From the Divisions of Cardiology (K.D.O., W.C.) and Metabolism,
Endocrinology, and Nutrition (K.L.O., A.C.), Department of Medicine, and the
Department of Pathology (C.E.A., M.F., K.H., T.N.W.), University of
Washington, Seattle.
Correspondence to Kevin D. O'Brien, MD, Division of Cardiology, Box 356422, University of Washington, 1959 NE Pacific St, Seattle, WA 98195. E-mail cardiac{at}u.washington.edu
Background—Because the content of
specific proteoglycans and apolipoproteins is increased in
atherosclerotic plaques and in vitro studies have suggested a role for
proteoglycans in mediating plaque apolipoprotein (apo) retention,
immunohistochemistry was performed to systematically examine the
relative locations of proteoglycans and apolipoproteins in human
atherosclerosis.
Methods and Results—The spatial relationships of versican,
biglycan, and apoE were compared on 68 human coronary artery
segments; apoA-I and apoB also were evaluated on an additional 20
segments. Nonatherosclerotic intima contained extensive deposits of
versican, whereas deposits of apoE, apoB, and apoA-I were much less
prevalent. In contrast, nearly all atherosclerotic segments contained
substantial deposits of biglycan, apoE, apoA-I, and apoB. There was a
high degree of colocalization of apoE and biglycan deposits. ApoA-I,
the major apolipoprotein of HDL, and apoB also were detected in regions
with apoE and biglycan deposition. Exceptions to the localization of
biglycan with apolipoproteins were found in regions that lacked intact
extracellular matrix because of necrosis or dense macrophage
accumulation. In vitro studies demonstrated that biglycan binds
apoE-containing but not apoE-free HDL and that biglycan also binds
LDL.
Conclusions—These results suggest that biglycan may bind apoE and
apoB in atherosclerotic intima. They also raise the possibility that
apoE may act as a "bridging" molecule that traps apoA-I–containing
HDL in atherosclerotic intima. Taken together, these findings are
consistent with the hypothesis that biglycan may contribute to
the pathogenesis of atherosclerosis by trapping
lipoproteins in the artery wall.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Comparison of Apolipoprotein and Proteoglycan Deposits in Human Coronary Atherosclerotic Plaques
Colocalization of Biglycan With Apolipoproteins
Key Words: muscle, smooth • cells • cholesterol • lipoproteins • immunohistochemistry
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