title: Reduced in vivo aortic uptake of radiolabeled oxidation-specific antibodies reflects changes in plaque composition consistent with plaque stabilization.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University of Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Torzewski
authors.forename: Peter X
authors.initials: PX
authors.lastname: Shaw
authors.forename: Kyoo-Rok
authors.initials: KR
authors.lastname: Han
authors.forename: Brian
authors.initials: B
authors.lastname: Shortal
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.forename: Wulf
authors.initials: W
authors.lastname: Palinski
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000918:Antibody Specificity; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis; D000939:Epitopes; D007150:Immunohistochemistry / Q000379:methods; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008077:Lipoproteins, LDL / Q000032:analysis* / Q000276:immunology; D008315:Malondialdehyde; D051379:Mice; D008817:Mice, Mutant Strains; D010084:Oxidation-Reduction; D011817:Rabbits; D016719:Radioimmunodetection / Q000379:methods*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde