RAGE deficiency does not affect non-alcoholic steatohepatitis and atherosclerosis in Western type diet-fed Ldlr-/- mice.

Non-alcoholic fatty liver disease is a spectrum of liver diseases ranging from steatosis only to non-alcoholic steatohepatitis (NASH). The latter is characterized by hepatic inflammation, which increases the risk of cardiovascular disease. It is poorly understood which factors contribute to the onset of hepatic inflammation characterizing the progression from steatosis to NASH. Previously, we demonstrated increased advanced glycation endproducts (AGEs) in the livers of NASH patients. We hypothesise that AGEs play a key role in NASH development by activating their proinflammatory receptor, RAGE. RAGE-deficient mice and wildtype littermates, both on Ldlr-/- background, were fed a Western type diet (WTD) for 3 or 12 weeks. Flow cytometry, histology, gene expression and AGE measurements were performed to evaluate the effects of RAGE deficiency. RAGE-deficient mice displayed reduced weight gain and visceral fat expansion compared to control mice. No difference in adipose tissue inflammation was observed between groups. RAGE deficiency did not affect WTD-induced monocytosis, circulating lipids or hepatic steatosis. WTD-induced hepatic neutrophil and macrophage accumulation and atherosclerotic plaque development was comparable between control and RAGE-deficient mice. No difference in AGE levels was observed. RAGE does not seem to play a major role in the development of NASH or atherosclerosis in a hyperlipidemic mouse model.

Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and an electrochemiluminescense-based multi-array platform.

BACKGROUND: In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available. METHODS: We measured, in a large ongoing cohort study (n = 574), by means of both a 4-plex multi-array biomarker assay developed by MesoScaleDiscovery (MSD) and single-biomarker techniques (ELISA or immunoturbidimetric assay), the following biomarkers of low-grade inflammation: C-reactive protein (CRP), serum amyloid A (SAA), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1). These measures were realigned by weighted Deming regression and compared across a wide spectrum of subjects' cardiovascular risk factors by ANOVA. RESULTS: Despite that both methods ranked individuals' levels of biomarkers very similarly (Pearson's r all≥0.755) absolute concentrations of all biomarkers differed significantly between methods. Equations retrieved by the Deming regression enabled proper realignment of the data to overcome these differences, such that intra-class correlation coefficients were then 0.996 (CRP), 0.711 (SAA), 0.895 (sICAM-1) and 0.858 (sVCAM-1). Additionally, individual biomarkers differed across categories of glucose metabolism, weight, metabolic syndrome and smoking status to a similar extent by either method. CONCLUSIONS: Multiple low-grade inflammatory biomarker data obtained by the 4-plex multi-array platform of MSD or by well-established single-biomarker methods are comparable after proper realignment of differences in absolute concentrations, and are equally associated with cardiovascular risk factors, regardless of such differences. Given its greater efficiency, the MSD platform is a potential tool for the quantification of multiple biomarkers of low-grade inflammation in large ongoing and future clinical studies.

Basic fibroblast growth factor, glutamine synthetase, and interleukin-6 in vitreous fluid from eyes with retinal detachment complicated by proliferative vitreoretinopathy.

PURPOSE: To investigate the presence of basic fibroblast growth factor (bFGF), glutamine synthetase (GS), and interleukin-6 (IL-6) in vitreous fluid from eyes with retinal detachment complicated by proliferative vitreoretinopathy (PVR). DESIGN: Comparative case series; experimental study. METHODS: In a prospective study, we measured bFGF, GS, IL-6, and total protein in vitreous fluid samples from 53 eyes from 53 consecutive patients with PVR operated on in our hospital. As controls, vitreous fluid samples from eyes with a macular hole (n = 9) or pucker (n = 11) were used. MAIN OUTCOME MEASURES: Laboratory data of the patient group were compared with the control group and correlated with various clinical data, especially with visual recovery and redetachment. RESULTS: For IL-6, bFGF, and total protein we found significantly higher levels in PVR patients' eyes than in control eyes (P =.03, P =.046, and P <.0001, respectively). Within the PVR group, no significant correlation was found for IL-6, bFGF, GS, or total protein with the various tested clinical variables. CONCLUSIONS: We found increased levels of IL-6, bFGF, and total protein in vitreous fluid from patients' eyes with PVR. Whether the increased levels of IL-6, bFGF, and total protein are the result of an injury-induced upregulation of these proteins as part of a self-protective mechanism of the retina to minimize photoreceptor damage after the mechanical injury induced by retinal detachment is, at present, not known.