Arteriosclerosis, Thrombosis, and Vascular Biology. 1998;18:1519-1522
© 1998 American Heart Association, Inc.
Brief Reviews |
Apoptosis in the Atherosclerotic Plaque
Quantitative and Qualitative Aspects
From the Department of Pathology AZ-Middelheim and Division of Pharmacology, University of Antwerp, Antwerp, Belgium.
Correspondence to Dr M. Kockx, Department of Pathology, AZ Middelheim, Lindendreef, 1, B-2020 Antwerp, Belgium. E-mail mark.kockx{at}uia.ua.ac.be
Abstract
Abstract—Several laboratories
have demonstrated the presence of apoptotic cell death in
atherosclerotic plaques. Apoptosis occurs in at least 2 stages.
The final "execution" phase, which includes DNA fragmentation, is
brief (
6 hours) and irreversible and can be detected by the terminal
deoxynucleotidyl transferase–mediated dUTP nick
end labeling (TUNEL) technique. The TUNEL technique is only selective
(rather than specific) for apoptotic nuclei, because these
contain a far greater degree of DNA fragmentation than do
nonapoptotic nuclei. Nonapoptotic cell nuclei that show
high levels of RNA synthesis and splicing can also be labeled. This
could explain the large variation in the reported percentages of
TUNEL-positive nuclei in the plaques. Therefore, the TUNEL technique
should be combined with additional techniques, such as markers of
transcription and morphological criteria. Recent studies
indicate that human fatty streaks differ from adaptive intimal
thickenings by the presence of cells containing pro-apoptotic
proteins. However, apoptotic cell death is present only in
advanced atherosclerotic plaques that show a dense macrophage
infiltration. This indicates that although both smooth muscle cells and
macrophages within the human fatty streaks become susceptible
to apoptosis, additional factors (mainly macrophage-
and lipid-derived factors) are necessary to terminate the cell
death pathway.
Key Words: atherosclerosis • apoptosis • BAX • TUNEL • lipids
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