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.
© 2022 Zhang et al.