Apolipoprotein E mediates the retention of high-density lipoproteins by mouse carotid arteries and cultured arterial smooth muscle cell extracellular matrices.
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.
Olin-Lewis
Katherine
K
Departments of Medicine, University of Washington, Seattle, Wash 98195-6426, USA.
Benton
Jeana L
JL
Rutledge
John C
JC
Baskin
Denis G
DG
Wight
Thomas N
TN
Chait
Alan
A
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D001158:Arteries / Q000166:cytology; D002339:Carotid Arteries / Q000378:metabolism*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D000882:Haplorhini; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism
D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D011509:Proteoglycans