Lipoprotein lipase enhances the interaction of low density lipoproteins with artery-derived extracellular matrix proteoglycans.
The association of plasma low density lipoproteins (LDL) with arterial proteoglycans (PG) is of key importance in LDL retention and modification in the artery wall. Lipoprotein lipase (LpL), the rate-limiting enzyme for hydrolysis of lipoprotein triglyceride, is known to bind both LDL and arterial PG. In the presence of LpL, cellular internalization and degradation of LDL is enhanced by a pathway initiated by interaction of LDL with a cell surface heparan sulfate proteoglycan. To determine whether LpL enhances the binding of LDL to arterial chondroitin sulfate (CS)PG and dermatan sulfate (DS)PG, the major extracellular PG of the artery wall, a microtiter plate assay was used to study LpL-PG-LDL interactions. Binding of LDL to both CSPG and DSPG was increased in the presence of LpL but differential effects were seen for the two PG. LpL enhanced the binding of LDL to CSPG a maximum of 20% and to DSPG a maximum of 40%. Heparin displacement of PG binding suggested a greater binding strength for DSPG-LpL-LDL with 0.25 micrograms heparin required to displace 50% of DSPG compared to 0.01 micrograms to displace 50% of CSPG. The greater enhancement of DSPG-LDL interaction by LpL is of particular interest since increases in DSPG correlate with the accumulation of aortic cholesterol. These data suggest that lipoprotein lipase may enhance the interaction of plasma low density lipoprotein with arterial chondroitin sulfate proteoglycan and dermatan sulfate proteoglycan and thus facilitate low density lipoprotein retention in the artery wall.
Edwards
I J
IJ
Department of Comparative Medicine, Bowman Gray School of Medicine, Winston-Salem, NC 27157-1040.
Goldberg
I J
IJ
Parks
J S
JS
Xu
H
H
Wagner
W D
WD
D000818:Animals; D001158:Arteries / Q000737:chemistry; D002809:Chondroitin Sulfates / Q000097:blood; D003871:Dermatan Sulfate / Q000097:blood; D005109:Extracellular Matrix / Q000737:chemistry*; D006493:Heparin / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008252:Macaca fascicularis; D011509:Proteoglycans / Q000097:blood*
D008077:Lipoproteins, LDL; D011509:Proteoglycans; D003871:Dermatan Sulfate; D006493:Heparin; D002809:Chondroitin Sulfates; D008071:Lipoprotein Lipase