Abstract
SummaryInterleukin 17A (IL17A) is reported to be involved in many inflammatory processes, but its role in aortic valve diseases remains unknown. We examined the role of IL17A based on an ApoE−/− mouse model with strategies as fed with high-fat diet or treated with IL17A monoclonal antibody (mAb). 12 weeks of high-fat diet feeding can elevate cytokines secretion, inflammatory cells infiltration and myofibroblastic transition of valvular interstitial cells (VICs) in aortic valve. Moreover, diet-induction accelerated interleukin 17 receptor A (IL17RA) activation in VICs. In an IL17A inhibition model, the treatment group was intra-peritoneally injected with anti-IL17A mAb while controls received irrelevant antibody. Functional blockade of IL17A markedly reduced cellular infiltration and transition in aortic valve. To investigate potential mechanisms, NF-κB was co-stained in IL17RA+ VICs and IL17RA+ macrophages, and further confirmed by Western blotting in VICs. High-fat diet could activate NF-κB nuclear translocation in IL17RA+ VICs and IL17RA+ macrophages and this process was depressed after IL17A mAb-treatment. In conclusion, high-fat diet can lead to IL17A upregulation, VICs myofibroblastic transition and inflammatory cells infiltration in the aortic value of ApoE−/− mice. Blocking IL17A with IL17A mAb can alleviate aortic valve inflammatory states.
Highlights
Diet-induction accelerated interleukin 17 receptor A (IL17RA) activation in valvular interstitial cells (VICs)
NF-κB was co-stained in IL17RA+ VICs and IL17RA+ macrophages, and further confirmed by Western blotting in VICs
To determine whether Interleukin 17A (IL17A) and IL17RA levels are altered in aortic valve inflammation, ApoE-/- mice models were established with High-fat diet (HFD) and aortic valves were collected from both normal diet (ND) and HFD ApoE-/- mice
Summary
1.1 Affymetrix Microarray Data and Data Analysis Microarray data of GSE77287 were obtained from the Gene Expression Omnibus (GEO; http://www. ncbi.nlm.nih.gov/geo/) database. 1.1 Affymetrix Microarray Data and Data Analysis Microarray data of GSE77287 were obtained from the Gene Expression Omnibus Calcific aortic valve tissues were extracted from patients with calcific aortic valve disease (CAVD) who underwent aortic valve replacement, and normal controls were obtained from non-CAVD cardiac transplant recipient hearts[16]. Gene expression profiles of three samples of calcific aortic valves and three age-matched normal controls were performed using Affymetrix Gene Chip microarrays[16]. The raw data and annotation files were downloaded for subsequent analysis, based on Affymetrix Human Gene 2.0 ST Array. The original data were preprocessed with background correction, normalization and calculating expression using the ‘affy’ package in R (version 3.4.2). Heatmap and PPI network were applied as indicated[17]. Heatmap and PPI network were applied as indicated[17]. 1.2 Animals
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