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Published on: April 3, 2017

Macrophage apoptosis exerts divergent effects on atherogenesis as a function of lesion stage

Emmanuel L Gautier1, Thierry Huby, Joseph L Witztum

  • 1INSERM U939, Hôpital de Pitié, Paris, France.

Circulation
|March 25, 2009
PubMed
Abstract

Insights

Macrophage apoptosis protects against early atherosclerosis but promotes advanced plaque growth when clearance is defective. This highlights stage-dependent roles in cardiovascular disease progression.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Pathology

Background:

  • Macrophage apoptosis clearance is impaired in advanced atherosclerotic plaques.
  • This defect suggests stage-dependent roles for macrophage apoptosis in plaque progression.

Purpose of the Study:

  • To investigate the impact of macrophage apoptosis on atherosclerosis at different lesion stages.
  • To determine how manipulating macrophage apoptosis affects plaque development.

Main Methods:

  • Targeted protection of macrophages against apoptosis in early and advanced lesions.
  • Induced apoptosis in lesional macrophages of advanced lesions.
  • Assessed plaque burden, size, chemokine expression, and monocyte recruitment.

Main Results:

  • In early lesions, increased macrophage resistance to apoptosis worsened plaque burden.
  • In early lesions, resistance to apoptosis also protected against progression to advanced lesions.
  • In advanced lesions, induced apoptosis increased lesion size due to cell accumulation and monocyte recruitment.

Conclusions:

  • Macrophage apoptosis is atheroprotective in early fatty streak lesions.
  • Defective clearance of apoptotic debris in advanced lesions promotes inflammation and monocyte recruitment.
  • These findings indicate a dual role for macrophage apoptosis in atherogenesis, dependent on lesion stage.

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