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(Circulation Research. 2002;90:1333.)
© 2002 American Heart Association, Inc.

Integrative Physiology

Apolipoprotein E Mediates the Retention of High-Density Lipoproteins by Mouse Carotid Arteries and Cultured Arterial Smooth Muscle Cell Extracellular Matrices

Katherine Olin-Lewis, Jeana L. Benton, John C. Rutledge, Denis G. Baskin, Thomas N. Wight, Alan Chait

From the Departments of Medicine (K.O.-L., D.G.B., A.C.) and Pathology (T.N.W.), University of Washington, Seattle, Wash; and the Department of Medicine (J.L.B., J.C.R.), University of California, Davis, Calif. Present address for T.N.W. is The Hope Heart Institute, Seattle, Wash.

Correspondence to Alan Chait, MD, Dept of Medicine, Box 356426, University of Washington, Seattle, WA 98195-6426. E-mail achait{at}u.washington.edu

Lipoprotein retention in the vascular extracellular matrix (ECM) plays a critical role in atherogenesis. Previous studies demonstrated the presence of apo A-I and E in atherosclerotic lesions, suggesting that HDL may be trapped by the artery wall. We sought to determine mechanisms by which HDL could be bound and retained by the arterial wall, and whether apo E was a principal determinant of this binding. We evaluated in situ accumulation of fluorescently labeled DiI-human HDL±apo E in perfused carotid arteries from apo E–null mice. Apo E was important in mediating HDL binding to the vascular wall, with a 48±16% increase in accumulation of DiI-labeled apo E–containing HDL (HDL₃+E) compared with DiI-apo E–free HDL (HDL₃-E) (P=0.003). To investigate possible mechanisms responsible for retention, we assessed binding of unlabeled HDL₃-E and HDL₃+E to ECM generated by cultured arterial smooth muscle cells. Similar to the in situ carotid artery data, HDL₃+E bound better to the ECM than did HDL₃-E (3-fold lower K_a and 3.5-fold higher B_max for HDL₃+E versus HDL₃-E). These differences were eliminated after either neutralization of arginine residues on apo E or digestion of matrix with chondroitin ABC lyase, suggesting that chondroitin and/or dermatan sulfate proteoglycans were responsible for apo E–mediated increased binding. These findings demonstrate that HDL can bind to both intact murine carotid arteries and smooth muscle cell–derived ECM, and that apo E is a principal determinant in mediating the ability of HDL to be trapped and retained via its interaction with ECM proteoglycans.

Key Words: apolipoprotein E • high-density lipoproteins • extracellular matrix • artery wall • proteoglycan

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