Affordable Access

deepdyve-link
Publisher Website

Atheroma Susceptible to Thrombosis Exhibit Impaired Endothelial Permeability In Vivo as Assessed by Nanoparticle-Based Fluorescence Molecular Imaging.

Authors
  • Stein-Merlob, Ashley F1
  • Hara, Tetsuya1
  • McCarthy, Jason R1
  • Mauskapf, Adam1
  • Hamilton, James A1
  • Ntziachristos, Vasilis1
  • Libby, Peter1
  • Jaffer, Farouc A2
  • 1 From the Cardiovascular Research Center, Cardiology Division (A.F.S., T.H., A.M., F.A.J.) and Center for Systems Biology (J.R.M.), Department of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Physiology and Biophysics, Boston University School of Medicine, MA (J.A.H.); Department of Biomedical Engineering, Boston University, MA (J.A.H.); Institute of Biological and Medical Imaging, Chair of Biological Imaging, Technical University of Munich, Germany (V.N.); and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (P.L.). , (Germany)
  • 2 From the Cardiovascular Research Center, Cardiology Division (A.F.S., T.H., A.M., F.A.J.) and Center for Systems Biology (J.R.M.), Department of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Physiology and Biophysics, Boston University School of Medicine, MA (J.A.H.); Department of Biomedical Engineering, Boston University, MA (J.A.H.); Institute of Biological and Medical Imaging, Chair of Biological Imaging, Technical University of Munich, Germany (V.N.); and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (P.L.). [email protected] , (Germany)
Type
Published Article
Journal
Circulation. Cardiovascular imaging
Publication Date
May 01, 2017
Volume
10
Issue
5
Identifiers
DOI: 10.1161/CIRCIMAGING.116.005813
PMID: 28487316
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The role of local alterations in endothelial functional integrity in atherosclerosis remains incompletely understood. This study used nanoparticle-enhanced optical molecular imaging to probe in vivo mechanisms involving impaired endothelial barrier function in experimental atherothrombosis. Atherosclerosis was induced in rabbits (n=31) using aortic balloon injury and high-cholesterol diet. Rabbits received ultrasmall superparamagnetic iron oxide nanoparticles (CLIO) derivatized with a near-infrared fluorophore (CyAm7) 24 hours before near-infrared fluorescence imaging. Rabbits were then either euthanized (n=9) or underwent a pharmacological triggering protocol to induce thrombosis (n=22). CLIO-CyAm7 nanoparticles accumulated in areas of atheroma (P<0.05 versus reference areas). On near-infrared fluorescence microscopy, CLIO-CyAm7 primarily deposited in the superficial intima within plaque macrophages, endothelial cells, and smooth muscle cells. Nanoparticle-positive areas further exhibited impaired endothelial barrier function as illuminated by Evans blue leakage. Deeper nanoparticle deposition occurred in areas of plaque neovascularization. In rabbits subject to pharmacological triggering, plaques that thrombosed exhibited significantly higher CLIO-CyAm7 accumulation compared with nonthrombosed plaques (P<0.05). In thrombosed plaques, nanoparticles accumulated preferentially at the plaque-thrombus interface. Intravascular 2-dimensional near-infrared fluorescence imaging detected nanoparticles in human coronary artery-sized atheroma in vivo (P<0.05 versus reference segments). Plaques that exhibit impaired in vivo endothelial permeability in cell-rich areas are susceptible to subsequent thrombosis. Molecular imaging of nanoparticle deposition may help to identify biologically high-risk atheroma. © 2017 American Heart Association, Inc.

Report this publication

Statistics

Seen <100 times