Figure 3. Translational applications of OSE Abs.

(A) E06 to oxidized phospholipid (oxPL) can be used to measure oxPL/apoB in human plasma as a biomarker of CVD. Because most oxPL is bound by Lp(A) lipoproteins, the assay primarily reflects the oxPL content on the most atherogenic Lp(A) particles (154). The 10-year predictive value of oxPL/apoB in death, myocardial infarction (MI), and stroke in the prospectively followed Bruneck population, which represents a general community, is shown (155). Groups 1, 2, and 3 represent the top, middle, and bottom tertiles, respectively. (B) Molecular imaging of murine atherosclerosis using MDA2, a malondialdehyde-specific monoclonal Ab. Nanoparticles consisting of micelles containing manganese (Mn) and MDA2 can increase relaxivity through binding to extracellular oxLDL, internalization into macrophages, and intracellular release as free Mn, thus becoming an indirect OSE-dependent macrophage-targeting agent. Noninvasive magnetic resonance imaging of OSEs is accomplished by injection of these nanoparticles and imaging of the abdominal aorta in cholesterol-fed Apoe^–/– mice. Note the lack of signal at the preinjection scan and the strong signal (white contrast) in the 48-hour scan (156). Arrow indicates lesions in the abdominal aorta. (C) Therapeutic use of the human OSE Ab IK17 (as a scFv) to inhibit atherosclerosis. High-plasma titers of IK17 scFv were achieved in cholesterol-fed Ldlr^–/–Rag1^–/– mice via adenoviral-mediated hepatic expression, leading to a 46% reduction in en face atherosclerosis, compared with that in control mice treated with an adenovirus–enhanced green fluorescent protein vector (92). Importantly, peritoneal macrophages isolated from Adv-IK17-scFv–treated mice had decreased lipid accumulation, consistent with the ability of IK17 to inhibit oxLDL uptake by macrophages. Images reprinted with permission from Biomarkers in Medicine (154), Arteriosclerosis, Thrombosis, and Vascular Biology (155), and Journal of the American College of Cardiology (156).