Role of Interleukin 17A in Aortic Valve Inflammation in Apolipoprotein E-deficient Mice
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40(4):729-738,2020
729
Role of Interleukin 17A in Aortic Valve Inflammation in Apolipoprotein E-deficient Mice* Fa-yuan LIU†, Peng BAI†, Ye-fan JIANG†, Nian-guo DONG1, Geng LI1, Chong CHU1# Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China The Author(s) 2020
Summary: 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, highfat 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. Key words: aortic valve inflammation; interleukin 17A; NF-κB pathway; intensity correlation analysis; colocalization
Aortic valve stenosis remains as the most prevalent valvular disease in Western countries[1], affecting over 25% of all patients over the age of 65[2]. Currently, there is no effective pharmacological therapy for aortic valve stenosis and surgical or interventional valve replacement serves as the only curative treatments. However, in patients who underwent transcatheter aortic valve replacement, up to 30% had oxygen dependence[3] and 60% had significant lung disease, which has been associated with increased morbidity and mortality[4]. Others reported unexpected side effects including chronic kidney disease and liver disease, all of which are considered to contribute to deaths after Fa-yuan LIU, E-mail: [email protected]; Peng BAI, E-mail: [email protected]; Ye-fan JIANG, E-mail: [email protected] † These authors contributed equally to this work. # Corresponding author, E-mail: [email protected] * This project was supported by grants from the National Key Research and Development Program of China (No. 2016YFA0101100), National Natural Science Foundation of China (No. 81700339 and No. 31330029), and Scientific Research Training Program for Young Talents sponsored by Union Hospital, Tongji Medical
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