RESUMEN
BACKGROUND: Kawasaki disease (KD) is an acute and systemic vasculitis whose etiology remains unclear. The most crucial complication is the formation of coronary artery aneurysm (CAA). Annexin A1 (ANXA1) is an endogenous anti-inflammatory agent and pro-resolving mediator involved in inflammation-related diseases. This study sought to investigate the serum ANXA1 levels in KD patients and further explore the relationship between ANXA1 and CAA, as well as additional clinical parameters. METHODS: Serum samples were collected from 95 KD patients and 39 healthy controls (HCs). KD patients were further divided into two groups: KD with CAAs (KD-CAAs) and KD non-CAAs (KD-NCAAs). Serum levels of ANXA1 and interleukin-6 (IL-6) were determined using enzyme-linked immunosorbent assays. RESULTS: Serum ANXA1 levels in the KD group were significantly lower than in the HC group. In particular, serum ANXA1 levels were substantially lower in the KD-CAA groups. Moreover, serum ANXA1 levels were positively correlated with N%, C-reactive protein (CRP), and IL-6 but negatively correlated with L% in the KD group. Positive correlations between serum ANXA1 levels and erythrocyte sedimentation rate (ESR), IL-6, and D-dimer (DD) were observed in the KD-CAA group. CONCLUSIONS: ANXA1 may be involved in the development of KD, and downregulation of ANXA1 may lead to the hypercoagulability seen in KD. IMPACT: For the first time, it was demonstrated that serum ANXA1 levels were significantly decreased in Kawasaki disease with coronary artery aneurysms. ANXA1 might be involved in the acute phase of Kawasaki disease. Low serum concentrations of ANXA1 might lead to the hypercoagulability stage in Kawasaki disease. ANXA1 might be a potential therapeutic target for patients with Kawasaki disease.
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Anexina A1/sangre , Aneurisma Coronario/sangre , Síndrome Mucocutáneo Linfonodular/sangre , Antiinflamatorios/farmacología , Coagulación Sanguínea , Sedimentación Sanguínea , Proteína C-Reactiva/biosíntesis , Preescolar , Enfermedad de la Arteria Coronaria/sangre , Vasos Coronarios , Ensayo de Inmunoadsorción Enzimática , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/biosíntesis , Humanos , Lactante , Interleucina-6/sangre , MasculinoRESUMEN
Kawasaki disease (KD) is an acute systemic vasculitis in children. Coronary artery lesions (CALs) are the most serious complications in KD, but the pathogenesis is still unclear so far. Adropin, a new biopeptide, plays an important role in metabolism and cardiovascular function. The aim of this study was to explore the relationship between adropin and KD. 66 KD patients and 22 healthy controls (HCs) were included in the study. KD patients were divided into KD with coronary artery lesions (KD-CALs) group and KD without CALs (KD-NCALs) group. The levels of serum adropin were determined by enzyme-linked immunosorbent assay (ELISA). Compared with the HC group, adropin concentrations were significantly increased in the KD group (p < 0.05), and the KD-CAL group had higher levels of adropin than those in the KD-NCAL group (p < 0.05). Pct (Procalcitonin) and DD (D-dimer) were positively correlated with adropin in the KD group (p < 0.05). Moreover, adropin had positive correlations with CRP (C-reactive protein) and DD in the KD-NCAL group and positive correlations with Pct, PLR (platelet-to-lymphocyte ratio), and DD in the KD-CAL group (p < 0.05). The receiver operating characteristic (ROC) curve showed that the best threshold value of serum adropin level was more than 2.8 ng/mL, with 72.2% sensitivity and 71.4% specificity for predicting CALs in children with KD.Conclusion: Adropin might be involved in the pathogenesis of KD and CALs and can be used as an auxiliary diagnostic biomarker of KD. What is Known: ⢠CALs in KD were mainly caused by inflammation, immune imbalance, and vascular endothelial dysfunction, and adropin is involved in metabolic diseases and cardiovascular diseases. What is New: ⢠In this study, we have found the relationship between adropin and KD, and serum adropin level can be used as an auxiliary diagnostic biomarker to predict CALs in KD.
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Enfermedad de la Arteria Coronaria , Péptidos y Proteínas de Señalización Intercelular/sangre , Síndrome Mucocutáneo Linfonodular , Proteína C-Reactiva , Estudios de Casos y Controles , Niño , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/etiología , Vasos Coronarios/diagnóstico por imagen , Humanos , Lactante , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/diagnóstico , Curva ROCRESUMEN
BACKGROUND: Kawasaki disease (KD) is a self-limited vasculitis with unknown etiologies, and coronary artery lesions (CALs) are the most common and serious complications. Retinol-binding protein 4 (RBP4) has been confirmed effects on vasodilation, platelet activation inhibition, and cardiovascular diseases by researches. Therefore, this study was aimed at investigating the relationship between RBP4 and inflammation as well as thrombogenesis in children with KD. METHODS: 79 subjects were from 62 children with KD and 17 healthy controls (HCs). The KD group was divided into KD with CALs (KD-CALs) and KD without CALs (KD-NCALs), and the serum RBP4 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the HC group, serum RBP4 levels in the KD group were significantly decreased (p < 0.05). RBP4, hemoglobin (Hb), and mean platelet volume (MPV) levels were higher, while platelet counts (Plt) and thrombin time (TT) levels were lower in the KD-NCALs group than in the KD-CALs group (p < 0.05). RBP4 had positive correlation with time point of intravenous immunoglobulin (IVIG), Hb, and percentage of leukomonocytes (L%) and negative correlation with the percentage of neutrophils (N%), MPV, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), prothrombin time (PT), fibrinogen (Fbg), and D-dimer (DD) in the KD group; RBP4 had positive correlation with the time point of IVIG and L% and negative correlation with N%, MPV, and NLR in the KD-NCALs group; and RBP4 had positive correlation with Hb and L% and negative correlation with N%, CRP, NLR, and PT in the KD-CALs group (p < 0.05). Multiple linear regression analysis confirmed that Hb and CRP in the KD group, MPV and N% in the KD-NCALs group, and PT and CRP in the KD-CALs group were independent predictors of RBP4 (p < 0.05). CONCLUSION: Lower RBP4 was observed in the KD group than in the HC group, and RBP4 had associations with markers of inflammation and thrombogenesis in children with KD.
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Inflamación/sangre , Síndrome Mucocutáneo Linfonodular/sangre , Proteínas Plasmáticas de Unión al Retinol/metabolismo , Femenino , Humanos , MasculinoRESUMEN
BackgroundTo investigate the serum C1q/tumor necrosis factor-related protein-1 (CTRP1) levels in children with acute Kawasaki disease (KD), as well as the relationship between CTRP1 levels and laboratory variables.MethodsEighty-seven children with KD and 38 healthy controls (HCs) were included in this study. General characteristics were obtained from all subjects. Serum CTRP1 levels in all subjects and serum tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) levels in KD patients were measured using enzyme-linked immunosorbent assay.ResultsCompared with the HC group, serum CTRP1 levels were significantly elevated in the KD group. Significantly higher serum TNF-α, IL-1ß, IL-6, and CTRP1 levels were observed in patients with KD with coronary artery lesions (KD-CALs) than in patients with KD without CALs (KD-NCALs). Serum CTRP1 levels were positively correlated with white blood cell counts (WBC), percentage of neutrophils (N%), thrombin time (TT), procalcitonin (Pct), TNF-α, IL-1ß, and IL-6 levels. Meanwhile, CTRP1 levels were negatively correlated with the percentage of leukomonocytes (L%) in KD patients. Furthermore, serum CTRP1 levels were positively correlated with the time point of intravenous immunoglobulin (IVIG), WBC, N%, TNF-α, IL-1ß, and IL-6 levels in the KD-CAL group.ConclusionCTRP1 may participate in the process of vasculitis and blood coagulation during the acute phase of KD.
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Síndrome Mucocutáneo Linfonodular/sangre , Proteínas/análisis , Proteínas/fisiología , Estudios de Casos y Controles , Preescolar , Vasos Coronarios , Ecocardiografía , Femenino , Humanos , Inmunoglobulinas Intravenosas , Interleucina-1beta/sangre , Interleucina-6/sangre , Masculino , Síndrome Mucocutáneo Linfonodular/diagnóstico por imagen , Síndrome Mucocutáneo Linfonodular/terapia , Factor de Necrosis Tumoral alfa/sangreRESUMEN
The effect of melatonin on juveniles with cardio fibrosis is poorly understood. We investigated whether HDACs participate in the anti-fibrotic processes regulated by melatonin during hypertrophic remodeling. Abdominal aortic constriction (AAC) was employed in juvenile rats resulting in pressure overload-induced ventricular hypertrophy and melatonin was subsequently decreased via continuous light exposure for 5 weeks after surgery. AAC rats displayed an increased cross-sectional area of myocardial fibers and significantly elevated collagen deposition compared to sham-operated rats, as measured by HE and Masson Trichrome staining. Continuous light exposure following surgery exacerbated the increase in the cross-sectional area of myocardial fibers. The expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 genes were all significantly enhanced in AAC rats with light exposure relative to the other rats. Moreover, the protein level of TNF-α was also upregulated in the AAC light exposure groups when compared with the sham. However, Smad4 protein expression was unchanged in the juveniles' hearts. In contrast, beginning 5 weeks after the operation, the AAC rats were treated with melatonin (10 mg/kg, intraperitoneal injection every evening) or vehicle 4 weeks, and sham rats were given vehicle. The changes in the histological measures of cardio fibrosis and the gene expressions of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 were attenuated by melatonin administration. The results reveal that melatonin plays a role in the development of cardio fibrosis and the expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 in cardiomyocytes.
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Kawasaki disease (KD) is an acute, self-limited vasculitis, and the etiology is still unclear. Coronary arterial lesions (CALs) are a major complication of KD. Excessive inflammation and immunologic abnormities are involved in the pathogenesis of KD and CALs. Annexin A3 (ANXA3) plays crucial roles in cell migration and differentiation, inflammation, cardiovascular and membrane metabolic diseases. The purpose of this study was to investigate the effect of ANXA3 on the pathogenesis of KD and CALs. There were 109 children with KD in the KD group [which was divided into two groups: 67 patients with CALs in the KD-CAL group, and 42 patients with noncoronary arterial lesions (NCALs) in the KD-NCAL group] and 58 healthy children in the control (HC) group. Clinical and laboratory data were retrospectively collected from all patients with KD. The serum concentration of ANXA3 was measured by enzyme-linked immunosorbent assays (ELISAs). Serum ANXA3 levels were higher in the KD group than in the HC group (P < 0.05). There was a higher concentration of serum ANXA3 in the KD-CAL group than in the KD-NCAL group (P < 0.05). Neutrophil cell counts and serum ANXA3 levels were higher in the KD group than in the HC group (P < 0.05) and quickly decreased when the patients were treated with IVIG after 7 days of illness. Platelet (PLT) counts and ANXA3 levels concurrently exhibited significant increases 7 days after onset. Furthermore, ANXA3 levels were positively correlated with lymphocyte and PLT counts in the KD and KD-CAL groups. ANXA3 may be involved in the pathogenesis of KD and CALs.
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OBJECTIVES: Intravenous immunoglobulin (IVIG) resistance was a major cause of coronary artery lesions in children with Kawasaki disease (KD). However, the cause of IVIG resistance in KD remains unknown. miR-221-3p has been confirmed involved in cardiovascular diseases and rheumatoid arthritis. The purpose of this study was to investigate the association between miR-221-3p and IVIG resistance in children with KD. METHODS: Fifty-five KD patients and 29 healthy controls (HCs) were enrolled in this study. KD patients were divided into group of sensitive to IVIG (IVIG-response, n = 42) and group of resistant to IVIG (IVIG-resistance, n = 13), group of 10 KD patients with coronary artery lesions (CALs, KD-CALs) and group of 10 sex- and age-matched KD patients without CALs (KD-NCALs). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of miR-221-3p. RESULTS: Compared with the HCs group, miR-221-3p were significantly increased in the KD group (p < 0.05), and the IVIG-resistance group had higher levels of miR-221-3p than those in the IVIG-response group (p < 0.05). CRP (C-reactive protein), PCT (procalcitonin), NLR (neutrophil-lymphocyte ratio) were positively correlated with miR-221-3p in KD patients. In addition, the group of IVIG resistance had a higher level of Kobayashi Score (p < 0.001). The receiver operating characteristic curve showed that miR-221-3p had a better value for diagnosis IVIG resistance in children with KD than Kobayashi Score with the AUC of 0.811 (95% CI, 0.672-0.951), 0.793 (95% CI, 0.618-0.968), respectively. Additionally, miR-221-3p was elevated (p < 0.05) and showed an AUC value of 0.83 (95% CI, 0.648-1.000, p < 0.05) for the prediction of the complication of coronary artery abnormalities in the group of KD with CALs. CONCLUSIONS: miR-221-3p might be involved in the pathogenesis of KD and IVIG resistance and miR-221-3p can be used as a new potential biomarker to predict IVIG resistance in children with KD.
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MicroARNs , Síndrome Mucocutáneo Linfonodular , Niño , Humanos , Biomarcadores , Proteína C-Reactiva/metabolismo , Inmunoglobulinas Intravenosas/uso terapéutico , MicroARNs/genética , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Polipéptido alfa Relacionado con Calcitonina , Estudios RetrospectivosRESUMEN
Kawasaki disease (KD) is a systemic vasculitis that predominantly damages medium- and small-sized vessels, and mainly causes coronary artery lesions (CALs). The diagnostic criterion of KD mainly depends on clinical features, so children could be easily misdiagnosed and could suffer from CALs. Through analysis, a total of 14 immune-related DEGs were obtained, of which IL1B, ADM, PDGFC, and TGFA were identified as diagnostic markers of KD. Compared with the non-KD group, KD patients contained a higher proportion of naive B cells, activated memory CD4 T cells, gamma delta T cells, and neutrophils, while the proportions of memory B cells, CD8 T cells, activated memory CD4 T cells, and activated NK cells were relatively lower. In conclusion, immune-related genes can be used as diagnostic markers of KD, and the difference in immune cells between KD and non-KD might provide new insight into understanding the pathogenesis of KD.
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BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis with coronary artery lesions (CALs) being the major concern. Syndecan-1 (SDC-1) is a major core protein expressed on the glycocalyx of endothelial cells. Shed SDC-1 in serum is regarded as a biomarker for endothelial activation or damage. METHODS: In this study, we aimed to determine the serum levels of SDC-1 and evaluate the relationship between serum levels of SDC-1 and the CALs in the acute phase of KD. Serum SDC-1 levels were measured in 119 children with KD and in 43 healthy children as normal controls and in 40 children with febrile disease. All KD patients were administrated a single dose of intravenous immunoglobulin and aspirin per os within 10 days of KD onset. RESULTS: Serum levels of SDC-1, in addition to albumin and hemoglobin, were significantly increased in patients with KD than in healthy controls and febrile controls. Furthermore, the serum levels of SDC-1, albumin and hemoglobin were significantly elevated in KD patients with CALs than those without CALs. Additionally, serum levels of SDC-1 were significantly correlated with levels of hemoglobin and serum albumin in patients with KD. After intravenous immunoglobulin therapy, serum levels of interleukin-6, soluble cell adhesion molecules-1 and resistin were reduced while serum levels of SDC-1 were significantly increased in KD patients. CONCLUSIONS: SDC-1 serum levels may mirror vascular endothelial damage and inflammation in KD. This might be utilized as a potential novel target for coronary artery protection in KD patients.