Circulating endothelial cells in Kawasaki disease

Nakatani, Keigo; Takeshita, Satoshi; Takahashi, Hiroshi; Kawamura, Yoichi; Tokutomi, Tomoharu; Sekine, Isao

doi:10.1046/j.1365-2249.2003.02091.x

Cited by 81 publications

(50 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These previous studies have elegantly demonstrated an essential role of Nlrp3 inflammasome in mediating the inflammatory response by macrophages, however, it remains unknown about the actions of Nlrp3 inflammasomes in vascular cell dysfunction or injury such as endothelial dysfunction, which has been suggested to the earliest step in the development of coronary arteritis as well as atherosclerosis. [33–35]. In the present study, we first demonstrated that LCWE-induced coronary arteritis in a mouse model for Kawasaki disease was suscessfuly developed as shown by enhanced endothelial expression of VCAM-1 and increased adhesion of leukocytes to the coronary arterial walls (Fig.…”

Section: Discussionsupporting

confidence: 50%

Endothelial Nlrp3 inflammasome activation associated with lysosomal destabilization during coronary arteritis

Yang

Boini

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

Inflammasomes play a critical role in the development of vascular diseases. However, the molecular mechanisms activating the inflammasome in endothelial cells and the relevance of this inflammasome activation is far from clear. Here, we investigated the mechanisms by which Nlrp3 inflammasome is activated to result in endothelial dysfunction during coronary arteritis by Lactobacillus casei (L. casei) cell wall fragments (LCWE) in a mouse model for Kawasaki disease. Endothelial dysfunction associated with increased vascular cell adhesion protein 1 (VCAM-1) expression and endothelial-leukocyte adhesion was observed during coronary arteritis in mice treated with LCWE. Accompanied with these changes, the inflammasome activation was also shown in coronary arterial endothelium, which was characterized by a marked increase in caspase-1 activity and IL-1β production. In cultured endothelial cells, LCWE induced Nlrp3 inflammasome formation, caspase-1 activation and IL-1β production, which were blocked by Nlrp3 gene silencing or lysosome membrane stabilizing agents such as colchicine, dexamethasome, and ceramide. However, a potassium channel blocker glibenclamide or an oxygen free radical scavenger N-Acetyl-L-cysteine had no effects on LCWE-induced inflammasome activation. LCWE also increased endothelial cell lysosomal membrane permeability and triggered lysosomal cathepsin B release into cytosol. Silencing cathepsin B blocked LCWE-induced Nlrp3 inflammasome formation and activation in endothelial cells. In vivo, treatment of mice with cathepsin B inhibitor also abolished LCWE-induced inflammasome activation in coronary arterial endothelium. It is concluded that LCWE enhanced lysosomal membrane permeabilization and consequent release of lysosomal cathepsin B, resulting in activation of endothelial Nlrp3 inflammasome, which may contribute to the development of coronary arteritis.

show abstract

Section: Discussionsupporting

confidence: 50%

Endothelial Nlrp3 inflammasome activation associated with lysosomal destabilization during coronary arteritis

Yang

Boini

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

show abstract

“…2 Data on other forms of vasculitis are limited, but recent data in Kawasaki's disease suggest that increased numbers of CECs may be common to all vasculitides. 16 It must be noted, however, that our previous study had limitations. In particular, patients with disease relapse or limited granulomatous disease due to WG were not included in our previous series.…”

Section: Discussionmentioning

confidence: 83%

Circulating endothelial cells in relapse and limited granulomatous disease due to ANCA associated vasculitis

Woywodt

Goldberg²,

Kirsch³

et al. 2006

Annals of the Rheumatic Diseases

View full text Add to dashboard Cite

Objectives: To evaluate numbers of circulating endothelial cells (CECs) in ANCA associated vasculitis and compare vasculitic relapse with limited granulomatous disease. Methods: Sixteen patients with vasculitic relapse of ANCA associated vasculitis and 12 patients with limited granulomatous disease due to Wegener's granulomatosis (WG) were studied. Six patients with newly diagnosed vasculitic disease and six patients with vasculitis with infectious complications were also studied. Twenty two patients in remission were studied, as were 20 healthy controls. Counting of CECs was performed with anti-CD146 driven immunomagnetic isolation and staining with Ulex Europaeus lectin 1(UEA-1). Results: Patients with vasculitic relapse had markedly increased numbers of circulating endothelial cells (12-800 cells/ml, median 88 cells/ml) as did patients with newly diagnosed systemic vasculitis (20-216 cells/ml, median 56 cells/ml). Patients with limited granulomatous disease due to WG had only slightly increased cell numbers (4-44 cells/ml, median 20 cells/ml), which were similar to those of patients in remission (4-36 cells/ml, median 16 cells/ml). Numbers of CECs in patients with granulomatous disease were significantly lower than in those patients with relapse or new onset vasculitis (p,0.001). Cell numbers in patients with relapse and new onset vasculitis declined with immunosuppressive treatment. Patients with infection had 4-36 cells/ml (median 10 cells/ml). A cut off value of 20 cells/ml for a positive result yielded 64% specificity and 95% sensitivity for active systemic vasculitis; the positive predictive value was 63% and the negative predictive value 95%. Conclusion: Markedly increased numbers of CECs discriminate active vasculitis from limited granulomatous disease and remission. These findings add further proof to the concept of CECs as a marker of ANCA associated small vessel vasculitis.

show abstract

“…In addition to enumeration, CEC phenotype can be characterized by quantifying the surface expression of endothelial biomarkers such as vascular cell adhesion molecule-1 (VCAM-1) to determine whether or not cells are activated (activated CEC) 5. Increased numbers of CEC have been demonstrated in various vascular diseases and pathological conditions such as peripheral vascular disease,6 sickle cell anemia,7 acute myocardial infarction and angina pectoris,8 acute coronary syndrome,5 Kawasaki disease,9 systemic inflammation,10 and pulmonary hypertension 11. Importantly, CEC predict future cardiovascular events in individuals with cardiac disease, independent of conventional cardiovascular disease risk factors 12-14.…”

mentioning

confidence: 99%

Circulating Activated Endothelial Cells in Pediatric Obesity

Kelly

Hebbel

Solovey

et al. 2010

The Journal of Pediatrics

View full text Add to dashboard Cite

Objective-We characterized the state of the vascular endothelium in pediatric obesity by comparing circulating endothelial cell (CEC) number and activation phenotype in severely obese children to normal weight, overweight, and obese children.Study design-We used immunohistochemical examination of buffy-coat smears to enumerate CEC and immunofluorescence microscopy to quantify activated CEC in 107 children and adolescents. Normal weight (body mass index [BMI] <85 th percentile; N=40), overweight (BMI 85 th -<95 th percentile; N=17), and obese (BMI 95 th -<99 th percentile; N=23) participants were recruited from a longitudinal study. Severely obese (BMI ≥99 th percentile; N=27) participants were recruited from a pediatric obesity clinic. Group means (adiposity; systolic blood pressure [SBP] quartiles) were compared with general linear models, adjusted for sex, age, and race. Pearson correlations characterized relations of CEC with cardiovascular risk factors.Results-Activated CEC increased across BMI groups (p<0.002) and SBP quartiles (p<0.05). CEC number and activated CEC were highest in the severely obese group. CEC number was significantly associated with SBP, diastolic blood pressure, and triglycerides. Activated CEC were significantly associated with SBP and HDL-cholesterol.Conclusions-The vascular endothelium was activated in relation to excess adiposity, particularly in the severely obese, and to elevated SBP in children and adolescents. KeywordsVascular Endothelium; Obesity; Children; Adolescents One of the fastest growing obesity categories in children is severe obesity, defined as an ageand sex-specific body mass index (BMI) ≥ 99 th percentile. Recent data indicate a 300% increase © 2010 Mosby, Inc. All rights reserved. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Address for NIH Public Access MethodsThis cross-sectional study included 107 children and adolescents (age = 13.1 ± 3.8, range 6-22 years; 68 males) who were categorized (following testing) into four adiposity groups based on age-and sex-specific BMI percentiles. Participants in the normal weight BMI < 85 th percentile; N = 40), overweight (BMI 85 th -<95 th percentile; N = 17), and obese (BMI 95 th -<99 th percentile; N = 23) groups were consecutively enrolled over a period of approximately one year from a longitudinal cohort study investigating the early development of obesity, insulin resistance, and other cardiovascular risk factors. The severely obese (BMI ≥ 99 th percentile; N = 27) group was comprised of children and adolescents initially entering the University of Minnesota Pediatri...

show abstract

Circulating endothelial cells in Kawasaki disease

Cited by 81 publications

References 27 publications

Endothelial Nlrp3 inflammasome activation associated with lysosomal destabilization during coronary arteritis

Endothelial Nlrp3 inflammasome activation associated with lysosomal destabilization during coronary arteritis

Circulating endothelial cells in relapse and limited granulomatous disease due to ANCA associated vasculitis

Circulating Activated Endothelial Cells in Pediatric Obesity

Contact Info

Product

Resources

About