Lipoprotein-proteoglycan complexes from injured rabbit aortas accelerate lipoprotein uptake by arterial smooth muscle cells.
Lipoprotein-proteoglycan (LP-PG) complexes are taken up more avidly by macrophages and smooth muscle cells (SMCs) than native lipoproteins (LPs). The enhanced uptake may contribute to lipid accumulation and foam cell formation during atherogenesis. Endothelial injury is known to alter proteoglycan (PG) synthesis and distribution in the neointima developed in response to injury. The present study examines the uptake and degradation of LP-PG complexes, derived from PG of injured aortas by arterial SMCs. Rabbit apo-B lipoprotein (LP), including VLDL, IDL and LDL was isolated by ultracentrifugation and coupled with PG extracted from normal aortas (NPG) or with PG from injured aortas (IPG). Rabbit aortic SMCs were cultured from intima-media explants, incubated with 125I-LP, 125I-LP-NPG or 125I-LP-IPG for 20 h at 37 degrees C. LP binding, internalization and degradation were markedly increased (P < 0.001) for LP-NPG and LP-IPG over native LP. Competition experiments indicated that more than 50% of the LP-PG complexes were taken up by the apo-B/E receptor pathway. Phagocytosis was the second important route of uptake of these complexes, whereas the scavenger receptor played a minor part in the uptake and degradation of LP-PG complexes. Data from this study indicate that LP-PG complexes accelerate LP uptake and degradation by SMC more than native LP. Therefore, these complexes may contribute to lipid accumulation by SMC, thus generating foam cells. Furthermore, LP-PG complexes prepared from PG of injured aortas are more effective in lipid accumulation than LP-PG complexes from PG of normal aortas.
Ismail
N A
NA
Department of Pathology, McGill University, Montreal, PQ, Canada.
Alavi
M Z
MZ
Moore
S
S
D000818:Animals; D001011:Aorta / Q000293:injuries*; D001055:Apolipoproteins B / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D005260:Female; D005487:Foam Cells / Q000473:pathology; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D010587:Phagocytosis; D011509:Proteoglycans / Q000378:metabolism*; D011817:Rabbits; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000378:metabolism; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008074:Lipoproteins; D008565:Membrane Proteins; D011509:Proteoglycans; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C032531:apolipoprotein B,E receptor