0000000000282082
AUTHOR
Joseph L. Witztum
Reduced In Vivo Aortic Uptake of Radiolabeled Oxidation-Specific Antibodies Reflects Changes in Plaque Composition Consistent With Plaque Stabilization
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 125 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 athero…
Human Oxidation-Specific Antibodies Reduce Foam Cell Formation and Atherosclerosis Progression
ObjectivesWe sought to assess the in vivo importance of scavenger receptor (SR)–mediated uptake of oxidized low-density lipoprotein (OxLDL) in atherogenesis and to test the efficacy of human antibody IK17-Fab or IK17 single-chain Fv fragment (IK17-scFv), which lacks immunologic properties of intact antibodies other than the ability to inhibit uptake of OxLDL by macrophages, to inhibit atherosclerosis.BackgroundThe unregulated uptake of OxLDL by macrophage SR contributes to foam cell formation, but the importance of this pathway in vivo is uncertain.MethodsCholesterol-fed low-density lipoprotein receptor knockout (LDLR−/−) mice were treated with intraperitoneal infusion of human IK17-Fab (2.…