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

Yang Zhang1, Yicong Ye1, Xiaoqiang Tang2

  • 1Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The Journal of Experimental Medicine
|June 10, 2022
PubMed

Insights

Elevated chemokine C-C motif chemokine ligand 17 (CCL17) levels correlate with aging and heart failure. Targeting CCL17 may offer a novel therapeutic strategy for age-related cardiac dysfunction and hypertrophy.

Area of Science:

  • Cardiovascular Science
  • Immunology
  • Aging Research

Background:

  • Circulating proteomic signatures are linked to aging and age-related diseases.
  • The role of secreted proteins in identifying therapeutic targets for disease is not fully understood.
  • Age is a significant risk factor for cardiovascular diseases, including heart failure.

Purpose of the Study:

  • To investigate the association between circulating protein levels, aging, and cardiac dysfunction.
  • To identify novel therapeutic targets for age-related cardiac hypertrophy and heart failure.
  • To explore the role of chemokine C-C motif chemokine ligand 17 (CCL17) in pathological cardiac remodeling.

Main Methods:

  • Serum proteomic profiling in age-stratified healthy populations and heart failure patients.
  • Analysis of C-C motif chemokine ligand 17 (CCL17) levels in relation to age and cardiac function.
  • In vivo studies using Ccll7-knockout (KO) mice and angiotensin II (Ang II) infusion.
  • Administration of anti-CCL17 neutralizing antibodies in animal models.

Main Results:

  • Circulating CCL17 levels increase with age and correlate with cardiac dysfunction.
  • CCL17 deficiency (Ccll7-KO) significantly repressed aging and Ang II-induced cardiac hypertrophy and fibrosis.
  • CCL17 manipulation affected T cell subset plasticity and differentiation.
  • Anti-CCL17 antibody treatment inhibited Ang II-induced pathological cardiac remodeling.

Conclusions:

  • Chemokine CCL17 is a novel therapeutic target for age-related and Ang II-induced pathological cardiac hypertrophy and heart failure.
  • Targeting CCL17 may represent a promising strategy to mitigate cardiac dysfunction associated with aging and specific cardiovascular insults.

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