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Updated: Oct 20, 2025

Implantation of an Isoproterenol Mini-Pump to Induce Heart Failure in Mice
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Early activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure

M Flamant1, N Mougenot2, E Balse1

  • 1Sorbonne Université, UPMC Univ Paris 06, INSERM, Institute of Cardiometabolism and Nutrition (ICAN), Team 3, UMR_S ICAN 1166 Team 3, 91 bd de l'hôpital, 75013, Paris, France.

Scientific Reports
|September 10, 2021
PubMed

Insights

Cardiac macrophages secrete CX3CL1, a protein that protects against heart failure by enhancing cardiomyocyte resistance to stress. This CX3CL1/CX3CR1 pathway delays heart failure progression following early cardiac remodeling.

Area of Science:

  • Cardiology
  • Immunology
  • Cell Biology

Background:

  • Cardiac myeloid CD11b/c cells may protect against heart failure (HF) by improving cardiomyocyte resistance to oxidative stress.
  • Early beta-adrenergic stimulation can induce cardiac hypertrophy and potentially lead to HF.

Purpose of the Study:

  • Characterize macrophages (Mφ) in early isoproterenol-infused hearts compared to controls and failing hearts.
  • Evaluate the role of upregulated CX3CL1 in cardiac remodeling and HF progression.
  • Investigate the CX3CL1/CX3CR1 axis as a potential therapeutic target for delaying HF.

Main Methods:

  • Flow cytometry and immunohistology to quantify Mφ populations.
  • Mφ-depletion experiments to assess their functional role.
  • Transcriptomic and secretomic analyses to identify secreted factors.
  • In vivo studies using siRNA and knockout mice to investigate the CX3CL1/CX3CR1 axis.
  • In vitro assays to examine the effects of CX3CL1 on cardiomyocytes and Mφ.

Main Results:

  • A transient increase in cardiac Mφ number was observed in isoproterenol-infused hearts, correlating with early concentric hypertrophy (ECH) and limited HF.
  • Mφ-enriched cells from ECH hearts secreted CX3CL1 and TNFα.
  • The CX3CL1/CX3CR1 axis was identified as a protective pathway that delays the transition to HF.
  • CX3CL1 promoted Mφ proliferation and expansion and supported cardiomyocyte hypertrophy synergistically with TNFα.

Conclusions:

  • The CX3CL1/CX3CR1 axis plays a transient protective role in ECH remodeling, delaying HF progression.
  • CX3CL1-secreting Mφ and their interaction with CX3CR1-expressing cardiomyocytes are crucial in this protective mechanism.
  • Targeting the CX3CL1/CX3CR1 pathway may offer a novel strategy for preventing or delaying heart failure.

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