@article{Mohri:2014:10.1371/journal.pone.0115728,
author = {Mohri, Z and Rowland, EM and Clarke, LA and De, Luca A and Peiffer, V and Krams, R and Sherwin, SJ and Weinberg, PD},
doi = {10.1371/journal.pone.0115728},
journal = {PLoS One},
title = {Elevated Uptake of Plasma Macromolecules by Regions of Arterial Wall Predisposed to Plaque Instability in a Mouse Model},
url = {http://dx.doi.org/10.1371/journal.pone.0115728},
volume = {9},
year = {2014}
}

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TY  - JOUR
AB  - Atherosclerosis may be triggered by an elevated net transport of lipid-carryingmacromolecules from plasma into the arterial wall. We hypothesised that whetherlesions are of the thin-cap fibroatheroma (TCFA) type or are less fatty and morefibrous depends on the degree of elevation of transport, with greater uptake leadingto the former. We further hypothesised that the degree of elevation can depend onhaemodynamic wall shear stress characteristics and nitric oxide synthesis. Placinga tapered cuff around the carotid artery of apolipoprotein E -/- mice modifiespatterns of shear stress and eNOS expression, and triggers lesion development atthe upstream and downstream cuff margins; upstream but not downstream lesionsresemble the TCFA. We measured wall uptake of a macromolecular tracer in thecarotid artery of C57bl/6 mice after cuff placement. Uptake was elevated in theregions that develop lesions in hyperlipidaemic mice and was significantly moreelevated where plaques of the TCFA type develop. Computational simulations andeffects of reversing the cuff orientation indicated a role for solid as well as fluidmechanical stresses. Inhibiting NO synthesis abolished the difference in uptakebetween the upstream and downstream sites. The data support the hypothesis thatexcessively elevated wall uptake of plasma macromolecules initiates thedevelopment of the TCFA, suggest that such uptake can result from solid and fluidmechanical stresses, and are consistent with a role for NO synthesis. Modificationof wall transport properties might form the basis of novel methods for reducingplaque rupture.
AU  - Mohri,Z
AU  - Rowland,EM
AU  - Clarke,LA
AU  - De,Luca A
AU  - Peiffer,V
AU  - Krams,R
AU  - Sherwin,SJ
AU  - Weinberg,PD
DO  - 10.1371/journal.pone.0115728
PY  - 2014///
SN  - 1932-6203
TI  - Elevated Uptake of Plasma Macromolecules by Regions of Arterial Wall Predisposed to Plaque Instability in a Mouse Model
T2  - PLoS One
UR  - http://dx.doi.org/10.1371/journal.pone.0115728
UR  - http://hdl.handle.net/10044/1/27771
VL  - 9
ER  - 

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