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In Vivo Human Single-Chain Fragment Variable Phage Display-Assisted Identification of Galectin-3 as a New Biomarker of Atherosclerosis

dc.contributor.authorHEMADOU, Audrey
dc.contributor.authorFONTAYNE, Alexandre
dc.contributor.authorLAROCHE‐TRAINEAU, Jeanny
dc.contributor.authorOTTONES, Florence
dc.contributor.authorMONDON, Philippe
dc.contributor.authorCLAVEROL, Stéphane
dc.contributor.authorDUCASSE, Éric
dc.contributor.authorSANCHEZ, Stéphane
dc.contributor.authorMOHAMAD, Sarah
dc.contributor.authorLORENZATO, Cyril
dc.contributor.authorDUONOR‐CERUTTI, Martine
dc.contributor.authorCLOFENT‐SANCHEZ, Gisèle
dc.contributor.authorJACOBIN‐VALAT, Marie‐Josée
dc.date.accessioned2021-10-07T16:27:48Z
dc.date.available2021-10-07T16:27:48Z
dc.date.issued2021-10-01
dc.identifier.issn2047-9980
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112572
dc.description.abstractEnBACKGROUND: Atherosclerosis is a complex pathology in which dysfunctional endothelium, activated leucocytes, macrophages, and lipid-laden foam cells are implicated, and in which plaque disruption is driven by many putative actors. This study aimed to identify accurate targetable biomarkers using new in vivo approaches to propose tools for improved diagnosis and treatment. METHODS AND RESULTS: Human scFv (single-chain fragment variable) selected by in vivo phage display in a rabbit model of atherosclerosis was reformatted as scFv fused to the scFv-Fc (single-chain fragment variable fused to the crystallizable fragment of immunoglobulin G format) antibodies. Their reactivity was tested using flow cytometry and immunoassays, and aorta sections from animal models and human carotid and coronary artery specimens. A pool of atherosclerotic proteins from human endarterectomies was co-immunoprecipitated with the selected scFv-Fc followed by mass spectrometry for target identification. Near-infrared fluorescence imaging was performed in Apoe −/− mice after injection of an Alexa Fluor 647-labeled scFv-Fc-2c antibody produced in a baculovirus system with 2 additional cysteine residues (ie, 2c) for future coupling to nanoobjects for theranostic applications. One scFv-Fc clone (P3) displayed the highest cross-reactivity against atherosclerotic lesion sections (rabbit, mouse, and human) and was chosen for translational development. Mass spectrometry identified galectin-3, a β-galactoside-binding lectin, as the leader target. ELISA and immunofluorescence assays with a commercial anti-galectin-3 antibody confirmed this specificity. P3 scFv-Fc-2c specifically targeted atherosclerotic plaques in the Apoe −/− mouse model. CONCLUSIONS: These results provide evidence that the P3 antibody holds great promise for molecular imaging of atherosclerosis and other inflammatory pathologies involving macrophages. Recently, galectin-3 was proposed as a high-value biomarker for the assessment of coronary and carotid atherosclerosis.
dc.language.isoen
dc.publisherWiley-Blackwell
dc.rights.urihttp://creativecommons.org/licenses/by-nc/
dc.title.enIn Vivo Human Single-Chain Fragment Variable Phage Display-Assisted Identification of Galectin-3 as a New Biomarker of Atherosclerosis
dc.typeArticle de revue
dc.identifier.doi10.1161/JAHA.120.016287
dc.subject.halSciences du Vivant [q-bio]
bordeaux.journalJournal of the American Heart Association
bordeaux.volume10
bordeaux.hal.laboratoriesCentre de Résonance Magnétique des Systèmes Biologiques (CRMSB) - UMR 5536*
bordeaux.issue19
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierhal-03366155
hal.version1
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-03366155v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20the%20American%20Heart%20Association&rft.date=2021-10-01&rft.volume=10&rft.issue=19&rft.eissn=2047-9980&rft.issn=2047-9980&rft.au=HEMADOU,%20Audrey&FONTAYNE,%20Alexandre&LAROCHE%E2%80%90TRAINEAU,%20Jeanny&OTTONES,%20Florence&MONDON,%20Philippe&rft.genre=article


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