In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 32, No. 4 ( 2012-04), p. 962-970
Abstract:
Myeloid-related protein (Mrp) 8/14 complex (is a highly expressed extracellularly secreted protein, implicated in atherosclerosis. In this study, we evaluated the feasibility of targeting Mrp in vivo through synthetic immuno-nanoprobes. Methods and Results— Anti-Mrp–14 and nonspecific IgG-conjugated gadolinium nanoprobes (aMrp-) were synthesized and characterized. Pharmacokinetics and vascular targeting via MRI of the formulations were assessed in vivo in high fat-fed apolipoprotein E deficient (ApoE −/− ), ApoE −/− /Mrp14 −/− (double knockout) and chow-fed wild-type (C57BL/6) mice. Bone marrow-derived myeloid progenitor cells were isolated from both ApoE −/− and double knockout mice, differentiated to macrophages, and were treated with LPS, with or without Mrp8, Mrp14, or Mrp8/14; conditioned media was used for in vitro studies. Mrp-activated cells secreted significant amounts of proinflammatory cytokines, which was abolished by pretreatment with aMrp-NP. We show in vitro that aMrp-NP binds endothelial cells previously treated with conditioned media containing Mrp8/14. MRI following intravenous delivery of aMrp-NP revealed prolonged and substantial delineation of plaque in ApoE −/− but not double knockout or wild-type animals. Nonspecific IgG-conjugated gadolinium nanoprobe-injected animals in all groups did not show vessel wall enhancement. Flow-cytometric analysis of aortic digesta revealed that aMrp-NP present in Ly-6G + , CD11b + , CD11c + , and CD31 + cells in ApoE −/− but not in double knockout animals. Conclusion— Targeted imaging with aMrp-NP demonstrates enhancement of plaque with binding to inflammatory cells and reduction in inflammation. This strategy has promise as a theranostic approach for atherosclerosis.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/ATVBAHA.111.244509
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2012
detail.hit.zdb_id:
1494427-3
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