(Circulation. 2000;102:2680.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Oxidized Low-Density Lipoprotein Is Associated With Apoptosis of Vascular Smooth Muscle Cells in Human Atherosclerotic Plaques
From the Division of Cardiology (Y.O., M.B., K.J.S., P.D.) and Division of Cardiovascular Surgery (A.K.), University Hospital of Geneva, Switzerland, and the Department of Microbiology and Molecular Pathology (H.I.), Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Correspondence to Dr P. Delafontaine, Division of Cardiology, University Hospital of Geneva, Rue Micheli-du-Crest 24, CH-1211 Geneva, Switzerland. E-mail patrice.delafontaine{at}hcuge.ch
Background—Cytotoxic oxidized LDL (oxLDL) has been shown to promote apoptosis in cultured vascular smooth muscle cells (VSMCs). We investigated the localization of oxLDL and its association with apoptosis and the expression of apoptosis-related proteins in early and advanced atherosclerotic lesions.
Methods and
Results—Atherosclerotic plaques (n=23) from
patients undergoing aortic, carotid, or femoral arterial surgery were
studied. In early lesions, oxLDL was located predominantly in the
superficial intima and in the media just beneath the internal elastic
lamina. Medial VSMCs staining positive for oxLDL showed expression of
BAX, a proapoptotic protein of the BCL-2 family. Apoptosis, as detected
by DNA in situ terminal deoxynucleotidyl transferase end-labeling
(TUNEL), was not present in these early lesions. In advanced plaques,
areas of the intima positive for oxLDL showed lower 
-smooth muscle
actin immunoreactivity (P<0.01) and higher BAX
immunoreactivity (P<0.05). Furthermore, these areas
showed an increased number of apoptotic VSMCs
(P<0.01). Western blot analysis revealed that oxLDL
increases BAX expression in cultured human coronary
VSMCs.
Conclusions—We conclude that in early atherosclerotic lesions, oxLDL-positive VSMCs express BAX, which increases the susceptibility of these cells to undergo apoptosis. This could be important in our understanding of the transition of early lesions into advanced atherosclerotic plaques, which are characterized by regions of cell death. In advanced plaques, oxLDL-positive areas of the intima show higher BAX immunoreactivity and TUNEL-positive VSMCs, and this may contribute to plaque instability and rupture.
Key Words: apoptosis • atherosclerosis • cells • muscle, smooth • lipoproteins
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