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From the Department of Pathology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC.
Correspondence to Dawn C. Schwenke, PhD, Department of Pathology, Bowman Gray School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1072. E-mail dschwenke@cpm.bgsm.wfu.edu.
Abstract In rabbits, the aortic arch and branch sites of the
descending thoracic and abdominal aortas are susceptible to
atherosclerosis. This study investigated the hypothesis
that the reported focal increase in LDL concentration and mean
residence time at susceptible aortic sites after feeding
cholesterol for 4 to 8 days precede atherosclerotic change
as indicated by increased aortic cholesterol concentration.
Cholesterol concentrations for all aortic sites of normal
rabbits were similar (
2.8 µmol/g). No change in aortic
cholesterol concentration could be detected after feeding
cholesterol for 8 days. However, after feeding
cholesterol for 12 and 16 days, cholesterol
concentrations for abdominal branch sites were increased compared with
abdominal branch sites of normal rabbits (4.47±0.50, n=8, and
4.85±0.33, n=11, µmol/g, respectively, versus 2.87±0.27, n=12,
µmol/g; P<.025 and P<.005, respectively). In
contrast, the cholesterol concentration of
atherosclerosis-resistant nonbranch
abdominal aorta was unchanged after feeding cholesterol for
16 days and was much less than that of the branch sites (2.72±0.12
versus 4.85±0.33 µmol/g, n=11; P<.001).
Cholesterol concentrations for other susceptible sites were
also increased after feeding cholesterol for 12 and 16
days. Cholesterol concentrations for susceptible sites were
linearly related to a combined measure of duration and extent of
hypercholesterolemia (P<.001 to
P<.0001), whereas no such relationship could be detected
for resistant sites. Most (59% to 93%) of the
cholesterol accumulating in susceptible aortic sites after
feeding cholesterol for 12 and 16 days was nonesterified,
suggesting that the increased cholesterol concentration did
not reflect development of foam cells or the insudation of plasma
lipoproteins. This study suggests that the reported focal increases in
LDL concentration and mean residence time at susceptible aortic sites
during cholesterol feeding precede
atherosclerosis.
Key Words: atherosclerosis cholesterol aorta susceptibility rabbit
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