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Quantifying progression and regression of thrombotic risk in experimental atherosclerosis
Author(s) -
Palekar Rohun U.,
Jallouk Andrew P.,
Goette Matthew J.,
Chen Junjie,
Myerson Jacob W.,
Allen John S.,
Akk Antonina,
Yang Lihua,
Tu Yizheng,
Miller Mark J.,
Pham Christine T. N.,
Wickline Samuel A.,
Pan Hua
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-269084
Subject(s) - fibrous cap , in vivo , medicine , vascular permeability , thrombosis , cardiology , magnetic resonance imaging , pathology , endocrinology , chemistry , biology , radiology , microbiology and biotechnology
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 per‐fluorocarbon 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.—Palekar, R. U., Jallouk, A. P., Goette, M. J., Chen, J., Myerson, J. W., Allen, J. S., Akk, A., Yang, L., Tu, Y., Miller, M. J., Pham, C. T. N., Wickline, S. A., Pan, H. Quantifying progression and regression of thrombotic risk in experimental atherosclerosis. FASEB J . 29, 3100‐3109 (2015). www.fasebj.org