(Circulation. 2001;103:1930.)
© 2001 American Heart Association, Inc.
Editorial |
Measuring Circulating Oxidized Low-Density Lipoprotein to Evaluate Coronary Risk
From the Divisions of Cardiovascular Diseases (S.T.) and Endocrinology and Metabolism (J.L.W.), Department of Medicine, University of California at San Diego, La Jolla, Calif.
Correspondence to Joseph L. Witztum, MD, Department of Medicine, University of California at San Diego, 9500 Gilman Drive, BSB 1080, La Jolla, CA 92093-0682. E-mail jwitztum@ucsd.edu
Key Words: Editorials • cholesterol • coronary disease • myocardial infarction • angina
The hypothesis that oxidized LDL (ox-LDL) is necessary, if not obligatory, in the development of atherosclerotic lesions was formulated >20 years ago with the seminal observation that uptake of native LDL by macrophages did not result in foam cell formation. In contrast, uptake of ox-LDL via scavenger receptors resulted in the unregulated accumulation of lipid.1 Since then, multiple studies in experimental animal models have provided firm evidence of an important role of ox-LDL in atherogenesis. However, the role of ox-LDL in the clinical arena has not yet been established. The report in this issue of Circulation by Ehara et al,2 as well as several other studies, lends support to the idea that the oxidation of LDL is also relevant in humans and continues to move ox-LDL research from the bench to the bedside.3
There is substantial evidence that ox-LDL is present in
vivo within atherosclerotic but not normal blood vessels. LDL that is
extracted from human and animal atherosclerotic lesions has all of the
physical, chemical, immunological, and biological properties of ox-LDL.
Monoclonal antibodies to epitopes of ox-LDL immunostain animal and
human atherosclerotic lesions. Products of lipid peroxidation, such as
oxidized cholesterol, fatty acids, phospholipids, and isoprostanes, are
found in atherosclerotic lesions and plasma. Autoantibodies to epitopes
of ox-LDL, reflecting the fact that ox-LDL is very immunogenic, are
found in lesions and plasma of animals and patients with various
manifestations of atherosclerosis. In addition, radiolabeled
oxidation-specific antibodies image ox-LDL in the artery of live
animals, and plasma autoantibody titers of
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