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 modifica tion in the artery wall. Lipoprotein lipase (LpL), the rate-limiting e nzyme for hydrolysis of lipoprotein triglyceride, is known to bind bot h LDL and arterial PG. In the presence of LpL, cellular internalizatio n and degradation of LDL is enhanced by a pathway initiated by interac tion of LDL with a cell surface heparan sulfate proteoglycan. To deter mine whether LpL enhances the binding of LDL to arterial chondroitin s ulfate (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 i n the presence of LpL but differential effects were seen for the two P G. LpL enhanced the binding of LDL to CSPG a maximum of 20% and to DSP G a maximum of 40%. Heparin displacement of PG binding suggested a gre ater binding strength for DSPG-LpL-LDL with 0.25 mug heparin required to displace 50% of DSPG compared to 0.01 mug to displace 30% of CSPG. The greater enhancement of DSPG-LDL interaction by LpL is of particula r interest since increases in DSPG correlate with the accumulation of aortic cholesterol. These data suggest that lipoprotein lipase may enh ance the interaction of plasma low density lipoprotein with arterial c hondroitin sulfate proteoglycan and dermatan sulfate proteoglycan and thus facilitate low density lipoprotein retention in the artery wall.