Cell Death in Human Atherosclerotic Plaques Involves both Necrosis and Apoptosis

  • Milita Crisby
  • Bengt Kallin
  • Johan Thyberg
  • Boris Zhivotovsky
  • Sten Orrenius
  • Vasilios Kostulas
  • Jan Nilsson
Part of the NATO ASI Series book series (NSSA, volume 294)

Abstract

The aim of the present study was to analyze the frequency and mechanism of cell death in atherosclerotic plaques with a recent history (<6 months) of rupture. Atherosclerotic plaques were obtained from patients with symptomatic ipsilateral carotid stenosis (>70% diameter reduction) undergoing carotid endarterectomy. In situ tailing nick translation of fragmented DNA, agarose gel electrophoresis of plaque DNA and electron microscopy were used to identify cell death by apoptosis (programmed cell death) and necrosis. The mean number of cell containing fragmented DNA in the plaques was 12.7 ± 3.5% (n=15). Focal accumulations of cells with DNA fragmentation occurred in the fibrous cap, at sites of rupture, close to lipid deposits and necrosis and was always accompanied by the presence of inflammatory cells. Electrophoretic separation of DNA isolated form part of plaques where the presence of DNA fragmentation had previously been demonstrated by in situ DNA nick translation resulted in multiple ladders of 180–200 base pairs characteristic of apoptosis. Electron microscopic analysis revealed presence of cells with morphological signs of degeneration in a frequency even higher than that found by in situ nick translation. Some of these cells had a characteristic apoptotic appearance with condensed chromatin and cytoplasm, but the large majority of the cells had an ultrastructure typical for cells undergoing cell death by necrosis with membrane disruption and swollen, disintegrating organelles. Thus, although apoptosis clearly takes place in atherosclerotic plaques necrosis appears to be a much more common mechanism for cell death. This may have negative consequences for plaque stability since cell death by necrosis induces a stronger inflammatory reaction than apoptotic cell death.

Keywords

Atherosclerotic Plaque Electron Microscopic Analysis Carotid Stenosis Electrophoretic Separation Lipid Deposit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Milita Crisby
    • 1
    • 2
  • Bengt Kallin
    • 1
  • Johan Thyberg
    • 3
  • Boris Zhivotovsky
    • 4
  • Sten Orrenius
    • 4
  • Vasilios Kostulas
    • 2
  • Jan Nilsson
    • 1
  1. 1.King Gustaf V Research Institute, Department of MedicineKarolinska HospitalStockholmSweden
  2. 2.Department of NeurologyHuddinge HospitalStockholmSweden
  3. 3.Department of Cell and Molecular BiologyKarolinska InstituteStockholmSweden
  4. 4.Institute of Environmental MedicineKarolinska InstituteStockholmSweden

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