TY - JOUR
T1 - Quantifying progression and regression of thrombotic risk in experimental atherosclerosis
AU - Palekar, Rohun U.
AU - Jallouk, Andrew P.
AU - Goette, Matthew J.
AU - Chen, Junjie
AU - Myerson, Jacob W.
AU - Allen, John S.
AU - Akk, Antonina
AU - Yang, Lihua
AU - Tu, Yizheng
AU - Miller, Mark J.
AU - Pham, Christine T.N.
AU - Wickline, Samuel A.
AU - Pan, Hua
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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 [19F] 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-NPmay 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.
AB - 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 [19F] 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-NPmay 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.
KW - Endothelium
KW - MRI
KW - Nanoparticles
KW - Thrombosis
UR - http://www.scopus.com/inward/record.url?scp=84940404076&partnerID=8YFLogxK
U2 - 10.1096/fj.14-269084
DO - 10.1096/fj.14-269084
M3 - Article
C2 - 25857553
AN - SCOPUS:84940404076
SN - 0892-6638
VL - 29
SP - 3100
EP - 3109
JO - FASEB Journal
JF - FASEB Journal
IS - 7
ER -