(Circulation. 2000;101:2450.)
© 2000 American Heart Association, Inc.
Brief Rapid Communications |
Relation Between Endothelial Cell Apoptosis and Blood Flow Direction in Human Atherosclerotic Plaques
From the Institut National de la Santé et de la Recherche Médicale, INSERM U541, Institut Fédératif de Recherche "Circulation," Hôpital Lariboisière, Paris, France (O.T., Z.M., C.H., A.T.); Service de Médecine Interne Gériatrique, Hôpital René Muret-Bigottini, Sevran, France (J.B.); and Service de chirurgie Thoracique et Vasculaire, Hôpital Beaujon, Clichy, France (G.L.).
Correspondence to Alain Tedgui, PhD, INSERM U541, Hôpital Lariboisière, 41 Bd de la Chapelle, 75010 Paris, France. E-mail tedgui{at}infobiogen.fr
Background—Blood flow characteristics influence endothelial cell apoptosis. However, little is known about the occurrence of endothelial cell apoptosis in human atherosclerosis and its relation to blood flow.
Methods and Results—A total of 42 human carotid atherosclerotic
plaques were retrieved by endarterectomy; they were
examined in the longitudinal axial direction. Plaques were included in
this study when upstream and downstream parts were clearly visible,
occlusion was absent, and immunostaining for luminal
endothelium was present all along the plaque. Using
these criteria, 13 plaques were processed for further
immunohistochemical studies (using anti-CD31, anti-Ki-67, and
anti-splicing factor antibodies) and in situ detection of
apoptosis (terminal dUTP nick end-labeling and ligase assay).
Eight plaques showed 
1 apoptotic endothelial
cell at the luminal surface. Quantitative analysis of
endothelial cell apoptosis in these plaques
showed a systematic preferential occurrence of apoptosis in the
downstream parts of plaques, where low flow and low shear stress
prevail, in comparison with the upstream parts (18.8±3.3% versus
2.7±1.2%, respectively, P<0.001).
Endothelial cell apoptosis was barely
detectable in plaque microvessels.
Conclusions—Our results suggest that in vivo local shear stress influences luminal endothelial cell apoptosis and may be a major determinant of plaque erosion and thrombosis.
Key Words: blood flow • stress, mechanical • atherosclerosis • apoptosis • endothelium
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