Articles |
From the Department of Internal Medicine (J.C.R., M.M.W., A.A.R.), School of Medicine, University of California, Davis; Scripps Research Institute (L.K.C.), La Jolla, Calif; and the Department of Medicine (I.J.G.), Columbia University College of Physicians & Surgeons, New York, NY.
Correspondence to John C. Rutledge, MD, Division of Cardiovascular Medicine, TB 172, Bioletti Way, University of California, Davis, CA 95616. E-mail jcrutledge{at}ucdavis.edu
Abstract Mechanisms responsible for the accumulation of
low-density lipoprotein (LDL) were investigated in a new model, the
perfused hamster aorta. To do this, we developed a method to study LDL
flux in real time in individually perfused arteries; each artery served
as its own control. Using quantitative fluorescence microscopy,
the rates of LDL accumulation and efflux were separately determined.
Perfusion of arteries with buffer plus lipoprotein lipase (LpL)
increased LDL accumulation 5-fold (0.1±0.03 mV/min [control] versus
0.5±0.05 mV/min [LpL]) by increasing LDL retention in the artery
wall. This effect was blocked by heparin and monoclonal antibodies
directed against the amino-terminal region of apolipoprotein B (apo B).
This suggests that specific regions of apo B are involved in LDL
accumulation within arteries. Also, the effect of hydrolysis of
triglyceride-rich lipoproteins on
endothelial barrier function was studied. We compared
endothelial layer permeability using a water-soluble
reference molecule, fluorescently labeled dextran. When LpL was
added to hypertriglyceridemic plasma,
dextran accumulation within the artery wall increased >4-fold
(0.024±0.01 mV/min [control] versus 0.098±0.05 mV/min [LpL]).
Under the same conditions, LpL increased LDL accumulation
3-fold
(0.016±0.003 mV/min [control] versus 0.047±0.013 mV/min [LpL]).
Rapid efflux of LDL from the artery wall indicated that increased
endothelial layer permeability was the primary
mechanism during periods of increased lipolysis. Our data demonstrate
two LpL-mediated effects that may increase the amount of LDL in the
artery wall. These findings may pertain to the observed relationship
between increased postprandial lipemia and
atherosclerosis.
Key Words: atherosclerosis artery low-density lipoprotein triglyceride proteoglycan
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