title: Quantifying progression and regression of thrombotic risk in experimental atherosclerosis.
abstract: Currently, there are no generally applicable noninvasive methods for defining the relationship between atherosclerotic vascular damage and risk of focal thrombosis. Herein, we demonstrate methods to delineate the progression and regression of vascular damage in response to an atherogenic diet by quantifying the in vivo accumulation of semipermeable 200-300 nm perfluorocarbon core nanoparticles (PFC-NP) in ApoE null mouse plaques with [(19)F] magnetic resonance spectroscopy (MRS). Permeability to PFC-NP remained minimal until 12 weeks on diet, then increased rapidly following 12 weeks, but regressed to baseline within 8 weeks after diet normalization. Markedly accelerated clotting (53.3% decrease in clotting time) was observed in carotid artery preparations of fat-fed mice subjected to photochemical injury as defined by the time to flow cessation. For all mice on and off diet, an inverse linear relationship was observed between the permeability to PFC-NP and accelerated thrombosis (P = 0.02). Translational feasibility for quantifying plaque permeability and vascular damage in vivo was demonstrated with clinical 3 T MRI of PFC-NP accumulating in plaques of atherosclerotic rabbits. These observations suggest that excessive permeability to PFC-NP may indicate prothrombotic risk in damaged atherosclerotic vasculature, which resolves within weeks after dietary therapy.
authors: *Department of Biomedical Engineering and Department of Medicine, Washington University, St. Louis, Missouri, USA.
authors: Rohun U
authors: RU
authors: Palekar
authors: *Department of Biomedical Engineering and Department of Medicine, Washington University, St. Louis, Missouri, USA.
authors: Andrew P
authors: AP
authors: Jallouk
authors: *Department of Biomedical Engineering and Department of Medicine, Washington University, St. Louis, Missouri, USA.
authors: Matthew J
authors: MJ
authors: Goette
authors: *Department of Biomedical Engineering and Department of Medicine, Washington University, St. Louis, Missouri, USA.
authors: Junjie
authors: J
authors: Chen
authors: *Department of Biomedical Engineering and Department of Medicine, Washington University, St. Louis, Missouri, USA.
authors: Jacob W
authors: JW
authors: Myerson
authors: *Department of Biomedical Engineering and Department of Medicine, Washington University, St. Louis, Missouri, USA.
authors: John S
authors: JS
authors: Allen
authors: *Department of Biomedical Engineering and Department of Medicine, Washington University, St. Louis, Missouri, USA.
authors: Antonina
authors: A
authors: Akk
authors: *Department of Biomedical Engineering and Department of Medicine, Washington University, St. Louis, Missouri, USA.
authors: Lihua
authors: L
authors: Yang
authors: *Department of Biomedical Engineering and Department of Medicine, Washington University, St. Louis, Missouri, USA.
authors: Yizheng
authors: Y
authors: Tu
authors: *Department of Biomedical Engineering and Department of Medicine, Washington University, St. Louis, Missouri, USA.
authors: Mark J
authors: MJ
authors: Miller
authors: *Department of Biomedical Engineering and Department of Medicine, Washington University, St. Louis, Missouri, USA.
authors: Christine T N
authors: CT
authors: Pham
authors: *Department of Biomedical Engineering and Department of Medicine, Washington University, St. Louis, Missouri, USA wicklines@aol.com hpan@dom.wustl.edu.
authors: Samuel A
authors: SA
authors: Wickline
authors: *Department of Biomedical Engineering and Department of Medicine, Washington University, St. Louis, Missouri, USA wicklines@aol.com hpan@dom.wustl.edu.
authors: Hua
authors: H
authors: Pan
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications* / Q000178:diet therapy / Q000209:etiology; D002199:Capillary Permeability; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D003460:Crystallization; D004036:Diet, Atherogenic / Q000009:adverse effects; D066273:Diet, Western / Q000009:adverse effects; D004195:Disease Models, Animal; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D005466:Fluorocarbons; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D053758:Nanoparticles; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000175:diagnosis; D011817:Rabbits; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology*
chemical_list: D001057:Apolipoproteins E; D005466:Fluorocarbons; D002784:Cholesterol
keywords: MRI; endothelium; nanoparticles; thrombosis