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

DOI Web Site 被引用文献1件
  • 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.
  • Peter X. Shaw
    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.
  • Kyoo-Rok Han
    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.
  • Brian Shortal
    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.
  • Karl J. Lackner
    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.
  • Joseph L. Witztum
    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.
  • Wulf Palinski
    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.
  • 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.

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<jats:p> <jats:bold> <jats:italic>Objective—</jats:italic> </jats:bold> 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. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> The aortic uptake of intravenously injected <jats:sup>125</jats:sup> I-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 <jats:sup>125</jats:sup> I-MDA2 uptake, high concordance of Sudan (lipid)-staining and <jats:sup>125</jats:sup> I-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 <jats:sup>125</jats:sup> I-MDA2 uptake, which coincided with reduced OxLDL and macrophages but more smooth muscle cells (SMCs) and collagen. In rabbits, areas of increased <jats:sup>125</jats:sup> I-MDA2 uptake were associated with high Sudan concordance and strong immunostaining for OxLDL and macrophages. Interestingly, advanced lesions with focally diminished <jats:sup>125</jats:sup> I-MDA2 uptake showed stronger immunostaining for SMCs and collagen, particularly at the fibrous cap. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusion—</jats:italic> </jats:bold> 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. </jats:p>

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