim, G., Ko, H., Byun, J. H., & Lee, H. D. (2018). Risk factors for the occurrence and persistence of coronary aneurysm in Kawasaki disease. Korean Journal of Pediatrics. https://doi.org/10.3345/kjp.2018.07052.

  10. Yahata, T., & Hamaoka, K. (2017). Oxidative stress and Kawasaki disease: How is oxidative stress involved from the acute stage to the chronic stage? Rheumatology (Oxford), 56, 6–13.

    Article  CAS  Google Scholar 

  11. Koibuchi, H., Kotani, K., Minami, T., Konno, K., & Taniguchi, N. (2016). Endothelial dysfunction by flow-mediated dilation assessed ultrasonically in patients with Kawasaki disease. Minerva Pediatrica, 68, 143–147.

    PubMed  Google Scholar 

  12. Mori, Y., Katayama, H., Kishi, K., Ozaki, N., Shimizu, T., & Tamai, H. (2016). Persistent high fever for more than 10 days during acute phase is a risk factor for endothelial dysfunction in children with a history of Kawasaki disease. Journal of Cardiology, 68, 71–75.

    Article  Google Scholar 

  13. Lubrano, V., & Balzan, S. (2016). Roles of LOX-1 in microvascular dysfunction. Microvascular Research, 105, 132–140. https://doi.org/10.1016/j.mvr.2016.02.006.

    Article  CAS  PubMed  Google Scholar 

  14. Tsai, K. L., Chang, Y. L., Huang, P. H., Cheng, Y. H., Liu, D. H., Chen, H. Y., & Kao, C. L. (2016). Ginkgo biloba extract inhibits oxidised low-density lipoprotein (oxLDL)-induced matrix metalloproteinase activation by the modulation of the lectin-like oxLDL receptor 1-regulated signalling pathway in human umbilical vein endothelial cells. Journal of Vascular Surgery, 63, 204–215.e1.

    Article  Google Scholar 

  15. Ji, K. T., Qian, L., Nan, J. L., et al. (2015). Ox-LDL induces dysfunction of endothelial progenitor cells via activation of NF-κB. BioMed Research International, 2015, 175291.

    PubMed  PubMed Central  Google Scholar 

  16. Stancel, N., Chen, C. C., Ke, L. Y., Chu, C. S., Lu, J., Sawamura, T., & Chen, C. H. (2016). Interplay between CRP, atherogenic LDL, and LOX-1 and its potential role in the pathogenesis of atherosclerosis. Clinical Chemistry, 62(2), 320–327. https://doi.org/10.1373/clinchem.2015.243923.

    Article  CAS  PubMed  Google Scholar 

  17. Arjuman, A., & Chandra, N. C. (2017). LOX-1: A potential target for therapy in atherosclerosis; an in vitro study. The International Journal of Biochemistry & Cell Biology, 91, 65–80. https://doi.org/10.1016/j.biocel.2017.08.013.

    Article  CAS  Google Scholar 

  18. Di Pietro, N., Formoso, G., & Pandolfi, A. (2016). Physiology and pathophysiology of oxLDL uptake by vascular wall cells in atherosclerosis. Vascular Pharmacology, 84, 1–7. https://doi.org/10.1016/j.vph.2016.05.013.

    Article  CAS  PubMed  Google Scholar 

  19. Freeman, A. F., & Shulman, S. T. (2006). Kawasaki disease: Summary of the American Heart Association guidelines. American Family Physician, 74(7), 1141–1148.

    PubMed  Google Scholar 

  20. Saguil, A., Fargo, M., & Grogan, S. (2015). Diagnosis and management of Kawasaki disease. American Family Physician, 91(6), 365–371.

    PubMed  Google Scholar 

  21. Newburger, J. W., Takahashi, M., & Burns, J. C. (2016). Kawasaki disease. Journal of the American College of Cardiology, 67, 1738–1749.

    Article  Google Scholar 

  22. Vostokova, A. A., Grunina, E. A., & Klemenov, A. V. (2016). Aftermaths of lesions of coronary arteries in Kawasaki disease. Angiol Sosud Khir, 22(1), 46–51.

    CAS  PubMed  Google Scholar 

  23. Singhal, M., Vignesh, P., Khandelwal, N., & Singh, S. (2018). Calcified saccular coronary artery aneurysm of Kawasaki disease. Journal of Clinical Rheumatology. https://doi.org/10.1097/RHU.0000000000000953.

  24. Tsuda, E., Tsujii, N., & Hayama, Y. (2018). Stenotic lesions and the maximum diameter of coronary artery aneurysms in Kawasaki disease. The Journal of Pediatrics, 194, 165–170.e2. https://doi.org/10.1016/j.jpeds.2017.09.077.

    Article  PubMed  Google Scholar 

  25. Gravel, H., Curnier, D., Dallaire, F., Fournier, A., Portman, M., & Dahdah, N. (2015). Cardiovascular response to exercise testing in children and adolescents late after Kawasaki disease according to coronary condition upon onset. Pediatric Cardiology, 36(7), 1458–1464. https://doi.org/10.1007/s00246-015-1186-5.

    Article  PubMed  Google Scholar 

  26. Chistiakov, D. A., Orekhov, A. N., & Bobryshev, Y. V. (2016). LOX-1-mediated effects on vascular cells in atherosclerosis. Cellular Physiology and Biochemistry, 38(5), 1851–1859. https://doi.org/10.1159/000443123.

    Article  CAS  PubMed  Google Scholar 

  27. Lubrano, V., & Balzan, S. (2014). LOX-1 and ROS, inseparable factors in the process of endothelial damage. Free Radical Research, 48(8), 841–848. https://doi.org/10.3109/10715762.2014.929122.

    Article  CAS  PubMed  Google Scholar 

  28. Zhao, W., Ma, G., & Chen, X. (2014). Lipopolysaccharide induced LOX-1 expression via TLR4/MyD88/ROS activated p38MAPK/NF-κB pathway. Vascular Pharmacology, 63(3), 162–172.

    Article  CAS  Google Scholar 

  29. Ishikawa, T., & Seki, K. (2018). The association between oxidative stress and endothelial dysfunction in early childhood patients with Kawasaki disease. BMC Cardiovascular Disorders, 18(1), 30. https://doi.org/10.1186/s12872-018-0765-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Takahashi, K., Oharaseki, T., & Yokouchi, Y. (2018). Histopathological aspects of cardiovascular lesions in Kawasaki disease. International Journal of Rheumatic Diseases, 21(1), 31–35. https://doi.org/10.1111/1756-185X.13207.

    Article  CAS  PubMed  Google Scholar 

  31. Chen, K. Y., Curtis, N., Dahdah, N., Kowalski, R., Cheung, M., & Burgner, D. P. (2016). Kawasaki disease and cardiovascular risk: A comprehensive review of subclinical vascular changes in the longer term. Acta Paediatrica, 105, 752–761.

    Article  Google Scholar 

  32. Duan, C., Du, Z. D., Wang, Y., & Jia, L. Q. (2014). Effect of pravastatin on endothelial dysfunction in children with medium to giant coronary aneurysms due to Kawasaki disease. World Journal of Pediatrics, 10, 232–237.

    Article  CAS  Google Scholar 

  33. Huang, M., Dong, G. Q., Jiang, H. Y., Zhang, J. Y., & Shi, X. J. (2015). Serum adiponectin levels in children with Kawasaki disease. Zhongguo Dang Dai Er Ke Za Zhi, 17(1), 35–39.

    CAS  PubMed  Google Scholar 

  34. Zhang, H., Xu, M. G., Xie, L. J., Huang, M., Shen, J., & Xiao, T. T. (2016). Meta-analysis of risk factors associated with atherosclerosis in patients with Kawasaki disease. World Journal of Pediatrics, 12(3), 308–313.

    Article  CAS  Google Scholar 

  35. Mostafavi, N., Haghjooy-Javanmard, S., Presidend, N., Manssori, N. S., & Kelishadi, R. (2015). Persistence of endothelial cell damage late after Kawasaki disease in patients without coronary artery complications. Advanced Biomedical Research, 4, 25. https://doi.org/10.4103/2277-9175.150393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pinto, F. F., Gomes, I., Loureiro, P., Laranjo, S., Timóteo, A. T., & Carmo, M. M. (2017). Vascular function long term after Kawasaki disease: Another piece of the puzzle? Cardiology in the Young, 27(3), 488–497. https://doi.org/10.1017/S1047951116000780.

    Article  PubMed  Google Scholar 

  37. McCrindle, B. W., & Harris, K. C. (2018). Coronary artery aneurysms after Kawasaki disease: Understanding the pathology. The Canadian Journal of Cardiology, 34(9), 1094–1097.

    Article  Google Scholar 

  38. Denby, K. J., Clark, D. E., & Markham, L. W. (2017). Management of Kawasaki disease in adults. Heart, 103(22), 1760–1769. https://doi.org/10.1136/heartjnl-2017-311774.

    Article  CAS  PubMed  Google Scholar 

  39. Kim, M. K., Song, M. S., & Kim, G. B. (2018). Factors predicting resistance to intravenous immunoglobulin treatment and coronary artery lesion in patients with Kawasaki disease: Analysis of the Korean nationwide multicenter survey from 2012 to 2014. Korean Circulation Journal, 48(1), 71–79.

    Article  CAS  Google Scholar 

  40. Lee, H. Y., & Song, M. S. (2016). Predictive factors of resistance to intravenous immunoglobulin and coronary aneurysm lesions in Kawasaki disease. Korean Journal of Pediatrics, 59(12), 477–482.

    Article  CAS  Google Scholar 

  41. Dionne, A., & Dahdah, N. (2018). A decade of NT-proBNP in acute Kawasaki disease, from physiological response to clinical relevance. Children, 5(10), 141.

    Article  Google Scholar 

Download references

What Are the Clinical Implications

Elevated plasma oxLDL concentration in the acute phase can predict CAL in KD.

A study on oxLDL/LOX-1 and its related signalling pathways may provide a new breakthrough for the prevention and treatment of CAL caused by KD.

Funding

This work was supported by grants from the Natural Science Foundation of Zhejiang Province (No. LQ16H020008, LQ15H020006), Medical and Health Project of Zhejiang Province (No. 2017KY465, 2014KYA41) and Science and Technology Project of Wenzhou (No. Y20170134), Zhejiang, China.

Author information

Authors and Affiliations

Authors

Contributions

Study conception and design: Yue-E He, Mao-Ping Chu; data acquisition: Yue-E He, Mao-Ping Chu, Hui-Xian Qiu, Rong-Zhou Wu; analysis and data interpretation: Xing Rong, Hai-Tang Xu, Ru-Lian Xiang; drafting of the manuscript; critical revision: Yue-E He, Mao-Ping Chu.

Corresponding author

Correspondence to Mao-Ping Chu.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The study was conducted according to the Declaration of Helsinki. The ethical committee of the Wenzhou Medical University approved the study. No animal studies were carried out by the authors for this article.

Informed Consent

The parents of all participants provided written informed consent.

Additional information

Associate Editor Craig Stolen oversaw the review of this article

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

He, YE., Qiu, HX., Wu, RZ. et al. Oxidised Low-Density Lipoprotein and Its Receptor-Mediated Endothelial Dysfunction Are Associated with Coronary Artery Lesions in Kawasaki Disease. J. of Cardiovasc. Trans. Res. 13, 204–214 (2020). https://doi.org/10.1007/s12265-019-09908-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-019-09908-y

Keywords

Navigation