HDL-ApoE content regulates the displacement of hepatic lipase from cell surface proteoglycans.
Human hepatic lipase (HL) is an interfacial enzyme that must be liberated from cell surface proteoglycans to hydrolyze lipoprotein triglyceride. Both high-density lipoprotein (HDL) and apolipoprotein (apo)A-I can displace HL from cell surface proteoglycans, much like heparin. HL displacement is inhibited by HDL-apoE content. Postprandial HDL is approximately twofold better at displacing HL than is fasting HDL, but only has approximately one-half the apoE content. Enriching native HDL with triglyceride decreases HDL-apoE content and increases HL displacement. Incubation of HDL with the anti-apoE antibody, 6C5, also increases HL displacement. In contrast, enrichment of synthetic HDL with apoE significantly inhibits HL displacement. HDL from fasted female normolipidemic subjects displaces HL approximately twofold better than HDL from male subjects. HDL from female subjects also has significantly less apoE than HDL from males. Normolipidemic females have increased circulating HDL-bound HL. Hyperlipidemia has little effect on the HL displacement ability of HDL from men, whereas HDL from hypercholesterolemic females exhibits impaired HL displacement. HL displacement from liver heparan sulfate proteoglycans therefore appears to be linked to interlipoprotein apoE exchange. Decreased HL displacement is associated with higher HDL-apoE levels and may therefore affect vascular triglyceride hydrolysis.
Young
Elizabeth K
EK
University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada. dsparks@ottawaheart.ca
Chatterjee
Cynthia
C
Sparks
Daniel L
DL
D001057:Apolipoproteins E / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000737:chemistry / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D015151:Immunoblotting; D008049:Lipase / Q000378:metabolism*; D008297:Male; D011509:Proteoglycans / Q000378:metabolism*; D012727:Sex Characteristics
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; C504173:LIPC protein, human; D011509:Proteoglycans; D008049:Lipase