CCL17 acts as a novel therapeutic target in pathological cardiac hypertrophy and heart failure

作者：Yang Zhang, Yicong Ye, Xiaoqiang Tang, Hui Wang, Toshiko Tanaka, Ran Tian, Xufei Yang, Lun Wang, Ying Xiao, Xiaomin Hu, Ye Jin, Haiyu Pang, Tian Du, Honghong Liu, Lihong Sun, Shuo Xiao, Ruijia Dong, Luigi Ferrucci, Zhuang Tian, Shuyang Zhang · 发表于：The Journal of Experimental Medicine · 年份：2022 · DOI：10.1084/jem.20200418 · 被引用次数：41 · 研究领域：Cardiac Fibrosis and Remodeling、Signaling Pathways in Disease、Heart Failure Treatment and Management

Circulating proteomic signatures of age are closely associated with aging and age-related diseases; however, the utility of changes in secreted proteins in identifying therapeutic targets for diseases remains unclear. Serum proteomic profiling of an age-stratified healthy population and further community-based cohort together with heart failure patients study demonstrated that circulating C-C motif chemokine ligand 17 (CCL17) level increased with age and correlated with cardiac dysfunction. Subsequent animal experiments further revealed that Ccll7-KO significantly repressed aging and angiotensin II (Ang II)-induced cardiac hypertrophy and fibrosis, accompanied by the plasticity and differentiation of T cell subsets. Furthermore, the therapeutic administration of an anti-CCL17 neutralizing antibody inhibited Ang II-induced pathological cardiac remodeling. Our findings reveal that chemokine CCL17 is identifiable as a novel therapeutic target in age-related and Ang II-induced pathological cardiac hypertrophy and heart failure.