Serum IP-10 and IL-17 from Kawasaki disease patients induce calcification-related genes and proteins in human coronary artery smooth muscle cells in vitro

Shun Fu Chang, Shih Feng Liu, Cheng Nan Chen*, Ho Chang Kuo*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

12 Scopus citations

Abstract

Background: Kawasaki disease (KD) is one of the major causes of heart disease and vasculitis in children under 5 years old in the world. Clinical evidence has shown that coronary artery calcification may develop in KD patients, however the mechanism has not been elucidated. Previous studies have found that interferon-γ-inducible protein (IP)-10 and interleukin (IL)-17 can be elevated and may play a role in KD development and coronary artery lesion formation. The purpose of this in vitro study was to investigate the possible role of plasma circulating IP-10 and IL-17 of KD patients in vascular calcification development and its underlying mechanism. Result: Human coronary artery smooth muscle cells (HCASMCs) were used in this study. We found that HCASMCs treated with IP-10/IL-17-containing KD serum and co-treated with IP-10/IL-17 recombinant proteins could induce a phenotype that may promote vascular calcification by the bone morphogenetic protein (BMP) 6 autocrine effect. Moreover, the BMP6 autocrine stimulation in IP-10/IL-17 co-treated HCASMCs could upregulate the smad1/5-runx2 signaling activation, thus increasing the expression of bone matrix-related proteins, i.e., osteopontin, osteocalcin, and alkaline phosphatase. Conclusions: The presented in vitro results provided new insights into the comprehension of the pathogenesis of vascular calcification in SMCs in KD progression. Although additional in vivo experimental models should be completed to confirm the in vivo relevance of these in vitro findings, the results related to the autocrine role of BMP6 may provide a new direction for theranostic drug development to treat KD.

Original languageEnglish
Article number36
JournalCell and Bioscience
Volume10
Issue number1
DOIs
StatePublished - 11 03 2020

Bibliographical note

Publisher Copyright:
© 2020 The Author(s).

Keywords

  • Bone morphogenetic protein 6
  • Calcification
  • Interferon-γ-inducible protein 10
  • Interleukin 17
  • Smooth muscle cells

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