Insights Into Coronary Artery Lesions in Kawasaki Disease

Zhang, Danfeng; Liu, Lingjuan; Huang, Xupei; Tian, Jie

doi:10.3389/fped.2020.00493

Cited by 26 publications

(26 citation statements)

References 101 publications

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“…KD is characterized by systemic medium-sized vascular inflammation, and coronary artery lesions (CALs) are the main complication of KD vasculitis. If there is no timely high-dose intravenous immunoglobulin (IVIG) therapy, CALs could occur in ~30% KD children and bring higher hospitalization costs [ 2 ]. Although the exact molecular mechanism of KD vasculitis still remains obscure, clinical and experimental evidence has shown that KD vasculitis is closely associated with increased vascular permeability that leads to vascular leakiness, decreased plasma proteins, and inflammatory cell infiltration of endothelium [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Overexpressed Neuropilin-1 in Endothelial Cells Promotes Endothelial Permeability through Interaction with ANGPTL4 and VEGF in Kawasaki Disease

Huang

Zhang

2021

Mediators of Inflammation

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Disrupted endothelial permeability plays a crucial role in the vasculitis pathogenesis of Kawasaki disease (KD), which leads to pathological vascular leak and facilitates inflammatory cell infiltration in vascular lesions; however, the mechanisms involved in the development of endothelial barrier dysfunction during KD vasculitis are still largely unclear. Here, we found that sera from patients with KD can induce endothelial cell (EC) hyperpermeability compared to sera from healthy controls. We observed that serum vascular endothelial growth factor (VEGF) levels were increased in KD patients and sera from KD patients upregulated the expression of VEGF receptor 2 (VEGFR2) and neuropilin-1 (NRP1) in human coronary artery endothelial cells (HCAECs). Intriguingly, compared with silence of VEGFR2 in HCAECs, NRP1 silence resulted in a marked decrease in EC permeability. Furthermore, soluble NRP1 (sNRP1) remarkably reduced the stimulation of EC permeability by sera from KD patients compared with bevacizumab treatment. Importantly, we showed that besides VEGF, angiopoietin-like-4 (ANGPTL4), a NRP1-binding vasoactive factor, was also increased in KD and contributed to the EC permeability in KD conditions. In addition, levels of both ANGPTL4 and VEGF were inversely correlated with albumin levels in the serum of KD patients. Collectively, the data demonstrated that overexpressed NRP1, along with upregulated VEGFR2, in HCAECs treated with KD sera promotes endothelial permeability via interaction with the increased ANGPTL4 and VEGF in KD. Neutralization of hyperpermeability factors by sNRP1 may be a novel therapeutic strategy for KD vasculitis.

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Section: Introductionmentioning

confidence: 99%

Overexpressed Neuropilin-1 in Endothelial Cells Promotes Endothelial Permeability through Interaction with ANGPTL4 and VEGF in Kawasaki Disease

Huang

Zhang

2021

Mediators of Inflammation

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“…Inflammation of ECs is closely associated with the onset and progression of KD and its complication—CALs, which has not been fully illustrated [ 25 ]. Here, we identified a novel Sema4D-plexin B axis-mediated proinflammatory cytokine production mechanism of ECs and highlighted the pathological involvement of Sema4D in KD-CALs.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil-Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease

Huang

Cao

et al. 2020

BioMed Research International

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Inflammation of endothelial cells (ECs) plays an important role in the pathogenesis of coronary artery lesions (CALs) in Kawasaki disease (KD). Semaphorin 4D (Sema4D) is the first semaphorin shown to have immunoregulatory functions by interacting with its receptors—plexin Bs. Recently, Sema4D has been reported to exert a proinflammatory effect on the endothelium and to be involved in cardiovascular disease. However, the role of Sema4D in KD remains unknown. This study was aimed at revealing the change of soluble Sema4D (sSema4D) in the serum of patients with KD and the effect of the sSema4D-plexin axis on the production of proinflammatory cytokines from human coronary endothelial cells (HCAECs) stimulated with sera from KD patients. Our results showed that serum sSema4D levels were specifically elevated in KD patients, especially in those with CALs, and correlated positively with disease severity and serum concentrations of interleukin- (IL-) 1β, IL-6, and IL-8. The disintegrin and metalloproteinase domain 17- (AMAM17-) mediated Sema4D shedding from neutrophils contributed to the elevation of sSema4D in the serum of KD patients. Furthermore, we found that Sema4D induced IL-1β production of HCAECs via plexin B2, whereas it promoted IL-6 and IL-8 production via plexin B1. Moreover, the expression of both plexin B1 and plexin B2 was upregulated in HCAECs treated with KD sera, and silencing of the two plexin receptors suppressed the overexpression of IL-1β, IL-6, and IL-8 in KD serum-treated HCAECs. Thus, our findings indicated that sSema4D released from neutrophils participates in the pathogenesis of KD-CALs by promoting inflammatory cytokine production of ECs via both plexin B1 and plexin B2, and Sema4D may be a novel predictor for KD-CALs and a candidate therapeutic target for anti-inflammatory strategies of KD.

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“…Papers with the keyword "coronary artery diseases" (CAD) researched regulators in patients with Kawasaki disease [31] and rheumatoid arthritis [32]. In addition, they studied the use of 18F-fluorodeoxyglucose positron emission tomography imaging [33] for identifying CAD and biomarker proprotein convertase subtilisin/kexin type-9 [34] for predicting CAD.…”

Section: Purple Cluster (Part 2)mentioning

confidence: 99%

Bibliometric analysis of the inflammatory mechanism in aortic disease

Wang

Zhou

YanXiang

et al. 2022

Rev. Cardiovasc. Med.

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Background:In view of the key role of inflammation in the pathogenesis of aortic disease, we visually analyzed the research hotspots of inflammatory mechanism in aortic disease in this work through the method of bibliometrics from the Web of Science (WOS) Core database over the past three decades. Methods: A visual bibliometric network of research articles on inflammatory mechanisms in aortic disease was obtained from VOSviewer and Citespace based on the WOS Core Collection. Results: A total of 1278 documents from January 1990 to February 2021 were selected for analysis. The United States and China had the highest percentage of articles, comprising 34.01% and 24.92% of articles worldwide, respectively. Harvard University has published the most articles in this field, followed by the

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Insights Into Coronary Artery Lesions in Kawasaki Disease

Cited by 26 publications

References 101 publications

Overexpressed Neuropilin-1 in Endothelial Cells Promotes Endothelial Permeability through Interaction with ANGPTL4 and VEGF in Kawasaki Disease

Overexpressed Neuropilin-1 in Endothelial Cells Promotes Endothelial Permeability through Interaction with ANGPTL4 and VEGF in Kawasaki Disease

Neutrophil-Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease

Bibliometric analysis of the inflammatory mechanism in aortic disease

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