on November 4, 2004
Published online before print November 4, 2004, doi: 10.1161/01.ATV.0000149378.98458.fe
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Submitted on March 16, 2004
Accepted on October 21, 2004
Reduced In Vivo Aortic Uptake of Radiolabeled Oxidation-Specific Antibodies Reflects Changes in Plaque Composition Consistent With Plaque Stabilization
Michael Torzewski ;
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.
* To whom correspondence should be addressed. 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.
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