Overweight, obesity and coronary artery lesions among Kawasaki disease patients.

BACKGROUND AND AIMS: Overweight is associated with increased cardiovascular disease in general populations. However, a similar relationship among Kawasaki Disease (KD) patients was unclear. The study aimed to investigate the relation between weight-for-height and coronary artery lesions (CAL) among KD patients, and whether laboratory indices modified this relation. METHODS AND RESULTS: All consecutive KD patients from January 2009 to December 2014 in a city in China were reviewed, and classified into overweight/obese and control groups. All patients were followed to assess the occurrence of CAL by echocardiography for two months from disease onset. The independent effect of overweight/obesity on CAL was evaluated after adjustment for confounders. The interaction effect between overweight and laboratory indices was examined. The prevalence of overweight/obesity among KD patients was 18.5% (95%CI: 16.0%, 21.0%). The proportion of male patients and the proportion of non-standard IVIG treatment were significantly higher in overweight/obese children in comparison with their counterparts. Overweight/obesity was associated with increased odds of total CAL (aOR = 1.69, 95%CI: 1.16, 2.45) and also increased odds of CAL after treatment (aOR = 1.96, 95%CI: 1.09, 3.51); after adjustment for age, gender, KD type, change of medical departments, number of days before admission, treatment regimen and laboratory index. Similar results were found using stratification analysis. In addition, patients at risk of overweight were also associated with significantly increased risk of CAL. There was interaction between weight-for-height and platelet, WBC, and albumin. CONCLUSIONS: Overweight/obesity may be an independent risk factor for CAL among KD patients. Some laboratory indicators may modify this association.

Dehydrocostus lactone suppresses ox-LDL-induced attachment of monocytes to endothelial cells.

Atherosclerosis is a cardiovascular disease that affects most people to at least some extent by old age. Many factors contribute to atherogenesis, and although it is extremely common, the mechanisms behind the pathogenesis of the disease remain poorly understood. Endothelial dysfunction is thought to be one of the main causes of atherosclerosis along with numerous other factors, such as oxidative stress and proinflammatory cytokine upregulation. The culmination of the complications that lead to atherogenesis is the formation of a fatty plaque on the intima of the arterial endothelium. In this study, we explore these aspects and others in regard to the treatment potential of dehydrocostus lactone (DHL), which is naturally occurring in certain flora such as the Saussurea lappa costus plant. Having long been used in traditional Chinese medicine, the effects of this plant are only just beginning to be studied by modern science. Among our most noteworthy findings are that DHL exerts an inhibitory effect against the increased expression of VCAM-1 and E-selectin induced by exposure to oxidized low-density lipoprotein (ox-LDL), which has been linked to the development and progression of atherosclerosis. The introduction of DHL also significantly diminished the downstream effects of VCAM-1 and E-selectin, such as the attachment of monocytes to the endothelium and the release of proinflammatory cytokines and chemokines, including TNF-α, MCP-1, and HMGB1. Furthermore, DHL is capable of rescuing the expression of KLF2, an important regulator of VCAM-1 and E-selectin expression. Together, our findings demonstrate the potential of DHL as a prophylactic or therapeutic treatment against ox-LDL-induced atherosclerosis via inhibition of the attachment of monocytes to endothelial cells.

Coronary artery lesion risk and mediating mechanism in children with complete and incomplete Kawasaki disease.

To compare the risk of coronary artery lesions (CAL) in children with complete and incomplete Kawasaki disease (KD) before and after immunoglobulin therapy and explore the mediation mechanisms underlying this association. All patients with KD admitted to the Wenzhou Medical University affiliated Yuying Children's Hospital were divided into complete and incomplete KD groups. The independent effect of KD type on the risk of CAL and the intermediate effect of admission time on the association between KD type and CAL were assessed. The incidence of CAL in children with incomplete KD was higher than that in children with complete KD (33.9% vs 23.0%, p<0.001), and was also higher before therapy (27.5% vs 14.8%). Among children without CAL before therapy, there was no statistical difference in the incidence of CAL after treatment between the two groups. Mediation analysis found that the mediating effect of admission time was 1.07 (95% C: 1.01 to 1.13), and the direct effect of KD type on CAL was 1.59 (95% CI 1.17 to 2.16); proportion mediated was 15.71%. In conclusion, the risk of CAL among patients with incomplete KD was higher than that for complete KD, especially before therapy. In patients without CAL before treatment, the risk of CAL after treatment was equivalent for the two groups. Delayed admission may be one of the important mediating mechanisms for the higher risk of CAL in incomplete KD children.

Serum miR-92a-3p as a New Potential Biomarker for Diagnosis of Kawasaki Disease with Coronary Artery Lesions.

Recent studies have suggested that serum microRNAs (miRNAs) are novel biomarkers for many cardiovascular diseases, but their role in Kawasaki disease (KD) is still unclear. We demonstrated that serum miR-92a-3p levels were significantly higher in children with KD compared with children with fever and controls (both P < 0.05). When the disease recovered, miR-92a-3p levels returned to those of controls. Clinical and pathological data showed that high levels of miR-92a-3p were significantly associated with coronary artery lesions (CALs). Analysis of the receiver operating characteristic (ROC) curve showed that serum miR-92a-3p had a sensitivity of 81.8% and a specificity of 66.7% for distinguishing KD with CALs from KD without CALs. The area under the curve was 0.816 (P < 0.05, 95% CI 0.669-0.962). Therefore, the miRNA miR-92a-3p may be used as a potential biomarker for diagnosis of KD and KD with coronary artery lesions.

Butyrate pretreatment attenuates heart depression in a mice model of endotoxin-induced sepsis via anti-inflammation and anti-oxidation.

OBJECTIVES: The depressed heart function is the main complication to cause death of septic patients in clinic. It is urgent to find effective interventions for this intractable disease. In this study, we investigated whether butyrate could be protective for heart against sepsis and the underlying mechanism. METHODS: Mice were randomly divided into three groups. Model group challenged with LPS (30 mg/kg, i.p.) only. Butyrate group received butyrate (200 mg/kg·d) for 3days prior to LPS administration (30 mg/kg). Normal group received saline only. 6h and 12h after LPS administration were chosen for detection the parameters to estimate the effects or mechanism of butyrate pretreatment on heart of sepsis. RESULTS: The data showed that septic heart depression was attenuated by butyrate pretreatment through improvement of heart function depression (P<0.01) and reduction of morphological changes of myocardium. The overexpression of proinflammatory factors, TNF-α, IL-6 and LTB4, in heart tissues induced by sepsis was significantly alleviated by butyrate pretreatment (P<0.01). As oxidative stress indicators, SOD and CAT activity, and MDA content in heart were deteriorated by LPS challenge, which was noticeably ameliorated by butyrate pretreatment (P<0.01 or P<0.05). CONCLUSIONS: In conclusion, pretreatment with butyrate attenuated septic heart depression via anti-inflammation and anti-oxidation.