title: Ultrasound-guided imaging of junctional adhesion molecule-A-targeted microbubbles identifies vulnerable plaque in rabbits.
abstract: Identification of vulnerable atherosclerotic plaques by imaging the molecular characteristics is intensively studied recently, in which verification of specific markers is the critical step. JAM-A, a junctional membrane protein, is involved in the plaque formation, while it is unknown whether it can serve as a marker for vulnerable plaques. Vulnerable and stable plaques were created in rabbits with high cholesterol diet with or without partial ligation of carotid artery respectively. Significant higher JAM-A expression was found in vulnerable plaques than that in stable plaques. Furthermore, JAM-A was not only expressed in the endothelium, but also abundantly expressed in CD68-positive area. Next, JAM-A antibody conjugated microbubbles (MBJAM-A) or control IgG-conjugated microbubbles (MBC) were developed by conjugating the biotinylated antibodies to the streptavidin modified microbubbles, and visualization by contrast-enhance ultrasound (CEUS). Signal intensity of MBJAM-A was substantially enhanced and prolonged in the vulnerable plaque and some of the MBJAM-A was found colocalized with CD68 positive macrophages. In addition, cell model revealed that MBJAM-A were able to be phagocytized by activated macrophages. Taken together, we have found that increase of JAM-A serves as a marker for vulnerable plaques and targeted CEUS would be possibly a novel non-invasive molecular imaging method for plaque vulnerability.
authors.affiliation: Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, 323 Hospital of PLA, Xi'an, China; Department of Physiology, Fourth Military Medical University, Xi'an, China.
authors.forename: Dan-Na
authors.initials: DN
authors.lastname: Bai
authors.affiliation: Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jing-Xi
authors.initials: JX
authors.lastname: Du
authors.affiliation: Department of Dermatology, Air Force General Hospital, Beijing, China. Electronic address: dermjin@fmmu.edu.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jia-Lei
authors.initials: JL
authors.lastname: Yang
authors.affiliation: Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Cai
authors.affiliation: Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Chang-Yang
authors.initials: CY
authors.lastname: Xing
authors.affiliation: Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: yuanlj@fmmu.edu.cn.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Yuan
authors.affiliation: Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: duanyy@fmmu.edu.cn.
authors.forename: Yun-You
authors.initials: YY
authors.lastname: Duan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D059305:Diet, High-Fat; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D062745:Junctional Adhesion Molecule A / Q000378:metabolism*; D008026:Ligation; D008262:Macrophage Activation; D008297:Male; D045423:Microbubbles; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D011817:Rabbits; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D062745:Junctional Adhesion Molecule A
keywords: Atherosclerosis; JAM-A; Macrophages; Ultrasound contrast imaging; Vulnerable plaque