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棕榈酸,一种关键代谢物,通过在川崎病中产生活性氧加重细胞衰老。

Palmitic Acid, A Critical Metabolite, Aggravates Cellular Senescence Through Reactive Oxygen Species Generation in Kawasaki Disease.

作者信息

Zhu Qiongjun, Dong Qianqian, Wang Xuliang, Xia Tianhe, Fu Yu, Wang Qiaoyu, Wu Rongzhou, Wu Tingting

机构信息

Children's Heart Center, The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Zhejiang, China.

出版信息

Front Pharmacol. 2022 Mar 23;13:809157. doi: 10.3389/fphar.2022.809157. eCollection 2022.

Abstract

Coronary artery lesions (CALs) are severe complications of Kawasaki disease (KD), resulting in stenosis and thrombogenesis. Metabolomic profiling of patients' plasma could assist in elucidating the pathogenesis of CALs and identifying diagnostic biomarkers, which are imperative for clinical treatment. The metabolic profiles between KD patients with CALs and without CALs (non-coronary artery lesion, or NCAL, group) indicated the most significantly differentially expressed metabolite, palmitic acid (PA), showed the most massive fold change at 9.879. Furthermore, PA was proven to aggravate endothelial cellular senescence by increasing the generation of reactive oxygen species (ROS) in KD, and those two phenotypes were confirmed to be enriched among the differentially expressed genes between KD and normal samples from GEO datasets. Collectively, our findings indicate that cellular senescence may be one of the mechanisms of vascular endothelial damage in KD. PA may be a biomarker and potential therapeutic target for predicting the occurrence of CALs in KD patients. All things considered, our findings confirm that plasma metabolomics was able to identify promising biomarkers and potential pathogenesis mechanisms in KD. To conclude, Palmitic acid could be a novel target in future studies of CALs in patients with KD.

摘要

冠状动脉病变(CALs)是川崎病(KD)的严重并发症,可导致血管狭窄和血栓形成。对患者血浆进行代谢组学分析有助于阐明CALs的发病机制并识别诊断生物标志物,这对临床治疗至关重要。患有CALs的KD患者与未患CALs(非冠状动脉病变,即NCAL组)的KD患者之间的代谢谱显示,差异表达最显著的代谢物棕榈酸(PA)的变化倍数最大,为9.879。此外,已证实PA通过增加KD患者体内活性氧(ROS)的生成来加重内皮细胞衰老,并且在来自GEO数据集的KD与正常样本之间的差异表达基因中,这两种表型均得到富集。总体而言,我们的研究结果表明细胞衰老可能是KD患者血管内皮损伤的机制之一。PA可能是预测KD患者发生CALs的生物标志物和潜在治疗靶点。综合考虑,我们的研究结果证实血浆代谢组学能够识别KD中有前景的生物标志物和潜在的发病机制。总之,棕榈酸可能是未来KD患者CALs研究中的一个新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe75/8983937/7ad9dbda3d0c/fphar-13-809157-g001.jpg

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