title: High-frequency ultrasound-guided disruption of glycoprotein VI-targeted microbubbles targets atheroprogressison in mice.
abstract: Targeted contrast-enhanced ultrasound (CEU) using microbubble agents is a promising non-invasive imaging technique to evaluate atherosclerotic lesions. In this study, we decipher the diagnostic and therapeutic potential of targeted-CEU with soluble glycoprotein (GP)-VI in vivo. Microbubbles were conjugated with the recombinant fusion protein GPVI-Fc (MBGPVI) that binds with high affinity to atherosclerotic lesions. MBGPVI or control microbubbles (MBC) were intravenously administered into ApoE(-/-) or wild type mice and binding of the microbubbles to the vessel wall was visualized by high-resolution CEU. CEU molecular imaging signals of MBGPVI were substantially enhanced in the aortic arch and in the truncus brachiocephalicus in ApoE(-/-) as compared to wild type mice. High-frequency ultrasound (HFU)-guided disruption of MBGPVI enhanced accumulation of GPVI in the atherosclerotic lesions, which may interfere with atheroprogression. Thus, we establish targeted-CEU with soluble GPVI as a novel non-invasive molecular imaging method for atherosclerosis. Further, HFU-guided disruption of GPVI-targeted microbubbles is an innovate therapeutic approach that potentially prevents progression of atherosclerotic disease.
authors.affiliation: Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Metzger
authors.affiliation: Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Vogel
authors.affiliation: Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Chatterjee
authors.affiliation: Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Borst
authors.affiliation: Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Seizer
authors.affiliation: Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schönberger
authors.affiliation: Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
authors.affiliation: Institute of Physiology, Eberhard Karls University Tübingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.affiliation: Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Langer
authors.affiliation: Department of Physics, Eberhard Karls University Tübingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Rheinlaender
authors.affiliation: Department of Physics, Eberhard Karls University Tübingen, Germany.
authors.forename: Tilman E
authors.initials: TE
authors.lastname: Schäffer
authors.affiliation: Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany. Electronic address: meinrad.gawaz@med.uni-tuebingen.de.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D003287:Contrast Media / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D057054:Molecular Imaging / Q000379:methods*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D010980:Platelet Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; C098341:platelet membrane glycoprotein VI
keywords: Atherosclerosis; Glycoprotein-VI; High-frequency ultrasound; Microbubbles; Targeted contrast-enhanced ultrasound