期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep21785
关键词
-
资金
- Wellcome Trust Clinical Research Fellowship, as part of the Wellcome Trust/GSK Fellowship programme [095034/Z/10/Z]
- British Atherosclerosis Society Binks Trust Travel Award [BASBT/13/001]
- NIH [HL R01 108229]
- British Heart Foundation (BHF)
- BHF
- Imperial College Healthcare Trust Biomedical Research Centre
- Wellcome Trust [095034/Z/10/Z] Funding Source: Wellcome Trust
- MRC [MR/M024903/1] Funding Source: UKRI
- British Heart Foundation [FS/07/053/24069, FS/13/12/30037] Funding Source: researchfish
- Medical Research Council [MR/M024903/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0514-10022] Funding Source: researchfish
We aimed to develop a quantitative antibody-based near infrared fluorescence (NIRF) approach for the imaging of oxidized LDL in atherosclerosis. LO1, a well-characterized monoclonal autoantibody that reacts with malondialdehyde-conjugated LDL, was labeled with a NIRF dye to yield LO1-750. LO1-750 specifically identified necrotic core in ex vivo human coronary lesions. Injection of LO1-750 into high fat (HF) fed atherosclerotic Ldlr(-/-) mice led to specific focal localization within the aortic arch and its branches, as detected by fluorescence molecular tomography (FMT) combined with micro-computed tomography (CT). Ex vivo confocal microscopy confirmed LO1-750 subendothelial localization of LO1-750 at sites of atherosclerosis, in the vicinity of macrophages. When compared with a NIRF reporter of MMP activity (MMPSense-645-FAST), both probes produced statistically significant increases in NIRF signal in the Ldlr(-/-)model in relation to duration of HF diet. Upon withdrawing the HF diet, the reduction in oxLDL accumulation, as demonstrated with LO1-750, was less marked than the effect seen on MMP activity. In the rabbit, in vivo injected LO1-750 localization was successfully imaged ex vivo in aortic lesions with a customised intra-arterial NIRF detection catheter. A partially humanized chimeric LO1-Fab-Cys localized similarly to the parent antibody in murine atheroma showing promise for future translation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据