Abstract
Ca2+/nuclear factor of activated T-cells (Ca2+/NFAT) signaling pathway may play a crucial role in the pathogenesis of Kawasaki disease (KD). We investigated the poorly understood Ca2+/NFAT regulation of coronary artery endothelial cells and consequent dysfunction in KD pathogenesis. Human coronary artery endothelial cells (HCAECs) stimulated with sera from patients with KD, compared with sera from healthy children, exhibited significant increases in proliferation and angiogenesis, higher levels of NFATc1 and NFATc3 and some inflammatory molecules, and increased nuclear translocation of NFATc1 and NFATc3. HCAECs stimulated with sera from patients with KD treated with cyclosporine A (CsA) showed decreased proliferation, angiogenesis, NFATc1 and inflammatory molecules levels as compared with results for untreated HCAECs. In conclusion, our data reveal that KD sera activate the Ca2+/NFAT in HCAECs, leading to dysfunction and inflammation of endothelial cells. CsA has cytoprotective effects by ameliorating endothelial cell homeostasis via Ca2+/NFAT.
Highlights
Www.nature.com/scientificreports mRNA levels were measured by qPCR (a: all samples were normalized to Human coronary artery endothelial cells (HCAECs) with 15% fetal bovine serum (FBS) treatment), and protein levels in HCAECs were measured by Western blot (b; healthy control (HC), n = 5 and Kawasaki disease (KD), n = 12)
NFATc1 mRNA levels in HCAECs treated with KD sera were higher than those treated with healthy control (HC) sera (n = 29, median 0.89 vs. n = 8, median 0.55, P = 0.0212) (Fig. 1a)
NFATc3 mRNA levels were higher in HCAECs treated with KD sera when compared with HC (n = 29, median 0.35 vs. n = 8, median 0.27, P = 0.0084) (Fig. 1a)
Summary
Recent studies have confirmed that vascular endothelial cells (VECs) play a very important role in the coronary artery injury of KD5. The Ca2+/NFAT signaling pathway plays an important role in maintaining normal structure and function of VECs. mRNA levels were measured by qPCR (a: all samples were normalized to HCAECs with 15% FBS treatment), and protein levels in HCAECs were measured by Western blot (b; HC, n = 5 and KD, n = 12). Genetic analysis revealed mutations in 16 sites of key genes of Ca2+/NFAT signaling pathway in children with KD; and the mutant rs1561876AA is strongly correlated with vasculitis in KD15,16. These findings further suggest that the Ca2+/NFAT signaling pathway plays an important role in KD coronary artery injury. The molecular mechanism of Ca2+/NFAT signaling pathway in KD coronary artery injury remain unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
