The role of Ca2+/NFAT in Dysfunction and Inflammation of Human Coronary Endothelial Cells induced by Sera from patients with Kawasaki disease
The role of Ca2+/NFAT in Dysfunction and Inflammation of Human Coronary Endothelial Cells induced by Sera from patients with Kawasaki disease
复制标题
Ca2+/NFAT在川崎病血清诱导人冠状动脉内皮细胞功能障碍和炎症中的作用
DOI：
10.1038/s41598-020-61667-y
复制
发表时间：
2020-03-13
影响因子：
4.6
通讯作者：
Gong, Fangqi
中科院分区：
文献类型：
--
作者：
Wang, Ying;Hu, Jian;Gong, Fangqi
活化t细胞Ca2+/核因子（Ca2+/NFAT）信号通路可能在川崎病（Kawasaki disease， KD）的发病机制中起重要作用。我们研究了尚不清楚的Ca2+/NFAT对冠状动脉内皮细胞的调节及其在KD发病机制中的功能障碍。与健康儿童血清相比，KD患者血清刺激的人冠状动脉内皮细胞（HCAECs）增殖和血管生成明显增加，NFATc1和NFATc3及一些炎症分子水平升高，NFATc1和NFATc3核易位增加。与未治疗的hcaec相比，经环孢素A （CsA）治疗的KD患者血清刺激的hcaec显示增殖、血管生成、NFATc1和炎症分子水平降低。总之，我们的数据显示，KD血清激活hcaec中的Ca2+/NFAT，导致内皮细胞功能障碍和炎症。CsA通过Ca2+/NFAT改善内皮细胞稳态，具有细胞保护作用。
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.