Role of Interleukin 17A in Aortic Valve Inflammation in Apolipoprotein E-deficient Mice

Abstract

Interleukin 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.

Keywords

aortic valve inflammation / interleukin 17A / NF-κB pathway / intensity correlation analysis / colocalization

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