Anti-IL1R1 monoclonal antibody, clone 35730 (49/20)

We assessed the predictive ability of selected biomarkers using N-terminal pro-brain natriuretic peptide (NT-proBNP) as the benchmark and tried to establish a multi-biomarker approach to heart failure (HF) in hypertensive patients. In 120 hypertensive patients with or without overt heart failure, the incremental predictive value of the following biomarkers was investigated: Collagen III N-terminal propeptide (PIIINP), cystatin C (CysC), lipocalin-2/NGAL, syndecan-4, tumor necrosis factor- (TNF-), interleukin 1 receptor type I (IL1R1), galectin-3, cardiotrophin-1 (CT-1), transforming growth factor (TGF-) and N-terminal pro-brain natriuretic peptide (NT-proBNP). The highest discriminative value for HF was observed for NT-proBNP (area under the receiver operating characteristic curve (AUC) = 0.873) and TGF- (AUC = 0.878). On the basis of ROC curve analysis we found that CT-1 > 152 pg/mL, TGF- < 7.7 ng/mL, syndecan > 2.3 ng/mL, NT-proBNP > 332.5 pg/mL, CysC > 1 mg/L and NGAL > 39.9 ng/mL were significant predictors of overt HF. There was only a small improvement in predictive ability of the multi-biomarker panel including the four biomarkers with the best performance in the detection of HFNT-proBNP, TGF-, CT-1, CysCcompared to the panel with NT-proBNP, TGF- and CT-1 only. Biomarkers with different pathophysiological backgrounds (NT-proBNP, TGF-, CT-1, CysC) give additive prognostic value for incident HF in hypertensive patients compared to NT-proBNP alone.

While increased VEGF-A has been associated with neovascular age-related macular degeneration (AMD), it is not known whether VEGF-A may also promote other age-related eye diseases. Here, we show that an increase in VEGF-A is sufficient to cause multiple distinct common aging diseases of the eye, including cataracts and both neovascular and non-exudative AMD-like pathologies. In the lens, increased VEGF-A induces age-related opacifications that are associated with ERK hyperactivation, increased oxidative damage, and higher expression of the NLRP3 inflammasome effector cytokine IL-1. Similarly, increased VEGF-A induces oxidative stress and IL-1 expression also in the retinal pigment epithelium (RPE). Targeting NLRP3 inflammasome components or Il1r1 strongly inhibited not only VEGF-A-induced cataract formation, but also both neovascular and non-exudative AMD-like pathologies. Moreover, increased VEGF-A expression specifically in the RPE was sufficient to cause choroidal neovascularization (CNV) as in neovascular AMD, which could be inhibited by RPE-specific inactivation of Flk1, while Tlr2 inactivation strongly reduced CNV. These findings suggest a shared pathogenic role of VEGF-A-induced andNLRP3 inflammasome-mediated IL-1 activation for multiple distinct ocular aging diseases.