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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2307.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Reduced In Vivo Aortic Uptake of Radiolabeled Oxidation-Specific Antibodies Reflects Changes in Plaque Composition Consistent With Plaque Stabilization

Michael Torzewski; Peter X. Shaw; Kyoo-Rok Han; Brian Shortal; Karl J. Lackner; Joseph L. Witztum; Wulf Palinski; Sotirios Tsimikas

From the Institute of Clinical Chemistry and Laboratory Medicine (M.T., K.J.L.), University of Mainz, Germany; the Department of Internal Medicine (K-R.H.), Hallym University, Seoul, Korea; and the Department of Medicine (P.X.S., B.S., J.L.W., W.P., S.T.), University of California, San Diego.

Correspondence to Sotirios Tsimikas, MD, Vascular Medicine Program, Department of Medicine, University of California, San Diego, 9500 Gilman Dr, BSB 1080, La Jolla, CA 92093-0682. E-mail stsimikas{at}ucsd.edu

Objective— Labeled oxidation-specific antibodies (Ox-AB) detect, quantify, and noninvasively image lipid-rich atherosclerotic lesions. However, it is unknown whether Ox-AB detect plaque stabilization.

Methods and Results— The aortic uptake of intravenously injected ¹²⁵I-MDA2 (Ox-AB to malondialdehyde [MDA]–low-density lipoprotein [LDL]) was quantitated in: (1) LDL receptor–/– mice with established atherosclerosis continued on Western diet (Progression) or switched to chow (Regression) or chow+vitamins E and C (Regression-VIT) for 6 months; and (2) Watanabe rabbits (3- to 57-months old) with naturally evolved atherosclerotic lesions. In mice, the Progression group had more extensive atherosclerosis, higher ¹²⁵I-MDA2 uptake, high concordance of Sudan (lipid)-staining and ¹²⁵I-MDA2 uptake, and stronger oxidized LDL (OxLDL) and macrophage immunostaining than both Regression groups. In contrast, the Regression groups showed Sudan-positive lesions with focally diminished ¹²⁵I-MDA2 uptake, which coincided with reduced OxLDL and macrophages but more smooth muscle cells (SMCs) and collagen. In rabbits, areas of increased ¹²⁵I-MDA2 uptake were associated with high Sudan concordance and strong immunostaining for OxLDL and macrophages. Interestingly, advanced lesions with focally diminished ¹²⁵I-MDA2 uptake showed stronger immunostaining for SMCs and collagen, particularly at the fibrous cap.

Conclusion— Ox-AB uptake is focally diminished in plaques displaying accepted features of plaque stability. Imaging techniques to detect the presence and depletion of OxLDL may be useful in assessing plaque stabilization.

In vivo plaque uptake of radiolabeled oxidation-specific antibodies (Ox-AB) was found to be significantly diminished in regressing lesions with reductions in OxLDL and macrophages and increases in smooth muscle cells and collagen. Thus, labeled Ox-AB may be useful to detect lipid-rich, oxidation-rich plaques and assess stabilization of pre-existing lesions.

Key Words: oxidation • lipoproteins • radionuclide • imaging • antibodies

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