Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2225-2231
© 1997 American Heart Association, Inc.
Articles |
DNA Fragmentation and Ultrastructural Changes of Degenerating Cells in Atherosclerotic Lesions and Smooth Muscle Cells Exposed to Oxidized LDL in Vitro
From the King Gustaf V Research Institute, Department of Medicine, Karolinska Hospital (S.J., M.C., J.N.) and the Department of Cell and Molecular Biology, Karolinska Institute (J.T.), Stockholm, Sweden.
Correspondence to Dr Stefan Jovinge, King Gustaf V Research Institute, Karolinska Hospital, S-171 76 Stockholm, Sweden. Email Stefan.Jovinge{at}medks.ki.se
Abstract Degeneration of smooth muscle cells in the fibrous
cap of atherosclerotic lesions is an important factor in plaque
rupture. Recent studies have suggested that many plaque cells are in a
process of apoptosis as determined by positive
deoxyribonucleotide-transferase-mediated dUTP end labeling.
In this study, we demonstrate the existence of a colocalization between
deoxyribonucleotide-transferase-mediated dUTP end
labeling-positive smooth muscle cells and oxidized LDL immunoreactivity
in human carotid plaques. Oxidized LDL was found to induce
deoxyribonucleotide-transferase-mediated dUTP end labeling
positivity in cultured human smooth muscle cells, but only in the
presence of tumor necrosis factor-
and interferon-
. Electron
microscopic analysis of cultured smooth muscle cells exposed to
oxidized LDL in the absence of cytokines demonstrated
cytoplasmic swelling and disruption of the plasma membrane, suggesting
cell death by oncosis. Cells exposed to both oxidized LDL and
cytokines were characterized by chromatin and cytoplasmic
condensation compatible with cell death by apoptosis. These
findings further support the notion that oxidized lipids play a role in
plaque cell death.
Key Words: apoptosis • cell death • oxidized LDL • TNF • IFN
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